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Sent on Friday, 2009 Mar 06Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
- 1: Org Biomol Chem. 2009 Mar 21;7(6):1154-66. Epub 2009 Jan 28.
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Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites.
School of Life Sciences, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, UK.
Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.
PMID: 19262935 [PubMed - in process]
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Related Articles
- Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites. [J Med Chem. 2005]
- Trypanocidal activity of melamine-based nitroheterocycles. [Antimicrob Agents Chemother. 2004]
- ReviewTargeting of toxic compounds to the trypanosome's interior. [Adv Parasitol. 2006]
- Targeted delivery of compounds to Trypanosoma brucei using the melamine motif. [Bioorg Med Chem. 2009]
- Review[Human African trypanosomiasis] [C R Seances Soc Biol Fil. 1996]
- Patient Drug Information
- Eflornithine (Vaniqa® ) Eflornithine is used to slow the growth of unwanted hair on the face in women, usually around the lips or under the chin. Eflornithine works by blocking a natural substance that is needed for hair to grow and is located ...
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- 2: Korean J Lab Med. 2009 Feb;29(1):48-52.
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[Evaluation of SD BIOLINE Chagas Ab Rapid Kit.]
[Article in Korean]Department of Life Science, College of Natural Science, Kyonggi University, Suwon, Korea.
BACKGROUND: Chagas' disease is caused by Trypanosoma cruzi, a protozoan parasite, which is transmitted by blood-sucking bugs or through blood transfusion or organ transplantation. It is endemic in Central and South America. The objective of this study was to compare the performance of immunochromatographic SD Bioline Chagas Ab Rapid (Standard Diagnostics, Korea) with three immunochromatographic kits for the detection of antibodies to T. cruzi. METHODS: A total of 320 serum specimens (140 positive and 180 negative) from National Reference Laboratory for Chagas and Leishmaniasis (NRLCL, Honduras) were used for the evaluation of four different test kits: SD Bioline Chagas Ab Rapid, Chagas Stat-Pak Assay (Chembio Diagnositc Systems, USA), OnSite Chagas Ab Rapid test-Cassette (CTK Biotech, USA), and Trypanosoma Detect Rapid Test (InBios International, USA). The results of four kits were compared with those of NRLCL. Cross-reactivity with other parasites was also evaluated. RESULTS: Compared with the results of NRLCL, sensitivity and specificity were 99.3% and 100% for both of SD and Chembio kits, 97.2% and 100% for InBios kit, and 97.9% and 98.8% for CTK kit. None of other parasites showed cross-reactivity. CONCLUSIONS: SD Bioline Chagas Ab Rapid kit showed test results highly correlating with those of National Reference Laboratory for Chagas and Leishmaniasis. It can be used for a rapid detection of Chagas' disease in endemic region and monitoring the disease among overseas travelers in Korea.
PMID: 19262078 [PubMed - in process]
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- Field evaluation of a rapid immunochromatographic assay for detection of Trypanosoma cruzi infection by use of whole blood. [J Clin Microbiol. 2008]
- [Evaluation of SD BIOLINE tetanus kit] [Korean J Lab Med. 2007]
- Validation of a rapid and reliable test for diagnosis of chagas' disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America. [J Clin Microbiol. 2005]
- ReviewStrategies for prevention of transfusion-associated Chagas' disease. [Transfus Med Rev. 1996]
- ReviewChagas' disease and blood transfusion: a New World problem? [Vox Sang. 1993]
- Patient Drug Information
- Pentoxifylline (Pentoxil® , Trental® ) Pentoxifylline is used to improve blood flow in patients with circulation problems to reduce aching, cramping, and tiredness in the hands and feet. It works by decreasing the thickness (viscosity) of blood. This change a...
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- 3: J Pharmacol Exp Ther. 2009 Mar 4. [Epub ahead of print]
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Pentamidine movement across the murine blood-brain and blood-CSF barriers; effect of trypanosome infection, combination therapy, P-glycoprotein and MRP.
King's College London.
During the first stage of Human African trypanosomiasis (HAT), T.b. gambiense are found mainly in the blood and pentamidine treatment is used. Pentamidine is predominately ineffective once the parasites have invaded the CNS. This lack of efficacy is thought to be due to the inability of pentamidine to cross the blood-brain barrier, although this has never been directly explored. This study addresses this using brain perfusion in healthy mice, P-glycoprotein-deficient mice and in a murine model of HAT (T.b. brucei). The influence of additional anti-trypanosomal drugs on pentamidine delivery to the CNS was also investigated. Results revealed that [(3)H]pentamidine can cross the blood-brain barrier, although a proportion was retained by the capillary endothelium and failed to reach the healthy or trypanosome-infected brain (up to day 21 p.i.). The CNS distribution of pentamidine was increased in the final (possibly terminal) stage of trypanosome infection partly due to loss of barrier integrity (day 28-35 p.i.) as measured by [(14)C]sucrose and [(3)H]suramin. Furthermore, pentamidine distribution to the CNS involved influx and efflux (via P-glycoprotein and multi-drug resistance associated protein (MRP)) transporters and was affected by the other anti-trypanosomal agents, suramin, melarsoprol and nifurtimox, but not eflornithine. These interactions could contribute to side effects or lead to the development of parasite resistance to the drugs. Thus great care must be taken when designing drug combinations containing pentamidine or other diamidine analogues. However, co-administration of P-glycoprotein and/or MRP inhibitors with pentamidine, or other diamidines, might provide a means of improving efficacy against CNS stage HAT.
PMID: 19261919 [PubMed - as supplied by publisher]
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Related Articles
- The blood-brain barrier significantly limits eflornithine entry into Trypanosoma brucei brucei infected mouse brain. [J Neurochem. 2008]
- Review[Human African trypanosomiasis] [C R Seances Soc Biol Fil. 1996]
- ReviewArsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis. [Parasitol Res. 2003]
- Distribution of suramin, an antitrypanosomal drug, across the blood-brain and blood-cerebrospinal fluid interfaces in wild-type and P-glycoprotein transporter-deficient mice. [Antimicrob Agents Chemother. 2007]
- Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl)furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue. [Acta Trop. 2004]
- 4: Int J Dermatol. 2009 Mar;48(3):286-9.
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Unusual clinical variants of cutaneous leishmaniasis in Sicily.
Department of Dermatology, Policlinico Universitario, Palermo, Italy.
Abstract Background The term "leishmaniasis" defines a group of vector-borne diseases caused by species of the genus Leishmania and characterized by a spectrum of clinical manifestations. Parasite properties (infectivity, pathogenicity, virulence), host factors, and host responses regulate heterogeneous disease expression. Sicily is one of the major islands of the Mediterranean Basin and is considered to be a hypo-endemic area for cutaneous leishmaniasis. Leishmania infantum is the most common species on the island. Methods Fifty patients (both sexes and different ages) with lesions clinically suggestive of cutaneous leishmaniasis were recorded over a 1-year period. The diagnosis was based on positive slit-skin smear and histopathologic studies when needed. Polymerase chain reaction (PCR) was performed as test confirmation. Results Twenty-five patients had typical solitary lesions of cutaneous leishmaniasis. Multiple lesions were present in five patients. In 20 patients, the lesions were very unusual, including erysipeloid, zosteriform, and lupoid leishmaniasis. The results of Leishmania isoenzyme characterization identified Leishmania infantum as the species responsible for the 20 atypical cases. Conclusion The global number of cases of cutaneous leishmaniasis in Sicily has increased in recent years, and such increases can be explained, in part, by the fact that, in this region, sandflies are present during a large part of the year. This is a result of the climatic variation in recent years (increasing temperature and humidity). There has also been an increase in the number of new and rare variants of cutaneous leishmaniasis. A knowledge of the unusual clinical variants of cutaneous leishmaniasis, as well as classical forms, allows early detection.
PMID: 19261018 [PubMed - in process]
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- [Interpretation of laboratory data during cryptic leishmaniasis in dog] [Parassitologia. 2004]
- Mediterranean leishmaniasis in HIV-infected patients: epidemiological, clinical, and diagnostic features of 22 cases. [Infection. 1998]
- [Leishmania infantum/HIV co-infection: cutaneous lesions following treatment of visceral leishmaniasis] [Ann Dermatol Venereol. 2006]
- Review[Feline leishmaniasis: what's the epidemiological role of the cat?] [Parassitologia. 2004]
- Review[Immunopathology of American tegumentary leishmaniasis] [Acta Cient Venez. 1998]
- 5: J R Army Med Corps. 2008 Sep;154(3):212-3.
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Sir William Leishman.
World Society for the History of Medicine.
- Personal Name as Subject:
- Leishman W
PMID: 19202834 [PubMed - indexed for MEDLINE]
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- Sir William Leishman: 1866-1926. [Lancet. 1966]
- Leishman. [Br Med J. 1966]
- Alphonse Laveran (1845-1922): discoverer of the malarial parasite and Nobel laureate, 1907. [J Med Biogr. 2002]
- Cushing's clips. [J Perioper Pract. 2007]
- Review"Modern" military surgery: 19th century compared with 20th century. [J Am Coll Surg. 2005]
- 6: Obesity (Silver Spring). 2008 Sep;16(9):1992-7.
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Trypanosoma cruzi infection of cultured adipocytes results in an inflammatory phenotype.
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Infection with Trypanosoma cruzi, the etiologic agent of Chagas disease is accompanied by an intense inflammatory reaction. Our laboratory group has identified adipose tissue as one of the major sites of inflammation during disease progression. Because adipose tissue is composed of many cell types, we were interested in investigating whether the adipocyte per se was a source of inflammatory mediators in this infection. Cultured adipocytes were infected with the Tulahuen strain of T. cruzi for 48-96 h. Immunoblot and quantitative PCR (qPCR) analyses demonstrated an increase in the expression of proinflammatory cytokines and chemokines, including interleukin (IL)-1 beta, interferon-gamma, tumor necrosis factor-alpha, CCL2, CCL5, and CXCL10 as well as an increase in the expression of Toll-like receptors-2 and 9 and activation of the notch pathway. Interestingly, caveolin-1 expression was reduced while cyclin D1 and extracellular signal-regulated kinase (ERK) expression was increased. The expression of PI3kinase and the activation of AKT (phosphorylated AKT) were increased suggesting that infection may induce components of the insulin/IGF-1 receptor cascade. There was an infection-associated decrease in adiponectin and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These data provide a mechanism for the increase in the inflammatory phenotype that occurs in T. cruzi-infected adipocytes. Overall, these data implicate the adipocyte as an important target of T. cruzi, and one which contributes significantly to the inflammatory response observed in Chagas disease.
PMID: 19186325 [PubMed - indexed for MEDLINE]
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- Trypanosoma cruzi Infection of Cultured Adipocytes Results in an Inflammatory Phenotype. [Obesity (Silver Spring). 2008]
- Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2. [Diabetes. 2008]
- Impaired production of proinflammatory cytokines and host resistance to acute infection with Trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88. [J Immunol. 2004]
- Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. [J Biol Chem. 2003]
- Review[Role of cytokines in resistance and pathology in Trypanosoma cruzi infection] [Rev Argent Microbiol. 1996]
- 7: Dermatol Online J. 2008 Nov 15;14(11):2.
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Pentoxifylline: a drug with wide spectrum applications in dermatology.
Pars Clinic, Rasht, Iran. ozargari@iranderma.com
Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.
PMID: 19094840 [PubMed - indexed for MEDLINE]
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- Is there a role for tumor necrosis factor-alpha inhibitors and especially thalidomide in dermatology? [Skinmed. 2005]
- Efficacy of ibuprofen and pentoxifylline in the treatment of phosgene-induced acute lung injury. [J Appl Toxicol. 1996]
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