Cell Infiltration In Lamina Propria Research Articles

Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1β in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1β in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Dysphonia in Polymyositis/Dermatomyositis in Adults.

The purpose of this study was to examine clinical dysphonia in patients with polymyositis (PM)/dermatomyositis (DM). The subjects were 21 Japanese patients with PM/DM (11 females, 10 males; mean age ± SD, 61.4 ± 16.2 years) who visited our department between April 2009 and March 2020. Dysphonia was evaluated by laryngoscopy and histopathological examination. Eight (38.1%) patients were aware of dysphonia. These patients included one with PM and 7 with DM, 5 were male and 3 were female, and the mean age at diagnosis was 62.0 (range 48 to 72) years. White lesions on the vocal cords were found in 7 of the patients with dysphonia. The patient without these white lesions had regurgitation into the nasal cavity. Histopathological examination revealed inflammation of lamina propria in the laryngeal white lesions. White lesions on the vocal cords were found in patients with dysphonia in patients with polymyositis (PM)/dermatomyositis (DM). Histopathological examination revealed fiber necrosis and inflammatory cell infiltration in lamina propria of the laryngeal lesions. White lesions on the vocal cords were relieved by treatment. Level of Evidence 2b (Individual retrospective cohort study).

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis.

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNFα therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. KEY MESSAGES: What are the new findings? Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy. The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody. Neutralization of eNAMPT ameliorates acute and chronic experimental colitis. Neutralization of eNAMPT limits the expression of IBD inflammatory signature. Neutralization of eNAMPT impairs immune cell infiltration in lamina propria.

The use of a 532-nm laser fitted with a balloon and a cylindrical light diffuser to treat benign biliary stricture: a pilot study

Endoscopic management of benign biliary stricture (BBS) remains challenging. Stenting is currently used for BBS management, but refractory BBS remains problematic. The aim of this study was to assess the safety and feasibility of a dilation balloon-equipped cylindrical light diffuser for BBS in a large animal model. A total of seven mini-pigs were used in the current study. Laser settings were chosen based on the findings of a previous animal study. Five animals were used in a preliminary study to establish process conditions. BBSs were created in the common bile ducts of the other two animals by intraductal radiofrequency ablation (RFA) via endoscopic retrograde cholangiography (ERC). At 4weeks post-RFA, laser ablation was performed using a customized balloon-equipped cylindrical diffuser at 10W for 10s while maintaining balloon inflation for 10s at 5atm. A follow-up ERC was performed at 4weeks post-laser ablation and the animals were sacrificed for histologic evaluation. BBS was observed in all animals by ERC at 4weeks post-RFA. The mean bile duct stricture diameter in the two animals as determined by ERC was 0.8mm. Laser ablations were performed without technical difficulty and no adverse event was encountered. At 4weeks post-laser ablation, mean biliary stricture diameter had dilated to 1.6mm on cholangiographic finding. On histologic examination, inflammatory cell infiltration in lamina propria and dense collagen deposition were observed, but there was no evidence of bile duct perforation. The devised balloon-equipped cylindrical laser light diffuser appears to be safe and feasible for the treatment of BBS. However, further studies and modifications are required before it can be applied clinically as a monotherapy.

Effect of a chamomile extract in protecting against radiation-induced intestinal mucositis.

Compounds that prevent radiation‐induced mucositis may offer new therapeutic strategies for maintaining intestinal integrity in patients undergoing radiotherapy. A specially formulated chamomile extract was studied with the hope of proving efficacy in this regard. Intestinal mucositis was induced in rats by exposing them to whole body gamma‐irradiation. Rats were treated orally with the extract for 5 days before and 2 days after radiation exposure. One day later, rats were sacrificed. Histological examination of segments of small intestine showed shortening and fusion of villi, activation of mucus secreting glands, inflammatory cell infiltration of lamina propria, and mucosal atrophy. Intestinal homogenates showed an increase in tumor necrosis factor, a pro‐inflammatory cytokine, and myeloperoxidase, an indicator of cellular infiltration, as well as in thiobarbituric acid reactive substances and a reduction in glutathione content. Intestinal injury was further evidenced by an increase in diamine oxidase and a reduction in citrulline levels in the serum. A rise in apoptosis was evidenced by an increase in cytosolic cytochrome c, caspase‐3, and depletion of mitochondrial B‐cell lymphoma‐2/ Bax ratio. Most histological changes and associated derangement in related parameters were largely prevented by the chamomile extract, thus paving the way to a new therapeutic approach towards the management of radiation‐induced intestinal mucositis.

PORTAL GASTROPATHY

Objectives: To study the characteristic histological features of Portal gastropathy and its correlation with Child-Pugh Score in liver cirrhosis patients. Study Design: Cross sectional study. Place and Duration: Department of Anatomy and Gastroenterology Unit, Isra University Hospital from June to December 2012. Subjects and Methods: Gastric biopsies from 85 cases of liver cirrhosis with portal gastropathy were collected by non probabilityconvenient sampling. Olympus XQ 140 (version 3) was used for 2 mm thick tissue specimens by punch biopsy. Tissue pieces were preserved in 10% formalin. 3-5 μ thick tissue specimens were stained with H & E for microscopic examination. Results: Portal Gastropathy was noted in 91.7% of total study subjects. Gastric glands showed increase counts and increased size noted in 60.12% and 57.65% of cases respectively. Pyloric antrum revealed inflammatory cell infiltration of lamina propria. 95.2% inflammatory cells comprised of lymphocytes. Capillary congestion and edema was noted in 9.4% of cases. Spearman correlation showed positive correlation of Portal gastropathy and Child Pugh Class (CPC) score (R2=0.5244, p=0.0001).Conclusion: Portal Gastropathy was noted in 91.7%. Histological showed increase in size, length and count of gastric glands, capillary congestion and inflammatory cell infiltration. Spearman correlation showed positive correlation of Portal gastropathy and Child Pugh Class (CPC) score (R2=0.5244, p=0.0001).

Morphological alterations in the jejunal mucosa of aged rats and the possible protective role of green tea.

Gastrointestinal disorders become more prevalent with ageing. This study is aimed to describe morphological changes that occur in the jejunal mucosa of male albino rats as a result of ageing and the protec-tive effect of green tea (GT) extract. The experiment was performed on sixty rats: thirty young-adult (6-month old, body mass 200-220 g) and thirty old (24-month-old, body mass 220-260 g) animals. Each group was further divided into two subgroups (n = 15 each): control rats and GT-treated rats that received 1.5 mL (300 mg/kg/day) of GT extract for 14 weeks by oral gavage. Sections of the jejunum were stained with hematoxylin and eosin, periodic acid Schiff, toluidine blue and Mallory trichrome methods. The presence of proliferating cell nuclear antigen (PCNA)- and CD68-positive cells was evaluated by immunohistochemical staining. Ultrathin sections were prepared and examined by a transmission electron microscope (TEM). Jejunal sections of the old control rats showed distortion of submucosa and attenuated muscularis externa with decreased height of intestinal villi. The villi also showed partial loss of acidophilic brush border with wide spaces between enterocytes. Swollen, short, blunt or broad villi with abundant mononuclear cell infiltration of lamina propria and congested blood vessels were evident both by light and electron microscopy. The number of PCNA- and CD68-positive cells in jejunal mucosa of old rats was higher than in young rats. The activity of glutathione peroxidase (GPX) and total antioxidant capacity (TAC) in the mucosa of old control rats were lower, whereas malondialdehyde (MDA) levels were higher in the jejunal homogenates of old rats as compared to young control rats. Administration of GT extract protected the jejunal mucosa from age-related changes by restoring its histological structure. The treatment of old rats with GT extract significantly decreased MDA levels in the jejunum and increased TAC and GPX activity. The age-related changes of the morphology of rat jejunum could be ameliorated by prolonged supplementation of the green tea extract.

Sa2004 Effects of AVX-470m, an Oral Polyclonal Anti-TNF Antibody, on Survival and Biomarkers in a Murine Model of Gastrointestinal Acute Radiation Syndrome

Intestinal mucositis is a common side-effect in patients undergoing radiotherapy and poses a severe dose-limiting factor in treatment1. Identification of compounds that prevent radiationinduced mucositis and improve intestinal restitution may offer new therapeutic strategies for maintaining intestinalmucosal integrity in patients undergoing radiotherapy. Pathogenesis of mucositis involves production of pro-inflammatory cytokines and reactive oxygen metabolites2,3 and increased apoptosis in intestinal epithelium, leading to loss of intestinal structure and function4. STW 5 is an herbal multi-component preparation having potent anti-oxidant and anti-inflammatory properties in intestinal inflammatory disorders,5,6, making it an attractive candidate to study its potential usefulness in mucositis. Intestinal mucositis was induced experimentally in rats by exposing them to whole body irradiation from a Caesium 137 source at a radiation dose of 6 Gray. Three days later, rats developed intestinal mucositis, judged by histological examination of the small intestine and measurement of associated parameters in intestinal homogenates and serum. STW5 was given orally for 5 days to rats in graded doses of 2 10 ml/kg before exposing them to radiation and continued for 3 days after exposure. Animals were sacrificed 24h later. Pretreatment with STW 5 led to dosedependent reduction in histological changes. A dose of 5 ml/kg was chosen to study in detail the protective effects of the preparation on relevant associated parameters. Histologically, irradiation caused shortening and fusion of villi, activation of mucus secreting glands, inflammatory cell infiltration of lamina propria and mucosal atrophy. Inflammation markers: tumor necrosis factor and myeloperoxidase activity in homogenates were also raised. The changes were associated with a rise in thiobarbituric acid reactive substances, reduction in glutathione and in protein content of intestinal homogenates. Biomarkers of intestinal tissue injury: plasma diamineoxidase was raised while citrulline7 was significantly reduced. Apoptosis was evidenced by a rise in cytosolic calcium, depletion of mitochondrial cytochrome c and B-cell lymphoma 2. Most histological changes and associated derangement in the parameters tested were largely prevented by STW 5. The findings pave the way to a new therapeutic approach in management of radiation induced mucositis. 1Costa G and Donaldson SS (1979) N Engl J Med 300, 1471-1474, 2MacNaughton WK (2000) Aliment Pharmacol Ther. 14, 523-528, 3Linard C et al (2003) Am J Physiol Gastrointest Liver Physiol. 285, 556-565, 4Wong TC et al (2006) J Pain Symptom Manage. 32, 27-37, 5Khayyal MT et al (2006) Phytomedicine. 13 Suppl 5, 56-66, 6Schempp H et al (2006) Phytomedicine. 2006;13 Suppl 5, 36-44 7Lutgens L and Lambin P (2007) World J. Gastroenterol., 13, 3033 3042

Effect of Trapidil in Ischemia/Reperfusion Injury on Rat Small Intestine

To investigate the effect of trapidil on the intestinal ischemia-reperfusion injury, we determined malondialdehyde levels as a indicator of lipid peroxidation, nitrite and nitrate levels as reflections of nitric oxide metabolism, and histopathological findings in rats subjected to 40 min of ischemia and 2 h of reperfusion. Histopathological evaluation demonstrated that trapidil treatment has a protective effect on intestinal mucosa and reduces inflammatory cell infiltration in lamina propria, which is consistently noted in the untreated ischemic and reperfused intestines. Possible mechanism of this effect may be explained by the reduced lipid peroxidation (mean malondialdehyde level 3.72 - 0.27 vs. 6.13 - 0.44, p < .0001) and improved nitric oxide metabolism (mean nitrite plus nitrate 38.21 - 2.33 vs. 30.14 - 1.47, p = .022).

BRONCHOESOPHAGEAL FISTULA AND DYNAMIC BRONCHOSCOPY.

BRONCHOESOPHAGEAL FISTULA AND DYNAMIC BRONCHOSCOPY.

Cycad (Zamia Puertoriquensis) Toxicosis in a Group of Dairy Heifers in Puerto Rico

tory parenchymal necrosis and lysis associated with groups of bacteria (probably secondary infection), with focal hemorrhages. Structurally distinct types of schizonts with slender merozoites (Fig. 14) or short stubby merozoites (Fig. 15) were seen. Intestinal coccidiosis was seen in echidna nos. 2, 4, and 5 (Figs. 16-20). Lesions were more severe in the small intestines of echidna nos. 2 and 5 and consisted of desquamation of epithelial cells of glands of Lieberkiihn and surface epithelium, hypertrophy of villous epithelium, and mononuclear cell infiltration in lamina propria. Gamonts and oocysts The intravascular schizonts in the lungs of the echidnas were structurally similar to schizonts of Sarcocystis, particularly of the Sarcocystis species in cattle, sheep, and goats. Some of the schizonts in the liver, lungs, and spleen were difficult to distinguish from tachyzoites of T. gondii. However, T. gondii tachyzoites always divide into 2 by endodyogeny, whereas the extraintestinal protozoa of the echidnas divided into many organisms by schizogony. Acknowledgements. We thank the staff of the Veterinary Research Institute in Melbourne who made 3 of the cases available for examination. were seen in all 3 echidnas. Oocysts were approximately 25 x 20 μm and were unsporulated (Figs. 18-20). Few schizonts were seen only in 1. echidna no. 2. A 45x 25-μm schizont with numerous tiny merozoites in the lamina propria of the small intestine is shown in Fig. 17. Protozoa in the lung and liver of echidna no. 1 did not 2. react to T. gondii, N, caninum, or S. cruzi antisera. Protozoa in extraintestinal tissues of echidnas were un3= identified. Protozoa in the intestines of echidnas in the present study appeared to be structurally similar to the intestinal 4.

Pathogenesis of Providencia alcalifaciens-induced diarrhea.

Providencia alcalifaciens is a member of the family Enterobacteriaceae. There are reports that P. alcalifaciens can cause diarrhea, but the mechanism(s) by which it causes diarrhea is known. We studied P. alcalifaciens isolated from a child and two adults with diarrhea for enteropathogenicity. The three isolates did not exhibit any characteristic adherence to cultured HEp-2 cell monolayers, and they did not produce enterotoxins, cytotoxins, or keratoconjunctivitis in the Sereny test. Two isolates invaded cultured HEp-2 cell monolayers, producing localized bacterial clusters and actin condensation. The pattern of actin condensation was different from that produced by enteropathogenic Escherichia coli but similar to that produced by Shigella flexneri. Invasion and actin condensation were poor for the third isolate. Histology of adult rabbit small intestinal loops inoculated with all three isolates revealed bacterial attachment to, penetration of, and microulcer formation on the surface epithelium and hyperemia, edema, and polymorphonuclear cell infiltration of lamina propria. All the isolates produced diarrhea in rabbits with removable intestinal ties, and some of these rabbits developed hindlimb paralysis. Intestinal histology of the rabbits with removable intestinal ties which developed diarrhea showed changes similar to that in adult rabbits on which ileal loop assays had been performed. Transmission electron microscopy of intestinal tissues also confirmed tissue penetration by the isolates. Nerve tissue histology of two rabbits that developed hindlimb paralysis showed focal mononuclear cell infiltration around peripheral nerve sheaths. It is concluded that some strains of P. alcalifaciens are enteropathogenic and that they cause diarrhea by invading the intestinal mucosal epithelium. However, the relevance to human disease of the hindlimb paralysis observed in this animal model is not clear.

Tropical Sprue (TS); Experience in a Tertiary Care Hospital

Background: Tropical sprue (TS) is a common cause of malabsorption in the tropics. No report has yet been published on TS in Bangladesh. This report aimed to describe clinical picture of TS patients in a tertiary care hospital. Methods: The data were collected from the admission and discharge registers and register of follow-up clinic of Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University during the period of 1981- 2004. Results: A total of 23 patients with a mean age of 36.42 years were diagnosed to have TS (8 females and 15 males). Mean duration of their symptoms was eight months. Important presenting features were loose motions (82.6%) and progressive weight loss (73.91. Approximately 43.47% patients presented with abdominal discomfort or pain, 26.02% with fever and 26.03% with skin changes. Mean hemoglobin and serum albumin levels were 9.71gm/dl and 31.16 gm/dl respectively. Fecal fat was positive in only eight cases. Contrast X-ray showed dilatation of small intestinal loops in four cases and flocculation of dye in two cases. Duodenal biopsy showed partial (16cases) or subtotal (four cases) villous atrophy with chronic inflammatory cell infiltrate in lamina propria in 91.3 % cases. Patients treated with tetracycline or ciprofloxacin along with folic acid showed good initial response with improvement of bowel motions, weight gain and anemia. Only two patients presented with recurrent attacks. In conclusion, TS is also prevalent in our country. A good number of TS patients presented with abdominal responses were pain and fever along with diarrhoea and weight loss. Small intestinal mucosal changes and treatment typical to TS. Key Words: Tropical sprue; clinical profile Key Message: The mal-absorptive disorder Tropical sprue is also prevalent in Bangladesh. Patients mostly presented with loose motions and progressive weight loss. A good number of TS patients’ present with abdominal pain and fever along with diarrhoea and weight loss. DOI: 10.3329/jbsp.v29i1.7166J Bangladesh Coll Phys Surg 2011; 29:16-20