New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Directional migration of leukocytes: their pathological roles in inflammation and strategies for development of anti-inflammatory therapies

Directional migration of leukocytes is indispensable to innate immunity for host defense. However, recruitment of leukocytes to a site of tissue injury also constitutes a leading cause for inflammatory responses. Mechanistically, it involves a cascade of cellular events precisely regulated by temporal and spatial presentation of a repertoire of molecules in the migrating leukocytes and their surroundings (microenvironments). Here I will summarize the emerging evidence that has shed lights on the underlying molecular mechanism for directional migration of leukocytes, which has guided the therapeutical development for innovative anti-inflammatory medicines.

Effective anti-inflammatory phenolic compounds from dandelion:identification and mechanistic insights using UHPLC-ESI-MS/MS,fluorescence quenching and anisotropy,molecular docking and dynamics simulation

This novel study identifi es the effective anti-inflammatory phenolic compounds in dandelion and provides mechanistic insights into their interactions with receptor proteins(toll-like receptor 4,TLR4;co-receptor myeloid differentiation protein-2,MD-2)using UHPLC-ESI-MS/MS,lipopolysaccharide(LPS)-stimulated THP-1 cell line,fluorescence quenching and anisotropy,molecular docking(single ligand and multi-ligand docking)and molecular dynamics simulation.A 50%aqueous methanol extract had a greater anti-inflammatory effect and higher chicoric acid content,compared with the 100%water and 100%methanol extracts.Chicoric acid,chlorogenic acid,methylophiopogonone A,caffeic acid,gallic acid monohydrate and 4’-O-demethylbroussonin A had relatively high binding energies and contents in all extracts.Chicoric acid competed with chlorogenic acid,4’-O-demethylbroussonin A and quercetin for MD-2.Among dandelion’s phenolics,chicoric acid most effectively hindered TLR4-MD-2 complex formation,with a quenching constant of 0.62×10^(6) L/mol for MD-2 or TLR4 at 320 K,and binding energies of-6.87 and-5.97 kcal/mol,respectively,for MD-2 and TLR4.

Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala,periaqueductal grey,and nucleus raphe Possible cellular mechanism

Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （NSAIDs）, or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic （intraperitoneal） administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

Post-endoscopic retrograde cholangiopancreatography complications:How can they be avoided?

Endoscopic retrograde cholangiopancreatography(ERCP) has a significant complication rate which can be lowered by adopting technical variations of proven beneficial effect and prophylactic maneuvers such as pancreatic stenting during ERCP or periprocedural non-steroidal anti-inflammatory drug administration.However,adoption of these prophylactic maneuvers by endoscopists is not uniform.In this editorial we discuss the beneficial effects of the aforementioned maneuvers.

Growth inhibition and apoptosis induction Sulindac on Human gastric cancer cells

AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC) cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG(2) and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX-2) and Bcl-2 were detected by Western dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG(2) and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG(2) cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24 hours incubation with sulindac at 2mmol x L(-1) and 4mmol x L(-1), the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2 and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater than that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

Diaphragm disease compared with cryptogenic multifocal ulcerous stenosing enteritis

As the use of drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) increases,so too do gastrointestinal ulcers,bleeding,perforation and obstruction.Diaphragm disease of the small intestine is formed by submucosal fibrosis and destruction of lamina muscularis due to chronic ulceration,which corresponds to the most severe stage of NSAID enteropathy.It may lead to stricture of the small intestine.If such ulcerations and strictures in the small intestine are multiple,differential diagnosis is between diaphragm disease and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE),because the gross findings of diaphragm disease are similar to those of CMUSE.We report a rare case of diaphragm disease caused by NSAID.It has been finally confirmed by capsule endoscopy and the origin of chronic obscure gastrointestinal bleeding was found to be multiple ulcers and strictures in the small intestine.After operation,we diagnosed the patient with diaphragm disease rather than CMUSE.

Education-based approach to addressing non-evidence-based practice in preventing NSAID-associated gastrointestinal complications

AIM:To evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NSAID)-associated gastrointestinal(GI)complications. METHODS:Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects.They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. RESULTS:Four hundred and forty-one of 456 specialists(96.7%)participated in the survey,and 382(83.7%)in the education-based study that recorded data from 3728 patients.The specialists overestimated the risk of GI complications with NSAIDs,underestimated the GI safety profile of coxibs,but were aware of the risk factors and of the current prevention strategies.Proton pump inhibitors were co-prescribed with NSAIDs in>80% of patients with and without risk factors.The educational program had little impact on prescribing habits.CONCLUSION:Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy.Our educational program did not alter these rates.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-y in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally rejected with methylprednisolone （30 mg/kg） and rosiglitazone （2 mg/kg） at 1 hour after injury, and methylprednisolone （15 mg/kg） at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better pro- moted recovery of neurological function after injury.

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.

Pharmacology of tetrandrine and its therapeutic use in digestive diseases

INTRODUCTIONTetrandrine (Tet) is a dibenzylisoquinoline alkaloid isolatedfrom Stephania tetrandra S. Moore, a Chinese herbalmedicine. In the past decade, lots of studies demonstrated that Tet has multiple bioactivities, It is promising to use Tet as an antifibrogenetic in liver or lung fibrosis with or without portal or pulmonary hypertension, as well as an immunomodulating and anticarcinoma drug.

CLINICAL STUDY ON 118 CASES OF ULCERATIVE COLITIS TREATED BY INTEGRATION OF TRADITIONAL CHINESE AND WESTERN MEDICINE

118 cases of ulcerative colitis were treated by integration of traditional Chinese and Western medicine. Another 86 cases of ulcerative colitis were treated by simple western drugs as controls. The therapeutic effects for both groups were observed and compared after two therapeutic courses of 40 consecutive days. As a result, 39 cases were cured, 60 cases improved and 19 cases failed, with a total effective rate of 84% in the treatment group; in the control group, 15 cases were cured, 37 cases improved and 34 cases failed, with a total effective rate of 60.5%. Statistically, the difference was very significant (P

Antioxidant Properties of Rosemary and Its Potential Uses as Natural Antioxidant in Dairy Products—A Review

Dairy products contain lipids rich in polyunsaturated fatty acids and their esters are easily oxidized by molecular oxygen over time. Deleterious changes in dairy products caused by lipid oxidation include not only loss of flavour or development of off-flavours, but also loss of colour, nutrient value, and the accumulation of compounds, which may be detrimental to the health of consumers. One of the most effective ways of retarding lipid oxidation in dairy products is to incorporate antioxidants. Sometimes synthetic phenolic antioxidant, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are used to delay this oxidation. Supplementation dairy products with natural antioxidants (polyphenolic compounds) are better using than synthetic antioxidant and could be potentially. The use of rosemary as natural antioxidant in dairy products can reduce the rate of lipid oxidation and hydrolysis besides may be beneficial in increasing the shelf life of these products. This supplementation will move these products into the functional food area under new category as healthy dairy products. This literature review covers the research that has focused on rosemary as antioxidant and anti-inflammatory agent that can inhibit the lipid oxidation and have health benefits by preventing carcinogens from binding to DNA, fight and stop pain. In this review, we survey the previous studies that were conducted on the application of rosemary extract as an antioxidant to extend the shelf life and to minimize nutritional losses of dairy product.

Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: Influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC

AIM:To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma,who developed serious side effects. METHODS:Serum levels of budesonide,6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging.All values were compared with a matched control patient without side effects. RESULTS:Serum levels of budesonide were 13-fold increased in the index patient.The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH- prednisolone,respectively,and serum levels of budesonide was diminished (1.0 vs.4.0 for 6β-OH-budesonide,4.2 vs. 10.7 for 16α-OH-prednisolone).Both patients had portosystemic SI (5.7 % and 3.1%) within the range of healthy subjects.CONCLUSION:Serum levels of budesonide Vary uP to 13-fold in AIH Patients with Child A eirrhosis in the absenee ofrelevant Portosystemic shunting.Redueed hePatiemetabolism,as indicated by redueed metabolite-to-drugratio,rather than Portosystemie shunting may explainsystemic side effects of this drug in cirrhosis

Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats

INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2].

Case report and review of esophageal lichen planus treated with fluticasone

Lichen planus is a fairly common chronic idiopathic disorder of the skin,nails and mucosal surfaces.Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature.Given its rarity,it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis.Currently,there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach.Systemic steroids are usually the first line treatment and offer a favorable response.In this report,we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk,as evidenced by objective clinical findings.Based on our review of related literature and experience in this patient,we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment.

JTE-522-induced apoptosis in human gastric adenocarinoma cell line AGS cells by caspase activation accompanying cytochrome C release,membrane translocation of Bax and loss of mitochondrial membrane potential

AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.

Shen's Experience in Application of the Drugs for Tonifying the Kidney to.Reduce and Withdraw Adrenocortical Hormone

Adrenocortical hormone (ACH) has antiinflammatory and antiallergic actions, changes stress state and controls the attack of some severe and obstinate diseases. The treatment of chronic diseases with ACH often leads to its dependence; especially oral administration of ACH for a long time is liable to inhibit the function of hypothalamus-pituitary-adrenocortical-thymic axis (HPAT), and results in the hypo-reservation of adrenal cortex. Hence, sudden ACH withdrawal or decrease often causes the disease recurrence, even adrenocortical crisis. Academician Shen Ziyin has a wealth of clinical experience in both the withdrawal and reduction of ACH and the keeping of therapeutical effectiveness to form his unique remedy in the application of drugs. Shen's rich experience is described as follows.

Anti-Inflammatory Glycosaminoglycan Oligosaccharides from Colwellia psychrerythraea 34H Capsule:Synthesis and Biological Evaluation

Capsular polysaccharides(CPS)of Colwellia psychrerythraea 34H consist of linear tetrasaccharides repeating units in a glycosaminoglycan-like fashion.Their biological function is likely involved in the cold adaptation of microbial organisms.The low availability of these glycosaminoglycan structures greatly limits the study of their functions and biological activities.Here,an efficient semisynthetic strategy for CPS tetrasaccharide derivatives is achieved by using disaccharide units degraded from hyaluronic acids.This new synthetic process is suitable for largescale preparation,and several rare tetrasaccharide derivatives containing GalA-GalNAc were readily obtained in high yields.Biological evaluation of their anti-inflammatory effects demonstrated that these CPS tetrasaccharides effectively attenuated the lipopolysaccharide-induced sepsis and acute lung injury by decreasing macrophage infiltration and secretion of microphage-related cytokines in mice.All these results suggest that this new type of CPS tetrasaccharide can be developed as an anti-inflammation agent.