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Sent on Tuesday, 2009 Mar 03Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
- 1: Bioorg Med Chem. 2009 Jan 31. [Epub ahead of print]
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Targeted delivery of compounds to Trypanosoma brucei using the melamine motif.
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee DD1 5EH, UK.
There is an urgent need for the development of new drugs for the treatment of human African trypanosomiasis. The causative organism, Trypanosoma brucei, has been shown to have some unusual plasma membrane transporters, in particular the P2 aminopurine transporter and related permeases, which have been used for the selective targeting of trypanocidal compounds to the organism. In this paper, we report the addition of melamine-based P2-targeting motifs to three different classes of compound in order to try and improve activity through increased selective uptake. The classes reported here are fluoroquinolones, difluoromethylornithine and artesunate derivatives.
PMID: 19250832 [PubMed - as supplied by publisher]
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Related Articles
- ReviewTargeting of toxic compounds to the trypanosome's interior. [Adv Parasitol. 2006]
- Trypanocidal activity of melamine-based nitroheterocycles. [Antimicrob Agents Chemother. 2004]
- Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs. [J Med Chem. 2001]
- Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites. [J Med Chem. 2005]
- ReviewDevelopment of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review). [Int J Mol Med. 2008]
- Patient Drug Information
- Esomeprazole (Nexium® ) Esomeprazole is used to treat gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the esophagus (food pipe between the mouth and stomach) in ...
- Omeprazole (Prilosec® , Prilosec® OTC, Zegerid® ) Prescription omeprazole is used alone or with other medications to treat ulcers (sores in the lining of the stomach or small intestine), gastroesophageal reflux disease (GERD), a condition in which backward flow of acid ...
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- 2: Parasitology. 2009 Mar 2:1-9. [Epub ahead of print]
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Arrested growth of Trypanosoma cruzi by the calpain inhibitor MDL28170 and detection of calpain homologues in epimastigote forms.
Departamento de Microbiologia Geral, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
SUMMARYIn this paper, we aimed to explore the effects of the calpain inhibitor III (MDL28170) and to detect calpain-like molecules (CALPs) in epimastigote forms of Trypanosoma cruzi isolate Dm28c. MDL28170 at 70 muM promoted a powerful reduction in the growth rate after 48 h. The IC50 value was calculated to be 31.7 muM. This inhibitor promoted an increase in the cellular volume, but not cell lysis, resulting in a trypanostatic effect. T. cruzi CALPs presented a strong cross-reactivity with anti-Drosophila melanogaster calpain and anti-cytoskeleton-associated protein from Trypanosoma brucei antibodies, and labelling was found mainly intracellularly. Furthermore, an 80 kDa reactive protein was detected by Western blotting assays. No significant cross-reactivity was found with anti-human brain calpain antibody. The expression of CALPs was decreased in cells kept for long periods in axenic cultures in comparison to a strain recently isolated from mice, as well as in MDL28170-treated cells, the latter being paralleled by an increased expression of cruzipain. Different levels of CALPs expression were also detected in distinct phylogenetic lineages, like Y strain (lineage TCI), Dm28c (TCII) and INPA6147 strain (Z3 zymodeme). These results may contribute for the investigation of the functions of CALPs in trypanosomatids.
PMID: 19250597 [PubMed - as supplied by publisher]
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- Trypanosoma cruzi: detection of a surface antigen cross-reactive to human C-reactive protein. [Exp Parasitol. 1998]
- Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma cruzi cell line displaying resistance to synthetic inhibitors of cysteine-proteinases. [Mol Biochem Parasitol. 2000]
- [Protective effect of calpain inhibitor-3 on hypoxic-ischemic brain damage of neonatal rats] [Zhonghua Er Ke Za Zhi. 2008]
- Trypanosoma cruzi I and Trypanosoma cruzi II: recognition of sugar structures by Arachis hypogaea (peanut agglutinin) lectin. [J Parasitol. 2002]
- ReviewProteins anchored via glycosylphosphatidylinositol and solubilizing phospholipases in Trypanosoma cruzi. [Biol Res. 1993]
- Patient Drug Information
- Allopurinol (Aloprim® , Zyloprim® ) Allopurinol is used to treat gout, high levels of uric acid in the body caused by certain cancer medications, and kidney stones. Allopurinol is in a class of medications called xanthine oxidase inhibitors. It works by re...
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- 3: J Chromatogr A. 2009 Feb 10. [Epub ahead of print]
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Isolation of secondary metabolites from Hortia oreadica (Rutaceae) leaves through high-speed counter-current chromatography.
Universidade Federal de São Carlos, Laboratório de Produtos Naturais, Departamento de Química, São Carlos, SP 13.565-905, Brazil.
High-speed counter-current chromatography (HSCCC) with a two-phase solvent system (hexane-ethanol-acetonitrile-water 10:8:1:1, v/v) was applied to examine the leaves of Hortia oreadica, which afforded the known limonoid guyanin (1), the alkaloids rutaecarpin (2) and dictamnine (6), the dihydrocinnamic acid derivatives methyl 5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoate (3), 5,8-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid (4), together with the new E-3,4-dimethoxy-alpha(3-hydroxy-4-carbomethoxyphenyl)cinnamic acid (5). The recovery of compounds 1-6 was determined by comparison with LC-atmospheric pressure chemical ionization MS/MS data: 66.2%, 93.1%, 102.5%, 101.2%, 99.0% and 84.9%, respectively. Compound 3 showed IC(50) of 23.6muM against Plasmodium falciparum and 15.6muM against Trypanosoma brucei rhodesienses and was not toxic to KB cells (IC(50)>100muM).
PMID: 19249788 [PubMed - as supplied by publisher]
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- [Isolation and purification of solanesol from potato leaves by high-speed counter-current chromatography and identification by atmospheric pressure chemical ionization mass spectrometry] [Se Pu. 2007]
- Preparative isolation and purification of alkaloids from the Chinese medicinal herb Evodia rutaecarpa (Juss.) Benth by high-speed counter-current chromatography. [J Chromatogr A. 2005]
- Preparative isolation and purification of two amides from Mallotus lianus Croiz by high-speed counter-current chromatography. [J Sep Sci. 2008]
- Isolation of high-purity casticin from Artemisia annua L. by high-speed counter-current chromatography. [J Chromatogr A. 2007]
- One step isolation and purification of liquiritigenin and isoliquiritigenin from Glycyrrhiza uralensis Risch. using high-speed counter-current chromatography. [J Chromatogr A. 2005]
- 4: J Vector Borne Dis. 2008 Dec;45(4):301-6.
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Comparison of Thymus vulgaris (Thyme), Achillea millefolium (Yarrow) and propolis hydroalcoholic extracts versus systemic glucantime in the treatment of cutaneous leishmaniasis in balb/c mice.
Skin Diseases and Leishmaniasis Research Center (Sedigheh Tahereh), Isfahan University of Medical Sciences, Isfahan, Iran.
BACKGROUND & OBJECTIVES: Leishmaniasis is a parasitic disease transmitted by sand flies. Many investigations are performed to find an effective and safe treatment for leishmaniasis. In this study, we evaluated the efficacy of herbal extracts of Thymus vulgaris (Thyme) and Achillea millefolium (Yarrow), propolis hydroalcoholic extract and systemic glucantime against cutaneous leishmaniasis in Balb/c mice. METHODS: A total of 45 mice were randomised into five groups each including nine mice. They were treated with pure ethanol 70 degrees, systemic glucantime, Achillea millefolium hydroalcoholic extract, Thymus vulgaris hydroalcoholic extract and propolis hydroalcoholic extract for six weeks. The statistical tests including student t-test were used for analysis. Data were analyzed by SPSS software, ver 13.00. RESULTS: Mean of ulcer size reduction were -17.66, -22.57, 43.29, 36.09 and 43.77% for the alcohol, glucantime, yarrow, thyme and propolis groups, respectively. The results were suggestive that Thymus vulgaris, Achillea millefolium and propolis hydroalcoholic extracts were significantly more effective in reduction of ulcer size as compared with glucantime (p = 0.006, 0.002 and 0.008, respectively). INTERPRETATION & CONCLUSION: Our results are suggestive that Thymus vulgaris, Achillea millefolium and propolis extracts are effective for treatment of cutaneous leishmaniasis in mice. Regarding these results, we suggest that efficacy of these extracts alone or in combination are evaluated against human cutaneous leishmaniasis as a randomized clinical trial.
PMID: 19248657 [PubMed - in process]
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Related Articles
- ReviewFinal report on the safety assessment of Yarrow (Achillea millefolium) Extract. [Int J Toxicol. 2001]
- Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis. [BMC Complement Altern Med. 2007]
- Antimotility effect of hydroalcoholic extract of yarrow (Achillea millefolium) on the guinea-pig ileum. [Pak J Biol Sci. 2007]
- A comparative study between the efficacy of systemic meglumine antimoniate therapy with standard or low dose plus oral omeprazole in the treatment of cutaneous leishmaniasis. [J Vector Borne Dis. 2008]
- ReviewAchillea millefolium L. s.l. revisited: recent findings confirm the traditional use. [Wien Med Wochenschr. 2007]
- 5: J Vector Borne Dis. 2008 Dec;45(4):292-300.
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Immunodiagnosis of bovine trypanosomiasis in Anambra and Imo states, Nigeria, using enzyme-linked immunosorbent assay: zoonotic implications to human health.
Department of Immunology, College of Health Sciences, University of Ibadan, Oyo State. mikezeani@yahoo.com
BACKGROUND & OBJECTIVES: The prevalence of trypanosomiasis was studied in cattle, being a major source of animal protein in Nigeria, thus, a very likely means of spread of Human African Trypanosomosis (HAT). METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to diagnose bovine trypanosomiasis in 264 samples collected from adult cattle of mixed breeds, age and sex, in Anambra and Imo states, Nigeria. RESULTS: Out of 264 samples analysed, 21 (7.96%) were seropositive for Trypanosoma congolense while 20 (7.58%) were seropositive for T. vivax and 8 (3.03%) were seropositive for T. brucei infections in both the states. INTERPRETATION & CONCLUSION: The predominant species was found to be T. congolense. Mixed infection of three species, T. vivax, T. congolense and T. brucei was found to dominate other mixed infections in both the states. ELISA detected the infection of the three species of trypanosomes in the same group of animals. The usefulness of antigen capture ELISA in the diagnosis of human or animal trypanosomiasis was established, and the possibility of the spread of HAT caused by T. brucei gambiense and T.b. rhodesiense through cattle was expressed.
PMID: 19248656 [PubMed - in process]
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Related Articles
- Application of a monoclonal antibody-based antigen detection enzyme-linked immunosorbent assay (antigen ELISA) for field diagnosis of bovine trypanosomiasis at Nguruman, Kenya. [Ann Trop Med Parasitol. 1992]
- Evaluation of an antigen detection-ELISA test for the diagnosis of trypanosomiasis in naturally infected cattle. [Trop Med Parasitol. 1995]
- Monoclonal antibodies that distinguish Trypanosoma congolense, T. vivax and T. brucei. [Parasite Immunol. 1987]
- ReviewInteractions between tsetse and trypanosomes with implications for the control of trypanosomiasis. [Adv Parasitol. 2003]
- ReviewTrypanosomosis in goats: current status. [Ann N Y Acad Sci. 2006]
- 6: J Vector Borne Dis. 2008 Dec;45(4):287-91.
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A comparative study between the efficacy of systemic meglumine antimoniate therapy with standard or low dose plus oral omeprazole in the treatment of cutaneous leishmaniasis.
Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
BACKGROUND & OBJECTIVES: Pentavalent antimony compounds are the first line of drugs in the treatment of cutaneous leishmaniasis. However, because of their potential toxic effects, many investigations are performed to find an effective and safe treatment for cutaneous leishmaniasis patients. Our objective in this investigation was to compare the effect of oral omeprazole and low dose systemic meglumine antimoniate (MA) and standard dose of systemic MA in the treatment of cutaneous leishmaniasis. METHODS: This was a randomized double-blinded clinical trial. In 150 patients with cutaneous leishmaniasis who were randomly divided into three groups and were treated with: (i) MA 60 mg/kg/day/ IM and oral placebo for three weeks; (ii) MA 30 mg/kg/day/IM and oral omeprazole 40 mg/day for three weeks; and (iii) MA 30 mg/kg/day/IM and oral placebo for three weeks. All the patients were visited every two weeks from the beginning of the trial up to six weeks and then at 8 and 12 weeks. The effectiveness of the treatment was classified in three levels as complete response, partial response and no response. Data were analyzed by SPSS 10 using KI square, Mann-Whitney, Kaplan-Mayer and ANOVA tests. RESULTS: Rate of complete response for three months (12 weeks) after starting the treatments was 93% for the group treated with standard dose of glucantime and placebo, 89% for the group treated with omeprazole and low dose glucantime and 80% for the group treated with low dose glucantime and placebo and these differences were significant (p < 0.05). The highest response rate was for the group treated with standard dose of glucantime and placebo. INTERPRETATION & CONCLUSION: Although oral omeprazole and low dose of systemic MA showed less efficacy in comparison to standard dose of systemic MA in the treatment of cutaneous leishmaniasis, it still can be considered as a replacement therapy in high risk patients (such as patients with heart, kidney and/or liver disease) under close supervision of physician.
PMID: 19248655 [PubMed - in process]
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Related Articles
- Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis. [Int J Dermatol. 2006]
- Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis. [BMC Complement Altern Med. 2007]
- Treatment of cutaneous leishmaniasis with a combination of allopurinol and low-dose meglumine antimoniate. [Int J Dermatol. 2002]
- ReviewISA 247: trans-ISA 247, trans-R 1524, ISA(TX)247, ISAtx 247, ISATx247, LX 211, LX211, R 1524, R-1524. [Drugs R D. 2007]
- ReviewAntiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. [Cochrane Database Syst Rev. 2007]
- 7: J Vector Borne Dis. 2008 Dec;45(4):255-72.
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Insect vectors of Leishmania: distribution, physiology and their control.
Division of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
Leishmaniasis is a deadly vector-borne disease that causes significant morbidity and mortality in Africa, Asia, Latin America and Mediterranean regions. The causative agent of leishmaniasis is transmitted from man to man by a tiny insect called sandfly. Approximately, 600 species of sandflies are known but only 10% of these act as disease vectors. Further, only 30 species of these are important from public health point. Fauna of Indian sub-zone is represented by 46 species, of these, 11 belong to Phlebotomine species and 35 to Sergentomyia species. Phlebotomus argentipes is the proven vector of kala-azar or visceral leishmaniasis in India. This review gives an insight into the insect vectors of human leishmaniasis, their geographical distribution, recent taxonomic classification, habitat, and different control measures including indoor residual spraying (IRS), insecticide-treated bednets (ITNs), environmental management, biological control, and emerging resistance to DDT. Role of satellite remote sensing for early prediction of the disease by identifying the sandflygenic conditions cannot be undermined. The article also underlines the importance of synthetic pheromones which can be used in near future for the control of these vectors.
PMID: 19248652 [PubMed - in process]
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- Review[Prevention and control of leishmaniasis vectors: current approaches] [Parassitologia. 2004]
- Vector control by insecticide-treated nets in the fight against visceral leishmaniasis in the Indian subcontinent, what is the evidence? [Trop Med Int Health. 2008]
- ReviewVector control in leishmaniasis. [Indian J Med Res. 2006]
- Phlebotomine sandflies (Diptera: Psychodidae) of Tamil Nadu and Pondicherry, southern India, in relation to visceral leishmaniasis. [Ann Trop Med Parasitol. 1994]
- ReviewControl of phlebotomine sandflies. [Med Vet Entomol. 2003]
- 8: Exp Parasitol. 2009 Mar;121(3):246-53. Epub 2008 Dec 6.
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Roles of the endosymbiont and leishmanolysin-like molecules expressed by Crithidia deanei in the interaction with mammalian fibroblasts.
Laboratório de Estudos Integrados em Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Crithidia deanei is an insect trypanosomatid that harbors a bacterial endosymbiont in its cytoplasm. In this work, we have demonstrated the influence of the endosymbiont on the interaction of C. deanei with mammalian fibroblasts, also implicating the surface leishmanolysin-like molecules of C. deanei in this process. The wild strain of C. deanei expressed a higher amount (2-fold) of leishmanolysin-like molecules in the parasite surface than the aposymbiotic strain. The treatment of parasites with anti-leishmanolysin antibodies or the fibroblasts with purified leishmanolysin-like molecules from C. deanei significantly reduced the association index. The aposymbiotic strain of C. deanei presented interaction rates about 2- and 3-fold lower with fibroblasts than the endosymbiont-bearing counterpart after 1 and 2h, respectively. However, the association indexes were similar after 3 and 4h of interaction. Additionally, we observed a 2-fold increase in the association index after 24-96 h of parasite-fibroblast interaction when compared to the interaction process performed for 4h, irrespective to the presence of the endosymbiont, suggesting that fibroblasts support multiplication and survival of C. deanei. Both parasite strains were able to induce fibroblast lysis. Interestingly, the wild strain led to a 2-fold increase in fibroblasts death in comparison to the aposymbiotic strain after 48-96 h. We also showed that both wild and aposymbiotic biotinylated live parasites recognized the same receptor in the fibroblast cells.
PMID: 19070618 [PubMed - indexed for MEDLINE]
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- Crithidia deanei: influence of parasite gp63 homologue on the interaction of endosymbiont-harboring and aposymbiotic strains with Aedes aegypti midgut. [Exp Parasitol. 2008]
- Influence of the endosymbiont of Blastocrithidia culicis and Crithidia deanei on the glycoconjugate expression and on Aedes aegypti interaction. [FEMS Microbiol Lett. 2005]
- Differential expression of proteolytic enzymes in endosymbiont-harboring Crithidia species. [FEMS Microbiol Lett. 2001]
- ReviewEndosymbiosis in protozoa of the Trypanosomatidae family. [FEMS Microbiol Lett. 1999]
- ReviewThe ubiquitous gp63-like metalloprotease from lower trypanosomatids: in the search for a function. [An Acad Bras Cienc. 2006]
- 9: Expert Opin Ther Targets. 2009 Jan;13(1):105-21.
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Trypanosoma cruzi targets for new chemotherapeutic approaches.
Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Laboratório de Biologia Celular, Avenue Brazil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. soeiro@ioc.fiocruz.br
BACKGROUND: Strategies for development of anti-parasite chemotherapy involve identification of active principles of plants, investigation of drugs already licensed for other pathologies, or validation of specific targets identified within key metabolic pathways. OBJECTIVE: To review the state of the art of drug targets against Trypanosoma cruzi with emphasis on sterol metabolism, kinetoplast DNA (kDNA) sites, trypanothione reductase, cysteine proteinase, hypoxanthine-guanine phosphoribosyltransferase, dihydrofolate reductase and glyceraldehyde-3-phosphate dehydrogenase. METHODS: Current knowledge, accumulated over the last three decades, on targets for design and development of new trypanocidal compounds is described. RESULTS/CONCLUSION: There is an urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox only allopurinol and a few sterol inhibitors have moved to clinical trials, despite the long list of natural and synthetic compounds assayed against T. cruzi. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity associated with a lack of definitive preclinical evidence of parasitological cure in animal models.
PMID: 19063710 [PubMed - indexed for MEDLINE]
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- ReviewAn insight on targets and patented drugs for chemotherapy of Chagas disease. [Recent Pat Antiinfect Drug Discov. 2007]
- ReviewMode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. [Comp Biochem Physiol A Mol Integr Physiol. 2007]
- ReviewChemotherapy of Chagas disease. [Curr Pharm Des. 2002]
- ReviewAnti-T. cruzi agents: our experience in the evaluation of more than five hundred compounds. [Mini Rev Med Chem. 2008]
- Review[The chemotherapy of Chagas disease] [Medicina (B Aires). 1999]
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