Endoscopic application of mussel-inspired phenolic chitosan as a hemostatic agent for gastrointestinal bleeding: A preclinical study in a heparinized pig model.

Marine mussels secrete adhesive proteins to attach to solid surfaces. These proteins contain phenolic and basic amino acids exhibiting wet adhesion properties. This study used a mussel-inspired hemostatic polymer, chitosan-catechol, to treat gastrointestinal bleeding caused by endoscopic mucosal resection in a heparinized porcine model. We aimed to evaluate the hemostatic efficacy and short-term safety of this wet adhesive chitosan-catechol. We used 15 heparinized pigs. Four iatrogenic bleeding ulcers classified as Forrest Ib were created in each pig using an endoscopic mucosal resection method. One ulcer in each pig was untreated as a negative control (no-treatment group). The other three ulcers were treated with gauze (gauze group), argon plasma coagulation (APC group), and chitosan-catechol hemostatic agent (CHI-C group) each. The pigs were sacrificed on Days 1, 5, and 10, and histological examination was performed (n = 5 per day). Rapid hemostasis observed at 2 min after bleeding was 93.3% (14/15) in the CHI-C group, 6.7% (1/15) in the no-treatment group, 13.3% (2/15) in the gauze group, and 86.7% (13/15) in the APC group. No re-bleeding was observed in the CHI-C group during the entire study period. However, a few re-bleeding cases were observed on Day 1 in the no-treatment, gauze, and APC groups and on Day 5 in the gauze and APC groups. On histological analysis, the CHI-C group showed the best tissue healing among the four test groups. Considering the results, chitosan-catechol is an effective hemostatic material with reduced re-bleeding and improved healing.

Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice.

AIM: Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. METHODS: C57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. RESULTS: KRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. CONCLUSIONS: These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression.

Overview of gastrointestinal cancer prevention in Asia.

"War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic, popularly consumed as a food ingredient in many Asian countries), capsaicin, 6-gingerol, flavopiridol, and silymarin (abundant in various Asian foods). Whereas in Western countries cancer chemotherapeutics involve strategies not only to block the growth of the primary tumor, but also to inhibit its progression to metastatic disease, the endless pursuit of effective agents for cancer prevention may be a unique and featured strategy in Asia. More active efforts for clinical application of these principles should be supported.

Dietary prevention of Helicobacter pylori-associated gastric cancer with kimchi.

To prove whether dietary intervention can prevent Helicobacter pylori-induced atrophic gastritis and gastric cancer, we developed cancer preventive kimchi (cpKimchi) through special recipe and administered to chronic H. pylori-initiated, high salt diet-promoted, gastric tumorigenesis mice model. H. pylori-infected C57BL/6 mice were administered with cpKimchi mixed in drinking water up to 36 weeks. Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively and explored underlying molecular changes to explain efficacies. Cancer preventive actions of anti-inflammation and anti-mutagenesis were compared between standard recipe kimchi (sKimchi) and special recipe cpKimchi in in vitro H. pylori-infected cell model. The erythematous and nodular changes, mucosal ulcerative and erosive lesions in the stomach were noted at 24th weeks, but cpKimchi administration significantly ameliorated. After 36th weeks, scattered nodular masses, some ulcers, and thin nodular gastric mucosa were noted in H. pylori-infected mice, whereas these gross lesions were significantly attenuated in cpKimchi group. On molecular analysis, significant expressions of COX-2 and IL-6, activated NF-κB and STAT3, increased apoptosis, and marked oxidative stresses were noted in H. pylori-infected group relevant to tumorigenesis, but these were all significantly attenuated in cpKimchi group. cpKimchi extracts imparted significant selective induction of apoptosis only in cancer cells, led to inhibition of H. pylori-induced proliferation, while no cytotoxicity through significant HO-1 induction in non-transformed gastric cells. In conclusion, daily dietary intake of cpKimchi can be an effective way either to rejuvenate H. pylori-atrophic gastritis or to prevent tumorigenesis supported with the concerted actions of anti-oxidative, anti-inflammatory, and anti-mutagenic mechanisms.

Omega-3 polyunsaturated fatty acids as an angelus custos to rescue patients from NSAID-induced gastroduodenal damage.

Nonsteroidal anti-inflammat ory drugs (NSAIDs) are one of the drug types frequently prescribed for their analgesic, anti-inflammatory, and antithrombotic actions, but carry a risk of major gastroduodenal damage from mild erosive changes to serious ulceration leading to fatal outcomes. From the long history of willow tree bark and its extracts being applied for the relief of pain and fever, the synthesis of acetylsalicylic acid, the development of selective cyclooxygenase 2 inhibitors (coxibs), and the identification of a G-protein-coupled receptor for prostaglandin, the popular combination regimen of an NSAID and a proton pump inhibitor was invented, but development was continued for further improvement. With regard to major NSAID adverse effects, gastrointestinal (GI) and cardiovascular (CV) risks still remained as problems to be solved. In this review, it is shown that n-3 polyunsaturated fatty acid (PUFA) based NSAIDs can be an angelus custos, supported with facts that an intake of essential n-3 PUFAs orchestrates concerted protective actions against two notorious side effects of NSAIDs, the aforementioned GI risk and CV risk of NSAIDs. Since pills containing n-3 PUFAs, omega-3-acid ethyl ester capsules (Lovaza, Omarcor), have already been safely prescribed to prevent atherosclerosis through lessening lipid burdening, the introduction of a drug delivery system such as a gastroretentive form of n-3 PUFA based NSAIDs will highlight newer hope for GI safety under the guarantee of reduced CV risk. Because n-3 PUFAs have been proven to attenuate cytotoxicity, inhibit lipid-raft-associated harmful signaling, and relieve oxidative stress relevant to NSAIDs, n-3 PUFA based NSAIDs will be next-generation GI-safe NSAIDs.

Comparison of clinical effectiveness of the emergent colonoscopy in patients with hematochezia according to the type of bowel preparation.

BACKGROUND AND AIMS: Colonoscopy (CFS) is a valuable diagnostic tool in patients with hematochezia. However, the optimal preparation method of emergent CFS for hematochezia has not been defined. We investigated the clinical effectiveness of bowel preparation of patients with hematochezia using polyethylene glycol (PEG) solution and glycerin or water enemas. METHODS: The medical records of the past 7 years were reviewed. Patients presenting with hematochezia that occurred within 24 h before admission were eligible for the study. All patients underwent CFS within 24 h after visiting the emergency room for hematochezia. Patients were classified into two groups according to the preparation method used (enema vs. PEG). RESULTS: Overall, 194 patients (125 enema vs. 69 PEG) were enrolled. The diagnostic rate of bleeding focus was lower in the enema group than in the PEG group (84% vs. 97.1%, P = 0.008). Performance of endoscopic hemostasis at the initial CFS was more frequent in the enema group than in the PEG group (40.8% vs. 10.1%, P < 0.001). The rate of repeated CFS was higher in the enema group than in the PEG group (44.0% vs. 18.8%, P < 0.001). Post-polypectomy bleeding (n = 33) was diagnosed during the initial study and was treated endoscopically. In cases of post-polypectomy bleeding, CFS (93.9%) was performed after an enema in all but two cases. CONCLUSIONS: In hematochezia patients, the PEG group showed a higher diagnostic rate and lower rate of repeated CFS. However, emergent CFS after an enema only seems to be useful in patients with severe hematochezia or if the bleeding focus can be presumed.