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Addis Ababa University

1. Belay, Tadesse. In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia .

Degree: 2014, Addis Ababa University

In vitro and in vivo anti-trypanosomal activity of dichloromethane and methanol crude leaf extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense field isolate Belay Tadesse Addis Ababa University, 2014 African Trypanosomosis is a neglected tropical disease of medical and veterinary importance. Parasite control relies on the use of few drugs whose resistance and unacceptable toxicities urged the investigation of new agents, preferably from natural sources. Though Dovyalis abyssinica has been reported to posses significant trypanocidal activity on Trypanosoma brucei in in vitro model, activity on trypanosome infected laboratory animals has not yet been worked out. The aim of the present study was, therefore, to investigate the in vitro and in vivo activity of D. abyssinica on T. congolense field isolate. To evaluate the effect on motility, 200 μl T. congolense infected blood was mixed with 50 μl of 20, 10, 2, 0.1, 0.015 mg/ml dichloromethane and methanol extracts. Reduction or cessation of motility was then microscopically monitored for 120 minutes, and the remaining in vitro mixtures were inoculated to healthy mice and monitored for development of infection for 21 days. Furthermore, fifty T. congolense infected mice were randomly grouped into ten groups of five and administered with curative doses (250, 200, 150 and 100 mg/kg) of dichloromethane and methanol and 28 mg/kg diminazene aceturate and dimethylsulfoxide. Following administration, parasitemia, packed cell volume (PCV), rectal temperature, body weight and survival time were iii monitored. Suppressive doses of the extracts (250 and 200 mg/kg) were administered 24 hours post-infection and parasitemia was monitored. Dichloromethane and methanol extracts at 20, 10, 2 mg/ml concentrations ceased parasite motility within one hour and eliminated subsequent infectivity in mice for 21 days. Administration of dichloromethane and methanol extracts at 250 and 200 mg/kg reduced (p<0.05) parasitemia and rectal temperature, and improved (p<0.05) PCV, mean body weight, and mean survival time compared to DMSO treatment. In conclusion, D. abyssinica at higher concentrations in vitro and higher curative doses in vivo in mice posses anti-trypanosomal activity. Keywords: Anti-trypanosomal, D. abyssinica, in vitro, in vivo, T. congolense, mice. Advisors/Committee Members: Getachew Abebe(Prof) (advisor).

Subjects/Keywords: Anti-trypanosomal; D. abyssinica; in vitro; in vivo; T. congolense; mice

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Belay, T. (2014). In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia . (Thesis). Addis Ababa University. Retrieved from http://etd.aau.edu.et/dspace/handle/123456789/6072

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Belay, Tadesse. “In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia .” 2014. Thesis, Addis Ababa University. Accessed December 13, 2019. http://etd.aau.edu.et/dspace/handle/123456789/6072.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Belay, Tadesse. “In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia .” 2014. Web. 13 Dec 2019.

Vancouver:

Belay T. In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia . [Internet] [Thesis]. Addis Ababa University; 2014. [cited 2019 Dec 13]. Available from: http://etd.aau.edu.et/dspace/handle/123456789/6072.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Belay T. In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate Belay Tadesse A Thesis Submitted to the Department of Pharmacology and Clinical Pharmacy Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science (Pharmacology) Addis Ababa University Addis Ababa, Ethiopia . [Thesis]. Addis Ababa University; 2014. Available from: http://etd.aau.edu.et/dspace/handle/123456789/6072

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Manitoba

2. Onyilagha, Chukwunonso. Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells.

Degree: Immunology, 2014, University of Manitoba

African trypanosomiasis is a fatal disease that affects human and livestock and poses massive agricultural and economic problems in the affected regions. There is currently no vaccine or satisfactory treatment for this disease. Understanding various regulatory mechanisms that influence resistance and/or susceptibility to the disease could help identify novel targets for treatment and/or development of a vaccine against the disease. This thesis focuses on investigating the contributions of regulatory T cells (Tregs), natural killer (NK) cells and myeloid-derived suppressor cells (MDSCs) in the immunopathogenesis of experimental T. congolense infection. Repeated low dose intradermal (i.d.) T. congolense infections predispose mice to enhanced susceptibility to an otherwise non-infectious dose challenge. I explored the mechanisms behind this and found that akin to intraperitoneal infection, low dose i.d. infection elicited strong immune response and expansion of Tregs in both the spleens and lymph nodes draining the infection site. Depletion of Tregs during primary or before challenge infection completely abolished low dose-induced enhanced susceptibility. Next, I found that infection with T. congolense is associated with increased numbers of NK cells in multiple tissue compartments. Depletion of NK cells prior to infection led to increased parasitemia and a significant reduction in numbers of IFN-g-producing cells in the spleens and liver of infected mice. NFIL3-/- mice (that genetically lack NK cell development) succumb acutely to infection, and this was accompanied by significant reduction in IFN-g and TNF-α production by CD3+ T cells in the infected mice. Adoptive transfer of wild-type NK cells into NFIL3-/- mice before infection rescued them from acute death, strongly confirming that NK cells may be contributing to optimal resistance following infection. Lastly, using cell analysis and depletion studies, I found that MDSC numbers increased during T. congolense infection and these cells contribute to enhanced susceptibility to the infection by suppressing CD4+ T cell proliferation and IFN-g production in an arginase-1-dependent manner. Collectively, the results of my studies identified important roles played by Tregs, NK cells, and MDSCs during T. congolense infection. They revealed important mechanisms that regulate susceptibility and resistance to this disease, which could be novel therapeutic targets in African trypanosomiasis. Advisors/Committee Members: Uzonna, Jude (Immunology) (supervisor), Soussi Gounni, Abdelilah (Immunology) (examiningcommittee), Kung, Sam (Immunology) (examiningcommittee), Keynan, Yoav (Medical Microbiology and Infectious Diseases) (examiningcommittee), Kaushik, Radhey (South Dakota State University) (examiningcommittee).

Subjects/Keywords: Trypanosoma congolense; Regulatory T cells; Natural killer cells; Myeloid-derived suppressor cells; Infection; Cytokines; Adoptive transfer; Resistance; Susceptibility; Proliferation; Immunosuppression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Onyilagha, C. (2014). Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. (Thesis). University of Manitoba. Retrieved from http://mspace.lib.umanitoba.ca/xmlui/handle/1993/32892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Onyilagha, Chukwunonso. “Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells.” 2014. Thesis, University of Manitoba. Accessed December 13, 2019. http://mspace.lib.umanitoba.ca/xmlui/handle/1993/32892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Onyilagha, Chukwunonso. “Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells.” 2014. Web. 13 Dec 2019.

Vancouver:

Onyilagha C. Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. [Internet] [Thesis]. University of Manitoba; 2014. [cited 2019 Dec 13]. Available from: http://mspace.lib.umanitoba.ca/xmlui/handle/1993/32892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Onyilagha C. Regulation of immunity to experimental Trypanosoma congolense infection: roles of regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. [Thesis]. University of Manitoba; 2014. Available from: http://mspace.lib.umanitoba.ca/xmlui/handle/1993/32892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.