Evaluation of antiinflammatory activity of Tephrosia purpurea in rats

Objective:To evaluate the antiinflammatory activity of orally administered ethanolic extract of Tephrosia purpurea in acute and subacute inflammation in rats.Methods:An ethanolic extract of Tephrosia purpurea was prepared.Carrageenan induced paw edema and cotton pellet granuloma were the models for acute and subacute inflammation respectively.Four groups of rats in each model were treated orally with 2%gum acacia,100 mg /kg of aspirin,500 mg/kg and 1 000 mg/kg of ethanolic extract of Tephrosia purpurea respectively.In carrageenan induced paw edema model, subplantar injection of 1%carrageenan was made into the hind paw of the rats sixty minutes after the administration of the respective drugs.The paw volume was measured immediately after injection of carrageenan,at 3 hours and at 6 hours.Then percentage inhibition of edema was calculated.In the cotton pellet granuloma model,animals were administered drugs for six days after placing cotton pellets in the axilla on each side.On the 7th day,dry weight of granuloma was calculated.Results:The rats treated with Tephrosia purpurea did not exhibit any significant decrease in paw volume and serum ceruloplasmin levels as compared to the control and aspirin treated groups in the acute inflammation model;while,there was a significant(P 【 0.01) decrease in the weight of granuloma in Tephrosia purpurea and aspirin treated groups as compared to control in subacute inflammation.Conclusions:The ethanolic extract of orally administered Tephrosia purpurea shows significant antiinflammatory effect in subacute inflammation but not in acute inflammation in rats.

Development of antiinflammatory agents and immunopharmacology in the People’s Republic of China

With the rapid advance of academic activities in the field of phar-macology,antiinflammatory and immunopharmacology has become abranch of pharmacology in our country.Under professor Zhou Jin-huang’s charge and concerns,the first national conference of anti-inflammatory and immunopharmacology was held at Huang Shan in1982.In following years,the frist training class for antiinflamma-tory and immunopharmacological studies was conducted in Hefei.

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Antiinflammatory and immunoregulatory effects of total glucosides of Yupingfeng powder

Background Yupingfeng, a traditional Chinese complex prescription, has been used efficaciously in China for the cure and prevention of inflammatory diseases related to immunodeficiency such as allergic rhinitis and chronic bronchitis. However, the active components of this prescription remain unclear. The present study focused on investigating the antiinflammatory and immunoregulatory effects of the glucosidic extract from Yupingfeng. Methods We tested animal models for ear swelling induced by dimethylbenzene in mice; palm swelling induced by carregeenin and granuloma induced by cotton pellet in rats; level of haemolysin, antibody generation by the splenic cells, delayed hypersensitivity and T cell subsets in spleen of immunosuppressed mice. Results Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg significantly inhibited mice＇s ear swelling induced by dimethylbenzene. Similarly glucosidic extract of 16 mg/kg, 32 mg/kg and 64 mg/kg inhibited rats＇ palm swelling induced by carregeenin and granuloma induced by cotton pellet. Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg improved the IgM level in serum and level of haemolysin in splenocytes in mice immunosuppressed by cyclophosphamide. Delayed hypersensitivity in mice suppressed by cyclophosphamide was enhanced by glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg. These results suggested that Yupingfeng could recover humoral and cellular immune function in mice with immunosuppression. Glucosidic extract of 48 mg/kg and 96 mg/kg significantly resisted the immunosuppressive mice ear swelling and maintained it at nearly normal level. The enhanced, delayed hypersensitivity actions of glucosidic extract, suppressed by cyclophosphamide, might be brought about by inducing TH cell and regulating T lymphocytes subset. Conclusions The glucosidic extract from Yupingfeng has antiinflammatory and immunoregulation action, suggesting that these glucosides are the principal active components of the traditional Chinese prescription Yupingfeng.

Anti-inflammatory effect and antihepatoma mechanism of carrimycin

BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates,as stopping aspirin therapy is associated with higher mortality rates.It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding,and every effort should be exercised to prevent the bleeding complications.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

State-of-the-Art management of knee osteoarthritis

Osteoarthritis(OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA. Numerous therapies aim to reduce symptoms of knee OA and continued research has helped to further understand the complex pathophysiology of its disease mechanism attempting to uncover new potential targets for the treatment of OA. This review article seeks to evaluate the current practices for managing knee OA and discusses emerging therapies on the horizon. These practices include non-pharmacological treatments such as providing patient education and self-management strategies, advising weight loss, strengthening programs, and addressing biomechanical issues with bracing or foot orthoses. Oral analgesics and anti-inflammatories are pharmacologicals that are commonly used and the literature overall supports that some of these medications can be helpful for managing knee OA in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon. Diseasemodifying osteoarthritis drugs are being researched as a treatment modality to potentially halt or slow disease progression but data at this time is limited and continued studies are being conducted to further investigate their effectiveness. Intra-articular injectables are also implemented to manage knee OA ranging from corticosteroids to hyaluronans to more recently plateletrich plasma and even stem cells while several other injection therapies are presently being studied. The goal of developing new treatment strategies for knee OA is to prolong the need for total knee arthroplasty which should be utilized only if other strategies have failed. High tibial osteotomy and unicompartmental knee arthroplasty are potential alternatives if only a single compartment is involved with more data supporting unicompartmental knee arthroplasty as a good treatment option in this scenario. Arthroscopy has been commonly used for many years to treat knee OA to address degenerative articular cartilage and menisci, however, several high-quality studies have shown that it is not a very effective treatment for the majority of cases and should generally not be considered when managing knee OA. Improving the management of knee OA requires a multi-faceted treatment approach along with continuing to broaden our understanding of this complex disease so that therapeutic advancements can continue to be developed with the goal of preventing further disease progression and even potentially reversing the degenerative process.

Changes of gastric ulcer bleeding in the metropolitan area of Japan

BACKGROUND The two main causes of gastric ulcer bleeding are Helicobacter pylori(H.pylori)infection and ulcerogenic medicines,although the number of cases caused by each may vary with age.In Japan,the rate of H.pylori infection has fallen over the last decade and the number of prescriptions for non-steroidal anti-inflammatory drugs(NSAIDs)and antithrombotic drugs is increasing as the population ages.Methods of treatment for gastric ulcer bleeding have advanced with the advent of hemostatic forceps and potassium-competitive acid blocker(P-CAB).Thus,causes and treatments for gastric ulcer bleeding have changed over the last decade.AIM To examine the trends of gastric ulcer bleeding over 10 years in the metropolitan area of Japan.METHODS This is a single-center retrospective study.A total of 564 patients were enrolled from inpatients admitted to our hospital with gastric ulcer bleeding between 2006 and 2016.Age,medication history,H.pylori infection,method of treatment,rate of rebleeding,and the length of hospitalization were analyzed.Factors associated with gastric ulcer bleeding were evaluated using Fisher’s exact test,Pearson’s Chi-squared test or Student’s t-test as appropriate.The Jonckheere-Terpstra test was used to evaluate trends.A per-protocol analysis was used to examine the rate of H.pylori infection.RESULTS There was a significant increase in the mean age over time(P<0.01).The rate of H.pylori infection tended to decrease over the study period(P=0.10),whereas the proportion of patients taking antithrombotic agents or NSAIDs tended to increase(P=0.07).Over time,the use of NSAIDs and antithrombotic drugs increased with age.By contrast,the rate of H.pylori infection during the study period fell with age.H.pylori-induced ulcers accounted for the majority of cases in younger patients(<70 years old);however,the rate decreased with age(P<0.01).The method of treatment trend has changed significantly over time.The main method of endoscopic hemostasis has changed from clipping and injection to forceps coagulation(P<0.01),and frequently prescribed medicines have changed from proton pump inhibitor to P-CAB(P<0.01).The rate of rebleeding during the latter half of the study was significantly lower than that in the first half.CONCLUSION These trends,gastric ulcers caused by ulcerogenic drugs were increasing with age and H.pylori-induced ulcers were more common in younger patients,were observed.

Comparison of intra-articular injection of parecoxib vs oral administration of celecoxib for the clinical efficacy in the treatment of early knee osteoarthritis

BACKGROUND Non-steroid anti-inflammatory drugs(NSAIDs)have played a crucial role in the treatment of osteoarthritis,especially in the early stages.However,the cardiovascular risk and adverse gastrointestinal reactions of oral NSAIDs in elderly people cannot be underestimated.Intra-articular injection of NSAIDs may be a new attempt for early knee osteoarthritis treatment.Parecoxib may be a suitable drug for intra-articular injection.AIM To observe the clinical efficacy of the intra-articular injection of parecoxib for early knee osteoarthritis.METHODS Early knee osteoarthritis patients(n=110)were retrospectively analyzed.These patients were divided into three groups:Basic treatment+oral glucosamine(group A,n=37),oral celecoxib+basic treatment+oral glucosamine(group B,n=37),and intra-articular injection of parecoxib+basic treatment+oral glucosamine(group C,n=36).Intra-articular injection of parecoxib was performed once every 2 wk at a dose of 40 mg each time,for three times total.The three groups were compared in terms of visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores and patient satisfaction before and after treatment.The levels of inflammatory cytokines in the synovial fluid were detected in the three groups before and after treatment.RESULTS All patients were followed up for an average of 15.5±2.7 mo.The clinical efficacy was estimated by VAS and HSS scores at 12 mo after treatment.Inflammatory cytokine levels in the synovial fluid were evaluated at 3 mo after treatment.VAS and HSS scores were significantly improved in each group compared with before(P<0.001).There were significant differences among the three groups in VAS and HSS scores(P<0.001).The clinical efficacy of group C was superior to that of groups A and B(P<0.001),while group B outperformed group A in this respect(P<0.001).The patient satisfaction was the highest in group C(P<0.001).After treatment,the levels of tumor necrosis factorα(TNF-α)and interleukin(IL)-6 in the synovial fluid decreased in each group compared with before(P<0.001),while the levels of IL-10 increased(P<0.001).The three groups differed significantly in the levels of TNF-a,IL-6 and IL-10 in the synovial fluid after treatment(P<0.001).CONCLUSION For patients with early knee osteoarthritis,intra-articular injection of parecoxib could effectively improve clinical symptoms.This method may be a reliable alternative for early knee osteoarthritis.

Helicobacter pylori-negative,non-steroidal anti-inflammatory drug:Negative idiopathic ulcers in Asia

Since the discovery of Helicobacter pylori(H.pylori)infection in the stomach,the bacteria infection and non-steroidal anti-inflammatory drugs(NSAIDs)use had been considered to be the 2 main causes of peptic ulcers.However,there have been recent reports of an increase in the proportion of peptic ulcers without these known risk factors;these are termed idiopathic peptic ulcers.Such trend was firstly indicated in 1990s from some reports in North America.In Asia,numerous studies reported that idiopathic ulcers accounted for a small percentage of all ulcers in the 1990s,but in the2000s,multiple studies reported that the proportion of idiopathic ulcers had reached 10%-30%,indicating that the incidence of idiopathic ulcers in Asia has also been rising in recent years.While a decline in H.pylori infection rates of general population in Asia is seen as the main reason for the increased incidence of idiopathic ulcers,it is also possible that the absolute number of idiopathic ulcer cases has increased.Advanced age,serious systemic complication,and psychological stress are considered to be the potential risk factors for idiopathic ulcers.Management of idiopathic ulcers is challenging,at present,because there is no effective preventative measure against recurrence in contrast with cases of H.pylori-positive ulcers and NSAIDs-induced ulcers.As it is expected that H.pylori infection rates in Asia will decline further in the future,measures to treat idiopathic ulcers will also likely become more important.

Controlling postoperative ileus by vagal activation

Postoperative ileus is a frequently occurring surgical complication, leading to increased morbidity and hospital stay. Abdominal surgical interventions are known to result in a protracted cessation of bowel movement. Activation of inhibitory neural pathways by nociceptive stimuli leads to an inhibition of propulsive activity, which resolves shortly after closure of the abdomen. The subsequent formation of an inflammatory infiltrate in the muscular layers of the intestine results in a more prolonged phase of ileus. Over the last decade, clinical strategies focusing on reduction of surgical stress and promoting postoperative recovery have improved the course of postoperative ileus. Additionally, recent experimental evidence implicated antiinflammatory interventions, such as vagal stimulation, as potential targets to treat postoperative ileus and reduce the period of intestinal hypomotility. Activation of nicotinic receptors on inflammatory cells by vagal input attenuates inflammation and promotes gastrointestinal motility in experimental models of ileus. A novel physiologicalintervention to activate this neuroimmune pathway is enteral administration of lipid-rich nutrition. Perioperative administration of lipid-rich nutrition reduced manipulation-induced local inflammation of the intestine and accelerated recovery of bowel movement. The application of safe and easy to use antiinflammatory interventions, together with the current multimodal approach, could reduce postoperative ileus to an absolute minimum and shorten hospital stay.

Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis:From divination to science

One unresolved issue of endoscopic retrograde cholangiopancreatography(ERCP)is post-ERCP pancreatitis (PEP),which occurs in up to 40%of patients.Identification of risk factors for PEP is especially important in the field of ERCP practice because it may assist physicians in taking protective measures in situations with high risk.A decade ago,Freeman et al meticulously evaluated a large number of potentially relevant risk factors for PEP,which can be divided into patient-relat-ed and procedure-related issues.In this commentary, we summarize this classic article and reevaluate the risk factors for PEP from the current point of view.This is followed by assessment of strategies for prevention of PEP that can be divided into mechanical and pharmacologic methods.

In vitro antioxidant and anti-inflammatory activities of Korean blueberry(Vaccinium corymbosum L.) extracts

Objective:To investigate in vitro antioxidant and anti-inflammatory activities of Korean blueberry(Vaccinium corymbosum L.).Methods:Total phenolic and flavonoid contents of the Korean blueberry water and ethanol extracts were determined before determining the potential of the extracts as antioxidant.Antioxidant activity of the extracts was determined by following some well established methods for free radical scavenging such as 2,2-diphenyl-picrylhydrazyl hydrate,1,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid),free radical induced DNA damage,superoxide dismutaselike and catalase assay etc.Furthermore,1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan and nitric oxide assay were performed to determine the anti-inflammatory activity of the extracts.Results:Total phenolic contents were found(115.0±3.0) and(4.2±3.0) mg GAE/100 g fresh mass for both extracts,respectively and flavonoid contents were(1 942.8±7.0) and(1 292.1±6.0) mg CE/100 g fresh mass for water and ethonal extracts,respectively.Both the extracts displayed significant scavenging activity of some radicals such as 2,2-diphenyl-picrylhydrazyl hydrate(IC_(50) at 1.8 mg/mL and 2.05 mg/mL,respectively),l,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid)(IC_(50) at1.5 mg/mL and 1.6 mg/mL,respectively) and nitrite(IC_(50) at 1.7 mg/mL and 1.5 mg/mL,respectively)etc.The extracts were found to prevent inflammation as well by reducing nitric oxide production and cytotoxicity in cell.Conclusions:The findings suggest that the fresh Korean blueberry could be used as a source of natural antioxidants and anti-inflammatory agents.

Triggers of histologically suspected drug-induced colitis

BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.

Effectiveness of therapeutic barium enema for diverticular hemorrhage

AIM:To evaluate the effectiveness of barium impaction therapy for patients with colonic diverticular bleeding.METHODS:We reviewed the clinical charts of patients in whom therapeutic barium enema was performed for the control of diverticular bleeding between August2010 and March 2012 at Yokohama Rosai Hospital.Twenty patients were included in the review,consisting of 14 men and 6 women.The median age of the patients was 73.5 years.The duration of the followup period ranged from 1 to 19 mo(median:9.8 mo).Among the 20 patients were 11 patients who required the procedure for re-bleeding during hospitalization,6patients who required it for re-bleeding that developed after the patient left the hospital,and 3 patients who required the procedure for the prevention of rebleeding.Barium(concentration:150 w%/v%)was administered per the rectum,and the leading edge of the contrast medium was followed up to the cecum by fluoroscopy.After confirmation that the ascending colon and cecum were filled with barium,the enema tube was withdrawn,and the patient’s position was changed every 20 min for 3 h.RESULTS:Twelve patients remained free of rebleeding during the follow-up period(range:1-19mo)after the therapeutic barium enema,including 9men and 3 women with a median age of 72.0 years.Re-bleeding occurred in 8 patients including 5 men and 3 women with a median age of 68.5 years:4developed early re-bleeding,defined as re-bleeding that occurs within one week after the procedure,and the remaining 4 developed late re-bleeding.The DFI(disease-free interval)decreased 0.4 for 12 mo.Only one patient developed a complication from therapeutic barium enema(colonic perforation).CONCLUSION:Therapeutic barium enema is effective for the control of diverticular hemorrhage in cases where the active bleeding site cannot be identified by colonoscopy.

Novel Cathelicidins with Potent Antimicrobial,Biofilm Inhibitory,and Anti-inflammatory Activities from the Frog Fejervarya multistriata

Antimicrobial peptides（AMPs）,a class of gene-encoded peptides,are the first line of immune system to defense microbial invasions in multicellular organisms.Cathelicidins are an important family of AMPs that have been identified exclusively in vertebrates.However,up to now,cathelicidins from amphibians are poorly understood.In the present study,we reported the identification and characterization of two novel cathelicidins（FM-CATH1 and FMCATH2） from the frog Fejervarya multistriata.The c DNA sequences encoding FM-CATHs were successfully cloned from the constructed lung c DNA library of F.multistriata.Both of the c DNA sequences encoding FM-CATHs are 447 bp in length,and the deduced mature peptides of FM-CATHs are composed of 34 residues.Structural analysis indicated that FM-CATH1 and FM-CATH2 mainly assume amphipathic alpha-helical conformations.Antimicrobial and bacterial killing kinetic analysis indicated that both FM-CATH1 and FM-CATH2 possess potent,broad-spectrum and rapid antimicrobial potency.And cytoplasmic membrane permeabilization analysis indicated that FM-CATH1 and FMCATH2 kill bacteria by inducing the permeabilization of bacterial membrane.Besides direct antimicrobial activities,FM-CATHs also exhibited significant inhibitory effect on the formation of bacterial biofilms at low concentrations below 1×MIC.Furthermore,FM-CATH1 and FM-CATH2 exhibited potent anti-inflammatory activities by inhibiting LPS-induced transcription and production of pro-inflammatory cytokines TNF-α,IL-1β,and IL-6 in mouse peritoneal macrophages.Meanwhile,FM-CATHs showed relatively low cytotoxic activity against mammalian normal and tumor cell lines,and low hemolytic activity against human erythrocytes.In summary,the identification of FM-CATHs provides novel clues for our understanding of the roles of cathelicidins in amphibian immune systems.The potent antimicrobial,biofilm inhibitory,anti-inflammatory activities,and low cytotoxicity of FM-CATHs imply their great potential in novel antibiotics development.

Split-dose or hybrid nonsteroidal anti-inflammatory drugs and Nacetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis

BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.

Anti-inflammatory Activity of Polysaccharide Isolated from Thamnolia Subuliformis

The present study aimed at isolating,purifying,characterizing the structure and estimating the anti-inflammatory activity of a polysaccharide named THSA which was obtained from Thamnolia subuliformis(Ehrh.) W.Culb(T.subuliformis).A newheteroglycan THSA was gained by hot water extraction and further continuously purification through Sephadex G-75 and Superdex 200 column chromatography.The structural characteristics of THSA were primarily investigated by molecular mass estimation,monosaccharide composition analysis and Fourier transforminfrared spectroscopy(FT-IR).The anti-inflammatory effects of THSA was also estimated in lipopolysaccharide(LPS)-stimulated mouse macrophages cell line RAW264.7 through the method of reverse transcription polymerase chain reaction(RT-PCR) and quantitative real-time PCR.The results indicate that THSA is composed of Glc,Gal,Man in the ratio 1:2.1:6.16,with average molecular weight of about 12.4 k Da,and significantly inhibits the mRNA expression of tumor necrosis factor alpha(TNF-α),IL-6 at100 or 1 000 μg/m L and increases the anti-inflammatory cytokine level of IL-10 at 100 μg/m L.It indicates that polysaecharide THSA has strong anti-inflammatory activity.