Thursday, September 17, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -8 of 8

1: Parasitol Res. 2009 Sep 16. [Epub ahead of print]

Ex vivo and in vivo biological behavior of Leishmania (Viannia) shawi.

Passero LF, Sacomori JV, Tomokane TY, Corbett CE, da Silveira FT, Laurenti MD.

Laboratório de Patologia de Moléstias Infecciosas (LIM-50), Depto. de Patologia, Universidade de São Paulo, São Paulo, SP, Brazil, felipepassero@usp.br.

Since the first description of Leishmania (Viannia) shawi, few studies were performed with this parasite. In the present work, the in vivo and ex vivo behavior of L. (Viannia) shawi infection was studied using murine model. Peritoneal macrophages from BALB/c and C57BL/6 mice were infected with promastigotes in the stationary phase of growth; after 24 h, the infection index and nitric oxide (NO) levels in the supernatant of the cultures were analyzed. BALB/c and C57BL/6 mice were infected into the hind footpad, and at each 2 weeks, mice were sacrificed, and the histological changes of the skin inoculation site, parasitism, and humoral immune responses were evaluated during 8 weeks. Ex vivo experiments showed that macrophages of BALB/c presented higher infection index and lesser NO levels than macrophages of C57BL/6. In vivo experiments showed that BALB/c presented higher lesion size than C57BL/6 mice; similarly, the histopathological changes and the parasitism in skin were more exacerbate in BALB/c mice. In draining lymph nodes, the main change was increase of germinative centers, and parasites were detected from 6 weeks pi onwards in both mice strain. IgG was detected in BALB/c mice from 4 weeks, while in C57BL/6, from 6 weeks pi onwards. Taken together, these results indicate that BALB/c showed a classical behavior of susceptibility when compared to C57BL/6 mice.

PMID: 19756748 [PubMed - as supplied by publisher]

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2: Appl Biochem Biotechnol. 2009 Sep 8. [Epub ahead of print]

Rational Approaches for Drug Designing Against Leishmaniasis.

Shukla AK, Singh BK, Patra S, Dubey VK.

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India.

Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.

PMID: 19756413 [PubMed - as supplied by publisher]

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3: J Infect Dev Ctries. 2009 Mar 1;3(2):123-9.

Cutaneous leishmaniasis in Iraq.

AlSamarai AM, AlObaidi HS.

Department of Medicine, Tikrit University College of Medicine, Tikrit, Iraq. galsamarrai@yahoo.com

OBJECTIVE: To determine the incidence ofcutaneous leishmaniasis (CL) in Alhaweja District and to clarify the secondary bacterial infection inCL. METHODOLOGY: A prospective survey was performed in the outpatient clinic of Alhaweja General Hospital. All the patients who presented at the dermatology clinic during the period from 1 October 2004 to the end of April 2005 were included in the study. The provisional diagnosis was dependent on clinical examination; however, biopsies and confirmatory tests were performed for questionable cases. Venous blood was drawn from patients with cutaneous leishmaniasis for determination of IgM. Swabs from the ulcer were taken for culture to determine secondary bacterial infections. RESULTS: A total of 107 cutaneous leishmaniasis cases were diagnosed during the study period with males representing 57% of the cases. The study participants ranged from 1-60 years. The incidence rate was 45 cases per 10,000. Clinically, 58% of patients had multiple lesions, while 42% had a single lesion. It was found that 36.5% of patients had dry type while 63.5% had wet type lesions. Most lesions were found on upper limbs (57%), while the fewest were found in the ear 1%. The highest number of cases was recorded during February (32.1%), while the lowest rate of cases was recorded in April (3.37%). According to cultures and smears, 73% of the cases were positive to giemsa stain and 43% were positive in cultures. Secondary bacterial infection occurred in 42% of lesions and Staphylococcus epidermidis was the most common bacteria (55%) isolated from lesions, followed by Staphylococcus aureus (33%). The mean of total IgM levels was significantly decreased in patients with CL in comparison with the control group. CONCLUSIONS: CL is endemic in Alhaweja district. CL is an important health problem since secondary bacterial infection was reported in 42% of cases and this infection my influence the natural course of the disease causing more destruction for skin. Giemsa stain was the most sensitive parasitic diagnostic test.

PMID: 19755742 [PubMed - in process]

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4: J Infect Dev Ctries. 2009 Sep 15;3(2):115-22.

PCR detection of Leishmania in skin biopsies.

Lemrani M, Hamdi S, Laamrani A, Hassar M.

Laboratoire des recherche et d'étude sur les Leishmanioses, Institut Pasteur du Maroc, Casablanca, Morocco. meryem.lemrani@pasteur.ma

INTRODUCTION: Cutaneous leishmaniasis (CL) is an endemic disease and one of the major health problems in Morocco. In 2006, the recorded total number of cases of CL was 3361, occurring predominantly in the rural population. A new and more sensitive diagnostic technique than current methods used is needed in this setting. The aim of this study was to assess the efficacy of polymerase chain reaction (PCR) to detect leishmanial parasites in skin biopsies of patients from different areas of endemicity in Morocco. METHODOLOGY: Biopsies from 26 patients with cutaneous ulcers suggestive of leishmaniasis were analysed by PCR using primers from the small subunit ribosomal gene. The ability of PCR to detect Leishmania was compared with smear-stained and in vitro culture. RESULTS: PCR exhibited superior sensitivity (84,6%) compared with direct microscopy smear (69,2%) and in vitro culture (69,2%). Our PCR assay also showed good specificity (100%). CONCLUSIONS: PCR should be considered a valuable, sensitive, and faster diagnostic tool in the diagnosis of cutaneous leishmaniasis, especially for those patients with negative parasitologic examination.

PMID: 19755741 [PubMed - in process]

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5: Biomedica. 2009 Mar;29(1):73-86.

[Sand flies (Diptera: Psychodidae) of Guaviare Province, Colombia, with 4 new records for the country]

[Article in Spanish]

Cabrera OL, Mosquera L, Santamaría E, Ferro C.

Grupo de Entomología, Subdirección de Investigación, Instituto Nacional de Salud, Bogota, D.C., Colombia. ocabrera@ins.gov.co

INTRODUCTION: Although cases of leishmaniasis have been reported in the province of Guaviare, Colombia, no entomological studies were included to identify the Lutzomyia sand fly vector species in that area. OBJECTIVE: Lutzomyia species were identified from four townships of Guaviare. Probable vectors were named based on those species involved in transmission in other areas. MATERIALS AND METHODS: Sampling was undertaken with CDC light traps suspended at heights between 1.5 m and 9 m. Additional sand flies were collected with Shannon traps and by aspiration of adult flies from daytime resting sites. RESULTS: Sand flies belonging to 37 different species were collected. 35 of them were recorded for the first time in Guaviare Province. Four species were new records for Colombia: Lutzomyia begonae, L. campbelli, L. sericea and L. nematoducta. The most abundant species were L. hirsuta 24.3% (148/610), L. yuilli 15.2% (93/610), L. davisi 10.3% (63/610), followed by L. fartigi, L. carrerai, L. antunesi, L. flaviscutellata and L. olmeca bicolor. CONCLUSION: Seven of these species of have been associated previously with endemic or epidemic transmission of leishmaniasis.

PMID: 19753841 [PubMed - in process]

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6: Biomedica. 2009 Mar;29(1):9-11.

[Mucosal complication of cutaneous leishmaniasis]

[Article in Spanish]

Zea DF, Prager M, Figueroa RA, Miranda MC.

Unidad Clínica, Centro Internacional de Entrenamiento e Investigaciones Médicas-CIDEIM, Call, Colombia. dzea@cideim.org.co

A 74-year-old man from the rural area of Caicedonia, Valle del Cauca Province, was diagnosed with uncontrolled hypertension, stage IV chronic renal failure and severe anemia. Fifteen years earlier, while living in Guaviare Province, he was diagnosed with leishmaniasis-with lesions located on the right upper and lower eyelids, left auricle and limbs. At that time, he received an incomplete treatment with antimonials. The patient had experienced 8 years of progressive mucosal lesions located in the upper lip, nasal mucosa and right upper and lower eyelids (figure 1). A histopathological diagnosis of leishmaniasis was made and confirmed by polymerase chain reaction (figure 2). Treatment with antimonials (Glucantime) was contraindicated due to the patient's comorbidities. Inpatient supervised treatment with miltefosine (Impavido 50 mg capsules) was initiated according to the national guidelines of 1.8 mg/kg/day for 28 days. Clinical follow up and routine laboratory tests (creatinine, BUN, liver function tests and complete blood counts) were done during and after treatment; no complications were reported. Medical follow up was continued until the Internal medicine, ophthalmology, and plastic surgery consultations were provided for subsequent management of the pathology. Mucocutaneous leishmaniasis is a serious preventable complication of cutaneous leishmaniasis. This case illustrated a failure in opportune diagnosis and treatment of this disease as a consequence of an inadequate leishmaniasis control program. The case indicated the effectiveness of miltefosine as a therapeutic option in patients for whom antimonial treatment is contraindicated.

PMID: 19753833 [PubMed - in process]

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7: FEBS J. 2009 Aug;276(15):4169-83. Epub 2009 Jul 3.Click here to read LinkOut

Structural effects of a dimer interface mutation on catalytic activity of triosephosphate isomerase. The role of conserved residues and complementary mutations.

Banerjee M, Balaram H, Balaram P.

Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

The active site of triosephosphate isomerase (TIM, EC: 5.3.1.1), a dimeric enzyme, lies very close to the subunit interface. Attempts to engineer monomeric enzymes have yielded well-folded proteins with dramatically reduced activity. The role of dimer interface residues in the stability and activity of the Plasmodium falciparum enzyme, PfTIM, has been probed by analysis of mutational effects at residue 74. The PfTIM triple mutant W11F/W168F/Y74W (Y74W*) has been shown to dissociate at low protein concentrations, and exhibits considerably reduced stability in the presence of denaturants, urea and guanidinium chloride. The Y74W* mutant exhibits concentration-dependent activity, with an approximately 22-fold enhancement of k(cat) over a concentration range of 2.5-40 microM, suggesting that dimerization is obligatory for enzyme activity. The Y74W* mutant shows an approximately 20-fold reduction in activity compared to the control enzyme (PfTIM WT*, W11F/W168F). Careful inspection of the available crystal structures of the enzyme, together with 412 unique protein sequences, revealed the importance of conserved residues in the vicinity of the active site that serve to position the functional K12 residue. The network of key interactions spans the interacting subunits. The Y74W* mutation can perturb orientations of the active site residues, due to steric clashes with proximal aromatic residues in PfTIM. The available crystal structures of the enzyme from Giardia lamblia, which contains a Trp residue at the structurally equivalent position, establishes the need for complementary mutations and maintenance of weak interactions in order to accommodate the bulky side chain and preserve active site integrity.

PMID: 19583769 [PubMed - indexed for MEDLINE]

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8: Bioorg Med Chem. 2009 Feb 15;17(4):1437-44. Epub 2009 Jan 15.Click here to read LinkOut

New potent imidazoisoquinolinone derivatives as anti-Trypanosoma cruzi agents: biological evaluation and structure-activity relationships.

Bollini M, Casal JJ, Alvarez DE, Boiani L, González M, Cerecetto H, Bruno AM.

Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.

A series of novel benzoimidazo and N-aryl-5-oxo-imidazo[1,2-b]isoquinoline-10-carbothioamides was developed. All the compounds were evaluated for their in vitro action against the epimastigote form of Trypanosoma cruzi. Four of them showed higher activity than Nifurtimox. Their unspecific cytotoxicity was evaluated using HeLa and L6 cells, being non-toxic at concentrations at least 15 and 200 times higher than that of T. cruzi IC(50.) To gain insight into the mechanism of action, their DNA binding properties and reactivity with glutathione were studied, and QSAR study was performed.

PMID: 19168363 [PubMed - indexed for MEDLINE]

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