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 - 5 of 5

1.	Saudi J Kidney Dis Transpl. 2010 Sep;21(5):872-5. Surrogate markers of subtle renal injury in patients with visceral leishmaniasis. Elnojomi N, Musa AM, Younis BM, Elfaki M, El-Hassan AM, Khalil E. The Leishmaniasis Research Group/Sudan, The Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. Abstract Sudanese Visceral Leishmaniasis (VL) is a disease of children that is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and renal injury. Microalbumi-nuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. We report the prevalence of subtle renal injury in 88 para-sitologically confirmed VL patients in a cross-sectional and hospital-based study. Blood and urine were collected before treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal serum urea and creatinine levels and no detectable urRBP. However, 40% of the patients had MA detected by ELISA, and 42% were reactive with turbidometry. The sensitivity, specificity, positive and negative predictive values for MA turbidometric technique were calculated as 100%; 96%; 95% and 100%, res-pectively. In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for MA measurement is a simple, inexpensive, sensitive, and specific technique with high predictive values.
	PMID: 20814123 [PubMed - in process]
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2.	Acta Trop. 2010 Aug 30. [Epub ahead of print] Studies of quinapyramine-resistance of Trypanosoma brucei evansi in China. Liao D, Shen J. Sichuan Academy of Animal Science, Lane7, Niu Sha Road, Chengdu610066, Sichuan, P.R.China. Abstract In the present article, we summarize our studies of antrycide-resistance of Trypanosoma brucei evansi in four aspects in the last recent several years, the analysis of quinapyramine-sensitive situation of T. b. evansi in China, biological characteristics of T. b. evansi population in quinapyramine-resistance and biological materials of quinapyramine-resistance in T. b. evansi population. Firstly, the correlative assays of effective dosage of quinapyramine on T.b. evansi disease between in vivo and in vitro methods showed that their relationship was parabolic with positive correlation. On the other hand, the IC(50) and CD(100) values of 12 T. b. evansi isolates, AHB, GDB1, GDB2, HNB, JSB1, JSB2, YNB, ZJB, GDH, GXM, HBM and XJCA, collected from buffaloes, horses, mules and camels across nine provinces of China were examined using the two methods, respectively. Among them, the nine isolates, AHB, GDB1, GDB2, HNB, JSB1, JSB2, YNB, ZJB and GDH, became quinapyramine-sensitive T. b. evansi. Secondly, T. evansi populations could rapidly obtain antrycide-resistance when they were passed through immunosuppressed mice treated with low doses of the drug. But, the replication rate of trypanosomes with antrycide-resistance decreases as the level of drug-resistance increases. Thirdly, the analysis of the HK, G6PDH, ALAT and ASAT isoenzymes showed that they were not involved in the quinapyramine-resistance of T.b. evansi. But the protein bands of 15.79kDa and 19.76kDa might be involved in the antrycide-resistance of T. b. evansi population. At genetic level, the gene, TbTA1, could be amplified from the T. b. evansi isolate sensitive to quinapyramine-sensitivity but the T. b. evansi isolate with quinapyramine-resistance using not only the RT-PCR technique, but also PCR technique. We used the SSH (Suppression Subtractive Hybridization) to clone highly or low expressed cDNA fragments caused by production of antrycide-resistance in T. b. evansi. The 5 low and 9 high expressed new cDNA fragments were amplified. Among them, the 3 low expressed cDNA fragments had the same sequence of 65 amino acids and the 3 high expressed cDNA fragments were located in chromosome VI, like T. brucei. Lastly, more work needs to be done in order to elucidate the mechanism of quinapyramine-resistance of Trypanosoma brucei evansi.
	PMID: 20813092 [PubMed - as supplied by publisher]
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3.	Int J Parasitol. 2009 Jul 15;39(9):963-73. Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil. Carranza JC, Valadares HM, D'Avila DA, Baptista RP, Moreno M, Galvão LM, Chiari E, Sturm NR, Gontijo ED, Macedo AM, Zingales B. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil. Abstract The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, approximately 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.
	PMID: 19504756 [PubMed - indexed for MEDLINE]
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4.	Int J Parasitol. 2009 Jul 15;39(9):955-61. Evidence for an ATP-sensitive K+ channel in mitoplasts isolated from Trypanosoma cruzi and Crithidia fasciculata. Costa AD, Krieger MA. Instituto Carlos Chagas (Fiocruz), Rua Prof. Algacyr Munhoz Mader, PR, Brazil. adcosta@tecpar.br Abstract Mammalian mitochondria, as well as rat, plant and Caenorhabditis elegans mitochondria, possess an ATP-sensitive K+ channel (mitoK(ATP)) that has been pharmacologically characterised. Opening of mitoK(ATP) and the subsequent K+ entry into the matrix was shown to have three effects on mitochondria physiology: (i) an increase in matrix volume (swelling), (ii) an acceleration of respiration, and (iii) an increase in reactive oxygen species (ROS) production. These effects on mitochondria bioenergetics have been shown to be part of distinct intracellular signalling pathways, to protect against cell death and to modulate gene transcription. To date, such a channel or its activity has not been described in trypanosomatids. In the present study, we show pharmacological evidence for the presence of a mitoK(ATP) in trypanosomatids. Cells were incubated in a hypotonic medium followed by mild detergent exposure to isolate mitoplasts from Trypanosoma cruzi and Crithidia fasciculata. Mitoplasts swelled when incubated in KCl medium due to respiration-driven K+ entry into the matrix. Swelling was sensitive to the presence of ATP when the mitoplast suspension was incubated in K+ -containing, but not in K+ -free, medium. The ATP inhibition of swelling was reversed by the mitoK(ATP) agonist diazoxide and the diazoxide-induced swelling was inhibited by the mitoK(ATP) blockers 5-hydroxydecanoate (5HD) or glibenclamide. Similar to mammalian and rat mitochondria, trypanosomatid mitoK(ATP) activity was modulated by the general protein kinase C (PKC) agonist phorbol 12-myristate 13-acetate (PMA) and antagonist chelerythrine. As expected, the potassium ionophore valinomycin could also reverse the ATP-inhibited state but this reversal was not sensitive to 5HD or glibenclamide. Dose response curves for ATP, diazoxide and 5HD are presented. These results provide strong evidence for the presence of an ATP-sensitive K+ in trypanosomatid mitochondria.
	PMID: 19504755 [PubMed - indexed for MEDLINE]
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5.	Int J Parasitol. 2009 Jul 15;39(9):985-93. Epub 2009 Feb 26. Chemical evaluation of fatty acid desaturases as drug targets in Trypanosoma cruzi. Alloatti A, Testero SA, Uttaro AD. Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Santa Fe, Argentina. Abstract Four positional isomers of Thiastearate (TS) and Isoxyl (Thiocarlide) were assayed as fatty acid desaturase inhibitors in Trypanosoma cruzi epimastigotes. 9-TS did not exert a significant effect on growth of T. cruzi, nor on the fatty acid profile of the parasite cells. One hundred micromolars of 10-TS totally inhibited growth, with an effective concentration for 50% growth inhibition (EC(50)) of 3.0+/-0.2microM. Growth inhibition was reverted by supplementing the culture media with oleate. The fatty acid profile of treated cells revealed that conversion of stearate to oleate and palmitate to palmitoleate were drastically reduced and, as a consequence, the total level of unsaturated fatty acids decreased from 60% to 32%. Isoxyl, a known inhibitor of stearoyl-CoA Delta9 desaturase in mycobacteria, had similar effects on T. cruzi growth (EC(50) 2.0+/-0.3microM) and fatty acid content, indicating that Delta9 desaturase was the target of both drugs. 12- and 13-TS were inhibitors of growth with EC(50) values of 50+/-2 and 10+/-3microM, respectively, but oleate or linoleate were unable to revert the effect. Both drugs increased the percentage of oleate and palmitate in the cell membrane and drastically reduced the content of linoleate from 38% to 16% and 12%, respectively, which is in agreement with a specific inhibition of oleate Delta12 desaturase. The absence of corresponding enzyme activity in mammalian cells and the significant structural differences between trypanosome and mammalian Delta9 desaturases, together with our results, highlight these enzymes as promising targets for selective chemotherapeutic intervention.
	PMID: 19249306 [PubMed - indexed for MEDLINE]
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