Friday, March 18, 2011

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 - 10 of 14

1.

Hemoflagellates.

Zeledón RA.
In: Baron S, editor.
Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 82.

Excerpt

The family Trypanosomatidae consists of many parasitic flagellate protozoans. Two genera, Trypanosoma and Leishmania, include important pathogens of humans and domestic animals. The diseases caused by these protozoa are endemic or enzootic in different parts of the world and constitute serious medical and economic problems. Because these protozoans require hematin obtained from blood hemoglobin for aerobic respiration, they are called hemoflagellates. The digenetic (two-host) life cycles of both genera involve an insect and a vertebrate. The family also includes the digenetic genus Phytomonas, which infects plants, and some monogenetic (one-host) species which infect only invertebrate hosts. The hemoflagellates have up to eight life cycle stages which differ in the placement and origin of the flagellum. Two stages—the amastigote and the trypomastigote—may occur in vertebrate hosts, and three stages,—the promastigote, paramastigote, and epimastigote—in invertebrate hosts (Fig. 82-1). Besides the nucleus and the flagellum, a trypanosomatic cell has a unique organelle called the kinetoplast. The kinetoplast appears to be a special part of the mitochondrion and is rich in DNA. Two types of DNA molecules, maxicircles which encode mainly certain important mitochondrial enzymes, and minicircles which serve a function in the processof RNA editing, have been found in the kinetoplast; when Giemsa stained, the kinetoplast is reddish purple and darker than the nucleus, contrasting with the pale blue cytoplasm. Monogenetic trypanosomatids are more primitive than the digenetic species and grow easily in synthetic culture media. Some digenetic species can be cultivated in complex synthetic media. The medium most commonly used is NNN medium, which has a solid phase of rabbit blood agar and a liquid phase of a physiologic salt solution. Liquid media are also available. Only the invertebrate stages appear in such media, and they may or may not be infectious for the vertebrate hosts, depending on the species. Replication of trypanosomatids occurs by single or multiple fission, involving first the kinetoplast, then the nucleus, and finally the cytoplasm. However, evidence for sexual reproduction has been presented.

Copyright © 1996, The University of Texas Medical Branch at Galveston
Books & Documents
PMID: 21413333 [PubMed]
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2.

Protozoa: Structure, Classification, Growth, and Development.

Yaeger RG.
In: Baron S, editor.
Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 77.

Excerpt

The Protozoa are considered to be a subkingdom of the kingdom Protista, although in the classical system they were placed in the kingdom Animalia. More than 50,000 species have been described, most of which are free-living organisms; protozoa are found in almost every possible habitat. The fossil record in the form of shells in sedimentary rocks shows that protozoa were present in the Pre-cambrian era. Anton van Leeuwenhoek was the first person to see protozoa, using microscopes he constructed with simple lenses. Between 1674 and 1716, he described, in addition to free-living protozoa, several parasitic species from animals, and Giardia lamblia from his own stools. Virtually all humans have protozoa living in or on their body at some time, and many persons are infected with one or more species throughout their life. Some species are considered commensals, i.e., normally not harmful, whereas others are pathogens and usually produce disease. Protozoan diseases range from very mild to life-threatening. Individuals whose defenses are able to control but not eliminate a parasitic infection become carriers and constitute a source of infection for others. In geographic areas of high prevalence, well-tolerated infections are often not treated to eradicate the parasite because eradication would lower the individual's immunity to the parasite and result in a high likelihood of reinfection. Many protozoan infections that are inapparent or mild in normal individuals can be life-threatening in immunosuppressed patients, particularly patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that many healthy persons harbor low numbers of Pneumocystis carinii in their lungs. However, this parasite produces a frequently fatal pneumonia in immunosuppressed patients such as those with AIDS. Toxoplasma gondii, a very common protozoan parasite, usually causes a rather mild initial illness followed by a long-lasting latent infection. AIDS patients, however, can develop fatal toxoplasmic encephalitis. Cryptosporidium was described in the 19th century, but widespread human infection has only recently been recognized. Cryptosporidium is another protozoan that can produce serious complications in patients with AIDS. Microsporidiosis in humans was reported in only a few instances prior to the appearance of AIDS. It has now become a more common infection in AIDS patients. As more thorough studies of patients with AIDS are made, it is likely that other rare or unusual protozoan infections will be diagnosed. Acanthamoeba species are free-living amebas that inhabit soil and water. Cyst stages can be airborne. Serious eye-threatening corneal ulcers due to Acanthamoeba species are being reported in individuals who use contact lenses. The parasites presumably are transmitted in contaminated lens-cleaning solution. Amebas of the genus Naegleria, which inhabit bodies of fresh water, are responsible for almost all cases of the usually fatal disease primary amebic meningoencephalitis. The amebas are thought to enter the body from water that is splashed onto the upper nasal tract during swimming or diving. Human infections of this type were predicted before they were recognized and reported, based on laboratory studies of Acanthamoeba infections in cell cultures and in animals. The lack of effective vaccines, the paucity of reliable drugs, and other problems, including difficulties of vector control, prompted the World Health Organization to target six diseases for increased research and training. Three of these were protozoan infections—malaria, trypanosomiasis, and leishmaniasis. Although new information on these diseases has been gained, most of the problems with control persist.

Copyright © 1996, The University of Texas Medical Branch at Galveston
Books & Documents
PMID: 21413323 [PubMed]
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3.

Protozoa: Pathogenesis and Defenses.

Seed J R.
In: Baron S, editor.
Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 78.

Excerpt

Resistance to parasitic protozoa appears to be similar to resistance against other infectious agents, although the mechanisms of resistance in protozoan infections are not yet as well understood. Resistance can be divided into two main groups of mechanisms: (1) nonspecific mechanism(s) or factor(s) such as the presence of a nonspecific serum component that is lethal to the parasite; and (2) specific mechanism(s) involving the immune system (Fig. 78-1). Probably the best studied nonspecific mechanisms involved in parasite resistance are the ones that control the susceptibility of red blood cells to invasion or growth of plasmodia, the agents of malaria. Individuals who are heterozygous or homozygous for the sickle cell hemoglobin trait are considerably more resistant to Plasmodium falciparum than are individuals with normal hemoglobin. Similarly, individuals who lack the Duffy factor on their red blood cells are not susceptible to P vivax. Possibly both the sickle cell trait and absence of the Duffy factor have become established in malaria-endemic populations as a result of selective pressure exerted by malaria. Epidemiologic evidence suggests that other inherited red blood cell abnormalities, such as thalassanemia and glucose-6-phosphate dehydrogenase deficiency, may contribute to survival of individuals in various malaria-endemic geographical regions. A second well-documented example of a nonspecific factor involved in resistance is the presence in the serum of humans of a trypanolytic factor that confers resistance against Trypanosoma brucei brucei, an agent of trypanosomiasis (sleeping sickness) in animals. There is evidence that other nonspecific factors, such as fever and the sex of the host, may also contribute to the host's resistance to various protozoan parasites. Although nonspecific factors can play a key role in resistance, usually they work in conjunction with the host's immune system (Fig. 78-1). Different parasites elicit different humoral and/or cellular immune responses. In malaria and trypanosome infections, antibody appears to play a major role in immunity. In both T cruzi and T brucei gambiense infections, antibody-dependent cytotoxic reactions against the parasite have been reported. Although antibody has been shown to be responsible for clearing the African trypanosomes from the blood of infected animals, recent evidence suggests that the survival time of infected mice does not necessarily correlate with the ability of the animal to produce trypanosome-specific antibody. In other words, resistance as measured by survival time may not solely involve the specific humoral immune system. Recent data suggest that cellular immunity is required for resistance to malaria. for example, vaccine trials with a sporozoite antigen indicated that both an active cellular response and sporozoite-specific antibody may be needed for successful immunization. Cellular immunity is believed to be the single most important defense mechanism in leishmaniasis and toxoplasmosis. In animals infected with Toxoplasma, the activated macrophage has been shown to play an important role in resistance. Accordingly, resistance to the protozoan parasites most likely involves nonspecific factors as well as specific humoral and/or cellular mechanisms. Cytokines are involved in the control of both the immune response and pathology. It has become apparent that there are subsets of both helper (h) and cytotoxic (c) T-cells that produce different profiles of cytokines. For example, the Th-1 subset produces gamma interferon (IFN-α), and interleukin-2 (IL-2) and is involved in cell-mediated immunity. In contrast the Th-2 subset produces IL-4 and IL-6, and is responsible for antibody-mediated immunity. The induction of a particular T-cell subset is key to recovery and resistance. The Th-1 subset and increased IFN-g are important in resistance to Leishmania, T cruzi and Toxoplasma infections, whereas the Th-2 response is more important in parasitic infections in which antibody is a key factor. It is important to recognize that the cytokines produced by one T-cell subset can up or downregulate the response of other T-cell subsets. IL-4 will downregulate Th-1 cells and exacerbate infection and/or susceptibility of mice to Leishmania. The cytokines produced by T and other cell types do not act directly on the parasites but influence other host cell types. The response of cells to cytokines includes a variety of physiological changes, such as changes in glucose, fatty acid and protein metabolism. For example, IL-1 and tumor necrosis factor will increase gluconeogenesis, and glucose oxidation. It should be noted that cytokines influence the metabolism not only of T-cells, but also a variety of other cell types and organ systems. Cytokines can also stimulate cell division and, therefore, clonal expansion of T and B-cell subsets. This can lead to increased antibody production and/or cytotoxic T-cell numbers. The list of cytokines and their functions is growing rapidly, and it would appear that these chemical messages influence all phases of the immune response. they are also clearly involved in the multitude of physiological responses (fever, decreased food intake, etc.) observed in an animal's response to a pathogen, and in the pathology that results. Unlike most viral and bacterial infections, protozoan diseases are often chronic, lasting months or years. When associated with a strong host immune response, this type of chronic infection is apt to result in a high incidence of immunopathology. The question also arises of how these parasites survive in an immunocompetent animal. The remainder of this chapter treats the mechanisms responsible for pathology, particularly immunopathology, in protozoan disease, and the mechanisms by which parasites evade the immune responses of the host. Finally, because of the very rapid advances in our knowledge of the host-parasite relationship (due primarily to the development of techniques in molecular biology), it is necessary to briefly mention the potential for developing vaccines to the pathogenic protozoa.

Copyright © 1996, The University of Texas Medical Branch at Galveston
Books & Documents
PMID: 21413293 [PubMed]
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4. Eur J Immunol. 2011 Jan 31. doi: 10.1002/eji.201040940. [Epub ahead of print]

Expression of IL-10-triggered STAT3-dependent IL-4Rα is required for induction of arginase 1 in visceral leishmaniasis.

Biswas A, Bhattacharya A, Kar S, Das PK.

Molecular Cell Biology Laboratory, Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.

Abstract

Although enhanced macrophage-specific arginase activity is directly related to increased parasite burden in cutaneous leishmaniasis (CL), the regulation and precise role of arginase in the disease outcome of visceral leishmaniasis (VL) has yet to be explored. As in CL, BALB/c mice infected with Leishmania donovani showed increased levels of arginase in acute infection. Arginase 1 is the major isoform associated with infection and while the IL-4-induced arginase pathway is operative in CL, IL-10 plays a crucial role in modulating arginase activity in VL, although a synergism with IL-4 is required. IL-10, in combination with IL-4, regulated both in vivo and ex vivo arginase 1 induction in a STAT6 and C/EBPβ-dependent fashion. Further investigation toward the cause of such synergism suggests that induction of a STAT3-dependent IL-10-mediated cascade in VL triggers the expression and surface localization of the IL-4 receptor alpha (IL-4Rα) which, in turn, enhances IL-4 responsiveness toward STAT6 and C/EBPβ-dependent signaling for arginase 1. This could also offer a mechanistic explanation for the fact that, in spite of the low level of IL-4 in VL, enhanced IL-4-Rα expression by IL-10 might markedly amplify IL-4-mediated arginase 1 signaling and provide a possible mechanism for synergistic induction of arginase 1.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID: 21413004 [PubMed - as supplied by publisher]
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5. Planta Med. 2011 Mar 16. [Epub ahead of print]

Antiplasmodial and Antitrypanosomal Activity of Tanshinone-Type Diterpenoids from Salvia miltiorrhiza.

Slusarczyk S, Zimmermann S, Kaiser M, Matkowski A, Hamburger M, Adams M.

Department of Pharmaceutical Biology and Botany, Medical University of Wroclaw, Wroclaw, Poland.

Abstract

In a medium throughput screen of 880 plant and fungal extracts for antiprotozoal activity, a dichloromethane extract of SALVIA MILTIORRHIZA roots was active against both TRYPANOSOMA BRUCEI RHODESIENSE and PLASMODIUM FALCIPARUM. With HPLC-based activity profiling in combination with on- and off-line spectroscopic methods (PDA, -MS (n), HR-MS, microprobe NMR), the active compounds were identified as tanshinone-type diterpenoids. Subsequent isolation and structure elucidation yielded the known substances miltirone ( 1), tanshinone II a ( 2), 1,2 dihydrotanshinquinone ( 3), methylenetanshinquinone ( 4), 1-oxomiltirone ( 5), 11-hydroxymiltiodiol ( 6), tanshinone I ( 7), methyltanshinonate ( 8), and cryptotanshinone ( 9). The IC (50)s of the compounds were determined against the two parasites and rat myoblast (L6) cells. They ranged from 4.1 µM to over 30 µM against P. FALCIPARUM K1 strain with selectivity indices (SI) from 0.3 to 1.9. IC (50)s against T. BRUCEI RHODESIENSE STIB 900 were from 0.5 µM ( 1, 4) to over 30 µM, and 4 showed the greatest selective activity with an SI of 24.

© Georg Thieme Verlag KG Stuttgart · New York.
PMID: 21412700 [PubMed - as supplied by publisher]
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6. Planta Med. 2011 Mar 16. [Epub ahead of print]

In vitro Screening of Traditional South African Malaria Remedies against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum.

Mokoka TA, Zimmermann S, Julianti T, Hata Y, Moodley N, Cal M, Adams M, Kaiser M, Brun R, Koorbanally N, Hamburger M.

Biosciences, CSIR, Pretoria, South Africa.

Abstract

Three hundred extracts were prepared from plants traditionally used in South Africa to treat malaria and screened IN VITRO for activity against TRYPANOSOMA BRUCEI RHODESIENSE, TRYPANOSOMA CRUZI, LEISHMANIA DONOVANI, and PLASMODIUM FALCIPARUM. For the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/mL, the IC (50) values against all four protozoal parasites and cytotoxic IC (50)s against rat myoblast L6 cells were determined. Amongst the most notable results are the activities of AGATHOSMA APICULATA (IC (50) of 0.3 µg/mL) against PLASMODIUM FALCIPARUM, as well as SALVIA REPENS and MAYTENUS UNDATA against LEISHMANIA DONOVANI with IC (50)s of 5.4 µg/mL and 5.6 µg/mL, respectively. This screening is the starting point for a HPLC-based activity profiling project in antiprotozoal lead discovery.

© Georg Thieme Verlag KG Stuttgart · New York.
PMID: 21412695 [PubMed - as supplied by publisher]
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7. Rev Inst Med Trop Sao Paulo. 2011 Feb;53(1):45-50.

Susceptibility of Cebus apella monkey (Primates: Cebidae) to experimental Leishmania (L.) infantum cha gasi-infection.

Carneiro LA, Silveira FT, Campos MB, Brígido Mdo C, Gomes CM, Corbett CE, Laurenti MD.

Departamento de Parasitologia, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Ananindeua, Pará, Brasil, 67030-000, lilianecarneiro@iec.pa.gov.br; marlianecampos@iec.pa.gov.br.

Abstract

In Amazonian Brazil, the Cebus apella monkey (Primates: Cebidae) has been associated with the enzootic cycle of Leishmania (V.) shawi, a dermotropic parasite causing American cutaneous leishmaniasis (ACL). It has also been successfully used as animal model for studying cutaneous leishmaniasis. In this work, there has been investigated its susceptibility to experimental Leishmania (L.) infantum chagasi-infection, the etiologic agent of American visceral leishmaniasis (AVL). There were used ten C. apella specimens, eight adult and two young, four males and six females, all born and raised in captivity. Two experimental infection protocols were performed: i) six monkeys were inoculated, intra-dermal via (ID), into the base of the tail with 2 x 10(6) promastigotes forms from the stationary phase culture medium; ii) other four monkeys were inoculated with 3 x 10(7) amastigotes forms from the visceral infection of infected hamsters by two different via: a) two by intravenous via (IV) and, b) other two by intra-peritoneal via (IP). The parameters of infection evaluation included: a) clinical: physical exam of abdomen, weigh and body temperature; b) parasitological: needle aspiration of the bone-marrow for searching of amastigotes (Giemsa-stained smears) and promastigotes forms (culture medium); c) immunological: Indirect fluorescence antibody test (IFAT) and, Delayed-type hypersensitivity (DTH). In the six monkeys ID inoculated (promastigotes forms) all parameters of infection evaluation were negative during the 12 months period of follow-up. Among the four monkeys inoculated with amastigotes forms, two IV inoculated showed the parasite in the bone-marrow from the first toward to the sixth month p.i. and following that they cleared the infection, whereas the other two IP inoculated were totally negative. These four monkeys showed specific IgG-antibody response since the third month p.i. (IP: 1/80 and IV: 1/320 IgG) toward to the 12th month (IP: 1/160 and IV: 1/5120). The DTH-conversion occurred in only one IV inoculated monkey with a strong (30 mm) skin reaction. Considering these results, we do not encourage the use of C. apella monkey as animal model for studying the AVL.

PMID: 21412619 [PubMed - in process]
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8. Rev Inst Med Trop Sao Paulo. 2011 Feb;53(1):3-11.

Forty years of visceral leishmaniasis in the State of Piaui: a review.

Drumond KO, Costa FA.

Laboratory of Animal Pathology, Agricultural Science Center, Universidade Federal do Piauí, Teresina, Piauí, Brasil.

Abstract

Visceral leishmaniasis (VL) has been known to occur in the state of Piauí since 1934. The typically rural disease began to appear in urban areas over time, being concentrated mainly in Teresina, the capital of Piauí. Teresina was also affected by the first urban epidemic of VL in Brazil. Over 1,000 cases of the disease were reported during urbanization (1981-1986). Human population growth and migration led to land occupation on the outskirts of Teresina. These factors have contributed to vector proliferation, increasing the incidence of VL. At present, the incidence of human and canine disease is quite high and uncontrolled in Piauí. It seems that some measures, such as the elimination of seropositive dogs, failed to significantly reduce the number of new VL cases in Teresina. Despite previously conducted studies, little is known about VL epidemiology in urban areas. The aim of this review is to reveal the situation of VL in Teresina during the last 40 years, focusing on the major factors that may contribute to the high incidence and persistence of VL infection.

PMID: 21412612 [PubMed - in process]
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9. Braz J Infect Dis. 2011 Feb;15(1):17-21.

An overview of a diagnostic and epidemiologic reappraisal of cutaneous leishmaniasis in Iran.

Farahmand M, Nahrevanian H, Shirazi HA, Naeimi S, Farzanehnejad Z.

Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.

Abstract

Cutaneous leishmaniasis (CL) is a widespread tropical infection which has a high incidence rate in Iran. Leishmania tropica, the causative agent of anthroponotic cutaneous leishmaniasis (ACL), and Leishmania major, which causes zoonotic cutaneous leishmaniasis (ZCL), are endemic in various parts of Iran with a high incidence rate. The aim of this study was to evaluate the reappraisal of the diagnosis and epidemiology of CL in Iran, by different clinical, parasitological and molecular assays among patients suspected of CL referred to the Department of Parasitology, at the Pasteur Institute of Iran during 2006-2009. Two hundred samples from patients with ulcerative skin lesions were collected, clinical analyses were applied, data questionnaire was completed and samples were examined for CL by using both direct microscopic and culture methods. Moreover, PCR assay was applied for detection of Leishmania species in CL isolates resulting from parasitological assay. Clinical observation revealed that the majority (58%) of lesions was single; double lesions were observed in 22% of patients, and only 20% of CL had multiple lesions. Out of 200 patients, Leishman body was observed in 77 samples (38.5%) by direct smear and 40% by cultivation assay. Most patients (21.3%) had a travel history to the Isfahan province, one of the most important endemic areas of CL located in center of Iran. PCR assay by kDNA indicated 32 and 18 out of 50 isolates respectively had similar patterns with standard L. major and L. tropica. In conclusion, clinical manifestations and an appropriate diagnostic assay with a parallel molecular characterization of CL may lead to a screening evaluation of disease, prognosis, treatment and control strategies.

PMID: 21412584 [PubMed - in process]
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10. Braz J Infect Dis. 2011 Feb;15(1):12-6.

Epidemiological and clinical characteristics of cutaneous leishmaniasis and their relationship with the laboratory data, south of Brazil.

Curti MC, Silveira TG, Arraes SM, Bertolini DA, Zanzarini PD, Venazzi EA, Fernandes AC, Teixeira JJ, Lonardoni MV.

Abstract

OBJECTIVE: To evaluate clinical, epidemiological and laboratorial aspects for the understanding of the disease characteristics and its relationship with diagnostic tests.

METHODS: A retrospective, descriptive and analytical study involving 2,660 American cutaneous leishmaniasis (ACL) suspected patients from southern Brazil was undertaken between April 1986 and December 2005. Data on population characteristics and laboratory tests were obtained. Diagnostic laboratory tests used were direct search for Leishmania spp. (DS), Montenegro skin test (MST) and indirect immunofluorescent assay (IFA).

RESULTS: 62.3% of patients were positive for at least one laboratory test. DS test was positive in 65.1%; MST in 92.3% and IFA in 70.0%. Although Cohen's Kappa test did not reveal any agreement with laboratory diagnosis for ACL, the association between MST and IFA tests increased positiveness to 98.9%; MST and DS to 97.2%; and IFA and DS to 85%. IFA and MST positiveness were higher among patients with < 2-month lesion-evolution time. Most ACL patients were male (72.6%) in the age range of 15-49 years, featuring lesions during two months or less (53.9%) and a cutaneous form of the disease (88.0%).

CONCLUSION: Findings suggest that for the adequate identification of ACL cases a combination of laboratory tests that involves the association of MST with at least another test should be used.

PMID: 21412583 [PubMed - in process]
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