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Absorption characteristics of the total alkaloids from Mahonia bealei in an in situ single-pass intestinal perfusion assay

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Chinese Journal of Natural Medicines 2014年第7期12卷 554-560页

作者： SUN Yu-He HE Xin YANG Xiao-Lin DONG Cui-Lan ZHANG Chun-Feng SONG Zi-Jing LU Ming-Xing YANG Zhong-Lin LI Ping State Key Laboratory of Natural Medicines China Pharmaceutical University School of pharmacy Nanjing University of Chinese Medicine Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research Jinan University The People's Hospital of Zhangqiu City

AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.

关键词： Mahoniae Caulis Total alkaloids In situ single-pass intestinal perfusion Absorption enhancers Protein inhibitors

intestinal lymphangiectasia in adults

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World Journal of Gastrointestinal Oncology 2011年第2期3卷 19-23页

作者： Hugh James Freeman Michael Nimmo Department of Medicine (Gastroen-terology) University of British Columbia Department of Pathology University of British Columbia

intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogamma-globulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial def inition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fe- cal alpha-1-antitrypsin levels, while others may present with iron def iciency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed moreextensive changes along the length of the small intes- tine. A critical diagnostic element in adults with lym- phangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or in? am- matory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. T

关键词： intestinal lymphangiectasia Adults Submucosa

Chidamide based combination regimen for treatment of monomorphic epitheliotropic intestinal T cell lymphoma following radical operation:Two case reports

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World Journal of Clinical Cases 2020年第7期8卷 1278-1286页

作者： Ting-Zhi Liu Yi-Jia Zheng Zhan-Wen Zhang Shan-Shan Li Jiao-Ting Chen Ai-Hua Peng Ren-Wei Huang Department of Hematology The Sixth Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Nuclear Medicine The Sixth Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Oncology The Sixth Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510655Guangdong ProvinceChina

BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been established.Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant.However,many patients are unable to tolerate the toxicities.Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma.CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index.Case one was a 61-year-old man.He complained of upper abdominal pain and intermittent black stool for 2 mo.Imaging examination revealed that the intestinal wall was thickened.He received a partial excision of the small intestine.A chidamidebased combination regimen was given postoperatively.Eleven months later,he presented with recurrence in the bilateral lungs.He passed away 15 mo after his diagnosis.Case two was a 35-year-old woman who complained of abdominal distention for 1 mo.Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon.Colon perforation and septic shock occurred on the fourth day of her admission.She was treated by sigmoid colostomy.Chidamide-based combination therapy was then provided.She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis.Compared to historical data,chidamide seems to improve the prognosis of MEITL slightly.CONCLUSION MEITL is a type of aggressive lymphoma.Chidamide is a new promising approach for the treatment of MEITL.

关键词： Monomorphic epitheliotropic intestinal T cell lymphoma Histone deacetylase inhibitor Chidamide Intensive chemotherapy Stem cell transplantation Case report

Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats

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World Journal of Gastroenterology 2018年第6期24卷 706-715页

作者： Chun-lan Xu Yu Guo lei Qiao li Ma Yi-Yi Cheng The Key Laboratory for Space Bioscience and Biotechnology School of Life Sciences Northwestern Polytechnical University

AIM To investigate the modulatory effect of recombinantexpressed vasoactive intestinal peptide(VIP) analogue(rVIPa) on trinitrobenzene sulfonic acid(TNBS)-induced colitis in rats. METHODS Forty-eight rats were randomized into six groups: normal control group(Control), model control group(TNBS), ethanol treatment group(ETOH), and VIP treatment groups with different dosage(rVIPa_(1nmol), rVIPa_(2nmol), rVIPa_(4nmol)). Diarrhea and bloody stool were observed. Colonic damage was evaluated histologically. The levels of tumor necrosis factor-α( TNF-α), interleukin-10(Il-10), myeloperoxidase(MPO) and endotoxin in colonic tissue and serum were determined by enzyme-linked immunosorbent assay(ElISA). The expression of occludin, ZO-1, Toll-like receptor 4(TlR4),and nuclear factor-kappa B p65(NF-κBp65), IκBα, and p-IκBα were detected by Western blot. RESULTS Administration with 2 nmol rVIPa prevented TNBSinduced necrosis, hyperemia, swelling, inflammation, etc., pathologic changes observed in the inner surface of colon in experimental rats. Moreover, rVIPa significantly decreased colonic TNF-α level(P intestinal mucosal barrier function in rats. The mechanism may be related to TlR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders.

关键词： Vasoactive intestinal peptide intestinal mucosal barrier Tight junction Toll-like receptors Recombinant expression

Small intestinal hemolymphangioma treated with enteroscopic injection sclerotherapy: A case report and review of literature

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World Journal of Gastroenterology 2020年第13期26卷 1540-1545页

作者： Nian-Jun Xiao Shou-Bin Ning Teng Li Bai-Rong Li Tao Sun Department of Gastroenterology Air Force Medical CenterBeijing 100142China Department of Pathology Air Force Medical CenterBeijing 100142China

BACKGROUND Hemolymphangiomas are rare malformations composed of both lymphatic and vascular vessels and are located in the pancreas,spleen,mediastinum,etc.Small intestinal hemolymphangioma is extremely rare and often presents as obscure gastrointestinal bleeding.It is rarely diagnosed correctly before the operation.Endoscopic injection sclerotherapy is usually used as a management of bleeding in esophageal varices and was occasionally reported as a treatment of vascular malformation.The treatment of small intestinal hemolymphangioma with enteroscopic injection sclerotherapy has not been reported.CASE SUMMARY A 42-year-old male complained of recurrent episodes of melena and dizziness,fatigue and reduced exercise capacity for more than 2 mo.Gastroduodenoscopy and blood test revealed a gastric ulcer and anemia.Treatment with oral protonpump inhibitors and iron did not improve symptoms.We then performed a capsule endoscopy and anterograde balloon-assisted enteroscopy and revealed a hemolymphangioma.Considering it is a benign tumor without malignant potential,we performed enteroscopic injection sclerotherapy.He was discharged 4 days later.At follow-up 3 mo later,the melena disappeared.Balloon-assisted enteroscopy revealed an atrophied tumor atrophied and no bleeding.Argon plasma coagulation was applied to the surface of the hemolymphangioma to accelerated healing.When he returned for follow-up 1 year later,anemia was resolved and the tumor had been cured.CONCLUSION Balloon-assisted enteroscopy and capsule endoscopy are effective methods for diagnosis of hemolymphangioma.Enteroscopic injection sclerotherapy is an effective treatment.

关键词： Hemolymphangioma Lymphangioma Small intestinal tumor Balloon assisted enteroscopy Obscure gastrointestinal bleeding Enteroscopic injection sclerotherapy Case report

Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress

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World Journal of Gastroenterology 2017年第36期23卷 6650-6664页

作者： Hiroyuki Uchida Yukari Nakajima Kazuo Ohtake Junta Ito Masahiko Morita Ayako Kamimura Jun Kobayashi Division of Pathophysiology Department of Clinical Dietetics and Human NutritionFaculty of Pharmaceutical ScienceJosai University Kyowa Hakko Bio Co. Ltd.Healthcare Products Development Center

AIM To determine whether oral glutathione(GSH)administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS Rats were divided into eight groups.One group was fed ad libitum,another was fed ad libitum and received oral GSH,and six groups were administrated saline(SA)or GSH orally during fasting.Mucosal height,apoptosis,and cell proliferation in the jejunum were histologically evaluated.i NOS protein expression(by immunohistochemistry),nitrite levels(by high performance liquid chromatography,as a measure of NO production),8-hydroxydeoxyguanosine formation(by ELISA,indicating ROS levels),glutathione/oxidized glutathione(GSH/GSSG)ratio(by enzymatic colorimetric detection),andγ-glutamyl transpeptidase(Ggt1)mR NA levels in the jejunum(by semi-quantitative RT-PCR)were also estimated. RESULTS O r a l G S H a d m i n i s t r a t i o n w a s d e m o n s t r a t e d t o drastically reduce fasting-induced intestinal atrophy in the jejunum.In particular,jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals[527.2±6.9 for 50 mg/kg GSH,567.6±5.4 for 500 mg/kg GSH vs 483.1±4.9(μm),P<0.01at 72 h].This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iN OS protein staining[0.337±0.016for 50 mg/kg GSH,0.317±0.017 for 500 mg/kg GSH vs 0.430±0.023(area of staining part/area of tissue),P<0.01 at 72 h]and NO[2.99±0.29 for 50 mg/kg GSH,2.88±0.19 for 500 mg/kg GSH vs 5.34±0.35(nmol/g tissue),P<0.01 at 72 h]and ROS[3.92±0.46for 50 mg/kg GSH,4.58±0.29 for 500 mg/kg GSH vs6.42±0.52(8-OHdG pg/μg DNA),P<0.01,P<0.05at 72 h,respectively]levels as apoptosis mediators in the jejunum.Furthermore,oral GSH administration attenuated cell proliferation decreases in the fasting jejunum[182.5±1.9 for 500 mg/kg GSH vs 155.8±3.4(5-Brd U positive cells/10 crypts),P<0.01 at 72h].Notably,both GSH concentration and Ggt1 m RNA expression in the jejunum were also attenuated in rats following oral administration of GS

关键词： intestinal atrophy Glutathione Apoptosis Cell proliferation Inducible nitric oxide synthase

Interleukin-22 receptor 1 is expressed in multinucleated giant cells:A study on intestinal tuberculosis and Crohn’s disease

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World Journal of Gastroenterology 2019年第20期25卷 2473-2488页

作者： Zi-Qi Yu Wen-Fei Wang You-Chao Dai Xin-Chun Chen Jian-Yong Chen Department of Gastroenterology and Hepatology Jiangxi Provincial People’s HospitalNanchang 330006Jiangxi ProvinceChina Jiangxi Medical College Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Microbiology and Immunology Shenzhen University Health Science CenterShenzhen 518000Guangdong ProvinceChina Department of Pharmaceutical/Medicinal Chemistry Institute of PharmacyFriedrich Schiller UniversityJena 07743Germany

BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

关键词： Crohn's disease intestinal tuberculosis Single-nucleotide polymorphism Interleukin-22 Interleukin-22 receptor 1 Multinucleated giant cells

Focus on the gut-brain axis: multiple sclerosis, the intestinal barrier and the microbiome

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World Journal of Gastroenterology 2018年第37期24卷 4217-4223页

作者： Carlos R Camara-Lemarroy Luanne M Metz V Wee Yong Department of Clinical Neurosciences Cumming School of Medicine University of Calgary Hotchkiss Brain Institute Cumming School of Medicine University of Calgary

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

关键词： Multiple sclerosis Microbiome intestinal barrier Bile acids Gut-brain axis

Elevated basal intestinal mucosal cytokine levels in asymptomatic first-degree relatives of patients with Crohn's disease

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World Journal of Gastroenterology 2000年第1期6卷 49-52页

作者： Indaram AVK Nandi S Weissman S Lam S Bailey B Blumstein M Greenberg R Bank S Division of Gastroenterology Long Island Jewish Medical CenterAlbert Einstein College of MedicineNew YorkUSA

AIM To determine levels of cytokines incolonic mucosa of asymptomatic first degreerelatives of Crohn’s disease patients.METHODS Cytokines(Interleukin(IL)1-Beta,IL-2,IL-5 and IL-8)were measured using ELISAin biopsy samples of normal looking colonicmucosa of first degree relatives of Crohn’sdisease patients(n = 9)and from normalcontrols(n = 10)with no family history ofCrohn’s disease.RESULTS Asymptomatic first degree relativesof patients with Crohn’s disease had significantlyhigher levels of basal intestinal mucosalcytokines(IL-2,IL-5 and IL-8)than normalcontrols.Whether these increased cytokinelevels serve as phenotypic markers for a geneticpredisposition to developing Crohns diseaselater on,or whether they indicate early(pre-clinical)damage has yet to be further defined.CONCLUSION Asymptomatic first degreerelatives of Crohn’s disease patients have higherlevels of cytokines in their normal-lookingintestinal mucosa compared to normal controls,This supports the hypothesis that increasedcytokines may be a cause or an early event inthe inflammatory cascade of Crohns disease andare not merely a result of the inflammatoryprocess.

关键词： Subject headings crohns disease cytokine/analysis intestinal mucosa