Defining the Pathways of Urogenital Schistosomiasis-Associated Urothelial Carcinogenesis through Transgenic and Bladder Wall Egg Injection Models

2017 ◽  
pp. 67-76 ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Michael H. Hsieh
Keyword(s):  
Bladder Wall ◽  
Urogenital Schistosomiasis ◽  
Egg Injection

scholarly journals Interleukin-4 Signaling Plays a Major Role in Urogenital Schistosomiasis-Associated Bladder Pathogenesis

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Chi-Ling Fu ◽  
Christina P. Ho ◽  
Loc Le ◽  
Kenji Ishida ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Ex Vivo ◽  
Bladder Wall ◽  
Interleukin 4 ◽  
Wild Type ◽  
Urogenital Schistosomiasis ◽  
Content Type ◽  
Helminth Infections

ABSTRACT Interleukin-4 (IL-4) is crucial in many helminth infections, but its role in urogenital schistosomiasis, infection with Schistosoma haematobium worms, remains poorly understood due to a historical lack of animal models. The bladder pathology of urogenital schistosomiasis is caused by immune responses to eggs deposited in the bladder wall. A range of pathology occurs, including urothelial hyperplasia and cancer, but associated mechanisms and links to IL-4 are largely unknown. We modeled urogenital schistosomiasis by injecting the bladder walls of IL-4 receptor-alpha knockout (Il4ra−/−) and wild-type mice with S. haematobium eggs. Readouts included bladder histology and ex vivo assessments of urothelial proliferation, cell cycle, and ploidy status. We also quantified the effects of exogenous IL-4 on urothelial cell proliferation in vitro, including cell cycle status and phosphorylation patterns of major downstream regulators in the IL-4 signaling pathway. There was a significant decrease in the intensity of granulomatous responses to bladder-wall-injected S. haematobium eggs in Il4ra−/− versus wild-type mice. S. haematobium egg injection triggered significant urothelial proliferation, including evidence of urothelial hyper-diploidy and cell cycle skewing in wild-type but not Il4ra−/− mice. Urothelial exposure to IL-4 in vitro led to cell cycle polarization and increased phosphorylation of AKT. Our results show that IL-4 signaling is required for key pathogenic features of urogenital schistosomiasis and that particular aspects of this signaling pathway may exert these effects directly on the urothelium. These findings point to potential mechanisms by which urogenital schistosomiasis promotes bladder carcinogenesis.

scholarly journals The possibilities of diagnosis and treatment of urogenital schistosomatosis in current conditions

2018 ◽  
Vol 6 (3) ◽  
pp. 5-11
Author(s):  
F. R. Asfandiyarov ◽  
V. Yu. Startsev ◽  
A. Yu. Kolmakov
Keyword(s):  
Bladder Cancer ◽  
Bladder Wall ◽  
Diagnosis And Treatment ◽  
Parasitic Infections ◽  
Wall Thickening ◽  
Oral Antibiotic ◽  
Outpatient Basis ◽  
Urogenital Schistosomiasis ◽  
Group I ◽  
Group Ii

Introduction.Globalization contributes to the increase in cases of “exotic” bacterial and parasitic infections importation from the countries of the tropical belt to the territory of our country and to European states.Purpose of research. Study and analysis of data on the methods of diagnosis and treatment of urogenital schistosomiasis at the present stageMaterials and methods. The study includes an analysis of the examination and treatment results of 181 patients with urogenital schistosomiasis (US) living in the province of Benguela, Republic of Angola. In 39 (21,5%) cases are revealed schistosomal bladder cancer. All patients with schistosomal bladder cancer (SBC) were operated. 142 patients (78.5%) were divided into two groups. Group I (n = 74) consisted of patients with uncomplicated MS, into group II (n = 68) patients had granulomatous proliferative inflammatory changes in the bladder.Results.Patients with US (n = 142) were examined on an outpatient basis. Cytological exmination of urine sediment (CEUS) showed that eggs of schistosomes were detected in 38 (26.8%) patients. Ultrasound showed specific granulomatous changes in the mucous membrane of the urinary bladder in 28 (19.7%) patients. In 7 (4.9%) cases it showed hydronephrosis, calcification. Bladder wall thickening were detected in 10 (7%) and 99 (69.7%) cases, respectively. Endoscopic examination showed the presence of granulomatous changes in the bladder in 68 (47.9%) patients. Patients of group I (n = 74) received «Praziquantel» in combination with oral antibiotic therapy, which resulted in the relief of macrohematuria and urination disorders. All patients of group II (n = 68) also underwent antibacterial and antiprotozoal therapy. In addition, 35 (24.6%) patients underwent transurethral resection of the bladder (TURB). The results of control observations showed the restoration of bladder mucous layer. Of the 33 (23.2%) patients in Group II who received only antibacterial and antiprotozoal therapy, granulomatous changes persisted in 7 (4.9%) patients. In connection with this, TURB was performed for these patients. Subsequent control studies showed regression of the formations in this group of patientsConclusions.CEUS and ultrasound are not sufficient for diagnosis of US. Cystoscopy is suitable for all patients with MS. It allows to estimate the volume of the bladder lesion, and to determine the indications for performing TURP in addition to the use of antiparasitic and antibacterial therapy.

scholarly journals Interleukin-4 signaling plays a major role in urogenital schistosomiasis-associated bladder pathogenesis

2019 ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Chi-Ling Fu ◽  
Christina P. Ho ◽  
Loc Le ◽  
Kenji Ishida ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Ex Vivo ◽  
Bladder Wall ◽  
Interleukin 4 ◽  
Wild Type ◽  
Urogenital Schistosomiasis ◽  
Helminth Infections ◽  
Bladder Pathology

AbstractIL-4 is crucial in many helminth infections, but its role in urogenital schistosomiasis, infection with Schistosoma haematobium worms, remains poorly understood due to a historical lack of animal models. The bladder pathology of urogenital schistosomiasis is caused by immune responses to eggs deposited in the bladder wall. A range of pathology occurs, including urothelial hyperplasia and cancer, but associated mechanisms and links to IL-4 are largely unknown. We modeled urogenital schistosomiasis by injecting the bladder walls of IL-4 receptor-alpha knockout(Il4ra−/−) and wild type mice with S. haematobium eggs. Readouts included bladder histology and ex vivo assessments of urothelial proliferation, cell cycle and ploidy status. We also quantified the effects of exogenous IL-4 on urothelial cell proliferation in vitro, including cell cycle status and phosphorylation patterns of major downstream regulators in the IL-4 signaling pathway. There was a significant decrease in the intensity of granulomatous responses to bladder-wall injected S. haematobium eggs in Il4ra−/− versus wild type mice. S. haematobium egg injection triggered significant urothelial proliferation, including evidence of urothelial hyperdiploidy and cell cycle skewing in wild type but not Il4ra−/− mice. Urothelial exposure to IL-4 in vitro led to cell cycle polarization and increased phosphorylation of AKT. Our results show IL-4 signaling is required for key pathogenic features of urogenital schistosomiasis, and that particular aspects of this signaling pathway may exert these effects directly on the urothelium. These findings point to potential mechanisms by which urogenital schistosomiasis promotes bladder carcinogenesis.

scholarly journals A Newly Identified Role for IL-22 in Bladder Immunity

2020 ◽  
Author(s):  
Jared Honeycutt ◽  
Loc Le ◽  
Yi-Ju Hsieh ◽  
Michael H. Hsieh
Keyword(s):  
Urinary Tract ◽  
Bladder Wall ◽  
Transferase Activity ◽  
Bladder Tissue ◽  
Bacterial Counts ◽  
Interleukin 22 ◽  
Expression Of Genes ◽  
Egg Injection ◽  
Wall Injection ◽  
Tract Infections

AbstractBacterial and parasitic urinary tract infections(UTI) affect many, but our understanding of associated immunity remains poor. Prior work indicates interleukin-22(IL-22) is a key cytokine during infection of other epithelia. We hypothesized IL-22 is crucial during UTI.IL-22-null(KO) and wild-type(wt) mice underwent bladder wall injection with S. haematobium eggs or transurethral infection with uropathogenic E. coli UTI89.IL-22 and its soluble binding protein, IL-22BP, were increased in the bladder after S. haematobium egg injection. Genes typically induced by IL-22(CXCL2, REG3G[antimicrobial defense protein]], S100A8, S100A9, and Areg) were expressed at higher levels following S. haematobium egg injection. IL-22 stimulation of bladder tissue induced REG3B expression. IL-22 receptor alpha-1 expression was detectable in the urothelium by immunofluorescence and qPCR.Injection of S. haematobium eggs into IL-22-KO vs wt mice triggered differential expression of genes related to transferase activity(transferring alkyl or aryl groups) and epithelial cell development. Numerous uroplakin genes were downregulated in egg-injected, IL-22-KO mice versus their wt counterparts. These decreases in uroplakin expression suggest that, as in the gut, IL-22 is important for replenishing the epithelium during infection-related injury.Following transurethral infection with UTI89, IL-22-KO mice had lower bacterial counts in their urine, bladder, and kidneys. Giving stabilized IL-22 cytokine (IL-22-Fc) to UTI89-infected mice led to higher kidney bacterial counts and increased morbidity.Our data suggest that IL-22 is indeed important in urinary tract immunity, and may interfere with clearance of bacteria from the urinary tract, potentially through its role in maintenance of mature urothelium.

scholarly journals Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)—pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings

2019 ◽  
Author(s):  
J Remppis ◽  
A Verheyden ◽  
A L Bustinduy ◽  
T Heller ◽  
N García-Tardón ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Point Of Care ◽  
Clinical Care ◽  
Bladder Wall ◽  
Wall Thickening ◽  
Point Of Care Ultrasound ◽  
Urogenital Schistosomiasis ◽  
Urinary Schistosomiasis ◽  
Resource Limited ◽  
Therapeutic Algorithms

Abstract Background Urogenital schistosomiasis (UGS) causes inflammation and fibrosis of the urinary tract. In resource-limited settings, affordable tools for morbidity assessment in clinical care are needed. Point-of-care ultrasound has not yet been validated for UGS-related pathology. Methods We developed a protocol for Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS), assessing pathology of the bladder wall, ureters and kidneys. Following standardized training, two clinicians performed FASUS on children and adults with hematuria in Lambaréné, Gabon. Recorded ultrasound clips were remotely reviewed by two ultrasound experts as a diagnostic reference. Results In 2015 and 2016, scans were performed in 118 patients. The image quality was sufficient in 90% of bladder views and more than 97% of kidney views. UGS-compatible pathology was detected in 51/118 (43%) by the operator and in 46/107 (43%) by the experts among baseline scans of sufficient quality. Inter-rater agreement between operators and experts was very good (κ > 0.8) for hydronephrosis and good (κ > 0.6) for bladder wall thickening. Conclusions FASUS is a promising clinical, point-of-care tool for detecting UGS-related urinary tract morbidity in symptomatic patients. Based on larger validation studies, appropriate diagnostic and therapeutic algorithms for the use of FASUS should be established.

Swim bladder mycosis in farmed rainbow trout Oncorhynchus mykiss caused by Phoma herbarum and experimental verification of pathogenicity

2020 ◽  
Vol 138 ◽  
pp. 237-246 ◽  
Author(s):  
J Řehulka ◽  
A Kubátová ◽  
V Hubka
Keyword(s):  
Rainbow Trout ◽  
Histopathological Examination ◽  
Periodic Acid ◽  
Bladder Wall ◽  
Swim Bladder ◽  
Cell Reactivity ◽  
Periodic Acid Schiff ◽  
Posterior Portion ◽  
Hepatic Congestion ◽  
Phoma Herbarum

In this study, spontaneous swim bladder mycosis was documented in a farmed fingerling rainbow trout from a raceway culture system. At necropsy, the gross lesions included a thickened swim bladder wall, and the posterior portion of the swim bladder was enlarged due to massive hyperplasia of muscle. A microscopic wet mount examination of the swim bladder contents revealed abundant septate hyphae, and histopathological examination showed periodic acid-Schiff-positive mycelia in the lumen and wall of the swim bladder. Histopathological examination of the thickened posterior swim bladder revealed muscle hyperplasia with expansion by inflammatory cells. The causative agent was identified as Phoma herbarum through morphological analysis and DNA sequencing. The disease was reproduced in rainbow trout fingerlings using intraperitoneal injection of a spore suspension. Necropsy in dead and moribund fish revealed extensive congestion and haemorrhages in the serosa of visceral organs and in liver and abdominal serosanguinous fluid. Histopathological examination showed severe hepatic congestion, sinusoidal dilatation, Kupffer cell reactivity, leukostasis and degenerative changes. Fungi were disseminated to the liver, pyloric caeca, kidney, spleen and heart. Although infections caused by Phoma spp. have been repeatedly reported in fish, species identification has been hampered by extensive taxonomic changes. The results of this study confirmed the pathogenicity of P. herbarum in salmonids by using a reliably identified strain during experimental fish infection and provides new knowledge regarding the course of infection.

CLINICAL SYMPTOMS, ULTRASOUND AND HISTOPATHOLOGY OF TUMORLIKE LESIONS OF THE BLADDER.

2017 ◽  
pp. 41-46
Author(s):  
Van Mao Nguyen ◽  
Thi Bich Chi Nguyen
Keyword(s):  
Bladder Cancer ◽  
Bladder Tumor ◽  
Clinical Symptoms ◽  
Bladder Wall ◽  
Lower Abdominal Pain ◽  
University Hospital ◽  
Wall Thickening ◽  
Health Examination ◽  
Ultrasound Images ◽  
Key Words Bladder Cancer

Background: Bladder cancer is one of the most frequent type of urinary cancer which has been ever increasing. For the better treatment, the early discovery and definite diagnosis of this disease played an important role. Objective: To describe some clinical symptoms and ultrasound features of tumorlike lesions of the bladder. To diagnose and classify the histopathology of tumorlike lesions of the bladder. Materials, method: cross - sectional study on 64 cases in Hue University Hospital and Hue central hospital from April, 2016 to February, 2017. Results: Hematuria was the most common reason that patients went to hospital (79.7%). Lower abdominal pain and irritation during urination accounting for 9.4% and 6.2% respectively. Only 3 patients with bladder cancer were accidentally discovered through periodic health examination (4.7%). The characteristics of hematuria in bladder tumor was flesh red urine (62.5%) and total hematuria (60.7%). With ultrasonography, the results of 64 patients were divided in 3 groups as follow: bladder tumor, which was the highest rate 87.5%, bladder polyp was 3.1% and focal bladder wall thickening was 9.4%. Of which, the vast majority of these ultrasound images was tumor - like lesions protruding in the lumen of the bladder (75%), the rest was wall thickening lesions (25%). Tumors were different in size, the biggest tumor was 7cm in diameter and the smallest was 0.6cm. Those with the diameter 3cm or bigger accounting for 42.2%, the smaller was 57.8%. Most cases have only one lesion (62.5%) and at lateral wall (46.6%). Histopathologically, cancer was 59/64 case (92.2%): urothelial carcinoma was 98.3 %, squamous cell carcinomawas 1.7% and 5 cases (7.8%) were benign. Most cancerous cases were poorly differentiated, grade II (50.9%) and grade III (32.2%). The stage T1NxMx was 20.3% and worse than T2MxNx was 79.7%. Conclusion: hematuria was the most popular symptom, suggesting bladder cancer. Clinical diagnosing bladder cancer was not high sensitive (61.01%). Ultrasound could detect bladder tumor with high sensitive (89.8%). These patients also needed histopathology classification to diagnose and finally choose the best method for the appropriate treatment. Key words: bladder cancer, histopathology, ultrasound, uroepithelial carcinoma, hematuria

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