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Sent on Tuesday, 2010 May 25Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Protein J. 2010 May 23. [Epub ahead of print]Partial Biochemical Characterization of a Metalloproteinase from the Bloodstream Forms of Trypanosoma brucei brucei Parasites.de Sousa KP, Atouguia J, Silva MS.Unidade de Ensino e Investigação de Clínica das Doenças Tropicais, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Rua da Junqueira, 100, 1349-008, Lisbon, Portugal. AbstractMetalloproteinases (MMP) belong to the family of cation dependent endopeptidases that degrade matrices at physiological pH and to cleave extracellular matrix proteins. They play an important role in diverse physiological and pathological processes; not only there diverse types of MMP differ in structure and functionally, but also their enzymatic activity is regulated at multiple levels. Trying to shed some light over the processes that govern the pathology of African Trypanosomiasis, the aim of the present study was to examine the proteolytic activity of the crude trypanosome protein extract obtained from the bloodstream forms of Trypanosoma brucei brucei parasites. We hereby report the partial biochemical characterization of a neutral Trypanosoma brucei-metalloproteinase that displays marked proteolytic activities on gelatin and casein, with a molecular mass of approximately 40 kDa, whose activity is strongly dependent of pH and temperature. Furthermore, we show that this activity can be inhibited by classical MMP inhibitors such as EDTA, EGTA, phenantroline, and also by tetracycline and derivatives. This study has a relevant role in the search for new therapeutical targets, for the use of metalloproteinases inhibitors as treatment strategies, or as enhancement to trypanocidal drugs used in the treatment of the disease. |
| PMID: 20496101 [PubMed - as supplied by publisher] | |
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| 2. | Parasitol Res. 2010 May 22. [Epub ahead of print]In vitro and in vivo antileishmanial efficacy of nitazoxanide against Leishmania donovani.Zhang R, Shang L, Jin H, Ma C, Wu Y, Liu Q, Xia Z, Wei F, Zhu XQ, Gao H.Institute of Military Veterinary, Academy of Military Medical Sciences, 1068 Qinglong Road, Changchun, 130062, Jilin Province, China. AbstractControl of Leishmania infection relies primarily on chemotherapy, and the current drug available for treating leishmaniasis is limited. Nitazoxanide (NTZ) is a broad spectrum antiparasitic agent with activity against protozoa, nematodes, cestodes, and trematodes. In the present study, the in vitro antileishmanial efficacy of NTZ was evaluated by incubation of Leishmania donovani promastigotes with NTZ, indicating that NTZ can affect the ultrastructure of parasite promastigote and efficiently inhibit the parasite growth. Moreover, 200 mug/ml NTZ inhibited >90% of promastigotes growth, showing similar activity of the reference drug amphotericin B (P > 0.05). Therapeutic efficacy of NTZ against L. donovani-infected BALB/c mice demonstrated that oral NTZ produced a significant reduction of parasite burden in spleen and liver from L. donovani-infected mice, compared with the untreated mice (P < 0.05). These results indicated NTZ may be a novel therapeutic drug for leishmaniasis. |
| PMID: 20495931 [PubMed - as supplied by publisher] | |
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| 3. | Rom J Morphol Embryol. 2010;51(2):391-4.A case of visceral leishmaniasis in Oltenia region (Romania).Găman A, Dobrea C, Găman G.Department of Pathophysiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania. gamanamelia@yahoo.com. AbstractVisceral leishmaniasis is produced by a protozoan parasite that belongs to the genus Leishmania. Transmission is made through sting, the vector being represented by a species of the genus Phlebotomus. The first case of visceral leishmaniasis in Romania was reported by Manicatide (1912). In 1934, it was described a focus of visceral leishmaniasis in Oltenia region (24 cases).The symptoms of disease are unspecific: fatigue, feverishness, cephalalgia, anorexia, nausea, obnubilation status. The fever is irregular, with high oscillations. Clinical, a sallow pallor of the skin, enlarge lymph nodes, hepatomegaly, splenomegaly, weight loss have been observed. Laboratory exams showed frequently severe anemic syndromes or other cytopenias, erythrocytes sedimentation rate was increased, hypergammaglobulin-emia with monoclonal peak has been found. Immunolectrophoresis showed hyper-IgG and hyper-IgM. Bone marrow biopsy showed lympho-plasmocyte infiltration, histiocytes, Leishman-Donovan bodies intracellular or extracellular. The prognosis of the disease is unfavorable in the absence of specific treatment with antimony. In case of resistance, it is used immunotherapy, amphotericin or miltefosine. |
| PMID: 20495762 [PubMed - in process] | |
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| 4. | J Antimicrob Chemother. 2010 May 22. [Epub ahead of print]CpG oligodeoxynucleotide augments the antileishmanial activity of miltefosine against experimental visceral leishmaniasis.Sane SA, Shakya N, Haq W, Gupta S.Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow, India. AbstractObjectives To evaluate the combination of CpG oligodeoxynucleotide (CpG ODN) and miltefosine for the treatment of experimental visceral leishmaniasis (VL). Methods The experiments were carried out using BALB/c mice and hamsters, infected with Leishmania donovani. CpG ODN was administered at various doses by the intraperitoneal (ip) route. The dose of CpG ODN (1 nM/single dose) showing best antileishmanial activity was given as free and liposomal forms with a subcurative dose of miltefosine, namely 2.5 and 5 mg/kg x 5 days in mice and hamsters, respectively. Results Among the various groups of mice, co-administered liposomal CpG ODN and miltefosine showed the best inhibitory effect (85% inhibition) compared with free CpG ODN and miltefosine, and miltefosine, free CpG ODN and liposomal CpG ODN separately. Production of Th1 cytokines, nitric oxide (NO), reactive oxygen species (ROS) and H(2)O(2) was enhanced. A remarkable increase in the phagocytosis index was also observed, indicating overall immunological support to antileishmanial activity of miltefosine by CpG ODN. Similar responses were observed in hamsters. Conclusions Promising antileishmanial efficacy was observed in animals treated with liposomal CpG ODN and miltefosine, strongly supported by enhancement of Th1 cytokines as well as NO, ROS and H(2)O(2) levels. The correlation of experimental findings in both the models (mouse and hamster) strengthens the potential of CpG ODN as an immunomodulator in combination with miltefosine against VL. |
| PMID: 20495208 [PubMed - as supplied by publisher] | |
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| 5. | J Biol Chem. 2010 May 21. [Epub ahead of print]Tor-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei.de Jesus TC, Tonelli RR, Nardelli SC, Augusto LD, Motta MC, Girard-Dias W, Miranda K, Ulrich P, Jimenez V, Barquilla A, Navarro M, Docampo R, Schenkman S.Universidade Federal de Sao Paulo, Brazil; AbstractTarget of rapamycin (TOR) kinases are highly conserved protein kinases that integrate signals from nutrients and growth factors to coordinate cell growth and cell cycle progression. It has been previously described that two TOR kinases control cell growth in the protozoan parasite Trypanosoma brucei, the causative agent of African trypanosomiasis. Here we studied an unusual TOR-like protein named TbTOR-like 1, containing a PDZ domain and found exclusively in kinetoplastids. TbTOR-like 1 localizes to unique cytosolic granules. After hyperosmotic stress the localization of the protein shifts to the cell periphery, differently from other organelle markers. Ablation of TbTOR-like 1 causes a progressive inhibition of cell proliferation, producing parasites accumulating in S/G2 phase of the cell cycle. TbTOR-like 1 knocked down cells have an increased area occupied by acidic vacuoles, known as acidocalcisomes, and are enriched in polyphosphate and pyrophosphate. These results suggest that TbTOR-like 1 might be involved in the control of acidocalcisome and polyphosphate metabolism in T. brucei. |
| PMID: 20495004 [PubMed - as supplied by publisher] | |
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| 6. | J Am Acad Dermatol. 2010 May 20. [Epub ahead of print]New World cutaneous lei shmaniasis: Current challenges in diagnosis and parenteral treatment.Zaghi D, Panosian C, Gutierrez MA, Gregson A, Taylor E, Ochoa MT.Albert Einstein College of Medicine, Bronx, New York. AbstractMany physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved. |
| PMID: 20494480 [PubMed - as supplied by publisher] | |
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| 7. | Exp Parasitol. 2010 May 19. [Epub ahead of print]Regulation of CD8(+) T Cell Responses to Infection With Parasitic Protozoa.Jordan KA, Hunter CA.Department of Pathobiology, University of Pennsylvania, 380 South University Ave, Philadelphia, PA 19104, USA. AbstractThere are over 10,000 species of parasitic protozoa, a subset of which can cause considerable disease in humans. Here we examine in detail the complex immune response generated during infection with a subset of these parasites: Trypanosoma cruzi, Leishmania sp, Toxoplasma gondii, and Plasmodium sp. While these particular species perhaps represent the most studied parasites in terms of understanding how T cells function during infection, it is clear that the lessons learned from this body of work are also relevant to the other protozoa known to induce a CD8+ T cell response. This review will highlight some of the key studies that established that CD8+ T cells play a major role in protective immunity to protozoa, the factors that promote the generation as well as maintenance of the CD8+ T cell response during these infections, and draw attention to some of the gaps in our knowledge. Moreover, the development of new tools, including MHC Class I tetramer reagents and the use of TCR transgenic mice or genetically modified parasites, has provided a better appreciation of how parasite specific CD8+ T cell responses are initiated and new insights into their phenotypic plasticity. Copyright © 2010. Published by Elsevier Inc. |
| PMID: 20493842 [PubMed - as supplied by publisher] | |
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| 8. | J Dermatol Sci. 2010 May 19. [Epub ahead of print]The expression of TLR 2, TLR4 and TLR9 in the epidermis of patients with cutaneous leishmaniasis.Tuon FF, Fernandes ER, Duarte MI, Amato VS.Department of Infectious Diseases, University of Sao Paulo, Medical School, Avenida Dr. Enéas de Carvalho Aguiar, 470, Cerqueira César, CEP 05403-000 São Paulo, SP, Brazil. |
| PMID: 20493664 [PubMed - as supplied by publisher] | |
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| 9. | Curr Med Chem. 2010 May 24. [Epub ahead of print]Inhibitors of the Purine Salvage Pathway: A Valuable Approach for Antiprotozoal Chemotherapy?Berg M, Van der Veken P, Goeminne A, Haemers A, Augustyns K.Department of Pharmaceutical Sciences, Research Unit of Medicinal Chemistry, Campus Drie Eiken, Universiteitsplein 1, BE-2610 Antwerpen (Wilrijk), Belgium. Koen.Augustyns@ua.ac.b. AbstractFor many years, the purine salvage pathway of parasitic protozoa has been regarded as an attractive chemotherapeutic target. Parasitic protozoa lack de novo synthesis and rely entirely on the purine salvage pathway to meet their purine demands. Because of the great phylogenetic difference between parasite and host, there are often sufficient distinctions that can be exploited to design specific inhibitors for the parasitic enzymes. As a result, this pathway has been thoroughly investigated over the last twenty years. It is only quite recently that the genome studies of Trypanosoma, Leishmania and Plasmodium have been published. Based on these genomic data however, the existence of by-pass mechanisms by other enzymes and transporter systems could be suggested. Taking into account such proposition, the question might arise as to whether inhibition of a single salvage enzyme will be able or not to cause parasite death or growth arrest. In this paper, the key enzymes in the purine salvage pathways of relevant pathogenic species from the genera Trypanosoma, Leishmania and Plasmodium are reviewed. Their potential as drug targets is critically evaluated and where possible, correlated to literature data on antiparasitic activity of their inhibitors. While many studies over the past ten years have yielded contradictory results, this review attempts to clarify these findings by discussing the latest elements of progress in the field. Additionally, as part of a broader discussion on substrate analogue types of inhibitors, special attention is paid to iminoribitol derivatives, serving as transition state analogues of nucleoside-processing enzymes and comprising the most potent inhibitors reported for purine salvage enzymes. More specifically, the development of three generations of immucillins and a newer series of N-(arylmethyl-) substituted iminoribitol derivatives will be discussed. Finally, this review also covers subversive substrates of salvage enzymes: compounds that are transformed by enzymatic activity into cytotoxic agents. Although not by directly intervening in the process of purine recovery, the subversive substrate approach might deliver antiprotozoal compounds that rely on salvage enzymes for their activity. |
| PMID: 20491648 [PubMed - as supplied by publisher] | |
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