Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage

Metal-based carbon monoxide (CO)-releasing molecules have been shown to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. We are interested in further development of metal-free CO-based therapeutics for oral administration. Thus, we examine the protective effect of representative CO prodrug, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin, a representative non-steroidal anti-inflammatory drug. Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry. Gastric mucosal mRNA and/or protein expressions of HMOX1, HMOX2, nuclear factor erythroid 2-related factor 2, COX1, COX2,

Microbiology and clinical characteristics of viridans group streptococci in patients with cancer

ABSTRACT This study assessed the microbiology, clinical syndromes, and outcomes of oncologic patients with viridans group streptococci isolated from blood cultures between January 1st, 2013 and December 31st, 2016 in a referral hospital in Mexico using the Bruker MALDI Biotyper. Antimicrobial sensitivity was determined using BD Phoenix 100 according to CLSI M100 standards. Clinical information was obtained from medical records and descriptive analysis was performed.Forty-three patients were included, 22 females and 21 males, aged 42 ± 17 years. Twenty (46.5%) patients had hematological cancer and 23 (53.5%) a solid malignancy. The viridans group streptococci isolated were Streptococcus mitis, 20 (46.5%); Streptococcus anginosus, 14 (32.6%); Streptococcus sanguinis, 7 (16.3%); and Streptococcus salivarius, 2 (4.7%). The main risk factors were pyrimidine antagonist chemotherapy in 22 (51.2%) and neutropenia in 19 (44.2%) cases, respectively. Central line associated bloodstream infection was diagnosed in 18 (41.9%) cases. Septic shock occurred in 20.9% of patients, with an overall mortality of 18.6%. Only four S. mitis revealed penicillin-resistance.Our results are similar to those of other series, identifying these bacteria as emerging pathogens with significant morbidity and mortality in oncologic patients. The MALDI-TOF system increased the rate of viridans group streptococci isolation in this population.

Effects of different doses of ginger-partitioned moxibustion on trefoil factor 1, mucin 5AC and epidermal growth factor receptor in rats with spleen deficiency syndrome / 针灸推拿医学（英文版）

Objective: To observe the effects of different doses of ginger-partitioned moxibustion on serum trefoil factor 1 (TFF1) and mucin 5AC (MUC5AC) levels, as well as the expression of epidermal growth factor receptor (EGFR) in gastric mucosa of rats with spleen deficiency syndrome, therefore, to explore the possible mechanism and the dose-effect characteristics of ginger-partitioned moxibustion in spleen deficiency syndrome. Methods: Seventy-five SPF grade Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a 3 moxa-cone ginger-partitioned moxibustion group (group C1), a 6 moxa-cone ginger-partitioned moxibustion group (group C2) and a 9 moxa-cone ginger-partitioned moxibustion group (group C3) using random number table method, 15 rats in each group. Except group A, rats in the other groups received intragastric administration of 4 ℃200% concentrated Da Huang (Radix et Rhizoma Rhei) to prepare spleen deficiency syndrome model. After successful modeling, rats in group B received no treatment; rats in group C1, C2 and C3 were treated with 3, 6 and 9 moxa-cone ginger-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12) respectively for 8 continuous days. The general symptom score of rats was observed. The serum levels of TFF1 and MUC5AC were detected by enzyme-linked immunosorbent assay (ELISA). The expression of EGFR protein in gastric mucosa was detected by immunohistochemistry. Results: After the treatment, compared with group A, the spleen deficiency symptom score was increased in group B, the levels of serum TFF1 and MUC5AC, the EGFR protein expression in gastric tissues of group C1, C2 and C3 were significantly increased (all P<0.01); compared with group B, the spleen deficiency scores were decreased in group C1, C2 and C3, and the serum levels of TFF1 and MUC5AC, as well as EGFR protein expression in gastric tissues were increased (all P<0.01). Compared with group C1, the spleen deficiency scores were decreased in group C2 and C3, the serum levels of TFF1 and MUC5AC, and the expression of EGFR protein in gastric tissues were increased (all P<0.01), however, there was no significant difference between group C2 and C3 (all P>0.05). The mechanism may be related to the increase of serum TFF1 and MUC5AC levels and activation of EGFR protein. Conclusion: Ginger-partitioned moxibustion can improve the symptoms, as well as promote the proliferation and repair of gastric mucosa in rats with spleen deficiency. The therapeutic efficacy of 6 or 9 moxa-cone ginger-partitioned moxibustion is better than that of 3 moxa-cone ginger-partitioned moxibustion, while the efficacies are equivalent between 6 and 9 moxa-cone ginger-partitioned moxibustion groups.

Effect of herbal cake-partitioned moxibustion on MEK1/2 and ERK1/2 expressions of gastric tissues in rats with spleen deficiency syndrome / 针灸推拿医学（英文版）

Objective:To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods:Sixty Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a ranitidine group (group C), and a herbal cake-partitioned moxibustion group (group D) by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang (Radix et Rhizoma Rhei). After successful modeling, the rats in group C were treated with 25 mg/(kg·bw) ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/(kg·bw) at 8:00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin (HE) staining. The protein expressions of MEK1/2 and ERK1/2 in the gastric tissues were detected by immunohistochemistry. Results:After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK1/2 and ERK1/2 in gastric tissues of the other groups were significantly higher (P<0.01). Compared with group B, the protein expressions of MEK1/2 and ERK1/2 in group C and D were significantly higher (allP<0.01). Compared with group C, the protein expressions of MEK1/2 and ERK1/2 in group D were significantly higher (P<0.01). Conclusion: Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK1/2 and ERK1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.

Effect of herbal cake-partitioned moxibustion on MEK1/2 and ERK1/2 expressions of gastric tissues in rats with spleen deficiency syndrome / 针灸推拿医学（英文版）

Objective:To observe the effect of herbal cake-partitioned moxibustion on the expressions of mitogen-activated protein kinase (MEK1/2) and extracellular regulatory protein kinase (ERK1/2) in gastric tissues of rats with spleen deficiency syndrome, and to explore the possible mechanisms of herbal cake-partitioned moxibustion in treating spleen deficiency syndrome. Methods:Sixty Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a ranitidine group (group C), and a herbal cake-partitioned moxibustion group (group D) by random digit, 15 rats in each group. Rat models of spleen deficiency syndrome were made by intragastric administration of 4℃ 200% concentrated Da Huang (Radix et Rhizoma Rhei). After successful modeling, the rats in group C were treated with 25 mg/(kg·bw) ranitidine by intragastric adminstration and rats in group D were treated with herbal cake-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), for 8 d. Excepted for rats in group A, all the other rats were treated with indomethacin at 5 mg/(kg·bw) at 8:00 a.m. on the second day after finishing all the intervention and sacrificed 7 h later to isolate the stomach. Histopathological changes of the gastric tissues were observed under light microscope after hematoxylin-eosin (HE) staining. The protein expressions of MEK1/2 and ERK1/2 in the gastric tissues were detected by immunohistochemistry. Results:After intervention, the gastric mucosal injury in group B was significantly severer than that in group A, with large breakage and ablating; the damage of gastric mucosa was decreased in group C compared with group B; the gastric mucosal surface remained relatively complete, and the status of breakage and ablating was significantly improved. After intervention, compared with group A, the protein expressions of MEK1/2 and ERK1/2 in gastric tissues of the other groups were significantly higher (P<0.01). Compared with group B, the protein expressions of MEK1/2 and ERK1/2 in group C and D were significantly higher (allP<0.01). Compared with group C, the protein expressions of MEK1/2 and ERK1/2 in group D were significantly higher (P<0.01). Conclusion: Herbal cake-partitioned moxibustion promotes the repair of gastric mucosa in rats with spleen deficiency syndrome, via improving protein expressions of MEK1/2 and ERK1/2 in gastric tissues, as well as activating MEK/ERK signaling pathway.

Effect of moxibustion stimulation on repair of injured gastric mucosa after common peroneal nerve transection / 针灸推拿医学（英文版）

Objective: To investigate the protective effect of moxibustion in initiating the endogenous protection information on gastric mucosa, and its relationship with the pathway of common peroneal nerve.Methods: Forty-eight Sprague-Dawley (SD) rats were randomly divided into a normal group (group A), a model group (group B), a moxibustion model group (group C) and a moxibustion model plus surgery group (group D), 12 in each group. Except for group A, rats in the other groups were treated with dehydrated ethanol and aspirin to prepare gastric mucosal damage model. The rats in group B were not treated with any interventions; rats in group C received moxibustion at Zusanli (ST 36), twice a day for continuous 3 d. The rats in group D were subjected to preparing the gastric mucosal damage model after the common peroneal nerve transection, followed by moxibustion at Zusanli (ST 36). After a 3-day intervention, ulcer index (UI) in each group was observed, and the levels of gastric mucosa-related repair cytokines of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and heat shock protein 70 (HSP70) were detected.Results: Compared with group A, the pathological changes and UI of group B were worse (P=0.000), but TNF-α in serum and tissue was changed significantly (P=0.000,P=0.002), IL-4 in serum and tissue was improved significantly (P=0.000, P=0.000). Compared with group B, TNF-α and IL-4 in group C and group D were significantly improved (TNF-α:P=0.003, P=0.016; IL-4:P=0.000,P=0.002). Compared with group C, the changes of UI in group B and group D were poor (both P=0.000); the levels of TNF-α and IL-4 in serum were significantly decreased (TNF-α:P=0.000,P=0.025; IL-4:P=0.000, P=0.034); and tissue HSP70 levels were decreased significantly (P=0.000,P=0.033).Conclusion: Zusanli (ST 36) can transmit information through the pathway of common peroneal nerve, regulate the release of gastric mucosal protective factors, and up-regulate the expression of cytothesis-related proteins, so as to achieve the effect in repairing gastric mucosa.

Repairing Effect of Huazhuo Jiedu Yukui Formula on Mucosal Damage of Rats with Ulcerative Colitis / 中国药房

OBJECTIVE:To explore the repairing effect and mechanism of Huazhuo jiedu yukui formula on the mucosal dam-age of rats with ulcerative colitis (UC). METHODS:72 rats were randomly divided into blank group,model group,mesalamine group(positive control,0.3 g/kg),Huazhuo jiedu yukui formula low-dose,medium-dose,high-dose groups(5,10,20 g/kg),12 in each group. Except for blank group,other groups were induced UC model. After 4 d of modeling,rats in administration groups received related medicines,ig,blank group and model group received normal saline,ig,once a day,for 2 weeks. After administra-tion,disease activity index(DAI)and mucosal damage index(CMDI)of rats were observed;IL-8,TNF-α contents in serum and cyclooxygenase 2 (COX-2) expression in colon tissue were detected. RESULTS:Compared with blank group,DAI and CMDI scores in model group were increased;IL-8,TNF-α contents in serum were increased;COX-2 expression in colon tissue was en-hanced,with statistical significances (P<0.05). Compared with model group,DAI and CMDI scores in model group were de-creased;IL-8,TNF-α contents in serum were reduced;COX-2 expression in colon tissue was weakened,with statistical signifi-cances (P<0.05). Compared with mesalamine group, the above-mentioned indicators in Huazhuo jiedu yukui formula medi-um-dose,high-dose groups changed more obviously (P<0.05),and effects of Huazhuo jiedu yukui formula showed significant dose-effect relationship. CONCLUSIONS:Huazhuo jiedu yukui formula can improve disease activity status of UC rats and reduce colon mucosal damage,and the effects of medium-dose and high-dose Huazhuo jiedu yukui formula were better than mesalamine, which may be related to reducing inflammatory reaction and inhibiting COX-2 expression in colon tissue.

Effects of moxibustion pretreatment on extracellular signal-regulated kinase signaling transduction pathway in the gastric tissues of rats with gastric mucosal damage / 针灸推拿医学（英文版）

Objective: To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor (EGFR), phosphorylation extracellular signal-regulated kinase 1/2 (p-ERK1/2) and activated protein-1 (AP-1), the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods: Thirty Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion at Zusanli (ST 36) and Zhongwan (CV 12), or Pishu (BL 20) and Weishu (BL 21), once a day, for a total of 8 d. Histological changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERK1/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-1 were measured by Western blots. Results: Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group (P Conclusion:Moxibustion at Zusanli (ST 36), Zhongwan (CV 12), Pishu (BL 20) and Weishu (BL 21) couldincrease EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.

Protective effect of halophyte Salsola komarovi Iljin against gastric ulcer Induced by alcohol treatment in rats / 동물의과학연구지

Salsola komarovi Iljin is a halophyte and herbaceous annual native to the sand dunes and beaches of Japan, northern China, Sakhalin, and Korea. The plants have been known as an ecologically important species for enhancing formation of sand dunes in Korea. The purpose of this study was to examine the anti-gastric ulcer effect of Salsola komarovi Iljin halophyte in an HCl-ethanol-induced gastritis model. SD rats (7-weeks-old) were divided into normal (I, n=10), control (II, 60% HCl-ethanol + water, n=10), 60% HCl-ethanol + Ranitidine 300 mg/kg (III, n=10), 60% HCl-ethanol + Salicornia herbacea L. 500 mg/kg (IV, n=10), 60% HCl-ethanol + 50% alcohol extract of Salsola komarovi Iljin 500 mg/kg (V, n=10), and 60% HCl-ethanol + water extract of Salsola komarovi Iljin 500 mg/kg (VI, n=10) groups. Salsola komarovi Iljin significantly suppressed gastric lesions and ulcers in the 60% HClethanol-induced gastric model. Especially, 500 mg/kg of 50% alcohol extract of Salsola komarovi Iljin showed significant inhibitory effects against gastritis. Especially, 50% alcohol extract of Salsola komarovi Iljin 500 mg/kg showed a significantly inhibitory effect, which was more potent than that of 300 mg/kg of Ranitidine. In histopathological analysis of the animal model, Salsola komarovi Iljin attenuated gastric ulcer formation. Our results suggest that Salsola komarovi Iljin has inhibitory effects against gastritis and gastric ulcers and could be developed as a new anti-gastric ulcer agent.

Simultaneous endoscopic removal of 5 coins from the stomach without causing mucosal injury using specially designed devices.

Endoscopic retrieval of foreign bodies is sometimes a challenging task. We report a case of simultaneous removal of 5 coins from the stomach without causing mucosal injury using a specially-designed devices consisting of retrieval net, endoscopic attachment balloon and a disposable tip attachment. This technique has not been described before.

Investigação de efeitos lesivos de doses antiinflamatórias e imunossupressoras de dexametasona sobre a mucosa gástrica em camundongos / Investigation of damage effects by antiinflammatory and immunosuppressive doses of dexamethasone on mice´s gastric mucosal

A dexametasona, potente glicocorticóide, pode causar inúmeras complicações, porém com incerto papel ulcerogênico no trato gastrintestinal. O objetivo do presente estudo foi investigar o papel da dexametasona nas doses antiinflamatórias e imunossupressoras na geração de lesão gástrica em camundongos Swiss Webster. Quarenta camundongos fêmeas foram divididos em três grupos. No Grupo I (n=16), os animais receberam 5 mg/kg/dia via intraperitoneal (IP) de dexametasona (dose imunossupressora); no Grupo II (n=16), 1,25 mg/kg/dia IP (dose antiinflamatória); e no Grupo III (n=8), solução fisiológica estéril IP (grupo controle). Os animais foram sacrificados em câmara de CO2 a cada três dias a partir do 3° ao 12° dia. Foram realizadas gastrectomia total, adrenectomia bilateral e esternectomia. A leucometria global e específica foi feita em cinco animais de cada grupo a cada três dias. Não foram encontradas alterações macroscópicas e histológicas no trato gastrintestinal nos diferentes grupos. Em dois camundongos do grupo I e em dois do grupo II, observamos degeneração balonizante das células da supra-renal. Esteatose hepática foi observada apenas em um animal do grupo I. Os animais imunossuprimidos apresentaram leucopenia com linfopenia, neutrofilia e monocitopenia e naqueles submetidos a doses antiinflamatórias notaram-se apenas leucopenia com linfopenia. O grupo controle manteve a contagem dentro da normalidade. Não foi observado dano à mucosa gástrica com o uso de doses antiinflamatórias e imunossupressoras, utilizando-se a via intraperitoneal. Estudos complementares comparando diferentes vias de administração, doses, animais de experimentação e preparações de glicocorticóides deverão ser conduzidos antes de afastar um papel ulcerogênico deste grupo de medicamentos.

Dexamethasone is a powerful glucocorticoid and it may result in some adverse effects, but it is uncertain whether it is ulcerogenic to the gastrointestinal tract. The aim of the present study was to investigate the antiinflammatory and immunosuppressive dose's effect of dexamethasone on the production of gastric mucosal damage in Swiss Webster mice. Forty female mice were separated in 3 groups. In Group I (n=16), the animals received 5 mg/kg/day (intraperitoneal route (IP) of dexamethasone (immunosuppressive dose); Group II (n=16): 1.25 mg/kg/day IP (antiinflammatory dose); and in Group III (n=8), saline solution IP (control group). The animals were sacrificed and necropsied at 3, 6, 9 and 12 days postinnoculation. Stomach, adrenal and sternal samples were collected and processed for microscopy studies. Global and specific counts of white blood cell were made in five animals in each group, each three days. Macroscopic and histological alterations on the gastrointestinal tract were not found in the different groups. In two mice of group I and in two of group II, balloon degeneration in adrenal cells was observed. In one animal of group I hepatic steatosis was found. The immunosuppressed animals presented leukopenia with lymphopenia, neutrofilia and monocytopenia and in those submitted to antiinflammatory doses it was noticed only leukopenia with lymphopenia. The control group kept the count within normality. Gastric mucosal damage with the use of antiinflammatory and immunosuppressive doses was not observed by using the intraperitoneal route. Complementary studies comparing different administration routes, doses, experimental animals and preparations of glucocorticoid must be undertaken before discarding a ulcerogenic role of this medicine group.

Mechanism of Study on Gastric Mucosal Lesion Restoration in Rats Treated by Electroacupuncture / 中国中医药信息杂志

Objective Through comparing the similarities and differences between respairing effect on rat’s gastric mucosal lesion by electroacupure (EA) at Meridian of Foot Yangming and Meridian of Foot Shaoyang, to explore the specificity of the correlation between Meridian of Foot and Stomach and the mechanism of the healing effect by EA at meridian of Foot Yangming for curing the gastric lesion. Methods Forty rats were randomly divided into 4 groups:blank group, model group, stomach tunnel group, gallbladder tunnel group. All rats (except normal group) were made model by water restraint stress (WRS). After corresponding experimental process, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-?) of plasma, gastric mucous tissue concentration was detected with radioimmunoassay, and the expression of EGFR mRNA of above tissue was detected by the reverse transcriptase-polymease chain reaction (RT-PCR) method. Results The gastric mucosal lesion index of Foot Yangming group decreased significantly in comparison with that of other groups, while EGF, TGF-? of gastric mucous tissue concentration level of Foot Yangming group was obviously higher than that of model group and gallbladder tunnel group. EA oould up-regulate the expression gastric mucosal EGFRmRNA, and there was a more significant difference in the group by EA at Meridian of Foot Yangming than that in the model group and gallbladder tunnel group. Conclusion The curative effect of EA at points of Meridian of Foot Yangming on the gastric mucosa may be realized by the synthesis, secretion and release of the related EGF family factor, such as EGF, TGF-? and so on. Such special regulation of electroacupuncture on gastric mucosal tissue was related to the gene expression of EGFRmRNA, and that may be further mechanism of the curative effect of EA at points of Meridean of Foot-Yangming on gastric mucosal lesion. There existed corresponding correlation between Meridian of Foot Yangming and Stomach.

Research on the Plasma Endothelin and Gastric Mucusal Pathology in Obstructive Jaundice / 中国普外基础与临床杂志

Objective To investigate the correla tion between the plasma endothelin (ET) and gastric mucosal pathology.Methods In this experiment,seven dogs who exper ienced common bile-duct ligation were in experiment group, the other three dogs who underwent sham-operation were control group. By using specific radio immun ological method, the plasma ET levels were determined in dogs before and after 1 ,4,7 d. The total bilirubin levels were determined before and after 1,4,7 d afte r operation by using carbazotic acid method.The gastric mucosa,7 d after operati on, was cut into slices and was examined under the electron microscope and the l ight microscope.Results In the experiment group,the levels of ET and total bilirubin rose continually and were higher than those in control gr oup. Vascular congestion and oedema were seen in gastric mucosa of common bile- duct ligated dogs. Under the electron microscope, we could see the dilated bloo d capillary and sludging of blood,the intenstitial mucusa cells oedema. Conclusion The increase of plasma ET might lea d to impairment of mucosal micro-circulation,which might be one of the pathogen s that could induce the gastric mucosal damages in common bile-duct ligated dog s.

The Protection of Heping Powder on Indomethacin-Induced Gastric Mucosal Damage in Rats / 中国医师杂志

Objective To investigate the protection of Heping powder on indomethacin-induced gastric mucosal damage in rat.Methods We used the indomethacin (20mg/kg) intramuscular injection,it induced gastric mucosal damage model in rats,compared the lesion index of Heping powder(3 dosage groups) and control groups.Superoxide dismutase(SOD) and Malonyl dialdehyde(MDA) levels in blood and gastric homogenate were measured as well.Results Gastric mucosal lesion index of all Heping powder dosage groups was obviously reduced(P