PubMed | Cairo University, Theodore Bilharz Research Institute and American University in Cairo
Type: | Journal: Acta tropica | Year: 2016
Infection of cattle and sheep with the parasite Fasciola gigantica is a cause of important economic losses throughout Asia and Africa. Many of the available anthelmintics have undesirable side effects, and the parasite may acquire drug resistance as a result of mass and repeated treatments of livestock. Accordingly, the need for developing a vaccine is evident. Triton-soluble surface membrane and tegumental proteins (TSMTP) of 60, 32, and 28 kDa previously shown to elicit protective immunity in mice against challenge F. gigantica infection were found to be strongly immunogenic in sheep eliciting vigorous specific antibody responses to a titer>1:16,000 as assessed by enzyme-linked immunosorbent assay. Furthermore, the 60 kDa fraction induced production of antibodies able to bind to the surface membrane of newly excysted juvenile flukes and mediate their attrition in antibody-dependent complement- and cell-mediated cytotoxicity assays, and significant (P<0.05) 40% protection of sheep against F. gigantica challenge infection. Amino acid micro sequencing of the 60 kDa-derived tryptic peptides revealed the fraction predominantly consists of F. gigantica enolase. The cDNA nucleotide and translated amino acid sequences of F. gigantica enolase showed homology of 92% and 95%, respectively to Fasciola hepatica enolase, suggesting that a fasciolosis vaccine might be effective against both tropical and temperate liver flukes.
PubMed | Benha University, Taif University, Theodore Bilharz Research Institute and Zagazig University
Type: Journal Article | Journal: Parasitology research | Year: 2016
Preventive chemotherapy with praziquantel is the mainstay of schistosomiasis control. However, drug resistance is an imminent threat, particularly with large-scale administration of praziquantel, in addition to much less efficacy against young schistosomes. Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growth-regulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities. This study investigates limonin as an alternative antischistosomal compound using two novel, single, oral dose regimens. In the current work, the therapeutic efficacy of different limonin dosing protocols was evaluated in experimentally infected mice harboring Schistosoma mansoni (Egyptian strain) juvenile or adult stages. Oral administration of limonin in a single dose of 50 or 100mg/kg on day 21 post-infection (p.i.) resulted in a significant worm burden reduction of 70.0 and 83.33%, respectively. The same dose given on day 56 p.i. reduced total worm burdens by 41.09 and 60.27%, respectively. In addition, significant reductions of 34.90 and 47.16% in the hepatic and 46.67 and 56.1% in the intestinal tissue egg loads, respectively, associated with significant alterations in the oogram pattern with elevated dead egg levels. Limonin produced ameliorations of hepatic pathology with reduction in dimensions and number of granulomas. Limonin also produced a variety of tegumental alterations in treated worms including tubercular disruption, edema, blebbing, and ulcerations. Results obtained by this work elucidated promising limonin bioactivity against S. mansoni juvenile and adult stages and provided a basis for subsequent experimental and clinical trials.
Abou-Elhakam H.,Cairo University |
Rabee I.,Theodore Bilharz Research Institute |
El Deeb S.,Cairo University |
El Amir A.,Cairo University
Pakistan Journal of Biological Sciences | Year: 2013
Yet no vaccine to protect ruminants against liver fluke infection has been commercialized. In an attempt to develop a suitable vaccine against Fasciola gigantica (F. gigantica) infection in rabbits, using 97 kDa Pmy antigen. It was found that, the mean worm burdens and bile egg count after challenge were reduced significantly by 58.40 and 61.40%, respectively. On the other hand, immunization of rabbits with Pmy induced a significant expression of humoral antibodies (IgM, total IgG, IgGl, IgG2 and IgG4) and different cytokines (IL-6, IL-10, IL-12 and TNF-oc). Among Ig isotypes, IgG2 and IgG4 were most dominant Post-infection (PI) while, recording a low IgGl level. The dominance of IgG2 and IgG4 suggested late T helperl (Thl) involvement in rabbit's cellular response. While, the low IgGl level suggested Th2 response to adult/7, gigantica worm Pmy. Among all cytokines, IL-10 was the highest in rabbits immunized with Pmy PI suggesting also the enhancement of Th2 response. It was clear that the native F. gigantica Pmy is considered as a relevant candidate for vaccination against fascioliasis. Also, these data suggested the immunoprophylactic effect of the native F. gigantica Pmy which is mediated by a mixed Thl/Th2 response. © 2013 Asian Network for Scientific Information.
Aly I.R.,Theodore Bilharz Research Institute |
Diab M.,Theodore Bilharz Research Institute |
El-Amir A.M.,Cairo University |
Hendawy M.,Theodore Bilharz Research Institute |
Kadry S.,Cairo University
Korean Journal of Parasitology | Year: 2012
Although schistosomicidal drugs and other control measures exist, the advent of an efficacious vaccine remains the most potentially powerful means for controlling this disease. In this study, native fatty acid binding protein (FABP) from Fasciola gigantica was purified from the adult worm's crude extract by saturation with ammonium sulphate followed by separation on DEAE-Sephadex A-50 anion exchange chromatography and gel filtration using Sephacryl HR-100, respectively. CD1 mice were immunized with the purified, native F. gigantica FABP in Freund's adjuvant and challenged subcutaneous!/ with 120 Schistosoma mansoni cercariae. Immunization of CD1 mice with F. gigantica FABP has induced heterol-ogous protection against S. mansoni, evidenced by the significant reduction in mean worm burden (72.3%), liver and intestinal egg counts (81.3% and 80.8%, respectively), and hepatic granuloma counts (42%). Also, it elicited mixed IgG 1/lg-G 2b immune responses with predominant IgG 1 isotype, suggesting that native F. gigantica FABP is mediated by a mixed Th1/Th2 response. However, it failed to induce any significant differences in the oogram pattern or in the mean granuloma diameter. This indicated that native F. gigantica FABP could be a promising vaccine candidate against S. mansoni infection. © 2012, Korean Society for Parasitology.
Al-Halfawy A.,Cairo University |
Gomaa N.E.,Cairo University |
Refaat A.,National Research Center of Egypt |
Wissa M.,Theodore Bilharz Research Institute |
Wahidi M.M.,Duke University
Journal of Bronchology and Interventional Pulmonology | Year: 2012
Background: Airway smooth muscle contraction causes bronchial constriction and is the main cause of bronchospasm in response to stimulants in asthma patients. In this pilot study, we tested the possibility of using a commercially available neurotoxin\-botulinum toxin A (BTX-A)\-to reduce bronchial hyperreactivity in dogs. Methods: Two bronchoscopic sessions were conducted in 6 healthy mongrel dogs. In the first session, BTX-A (concentration 10 U/mL) was injected in small aliquots submucosally in 1 caudal lobe and its subsegments, leaving the other side as control. During the second bronchoscopy conducted 2 weeks later, the airway calibers of the treated and untreated sides were measured in each animal before and after instillation of methacholine in the airways to induce bronchial hyperreactivity (concentration 25mg/mL). Results: The mean pretreatment diameter was 3.356 (±1.294)mm and 2.765 (±0.603)mm in the treated and untreated airways, respectively. After provocation with methacholine, the diameter of the treated airways was 1.985 (±0.888)mm versus 0.873 (±0.833)mm in the untreated airways (P=0.000). Local injection of BTX-A in the airway resulted in reduction of bronchial hyperreactivity by 58.6% (P=0.001). There were no complications resulting from the submucosal injection of BTX-A in the airways. Conclusions: Endobronchial injection of BTX-A reduces bronchial hyperreactivity in the airways of healthy dogs. Copyright © 2012 by Lippincott Williams & Wilkins.
El Ridi R.,Cairo University |
Aboueldahab M.,Cairo University |
Tallima H.,Cairo University |
Salah M.,Theodore Bilharz Research Institute |
And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2010
The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl 2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Abdelaziz Hassan A.M.,Theodore Bilharz Research Institute |
Elsebae M.M.A.,Theodore Bilharz Research Institute |
Nasr M.M.A.,Theodore Bilharz Research Institute |
Nafeh A.I.,Theodore Bilharz Research Institute
International Journal of Surgery | Year: 2012
Background: Since the implement of laparoscopic cholecystectomy as the gold standard treatment for gall bladder stones, there has been a trend toward minimizing the required number and size of ports to reduce postoperative pain with better cosmetic results. We conducted this study to evaluate the feasibility, safety, advantages and complications of single incision laparoscopic cholecystectomy using the conventional laparoscopic instruments. Methods and patients: Eighty patients (68 females and 12 males) with uncomplicated symptomatic gall bladder stones underwent elective laparoscopic cholecystectomy via single trans-umbilical incision using the conventional laparoscopic instruments. Results: The mean operative time was 61.75 min (range: 40-105 min) and the mean estimated blood loss was 17.21 ml (range: 5-90 ml). Gall bladder perforation occurred in five cases (6.25%) with calculi spillage in four of them. It was managed by using laparoscopic stone removal forceps. Troublesome cystic artery bleeding occurred in 2 cases (2.5%) while gall bladder bed bleeding happened in one case (1.25%) with liver cirrhosis and managed by argon beam coagulation. An intraoperative cholangiography was performed in 3 cases and a drain was inserted in one case. There was no conversion to the open technique in any of the cases. 49 patients (94.2%) discharged on the 1st postoperative day and 3 patients (5.8%) discharged on the 2nd postoperative day. The average wound length measured on 3rd postoperative month was 1.58 cm (range, 1.3-2.1 mm); while average score of patient satisfaction of the surgery was of 9.32 (range, 7-10). Conclusion: In uncomplicated gall bladder disease; single incision laparoscopic cholecystectomy is feasible and safe. It has an excellent esthetic results and high grade of patient satisfaction. It could be performed with the conventional laparoscopic instruments and its scale of application could be widened once enough experience attained. © 2012 Surgical Associates Ltd.
Shaker O.,Cairo University |
Hammam O.,Theodore Bilharz Research Institute |
Wishahi M.,Theodore Bilharz Research Institute |
Roshdi M.,Theodore Bilharz Research Institute
Urologic Oncology: Seminars and Original Investigations | Year: 2013
Objectives: Study TGF-β1 pathway in bladder carcinoma. Design and methods: Eighty-one patients were enrolled: 16 chronic cystitis and 60 malignant bladder lesions; 15 schistosomal squamous cell carcinoma (SQCC), 45 transitional cell carcinoma (TCC). Five healthy individuals served as controls. mTGF-β1, protein, and its receptor expression in urine and bladder tissue were measured using in situ hybridization and immunohistochemical techniques, respectively. Results: Overexpression of TGF-mRNA in invasive TCC group was compared with superficial TCC, high grade TCC was compared with low grade, and SQCC was compared with TCC. TGF-β1 protein and its receptor I (TGF-βR1) were overexpressed in urine samples in malignant group compared with chronic cystitis and in SQCC group compared with TCC group. TGF-ß1 protein and its receptor were significantly increased in schistosomal malignant group compared with non-schistosomal group. Conclusion: Expression of TGF-ß1 and TGF-ßR1 could be used as biological markers of bladder carcinoma. © 2013 Elsevier Inc.
Nasr M.,Theodore Bilharz Research Institute |
Ezzat H.,Theodore Bilharz Research Institute |
Elsebae M.,Theodore Bilharz Research Institute
World Journal of Surgery | Year: 2010
Background Although lateral internal sphincterotomy has been the gold standard of treatment for chronic anal fissure, the main concern remains its effects on anal continence. Intrasphincteric injection of botulinum toxin seems to be a reliable option providing temporary alleviation of sphincter spasm and allowing the fissure to heal. The aim of the present prospective controlled randomized study was to compare the outcome of lateral internal sphincterotomy and botulinum toxin injection treatments in patients with uncomplicated chronic anal fissure. Methods Eighty consecutive patients with uncomplicated chronic anal fissure who had failed conservative treatment were randomized to receive either intrasphincteric injection of botulinum toxin (BT) or lateral internal sphincterotomy (LIS). Postoperative pain relief, healing of fissure, continence scores, and fissure relapse during 18 weeks of follow- up were the outcomes assessed. Results There was a statistically significantly higher healing in the LIS group than the BT group (p = 0.0086 and 95% CI = 7.38-45.69%). In addition, LIS was associated with a high rate of anal incontinence as compared to BT (p = 0.0338 and 95% CI = -1.64-27.53%). The recurrence rate in the BT group was significantly higher statistically than that in the LIS group (p = 0.0111 and 95% CI = 6.68-46.13%). Conclusions Surgical internal sphincterotomy has a higher healing rate and a lower recurrence rate than intrasphincteric injection of botulinum toxin in the treatment of uncomplicated chronic anal fissure. Injection of botulinum toxin, however, is a simple noninvasive technique that avoids the greater risk of incontinence. It could be used as the first therapeutic approach in patients without clinical risk factors of recurrence. © The Author(s) 2010.
PubMed | Cairo University and Theodore Bilharz Research Institute
Type: Journal Article | Journal: Journal of advanced research | Year: 2015
Artemether (ART), the methylated derivative of artemisinin, is an efficacious antimalarial drug that also displays antischistosomal properties. This study was designed to evaluate the immunomodulatory action of a single intramuscular dose (50mg/kg body weight) of ART in comparison with PZQ treatment (42days PI). ART administration was 7, 14, 21 and 45days PI. ART effect was studied parasitologically, histopathologically and immunologically. It was found that maximum effect was reached when ART treatment interfered with 14 or 21days old schistosomula. ART treatment 14 or 21days PI was associated with shift from Th2 to Th1 predominancy (decrease in IL-4 and upgrading of serum IFN- levels). In conclusion, ART is a promising drug in control of schistosomiasis mansoni due to its reductive effect on worm burden and its role in improvement of hepatic granulomatous lesions.