12958 Chemuliti, J.K., Njiru, Z.K. & Bukachi, S., 2003. Disease conditions of camels in non-traditional camel keeping areas of Kajiado District in Kenya: a case study. Journal of Camel Practice and Research, 10 (2): 207-210.
Chemuliti: Kenya Trypanosomiasis Research Institute, P.O.Box 326, Kikuyu, Kenya.
A cross-sectional study was undertaken in a non-traditional camel keeping area of three divisions of Kajiado District in Kenya to identify and to quantify camel diseases. Three hundred and forty seven camels were examined. Blood and faecal samples were collected from each camel for laboratory examination for haemoparasites, anaemia and helminths. Trypanosomiasis, helminthosis, abscesses, mange and tick infestation were the most prevalent diseases. The point prevalence of trypanosomiasis was 7.8 percent. The point prevalence of helminth infestations was 52.7 percent, with a mean egg count per gram faeces of 163.4. Tick infestations were observed in 186 (53.6 percent), abscesses in 38 (11 percent) and mange in 32 (9.2 percent) camels. Diarrhoea, eye infections, wounds, mastitis, fracture, carpal joint deformity and facial nerve paralysis were also observed. It was concluded that camel diseases in the study area were similar to those reported in traditional environment, but the picture is complicated by the presence of tsetse-transmitted trypanosomiasis. Improvements in disease surveillance, control and management by the veterinary department and farmers are recommended so as to reduce the prevalence and consequences of disease in the district for improving camel productivity.
12959 Hutin, Y.J.F., Legros, D., Owini, V., Brown, V., Lee, E., Mbulamberi, D. & Paquet, C., 2004. Trypanosoma brucei gambiense trypanosomiasis in Terego County, Northern Uganda, 1996: a lot quality assurance sampling survey. American Journal of Tropical Medicine and Hygiene, 70 (4): 390-394.
Brown: Epicentre 8, Rue Saint Sabin, F-75011 Paris, France. [[email protected]]
We estimated the pre-intervention prevalence of T. b. gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2 percent. This estimate was consistent with the 1.1 percent period prevalence calculated on the basis of cases identified through passive and active screening in 1996-99. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-98. Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programmes.
12960 Mahama, C.I., Mohammed, H.A., Abavana, M., Sidibé, I., Koné, A. & Geerts, S., 2003. Tsetse and trypanosomoses in Ghana in the twentieth century: a review. Revue d'Élevage et de Médecine Vétérinaire des Pays Tropicaux, 56 (1-2): 27-32.
Geerts: Institute of Tropical Medicine, Nationale straat 155, 2000 Antwerpen, Belgium. [[email protected]]
African animal trypanosomiasis, transmitted by tsetse flies, is a major constraint limiting the optimal utilization of land for agricultural production in tsetse-infested areas of Ghana. In the past 50 years various workers have made attempts at mapping the distribution of tsetse flies and the disease they transmit with a view to instituting appropriate control measures. Due to the increasing human population and agricultural expansion, there has been a retreat of the morsitans group of tsetse flies into protected areas. From the standpoint of livestock production, therefore, members of the palpalis group remain the most important vectors of trypanosomiasis as they are able to persist even in areas of intense land use. The optimal exploitation of trypanotolerance as a means of trypanosomiasis control is hampered by increased crossbreeding with trypanosusceptible breeds. Although the incidence of sleeping sickness has decreased drastically over the last decades, the current status of the disease has not been investigated. This paper takes a retrospective look at the problem of tsetse and trypanosomiasis in Ghana, assesses the current disease situation and highlights some research perspectives that are relevant to the sustainable control of the disease.
12961 Ogunsanmi, A.O. & Taiwo, V.O., 2004. Comparative studies on erythrocyte calcium, potassium, haemoglobin concentration, osmotic resistance and sedimentation rates in grey duiker (Sylvicapra grimmia), sheep and goats experimentally infected with Trypanosoma congolense. Veterinarski Arhiv, 74 (3): 201-216.
Taiwo: Department of Veterinary Pathology, University of Ibadan, Nigeria. [[email protected]]
A comparative study of the haemoglobin (Hb) concentration, erythrocyte sedimentation rates (ESR), osmotic resistance (EOR) and erythrocyte dynamics of calcium (Ca++) and potassium (K+) ions was carried out on 10 grey duiker (Sylvicapra grimmia), 15 female West African dwarf sheep and 15 female Yankassa goats during the course of experimental Trypanosoma congolense infection. Grey duiker developed a transient parasitaemia and mild anaemia, while sheep and goats developed progressive parasitaemia, pyrexia, anaemia and loss of condition necessitating their treatment at 49 days post-infection to prevent imminent mortality. Grey duiker maintained consistently unchanged levels of Hb concentration, ESR and erythrocyte Ca++ levels, and transiently reduced EOR and erythrocyte K+ levels throughout the course of T. congolense infection. On the other hand, infected sheep and goats developed progressive decreases in Hb concentration, EOR and erythrocyte K+ levels, progressive increases in ESR and erythrocyte Ca++ levels. These changes were much more severe in infected goats and sheep. This study has shown that the relative trypanotolerance of infected grey duiker is based on their superior ability to control parasitaemia, maintain erythrocytic structural integrity and homeostasis, and hence limit anaemia and other deleterious effects of trypanosome infection than is the case with its domestic small ruminant counterparts. Thus, grey duiker may be a substitute for African buffalo in research efforts to unravel the mystery of trypanotolerance, especially in both wild and domesticated ruminants. These animals also offer valuable substitutes for animal protein sources for the teeming human population in tsetse and trypanosomiasis endemic areas where their mass domestication and rearing are encouraged.
12962 Stephenson, J., 2004. Diagnosing sleeping sickness. Journal of the American Medical Association, 291 (19): 2309.
This news item makes reference to the technical advances described by Papadoupolos et al. [see under 12940].
12963 Waiswa, C. & Katunguka-Rwakishaya, E., 2004. Bovine trypanosomiasis in south-western Uganda: packed-cell volumes and prevalences of infection in the cattle. Annals of Tropical Medicine and Parasitology, 98 (1): 21-27.
Waiswa: Department of Veterinary Medicine, Makerere University, PO Box 7062, Kampala, Uganda. [[email protected]]
Following confirmed cases of trypanosomiasis and reports of trypanosome-attributable deaths among local cattle, a cross-sectional study was undertaken to determine the prevalence of bovine infection with trypanosomes in southwestern Uganda. Cattle from ten different localities were checked by the microscopical examination of wet blood smears and thin, stained blood smears, and by blood centrifugation followed by the examination of the resultant buffy coats. Of 1 309 cattle investigated, 6.42 percent (5.56 percent and 7.26 percent of those from the Mbarara and Mubende districts, respectively) were found to be infected. Of the positive animals, 71 (84.5 percent), 11 (13.1 percent) and two (2.4 percent) appeared to be infected with Trypanosoma vivax only, T. congolense only and both T. vivax and T. congolense, respectively. The prevalence of infection with T. vivax was significantly higher than that with T. congolense (P<0.001). The mean packed-cell volumes (PCV) for the trypanosome-positive animals were lower than those for the trypanosome-negative, whether the cattle considered were all those investigated (22.3 percent vs. 29.0 percent) or just those from the Mbarara (22.8 percent vs. 28.2 percent) or Mubende (21.5 percent vs. 29.7 percent) districts. Southwestern Uganda has been relatively free of both human and bovine trypanosomiasis for the past three decades. The factors leading to the current resurgence of bovine trypanosomiasis need further investigation.
12964 Maina, N., Ngotho, J.M., Were, T., Thuita, J.K., Mwangangi, D.M., Kagira, J.M., Ndung’u, J.M. & Sternberg, J., 2004. Proinflammatory cytokine expression in the early phase of Trypanosoma brucei rhodesiense infection in vervet monkeys (Cercopithecus aethiops). Infection and Immunity, 72 (5): 3063-3065.
Sternberg: Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB29 2TZ, UK. [[email protected]]
A vervet monkey model of trypanosomiasis was used to study inflammatory cytokine responses in serum and cerebrospinal fluid (CSF). Gamma interferon levels were transiently up-regulated in serum between days 6 and 8 of infection, followed by a sustained up-regulation of tumour necrosis factor alpha (TNF-a) and soluble TNF receptor 1. At no time were these cytokines detectable in the CSF.
12965 Nega Tewelde, Getachew Abebe, Eisler, M., McDermott, J., Greiner, M., Afework, Y., Kyule, M., Münstermann, S., Zessin, K.-H. & Clausen, P.-H., 2004. Application of field methods to assess isometamidium resistance of trypanosomes in cattle in western Ethiopia. Acta Tropica, 90 (2): 163-170.
Clausen: Institute for Parasitology and International Animal Health, Freie Universität Berlin, Königsberg 67, D-14163 Berlin, Germany. [[email protected]]
This study assessed the degree of isometamidium resistance of trypanosomes infecting cattle in the upper Didessa valley of western Ethiopia. An initial prevalence study was conducted to identify sites with a high risk of trypanosomosis in cattle. The trypanosome prevalence varied widely, with two sites, Kone (21.3 percent) and Village 1 settlement (15 percent) having a relatively high prevalence based on the phase-contrast buffy-coat technique (BCT). In the highest risk area, the Kone settlement, an isometamidium block treatment study was conducted from April to June 2001. A total of 300 cattle were included in this study, 100 from each of three villages (Cheleleki, Kolu and Burka). At day minus 14 of the study, all 300 cattle were treated with diminazene aceturate at 7 mg/kg body weight. Subsequently, these cattle were ear-tagged and randomly assigned into two groups, 50 as controls and 50 for isometamidium treatment in each village. Fourteen days later (day 0), the 50 treatment cattle were given isometamidium chloride at 1 mg/kg body weight. Both groups of cattle were then examined for trypanosome parasites using BCT every 14 days until day 84. The two indices used in assessing isometamidium resistance, namely the proportion of infections during an eight-week follow-up period and the ratio of mean hazards in an isometamidium treated versus untreated group, provided consistent results across the three villages. In Burka village, both indices demonstrated the presence of isometamidium resistance trypanosome infections while in Cheleleki and Kolu villages, neither index indicated significant levels of resistance. There were significant differences between the Kaplan-Meier survival estimates of the control and treatment groups in Cheleleki and Kolu but not in Burka.
12966 Sekoni, V.O. & Rekwot, P.I., 2003. Effect of chemotherapy on elevated ejaculation time and deteriorated semen characteristics consequent to trypanosomosis in Zebu × Friesian crossbred bulls. Revue d'Élevage et de Médecine Vétérinaire des Pays Tropicaux, 56 (1-2): 37-42.
Sekoni: National Animal Production Research Institute, Ahmadu Bello University, PMB 1096, Shika, Zaria, Nigeria. [[email protected]]
The effect of the trypanocide Novidium® on elevated ejaculation time and deteriorated semen characteristics was studied in Zebu × Friesian crossbred bulls infected with Trypanosoma vivax or T. congolense. The bulls were divided into three groups, A, B and C. Groups A and B comprised four bulls each, while group C had two bulls which served as controls. Groups A and B were infected with 2×106 T. vivax or T. congolense, respectively, while group C was left uninfected. Blood samples from treated bulls were all negative for trypanosomes four days after chemotherapy. The body temperature of the treated animals normalized. Clinical signs associated with trypanosomiasis, such as anaemia, cachexia and ruffled hair coat, disappeared gradually in treated bulls. There was only a marginal improvement in the semen characteristics of a bull infected with T. vivax at 24 weeks postchemotherapy. However, all bulls infected with T. vivax or T. congolense irrespective of chemotheraphy still had poor semen characteristics manifested by all or some of the following: decreased volume of semen, oligospermia, azoospermia and elevated incidence of sperm morphological abnormalities. They were thus unfit for breeding. T. congolense was more pathogenic than T. vivax in the study.Therefore, chronic trypanosomiasis due to either T. vivax or T. congolense could be an important causative agent of infertility or sterility in Zebu × Friesian crossbred bulls.
12967 Sekoni, V.O. & Rekwot, P.I., 2002. Genital lesions associated with Trypanosoma vivax and Trypanosoma congolense infections in Zebu/Friesian crossbred bulls. Bulletin of Animal Health and Production in Africa, 50 (4): 260-262.
Sekoni: National Animal Production Research Institute, Ahmadu Bello University P.M.B. 1096 Shika - Zaria, Nigeria.
Six crossbred Zebu/Friesian bulls were divided into three lots of two animals each. One lot was infected with T. vivax, another with T. congolense, and a third left as control. It was found that trypanosomiasis has a devastating effect on the male genitalia, with T. congolense causing more genital lesions than T. vivax. The study indicated that pathogenic trypanosomes may be important causes of infertility or sterility. To prevent or ameliorate consequences of trypanosomiasis, crossbred bulls should be closely monitored and managed with adequate veterinary care.
12968 Taylor K. & Authié, E. M.-L., 2004. Pathogenesis of animal trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 331-353.
Taylor: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
This overview of pathogenesis of animal trypanosomiasis deals first with the various causative organisms and the various domestic animal hosts to be covered. African trypanosomiasis and South American T. vivax infections are treated from the viewpoint of general signs and lesions, starting with bovine trypanosomiasis, continuing with the disease in small ruminants, camels, horses, donkeys, carnivores and swine. Surra caused by T. evansi is described, along with its geographical distribution and effects on hosts. Dourine caused by T. equiperdum is likewise treated. The infection process and pathogenesis of African trypanosomes are covered; the progress of the disease in the skin and afferent lymphatics, the draining lymph node and efferent lymphatics, the blood, the spleen and liver, bone marrow, the heart, the endocrine and reproductive organs, and the central nervous system are covered in some detail. The immune responses are then dealt with, covering the induction of adaptive immune responses, antibody responses to variant antigens and parasite clearance, antibody responses to invariant antigens, and immune suppression (B cell, T cell and monocyte effector functions). Systemic pathology is dealt with covering leucopenia, thrombocytopenia, anaemia including erythrocyte destruction and dyserythropoiesis. Other blood complications include disseminated coagulation and hypocomplementaemia. The various factors contributing to the pathological picture, coming from respectively the host animal and the parasite itself, are itemised, with a detailed account of the research that has thrown light on these factors. Rodent models provide an alternative to using the larger domestic animals for the conduct of research on animal trypanosomiasis, but care is needed in transferring the results to other hosts.
[See also 27: 12961]
12969 Duleu, S., Vincendeau, P., Courtois, P., Semballa, S., Lagroye, I., Daulouede, S., Boucher, J.L., Wilson, K.T., Veyret, B. & Gobert, A.P., 2004. Mouse strain susceptibility to trypanosome infection: An arginase-dependent effect. Journal of Immunology, 172 (10): 6298-6303.
Gobert: Unité de Microbiologie, Institut National de la Recherche Agronomique de Clermont-Ferrand-Theix, 63122 Saint-Genes-Champanelle, France. [[email protected]]
12970 Jabbar, M.A. & Diedhiou, M.L., 2003. Does breed matter to cattle farmers and buyers? Evidence from West Africa. Ecological Economics, 45 (3): 461-472.
Jabbar: International Livestock Research Institute (ILRI), PO Box 5689, Addis Ababa, Ethiopia. [[email protected]]
World agriculture is based on a small number of animal species and a decreasing number of breeds within each species. Several breeds of West African shorthorn cattle (Bos taurus brachyceros) are now at high risk of extinction due to interbreeding. The West African shorthorn breeds are particularly important resources because of their superior abilities to resist diseases, particularly trypanosomosis, and being productive under high humidity, heat stress, water restriction and with poor quality feed. An analysis of farmers’ breeding practices and breed preferences in a sample area in southwest Nigeria confirmed a strong trend away from trypanotolerant breeds, especially Muturu, and identified the traits farmers find least desirable in these breeds relative to zebu (Bos indicus) breeds. An analysis of cattle market prices found that buyers have preferences for specific breeds for specific purposes and that though in general price differences due to breed are small, in some cases buyers pay significantly different prices for certain breeds consistent with their preferences. The best hopes for increased utilization of breeds at risk such as Muturu is likely in other areas of West Africa, for example in southeast Nigeria, where the Muturu is better suited to the farming systems and there is a large market for this breed to provide incentives to cattle breeders.
12971 Murray, M., d’Ieteren, G.D.M. & Teale, A.J., 2004. Trypanotolerance. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 461-477.
Murray: Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Glasgow, UK.
The ability of some strains of African cattle to survive in tsetse infested areas without special treatment is known as trypanotolerance. This is best known and studied in Bos taurus breeds of West and Central Africa, such as the N’Dama and the West African Shorthorn. Using these breeds is the major, or only, option in 19 countries of the most humid parts of West and Central Africa. While it has been unequivocally established that they have significant innate resistance to trypanosomiasis and that their productivity is satisfactory when assessed on a per metabolic unit basis, livestock owners do often cross or replace these breeds with trypanosusceptible cattle breeds. This trend may be due to ongoing changes in disease risk or to the higher prices fetched by these susceptible breeds at market. Research into trypanotolerance focuses on retention and improvement of the desired traits, and on the possibility of conferring the trypanotolerant traits to susceptible breeds, while avoiding negative trade-offs. Matters under study include the breed’s ability to control parasite proliferation, to limit the pathological effects of infection, and to acquire better control of infection. All these variables have been compared in N’Dama on the one hand, and Boran cattle on the other, and have given a more detailed picture of the advantages enjoyed by the N’Dama in tsetse challenge areas. Results emerging from heritability studies show that trypanotolerance is a heritable trait within the N’Dama population. The search is on for markers that could expedite selection for desired traits. Trypanotolerance is also affected by environmental factors such as nutrition, workload and trypanosomiasis-tsetse risk; greater knowledge of the impact of these is leading to refinement of ideas of how best to fashion intervention strategies. Further research engages with the possibility that N’Dama may have superior abilities to withstand the stresses of living in humid areas alongside other disease challenges, making do with lower food intake, and possibly having better water utilization. Field workers are now fully aware that within trypanotolerant stocks there will be a great innate variability, on top of the complex interplay of genetic and environmental factors; analysis has to be done with care and with regard for this variability. Studies have indicated the absolute requirement for a functioning immune system; research aims at illustrating differences in immune response in tolerant and susceptible lines. Ingenious experimental design using bone marrow chimaerism in cattle and sublethal radiation techniques, is helping to lead to the conclusion that resistant cattle types develop more focussed and mature antibody responses to infection than do susceptible cattle; they may also have a better immunological memory, and maintain a more normal blood condition in respect of erythrocyte and leucocyte profiles. Gene mapping is in progress and has had success in locating loci important in resistance (in mice) to T. congolense infection. Comparable genetic analysis in cattle will follow. A range of options for intervention are now available, but funding and infrastructure are current restraints. Research should concentrate on genetic improvements, transferring trypanotolerant characteristics to other breeds, and large scale breeding and distribution of the results, with interventions planned within integrated control strategies.
12972 Voh, A.A. Jr., Larbi, A., Olorunju, S.A.S., Agyemang, K., Abiola, B.D. & Williams, T.O., 2004. Fertility of N’Dama and Bunaji cattle to artificial insemination following oestrus synchronization with PRID and PGF2a in the hot humid zone of Nigeria. Tropical Animal Health and Production, 36 (5): 499-511.
Voh: Artificial Insemination Unit, National Animal Production Research Institute, Ahmadu Bello University, Federal Ministry of Agriculture and Rural Development, PMB 1096, Shika, Zaria, Nigeria. [[email protected]]
Shortage of trypanotolerant breeding stock is a constraint on the expansion of such animals in unexploited areas of the humid and subhumid zones. Using 116 cows and heifers, a study was undertaken to determine the effectiveness of a progesterone-releasing intravaginal device (PRID) and prostaglandin F2a (PGF2a) in synchronizing oestrus in N’Dama and Bunaji cows and heifers and the fertility following artificial insemination at the synchronized oestrus. N’Dama cattle showed significantly better oestrus response rate, pregnancy rate and conception rate than Bunaji cattle following both PRID and PGF2a treatments. The pregnancy rate and conception rate following PGF2a treatment were better than for PRID, although the oestrus response rate did not differ. It is concluded that both PRID and PGF2a are effective in synchronizing oestrus in N’Dama and Bunaji cattle in the hot humid zone of Nigeria and the fertility to artificial insemination at the synchronized oestrus was normal and acceptable. Thus, PRID and PGF2a can be used effectively in intensive breeding programmes for the rapid multiplication and distribution of both cattle breeds, especially the N’Dama, which is a unique and beneficial animal genetic resource for the tsetse infested hot humid zone of Nigeria.
12973 Bett, B., Machila, N., Gathura, P.B., McDermott, J.J. & Eisler, M.C., 2004. Characterisation of shops selling veterinary medicines in a tsetse-infested area of Kenya. Preventive Veterinary Medicine, 63 (1-2): 29-38.
Bett: Trypanosomiasis Research Centre, Kenya Agricultural Research Institute, PO Box 362, Kikuyu, Kenya. [[email protected]]
In a tsetse-infested area of Kenya, we characterized veterinary-drug outlets based on personnel and business characteristics to assess their capacities to provide clinical veterinary services. Structured questionnaires were administered to the retailers and sought information on the characteristics of the owners, salespersons and businesses. A total of 41 retail outlets (20 agro-veterinary, 11 pharmacy, and 10 general shops) were identified. There was poor response to questions on owner characteristics. Proprietors, who had no more than secondary education owned 15 out of 28 shops. Few shops (4/29) were owned by proprietors who had professional qualifications (in animal health). Most salespersons had only secondary education but no qualifications. Animal-health assistants, veterinarians and manufacturer’s package inserts (drug leaflets) were the preferred information sources for the retailers. We concluded that drug retailers were poorly equipped with the technical knowledge necessary for drug dispensation and advice.
12974 Chaka, H. & Abebe, G., 2003. Drug resistant trypanosomes: a threat to cattle production in the Southwest of Ethiopia. Revue d'Élevage et de Médecine Vétérinaire des Pays Tropicaux, 56 (1-2): 33-36.
Abebe: National Animal Health Research Centre, PO Box 04, Sebeta, Ethiopia. [[email protected]]
Trypanosomiasis is an important disease of cattle in the southwest of Ethiopia. At present chemotherapy and chemoprophylaxis are the only practical methods available for the control of animal trypanosomiasis, but their effectiveness is being eroded by the emergence of drug resistant trypanosomes. Of the drugs available for the treatment of animal trypanosomiasis, Berenil (diminazene aceturate) and Trypamidium (isometamidium chloride) have been used the most because of their availability and relatively low toxicity to cattle. In this study, four stocks of Trypanosoma congolense, originally isolated from cattle in the southwest of Ethiopia (Ghibe, Bedelle, Sodo and Arbaminch), were tested for Berenil and Trypamidium sensitivity using Swiss white mice and indigenous Zebu cattle. The results on the limited number of stocks indicated the existence of drug resistant strains of T. congolense. Isolates from Ghibe, Bedelle and Sodo were resistant to a therapeutic dose of diminazene aceturate (3.5 mg/kg) and to standard therapeutic and prophylactic doses of isometamidium chloride (0.5 and 1 mg/kg). However, all three stocks were found to be sensitive to 7 mg/kg diminazene aceturate. The fourth, the Arbaminch stock, was found to be resistant to the manufacturers recommended dosage of diminazene aceturate and isometamidium chloride.
12975 Gall, Y., Woitag, T., Bauer, B., Sidibe, I., McDermott, J., Mehlitz, D. & Clausen, P.H., 2004. Trypanocidal failure suggested by PCR results in cattle field samples. Acta Tropica, 92 (1): 7-16.
Clausen: Institute for Parasitology and International Animal Health, Freie Universitat Berlin, Koenigsweg 67, D-14163 Berlin, Germany. [tropvelm@zedat,fu-berlin]
The aim of this study was to assess whether the polymerase chain reaction (PCR) allows sensitive screening of suspected treatment failures in areas where drug resistance against African animal trypanosomosis (AAT) appears to be a problem. PCR was used to detect trypanosome infections prior to, and 14 and 28 days after controlled treatment of 738 cattle from 10 villages in Kenedougou, Burkina Faso with isometamidium chloride and diminazene aceturate. Using three sets of primers, PCR was three to four times more sensitive and better at species identification than standard microscopic examination. The better sensitivity and species specificity of PCR have important advantages for drug resistance studies in the field.
12976 Holmes, P.H., Eisler M.C. & Geerts S., 2004. Current chemotherapy of animal trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 431-444.
Holmes: University of Glasgow, Glasgow, UK.
Three compounds are in use to control animal trypanosomiasis in Africa: isometamidium chloride, homidium (bromide and chloride), and diminazene aceturate. These have been available for the past 40 years; there is a risk that resistance to these drugs will develop, making them less useful. There are disincentives for investment in new drugs: there is already a spread of generic products; and the cost of developing new drugs is very high while the market for them is relatively small. Strategies for trypanocidal drug usage are outlined: routine block treatments using prophylactic drugs; strategic block treatments carried out when challenge is judged to high enough to justify it; and monitoring and treatment of individual animals found to be infected, usually using a curative drug. In recent years the move towards privatization of services and away from central provision of these, has led to greater burdens on resource-poor farmers and the risk that treatments will not be well designed or based on accurate diagnosis. Resistance to drugs is widely reported. Possible mechanisms for the emergence of resistance are described by reference to the different drugs. Work aimed at testing whether drug-resistant trypanosome strains are less virulent is described. Methods of detecting drug resistance are summarized under the tests in ruminants, tests in mice, in vitro studies, trypanocidal drug-ELISAs, and block treatment studies and longitudinal parasitological data; notes on potential new tests for the detection of resistance are given. How the onset of development of drug resistance may be delayed is discussed against the background of our present knowledge and field experience. Measures to be considered are: reduction in the number of treatments by integrating drug usage with other control measures; using the correct dosage; avoiding exposure of the whole parasite population to a drug as this may promote the evolution of resistance; and banning the use of quinapyramine in cattle due to its capacity to induce multi-drug resistance. Guidelines are given for action to be taken when drug resistance is detected, and a table of appropriate action to be taken according to the severity of the resistance problem is presented. The need for quality control of trypanocidal drugs is stressed. Lines for further investigations are indicated.
12977 Wesongah, J.O., Jones, T.W., Kibugu, J.K. & Murilla, G.A., 2004. A comparative study of the pharmacokinetics of isometamidium chloride in sheep and goats. Small Ruminant Research, 53 (1-2): 9-14.
Wesongah: Kenya Trypanosomiasis Research Institute, PO Box 362, Kikuyu, Kenya. [[email protected]]
A study was carried out to determine and compare the pharmacokinetics of isometamidium in groups of six animals each of sheep and goats treated by intramuscular injection with isometamidium chloride (Samorin®, Rhone Merieux, Lyon, France) at 0.5 mg/kg body weight. The animals were bled at pre-determined time intervals and serum isometamidium concentrations monitored using isometamidium-ELISA for a period of over 60 days post-treatment. Pharmacokinetic evaluation was carried out using a non-compartment analysis. Mean residence time (MRT) in sheep was higher but not significantly different from that observed in goats. Whereas the mean Cmax values observed in both species were similar, the Tmax value of 12.7 h obtained in goats was significantly longer suggesting a slower rate of absorption of the drug from injection site. Also, the elimination half-life obtained in goats of 188 h was significantly shorter than that observed in sheep suggesting rapid elimination rate of the drug in the latter. At 60 days no drug was detectable in either sheep or goats.
12978 Magez, S., Truyens, C., Merimi, M., Radwanska, M., Stijlemans, B., Brouckaert, P., Brombacher, F., Pays, E. & de Baetselier, P., 2004. P75 tumor necrosis factor-receptor shedding occurs as a protective host response during African trypanosomiasis. [Mice.] Journal of Infectious Diseases, 189 (3): 527-539.
Magez: Laboratory of Cellular and Molecular Immunology, Department of Cellular and Molecular Recognition, Flanders Interuniversity Institute for Biotechnology, Free University of Brussels (VUB), Pleinlaan 2, 1050 Brussels, Belgium. [[email protected]]
In experimental murine trypanosomiasis, resistance is often scored as the capacity to control peak parasitaemia levels, which results in prolonged survival. Infection-induced pathology has not systematically been used as a resistance criterion. Because this parameter could be the most relevant for comparative analysis of natural and experimental infections, as well as for understanding of pathology-associated immune alterations, we analysed Trypanosoma brucei infections in four different established conventional mouse models, as well as in tumour necrosis factor (TNF)-deficient and TNF-receptor-deficient mice. Results indicate the following: (1) there is no correlation between peak parasitaemia control or survival and the induction of infection-associated anaemia, loss of body weight, liver pathology, reduced locomotor activity, and general morbidity; (2) serum levels of TNF, interferon-g, and interleukin-10, which are known to affect survival, do not correlate with induction of pathology; and (3) infection-induced occurrence of lipopolysaccharide hypersensitivity does not correlate with survival. However, one parameter that was found to correlate with the inhibition of trypanosomiasis-associated pathology in all models was the shedding of soluble p75 TNF-receptor during peak parasitaemia stages. These results are important for future cytokine and trypanosomiasis pathology studies, because the interplay between TNF and the soluble receptors it sheds has not been considered in either human clinical sleeping sickness studies or in veterinary trypanosomiasis research.
12979 Nesslany, F., Brugier, S., Mouriès, M. A., le Curieux, F. & Marzin, D., 2004. In vitro and in vivo chromosomal aberrations induced by megazol. [Mouse cells.] Mutation Research, Genetic Toxicology and Environmental Mutagenesis, 560 (2): 147-158.
Marzin: Laboratoire de Toxicologie Génétique, Institut Pasteur de Lille, 1 rue du Pr. Calmette, 59019, Lille Cedex, France. [[email protected]]
With the re-emergence of Human African Trypanosomiasis (HAT) on the one hand, which is increasingly resistant to current therapies, and the stage-dependent effectiveness or even the prohibitive cost of these therapies on the other hand, megazol, a 5-nitroimidazole thiadiazole highly active against various trypanosome species, was assessed for its genotoxic potential. Very little information has become available until now. Two batches of megazol were provided by two different suppliers: Far-Manguinhos, a part of the Fiocruz foundation, under the Brazilian Minister of Health, and Delphia, a French company. These two batches, obtained by different synthetic routes, were studied by means of the in vitro micronucleus assay on L5178Y mouse lymphoma cells, in its microscale version. Both batches of megazol displayed a strong genotoxic activity in this screening assay. A second batch from Delphia was then investigated by using two tests, i.e. the in vitro metaphase analysis with human lymphocytes and the in vivo micronucleus test in rat bone-marrow. Megazol was shown to be a potent inducer of in vitro and in vivo chromosomal aberrations. Although megazol is a potent trypanocidal agent and is orally bio-available, its toxicity dictates that it should not be developed further for the treatment of HAT and Chagas’ disease. All development work has therefore been discontinued.
12980 Boda, C., Enanga, B., Dumet, H., Chauviere, G., Labrousse, F., Couquet, C., Saivin, S., Houin, G., Perie, J., Dumas, M. & Bouteille, B., 2004. Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep. Veterinary Parasitology, 121 (3-4): 213-223.
Boda: Institut d’Epidémiologie Neurologique et de Neurologie Tropicale (EA3174), Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France. [[email protected]]
Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80 mg/kg. After a transient non-parasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considered as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8 h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, for uninfected sheep treated with a single oral dose, results indicated limited megazol availability, and very weak concentrations compared with those seen in mice and monkeys. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.
12981 Camacho, M. del R., Phillipson, J.D., Croft, S.L., Yardley, V. & Solis, P.N., 2004. In vitro antiprotozoal and cytotoxic activities of some alkaloids, quinones, flavonoids, and coumarins. Planta Medica, 70 (1): 70-72.
Camacho: Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, London, UK. [[email protected]]
Twenty-six pure plant-derived compounds including alkaloids, quinones, flavonoids, and coumarins, obtained from five species of Central American plants associated with traditional uses, were tested in vitro for antiprotozoal and cytotoxic activities. The quinone l-acetyl-benzoisochromanquinone displayed significant antiprotozoal activity against Leishmania donovani promastigotes and amastigotes, Trypanosoma cruzi amastigotes, and T. brucei brucei bloodstream form trypomastigotes, with IC50 values of 2.32, 1.98, 6.60, and 0.65 mM, respectively. The quinones, benzo[g]isoquinoline-5,10-dione had an IC50 value of 4.2 mM against Plasmodium falciparum and 1-hydroxybenzoisochromanquinone an IC50 value of 3.3 mM against T. b. brucei trypomastigotes. The remaining compounds were either weakly active or inactive.
12982 Comini, M.A., Guerrero, S.A., Haile, S., Menge, U., Lünsdorf, H. & Flohé, L., 2004. Validation of Trypanosoma brucei trypanothione synthetase as drug target. Free Radical Biology and Medicine, 36 (10): 1289-1302.
Flohé: Prof. Dr. Leopold Flohé, MOLISA GmbH, Universitatsplatz 2, D-39106 Magdeburg, Germany. [[email protected]]
12983 de Koning, H.P., Anderson, L.F., Stewart, M., Burchmore, R.J.S., Wallace, L.J.M. & Barrett, M.P., 2004. The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in African trypanosomes. Antimicrobial Agents and Chemotherapy, 48 (5): 1515-1519.
de Koning: Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK. [H/[email protected]]
Resistance to diminazene aceturate (Berenil) is a severe problem in the control of African trypanosomiasis in domestic animals. It has been speculated that resistance may be the result of reduced diminazene uptake by the parasite. We describe here the mechanisms by which [3H]diminazene is transported by Trypanosoma brucei brucei bloodstream forms. Diminazene was rapidly accumulated through a single transporter, with a Km of 0.45 +/- 0.11 mM, which was dose-dependently inhibited by pentamidine and adenosine. The Ki values for these inhibitors were consistent with this transporter being the P2/TbAT1 adenosine transporter. Yeast expressing TbAT1 acquired the ability to take up [3H]diminazene and [3H]pentamidine. TbAT1-null mutants had lost almost all capacity for [3H]diminazene transport. However, this cell line still displayed a small but detectable rate of [3H]diminazene accumulation, in a nonsaturable manner. We conclude that TbAT1 mediates [3H]diminazene transport almost exclusively and that this explains the observed diminazene resistance phenotypes of TbAT1-null mutants and field isolates.
12984 Gertsch, J., Niomawë, Gertsch-Roost, K. & Sticher, O., 2004. Phyllanthus piscatorum, ethnopharmacological studies on a women’s medicinal plant of the Yanomamï Amerindians. Journal of Ethnopharmacology, 91 (2-3): 181-188.
Gertsch: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. [[email protected]]
The shrub Phyllanthus piscatorum (Euphorbiaceae) is cultivated by various ethnic groups of the Amazon because of its piscicidal properties. During ethnobotanical fieldwork among the Yanomamï Amerindians in Venezuela we observed that Phyllanthus piscatorum was exclusively cultivated and used by the women. Aerial parts of this herbaceous shrub are employed as fish poison and medicine to treat wounds and fungal infections. In addition, the leaves are used as tobacco substitute. Ethnobotanical data regarding the context of the use of this plant are presented. To validate ethnobotanical information related to its medicinal indications, both antimicrobial and antiprotozoal, properties of water, methanol (MeOH) and dichloromethane (DCM) extracts were studied. No activity against Gram-positive bacterial strains but significant activity against the fungi Aspergillus fumigatus, Aspergillus flavus and the yeast Candida albicans were found. All extracts showed weak in vitro activity against Plasmodium falciparum and Trypanosoma brucei rhodesiense. The extracts were further investigated for cytotoxic effects in an in vitro test system with leukemia Jurkat T, HeLa, and human peripheral mononuclear blood cells (PBMCs). During the first 48 h the extracts did not exhibit any cytotoxicity. After 72 h the DCM extract potently inhibited viability of HeLa cells. Although in several communities along the upper Orinoco the cultivation and use of Phyllanthus piscatorum is being lost because of the ongoing acculturation, the traditional medicinal use of Phyllanthus piscatorum might provide an effective and cheap remedy against dermatological diseases linked with Candida albicans infections.
12985 Gertsch, J., Tobler, R.T., Brun, R., Sticher, O. & Heilmann, J., 2003. Antifungal, antiprotozoal, cytotoxic and piscicidal properties of justicidin B and a new arylnaphthalide lignan from Phyllanthus piscatorum. Planta Medica, 69 (5): 420-424.
Heilmann: Department of Chemistry and Applied BioSciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. [[email protected]]
Using the activity against Candida albicans as a lead, the bioactivity-guided fractionation of the dichloromethane extract of Phyllanthus piscatorum resulted in the isolation of the arylnaphthalide lignan justicidin B, which was found to be present in high amounts, and a new C-11 hydroxylated derivative that we named piscatorin. We provide evidence that justicidin B is the main active principle of P. piscatorum, showing the same biological effects that were found for the raw extracts. Justicidin B inhibited the growth of the pathogenic fungi Aspergillus fumigatus (MIC ³ 1 mg/ml), Aspergillus flavus (MIC ³ 12 mg/ml) and Candida albicans (MIC ³ 4 mg/ml), but was not effective against Cryptococcus neoformans and Blastoschizomyces capitatus. Justicidin B also exhibited a strong activity against the trypomastigote form of Trypanosoma brucei rhodesiense (IC50 = 0.2 mg/ml) and moderate activity against Trypanosoma cruzi (IC50 = 2.6 mg/ml). Testing against Plasmodium falciparum showed only weak activity. This is the first report on the in vitro fungicidal and antiprotozoal effects of justicidin B. In addition both compounds exhibited a non-specific cytotoxicity in neoplastic and primary cell cultures. No antibacterial effects were detected. Both compounds were piscicidal against zebra fish, and it is shown for the first time that piscatorin and justicidin B are the piscicidal principles of P. piscatorum, exhibiting a potency that is comparable to rotenone.
12986 Hoet, S., Opperdoes, F., Brun, R., Adjakidjé, V. & Quetin-Leclercq, J., 2004. In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants. Journal of Ethnopharmacology, 91 (1): 37-42.
Hoet: Laboratoire de Pharmacognosie, Université Catholique de Louvain, Av. E. Mounier 72, UCL 72.30-CHAM, B-1200, Brussels, Belgium. [[email protected]]
The in vitro antitrypanosomal activities of methylene chloride, methanol and aqueous extracts of the leaves and twigs of five plant species traditionally used in Benin for the treatment of sleeping sickness were evaluated on Trypanosoma brucei brucei and their selectivity was analysed on Leishmania mexicana mexicana and J774 macrophage-like murine cells. The results showed that the four most active extracts had MIC values £19 mg/ml (Hymenocardia acida twig and leaf, Strychnos spinosa leaf, Trichilia emetica leaf methylene chloride extracts). All these extracts had a lower activity on L. m. mexicana and J774 cells. Determination of the IC50 values of the methylene chloride leaf extracts on two strains of trypanosomes (T. b. brucei and T. b. rhodesiense) and two mammalian cell lines (L6 and J774 cells) showed that all extracts possessed some antitrypanosomal activity with IC50 values ranging from 1.5 to 39 mg/ml. All were also toxic to the mammalian cells, but usually with higher IC50 values. The only exception was the S. spinosa methylene chloride leaf extract which had no toxicity on J774 cells. Although tannins have been identified in most of the species studied, they could not be detected in the most active extracts, just as in the case of alkaloids. The presence of flavonoids and quinones may at least in part explain the observed activities of some of the active extracts.
12987 Hoet, S., Stévigny, C., Block, S., Opperdoes, F., Colson, P., Baldeyrou, B., Lansiaux, A., Bailly, C. & Quetin-Leclercq, J., 2004. Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal activity, cytotoxicity, and interaction with DNA and topoisomerases. Planta Medica, 70 (5): 407-413.
Quetin-Leclercq: Laboratoire de Pharmacognosie, Unité d'Analyse Chimique et Physico-Chimique des Médicaments, Université Catholique de Louvain 72.30, Avenue E. Mounier 72, 1200 Bruxelles, Belgium. [[email protected]]
Cassytha filiformis, a widely distributed parasitic plant, contains several aporphine alkaloids and is often used in African folk medicine to treat cancer, African trypanosomiasis and other diseases. In a previous investigation, we showed that the alkaloid plant extract and the isolated aporphines possessed in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity of the alkaloid extract (IC50=2.2 mg/ml) and its three major aporphine alkaloids (actinodaphnine, cassythine and dicentrine) on Trypanosoma brucei brucei as well as that of four related commercially available aporphines (bulbocapnine, glaucine, isocorydine, boldine). Only the three alkaloids from C. filiformis were active on the trypanosomes in vitro (IC50 = 3-15 mM). Additionally, we compared the cytotoxicity of these seven compounds on HeLa cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2 mM) in the series. To elucidate their mechanism of action, the binding mode of these molecules to DNA was studied by UV absorption, circular and linear dichroism spectroscopy. The results of the optical measurements indicated that all seven aporphines effectively bind to DNA and behave as typical intercalating agents. Biochemical experiments showed that actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines. These interactions with DNA may explain, at least in part, the effects observed on cancer cells and trypanosomes.
12988 Lorente, S.O., Rodrigues, J.C.F., Jiménez, C.J., Joyce-Menekse, M., Rodrigues, C., Croft, S.L., Yardley, V., de Luca-Fradley, K., Ruiz-Pérez, L.M., Urbina, J., de Souza, W., Pacanowska, D.G. & Gilbert, I.H., 2004. Novel azasterols as potential agents for treatment of leishmaniasis and trypanosomiasis. Antimicrobial Agents and Chemotherapy, 48 (8): 2937-2950.
Gilbert: Welsh School for Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3XF, UK. [[email protected]]
This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. Azasterols are a known class of (S)-adenosyl-L-methionine: D24-sterol methyltransferase (24-SMT) inhibitors in fungi, plants, and some parasitic protozoa. The compounds prepared showed activity at micromolar and nanomolar concentrations when tested against Leishmania spp. and Trypanosoma spp. The enzymatic and sterol composition studies indicated that the most active compounds acted by inhibiting 24-SMT. The role of the free hydroxyl group at position 3 of the sterol nucleus was also probed. When an acetate was attached to the 3b-OH, the compounds did not inhibit the enzyme but had an effect on parasite growth and the levels of sterols in the parasite, suggesting that the acetate group was removed in the organism. Thus, an acetate group on the 3b-OH may have application as a prodrug. However, there may be an additional mode(s) of action for these acetate derivatives. These compounds were shown to have ultrastructural effects on Leishmania amazonensis promastigote membranes, including the plasma membrane, the mitochondrial membrane, and the endoplasmic reticulum. The compounds were also found to be active against the bloodstream form (trypomastigotes) of Trypanosoma brucei rhodesiense, a causative agent of African trypanosomiasis.
12989 Männer, J., Seidl, W., Heinicke, F. & Hesse, H., 2003. Teratogenic effects of suramin on the chick embryo. Anatomy and Embryology, 206 (3): 229-237.
Männer: Department of Embryology, Georg-August-University of Göttingen, Kreuzbergring 36, 37075 Göttingen, Germany. [[email protected]]
Suramin, a polysulfonated naphthylamine, has been used for the chemotherapy of trypanosomiasis and onchocerciasis since about the 1920s. Currently, it is also being tested as an anticancer agent. It is hoped that suramin might stop the progression of some kinds of cancer since it has been found to inhibit the proliferation and migration of cells and the formation of new blood vessels. These processes are not only essential for the development and progression of cancer, but also for normal embryonic development. Suramin might, therefore, be a potent teratogen. In the literature, however, we have found only scant information on this subject. In the present study, we demonstrate the teratogenic effects of suramin on chick embryos. Suramin was injected into the coelomic cavity of chick embryos on incubation day (ID) 3. Following reincubation until ID 8, suramin-treated embryos (n = 50) were examined for congenital malformations and compared with a control group (n = 30). The survival rate of suramin-treated embryos was markedly reduced compared with controls (50 percent vs 90 percent). Among the 25 survivors the following malformations were recorded: caudal dysgenesia (100 percent), median facial clefts with hypertelorism (92 percent), malformations of the aortic arch arteries (88 percent), hypo-/aplasia of the allantoic vesicle (84 percent), microphthalmia (52 percent), abnormalities of the great arterial trunks (44 percent), unilateral or bilateral cleft lips (40 percent), heart defects with juxtaposition of the right atrial appendage (36 percent), persistence of the lens vesicle (32 percent), median clefts of the lower beak (8 percent), omphalocele (4 percent), and cloacal exstrophy (4 percent). These results show that suramin is a potent teratogen. The possible implications of our findings for human beings and the possible teratogenic mechanisms of suramin are discussed. Use of suramin in experimental teratology might help to clarify the morphogenesis of median facial clefts and of some congenital heart defects.
12990 Nyasse, B., Nono, J., Sonke, B., Denier, C. & Fontaine, C., 2004. Trypanocidal activity of bergenin, the major constituent of Flueggea virosa, on Trypanosoma brucei. Pharmazie, 59 (6): 492-494.
Nyasse: Department of Organic Chemistry, Higher Teachers Training College, University of Yaounde 1, Cameroon. [[email protected]]
The presence of bergenin in substantial amounts in the methanol extract of Flueggea virosa (Euphorbiaceae) leaves was established as a strong chemotaxomic point of differentiation between Flueggea virosa and Securinega virosa. Bergenin showed an inhibitory effect on the growth of the bloodstream form of Trypanosoma brucei with an IC50 value of 1 mM.
12991 Olbrich, C., Gessner, A., Schröder, W., Kayser, O. & Müller, R.H., 2004. Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene - cytotoxicity testing and mouse serum adsorption. Journal of Controlled Release, 96 (3): 425-435.
Olbrich: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, The Free University of Berlin, Kelchstr. 31, D-12169 Berlin, Germany. [[email protected]]
Sleeping sickness is a widely distributed disease in large parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodesiense, transmitted by the tsetse fly. After a haemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To test the possible delivery of the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic acid (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. In the search for a potential delivery mechanism, the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain; this was demonstrated using PBCA nanoparticles coated with polysorbate 80 (referred to here as the LDL uptake mechanism). Accordingly the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles, and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. The observation that Apo-E could be detected when the particles were incubated in human serum but was absent after mouse serum incubation, is potentially critical for the delivery via the LDL-uptake mechanism. The data demonstrate that LDC nanoparticles, with 33 percent (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies are needed to demonstrate its utility as a brain delivery system.
12992 Pandey, S., Fletcher, K.A., Baker, S.N., Baker, G.A., DeLuca, J., Fennie, M.F. & O’Sullivan, M.C., 2004. Solution aggregation of anti-trypanosomal N-(2-naphthylmethyl)ated polyamines. Journal of Photochemistry and Photobiology A, Chemistry, 162 (2-3): 387-398.
Pandey: Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA. [[email protected]]
Trypanosomatidae parasites are responsible for many human and animal diseases including African sleeping sickness, Chagas’ disease, and nagana cattle disease. Since current treatment of trypanosome infections is difficult and often ineffective in controlling the chronic phases of these diseases, more effective anti-trypanosomal drugs are urgently needed. One class of polyamines containing hydrophobic side chains shows promise. We have made preliminary studies of novel spermine and spermidine analogues bearing one or two N-substituted 2-naphthylmethyl groups dissolved in aqueous solution. Our studies suggest the pH-dependent formation of fluorescent aggregates. Such spectral changes may be used to explore the mechanism by which N-(2-naphthylmethyl) polyamine analogues exert their toxic effects, and help the design of improved candidates for anti-trypanosomal chemotherapy.
12993 Ramírez, I., Carabot, A., Meléndez, P., Carmona, J., Jimenez, M., Patel, A.V., Crabb, T.A., Blunden, G., Cary, P.D., Croft, S.L. & Costa, M., 2003. Cissampeloflavone, a chalcone-flavone dimer from Cissampelos pareira. Phytochemistry, 64 (2): 645-647.
Ramírez: Faculty of Pharmacy, University of Los Andes, Mérida ZP-5101, Venezuela.
From the aerial parts of Cissampelos pareira (Menispermaceae), a chalcone-flavone dimer has been isolated, the molecular structure of which has been fully worked out. The compound has been assigned the trivial name cissampeloflavone. The compound has good activity against Trypanosoma cruzi and T. brucei rhodesiense and has a low toxicity to the human KB cell line.
12994 Stewart, M.L., Bueno, G.J., Baliani, A., Klenke, B., Brun, R., Brock, J.M., Gilbert, I.H. & Barrett, M.P., 2004. Trypanocidal activity of melamine-based nitroheterocycles. Antimicrobial Agents and Chemotherapy, 48 (5): 1733-1738.
Barrett: Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK. [[email protected]]
A series of nitroheterocyclic compounds were designed with linkages to melamine or benzamidine groups that are known substrates of the P2 aminopurine and other transporters in African trypanosomes of the brucei group. Several compounds showed in vitro trypanotoxicity with 50 percent inhibitory concentrations in the submicromolar range. Although most compounds interacted with the P2 transporter, as judged by their ability to inhibit adenosine transport via this carrier, uptake through this route was not necessary for activity since TbAT1-null mutant parasites, deficient in this transporter, retained sensitivity to these drugs. One compound, a melamine-linked nitrofuran, also showed pronounced activity against parasites in mice. Studies into the mode of action of this compound indicated that neither reductive, nor oxidative, stress was related to its trypanocidal activity ruling out a genotoxic effect in T. brucei, distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles.
12995 Sturk, L.M., Brock, J.L., Bagnell, C.R., Hall, J.E. & Tidwell, R.R., 2004. 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 Tropica, 91 (2): 131-143.
Tidwell: Department of Pathology and Laboratory Medicine, CB# 7545, Room 805, Brinkhous-Bullitt Building, School of Medicine, Chapel Hill, NC27599, USA. [[email protected]]
The current epidemic of sleeping sickness, also known as human African trypanosomiasis, in sub-Saharan Africa places nearly 60 million people at risk for developing this life-threatening infection. Although effective treatments for early-stage sleeping sickness exist, these drugs usually require extended dosing schedules and intravenous administration. New treatments are also needed for cerebral (late) stage trypanosomiasis. 2,5-bis(4-amidinophenyl)furan (DB75), a pentamidine analogue, has potent in vitro and in vivo anti-trypanosomal activity. However, DB75 does not exhibit significant oral bioavailability and has proved to be ineffective against mouse models of late-stage sleeping sickness regardless of administration route. To circumvent the limited oral bioavailability of DB75, an N-methoxy prodrug 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289) was designed and developed initially as a compound to treat AIDS-related Pneumocystis carinii pneumonia (PCP). Despite excellent oral activity against early-stage sleeping sickness, oral administration of DB289 exhibited limited efficacy in mouse models of late-stage disease. DB289 has recently entered Phase II(b) clinical trials to treat primary-stage sleeping sickness in Central Africa. The current study takes advantage of the innate fluorescence of DB75 and DB289 along with specific and sensitive quantitative analyses to examine plasma and brain distribution of these compounds. Animals were dosed with intravenous DB75, oral DB289, and intravenous DB289. Following intravenous administration, DB75 was readily detectable in whole brain extracts and persisted for long periods. Fluorescence microscopy revealed that DB75 did not penetrate into brain parenchyma, however, but was sequestered within cells lining the blood-brain and blood-cerebrospinal fluid barriers. In contrast, brain tissue of mice treated with oral DB289 exhibited diffuse fluorescence within the brain parenchyma, suggesting that the prodrug was not trapped within blood-brain barrier cells (BBB). However, maximal brain concentrations of the active compound DB75 were very low (13 nmol/mg of tissue at 24h). Intravenous administration of DB289 resulted in a qualitatively similar fluorescence pattern to oral DB289, indicating again that DB289 and DB75 were present within brain parenchyma, not only in barrier regions. Furthermore, peak DB75 tissue levels were higher (61 nmol/mg of tissue at 24h) than with oral prodrug. The near five-fold increase in brain levels of DB289 combined with parenchymal localization of compound fluorescence after intravenous administration suggest that the unaltered prodrug penetrates the blood-brain barrier, and may be subject to in situ biotransformation. Intravenous administration of DB289 should be evaluated in mouse models of late-stage sleeping sickness.
[See also 27: 12921, 12926, 12928, 12945, 13052]
12996 Barry, D. & Carrington, M., 2004. Antigenic variation. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 25-37.
Barry: Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, Glasgow, UK.
Protozoan parasites that live in the mammalian bloodstream and tissues are attacked by the host immune system response which may kill the majority of forms but miss the steady output of pre-emptively produced rarer antigenic forms. The latter survivors then proliferate before a new immune response is mounted by the host. This cycle is termed antigenic variation. In the case of the trypanosome the antigenic variation expresses itself in the protective coat of the protozoan, and each variant type is termed a variable antigen type (VAT). VAT expression sequences seem to be unpredictable, apparently giving the parasite an advantage and making it less vulnerable to antibody action. While VATs of the blood stream forms have a rich diversity, the metacyclic VATs are much less so and this has led to some hope for a vaccine to be developed against them. The trypanosome coat is composed of a large number of variant surface glycoproteins. These represent 15-20 percent of the total cell protein and more than 95 percent of the cell surface protein. The VSG is tied to the cell surface by a link to a GPI (glycosylphosphatinositol) anchor. An oligosaccharide from the GPI does elicit a moderate immune reaction, and is common to many VSGs. The VSGs of Trypanosoma brucei, T. evansi and T. equiperdum are very similar, but differ significantly from those of T. congolense and T. vivax. Concerning the first three species, the VSG polypeptide is usually between 420 and 460 amino acid residues long. The biochemical properties of the VSGs are summarized. The manner in which the elongated shape of the VSGs allow them to pack side by side and block access of host immunoglobulins to other cell surface proteins is explained with the help of both text and coloured plates. The underlying mechanism of VSG expression has yet to be fully resolved, although enough is known to say it is very complex. Each VSG is encoded by a gene or by parts of different genes. Genes may be left silent until activated. Genome research is currently throwing light on the repertoire of genes available for VSG production, but much remains to be clarified. Various mechanisms have been put forward for the precise regulation of gene action, and these have generated several research avenues that are described. Broadly speaking, a very precise ordering of trypanosome gene expression is conducted in such a manner that an unpredictable output of VSGs results, promoting the survival of the parasite against immune attack.
[See also 27: 12925, 12952]
12997 Acosta-Serrano, A., O’Rear, J., Quellhorst, G., Lee, S.H., Hwa, K.Y., Krag, S.S. & Englund, P.T., 2004. Defects in the N-linked oligosaccharide biosynthetic pathway in a Trypanosoma brucei glycosylation mutant. Eukaryotic Cell, 3 (2): 255-263.
Englund: Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21205, USA. [[email protected]]
12998 Alsford, S. & Horn, D., 2004. Trypanosomatid histones. Molecular Microbiology, 53 (2): 365-372.
Horn: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. [[email protected]]
12999 Aphasizhev, R., Aphasizheva, I. & Simpson, L., 2004. Multiple terminal uridylyltransferases of trypanosomes. FEBS Letters, 572 (1-3): 15-18.
Aphasizhev: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA. [[email protected]]
13000 Arhin, G.K., Shen, S.Y., Irmer, H., Ullu, E. & Tschudi, C., 2004. Role of a 300-kilodalton nuclear complex in the maturation of Trypanosoma brucei initiator methionyl-tRNA. Eukaryotic Cell, 3 (4): 893-899.
Tschudi: Life Science School, Fudan University, Shanghai, People’s Republic of China 200433. [[email protected]]
13001 Bakshi, R.P. & Shapiro, T.A., 2004. RNA interference of Trypanosoma brucei topoisomerase IB: both subunits are essential. Molecular and Biochemical Parasitology, 136 (2): 249-255.
Shapiro: Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
13002 Bhattacharya, G., Herman, J., Delfin, D., Salem, M.M., Barszcz, T., Mollet, M., Riccio, G., Brun, R. & Werbovetz, K.A., 2004. Synthesis and antitubulin activity of N1- and N4-substituted 3,5-dinitro sulfanilamides against African trypanosomes and Leishmania. Journal of Medicinal Chemistry, 47 (7): 1823-1832.
Werbovetz: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA. [[email protected]]
13003 Bhattacharyya, M.K., Norris, D.E. & Kumar, N., 2004. Molecular players of homologous recombination in protozoan parasites: implications for generating antigenic variation. Infection, Genetics and Evolution, 4 (2): 91-98.
Kumar: The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA. [[email protected]]
13004 Biebinger, S., Helfert, S., Steverding, D., Ansorge, I. & Clayton, C., 2003. Impaired dimerization and trafficking of ESAG6 lacking a glycosyl-phosphatidylinositol anchor. Molecular and Biochemical Parasitology, 132 (2): 93-96.
Clayton: Zentrum für Molekular Biologie der Universität Heidelberg, Im Nevenheimer Feld 282, 69120 Heidelberg, Germany. [[email protected]]
13005 Bouvier, L.A., Silber, A.M., Lopes, C.G., Canepa, G.E., Miranda, M.R., Tonelli, R.R., Colli, W., Alves, M.J.M. & Pereira, C.A., 2004. Post genomic analysis of permeases from the amino acid/auxin family in protozoan parasites. Biochemical and Biophysical Research Communications, 321 (3): 547-556.
Pereira: Laboratorio de Biologia Molecular de Trypanosoma cruzi, Instituto de Investigaciones Médicas Alfredo Lanari, Consejo Nacional de Investigaciones Cientificas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina. [[email protected]]
13006 Briggs, L.J., McKean, P.G., Baines, A., Moreira-Leite, F., Davidge, J., Vaughan, S. & Gull, K., 2004. The flagella connector of Trypanosoma brucei: an unusual mobile transmembrane junction. Journal of Cell Science, 117 (9): 1641-1651.
Gull: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. [[email protected]]
13007 Bringaud, F., Biteau, N., Zuiderwijk, E., Berriman, M., El-Sayed, N.M., Ghedin, E., Melville, S.E., Hall, N. & Baltz, T., 2004. The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei. Molecular Biology and Evolution, 21 (3): 520-528.
Bringaud: Laboratoire de Génomique Fonctionelle des Trypanosomatides, UMR-5162 CNRS, Université Victor Segalen Bordeaux II, Bordeaux, France. [[email protected]]
13008 Camargo, R.E., Uzcanga, G.L. & Bubis, J., 2004. Isolation of two antigens from Trypanosoma evansi that are partially responsible for its cross-reactivity with Trypanosoma vivax. Veterinary Parasitology, 123 (1-2): 67-81.
Bubis: Laboratorio de Química da Proteínas, Departamento de Biología Celular, División de Ciencias Biológicas, Universidad Simón Bolívar, Apartado 89.000, Valle de Sartenejas, Baruta, Caracas, 1081-A. Venezuela. [[email protected]]
13009 Clement, S.L., Mingler, M.K. & Koslowsky, D.J., 2004. An intragenic guide RNA location suggests a complex mechanism for mitochondrial gene expression in Trypanosoma brucei. Eukaryotic Cell, 3 (4): 862-869.
Koslowsky: 2209 Biomedical Physical Science Building, Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. [[email protected]]
13010 Chibale, K. & Musonda, C.C., 2003. The synthesis of parasitic cysteine protease and trypanothione reductase inhibitors. Current Medicinal Chemistry, 10 (18): 1863-1889.
Chibale: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
The presence of parasitic cysteine proteases and trypanothione reductase in the parasitic protozoa of the genera Trypanosoma and Leishmania has made these enzymes attractive targets for the development of antitrypanosomal and antileishmanial agents. Furthermore, the presence of cysteine proteases in Plasmodium falciparum has presented additional opportunities for the development of chemical scaffolds that could potentially be utilized against all of the aforementioned parasites. While previous reviews on parasitic cysteine proteases and trypanothione reductase covered various aspects, none emphasized the chemistry behind the synthesis of described inhibitors. This review focuses on recent developments in the synthesis of low-molecular weight inhibitors of these enzymes with a bearing on the human diseases of leishmaniasis, malaria and trypanosomiasis. Only those inhibitors whose synthesis has been described in the open literature during the period 1993-mid 2002 have been highlighted. The review thus excludes what may be in the patent literature.
13011 Comini, M. & Flohé, L., 2004. Mechanism of trypanothione biosynthesis and validation of trypanothione synthetase as drug target for African trypanosomes. Free Radical Biology and Medicine, 36 (Suppl.): S80.
Comini: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
13012 Cordeiro, A.T., Michels, P.A.M., Delboni, L.F. & Thiemann, O.H., 2004. The crystal structure of glucose-6-phosphate isomerase from Leishmania mexicana reveals novel active site features. European Journal of Biochemistry, 271 (13): 2765-2772.
Thiemann: Laboratory of Protein Crystallography and Structural Biology, Department of Physics and Informatics, Physics Institute of São Carlos, University of São Paulo, Avenue Trabalhador Sãocarlense 400, PO Box 369, 13566-590, São Carlos SP, Brazil. [[email protected]]
13013 Das, A. & Bellofatto, V., 2004. Genetic regulation of protein synthesis in trypanosomes. Current Molecular Medicine, 4 (6): 577-584.
Bellofatto: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07013, USA. [[email protected]]
13014 de Souza, W. & da Cunha-e-Silva, N.L., 2003. Cell fractionation of parasitic protozoa - A review. Memorias do Instituto Oswaldo Cruz, 98 (2): 151-170.
de Souza: Laboratório de Ultrastrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, BlocoG, Ilha do Fundão, 21941-900 Rio de Janeiro, RJ, Brazil. [[email protected]]
Cell fractionation, a methodological strategy for obtaining purified organelle preparations, has been applied successfully to parasitic protozoa by a number of investigators. Here we present and discuss the work of several groups that have obtained highly purified subcellular fractions from trypanosomatids, Apicomplexa and trichomonads, and whose work have added substantially to our knowledge of the cell biology of these parasites.
13015 Dhir, V. & Field, M.C., 2004. TbRAB23; a nuclear-associated Rab protein from Trypanosoma brucei. Molecular and Biochemical Parasitology, 136 (2): 297-301.
Field: Department of Biological Sciences, Imperial College London, London SW7 2AY, UK. [[email protected]]
13016 Dix, A.P., Borissow, C.N., Ferguson, M.A.J. & Brimacombe, J.S., 2004. The synthesis of some deoxygenated analogues of early intermediates in the biosynthesis of glycosylphosphatidylinositol (GPI) membrane anchors. Carbohydrate Research, 339 (7): 1263-1277.
Brimacombe: School of Life Sciences (Chemistry), Carnelly Building, University of Dundee, Dundee DD1 4HN, UK. [[email protected]]
13017 Dong, G., Chakshusmathi, G., Wolin, S.L. & Reinisch, K.M., 2004. Structure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch. EMBO Journal, 23 (5): 1000-1007.
Department of Cell Biology, Sterling Hall of Medicine, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8002, USA. [[email protected]]
13018 Duncan, R., 2004. DNA microarray analysis of protozoan parasite gene expression: outcomes correlate with mechanisms of regulation. Trends in Parasitology, 20 (5): 211-215.
Duncan: Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), 1401 Rockville Pk, Rockville, MD 20852, USA. [[email protected]]
DNA microarray analysis has been successfully applied to most of the protozoan parasites that cause human disease, but has not made equal progress in all cases. The results for kinetoplastid parasites (Leishmania and Trypanosoma) are primarily at the stage of validation and new gene discovery. By contrast, the results for apicomplexan parasites (Plasmodium and Toxoplasma) have advanced to the analysis of coordinate regulation of clusters of genes. This difference in progress relates to the more complete genome sequence identified for the apicomplexans and, more significantly, to the differences in the regulation of gene expression between these two groups.
13019 Duncan, R.C., Salotra, P., Goyal, N., Akopyants, N.S., Beverley, S.M. & Nakhasi, H.L., 2004. The application of gene expression microarray technology to kinetoplastid research. Current Molecular Medicine, 4 (6): 611-621.
Duncan: Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER, FDA, Bethesda, MD, USA. [[email protected]]
13020 Ellis, J., Sarkar, M., Hendriks, E. & Matthews, K., 2004. A novel ERK-like, CRK-like protein kinase that modulates growth in Trypanosoma brucei via an autoregulatory C-terminal extension. Molecular Microbiology, 53 (5): 1487-1499.
Matthews: School of Biological Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK. [[email protected]]
13021 Engstler, M., Thilo, L., Weise, F., Grünfelder, C.G., Schwarz, H., Boshart, M. & Overath, P., 2004. Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei. Journal of Cell Science, 117 (7): 1105-1115.
13022 Engstler, M., Thilo, L., Weise, F., Grunfelder, C.G., Schwarz, H., Boshart, M. & Overath, P., 2004. Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei. (vol 117, pg 1105, 2004) [Correction] Journal of Cell Science, 117 (16): 3703. [see 13021, above]Overath: Ludwigs-Maximilians-Universität, Department Biologie I, Bereich Genetik, Maria-Ward-Strasse 1a, D-80638 München, Germany. [[email protected]]
Overath: Ludwigs-Maximilians-Universität, Department Biologie I, Bereich Genetik, Maria-Ward-Strasse 1a, D-80638 München, Germany. [[email protected]]
13023 Ersfeld, K., 2003. Genomes and genome projects of protozoan parasites. Current Issues in Molecular Biology, 5 (3): 61-74.
Ersfeld: School of Biological Sciences, 2.205 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Protozoan parasites are causing some of the most devastating diseases world-wide. It has now been recognised that a major effort is needed to be able to control or eliminate these diseases. Genome projects for the most important protozoan parasites have been initiated in the hope that the read-out of these projects will help to understand the biology of the parasites and identify new targets for urgently needed drugs. Here, the current status of protozoan parasite genome projects, the present findings obtained as a result of the availability of genomic data and the potential impact of genome information on disease control, are reviewed and discussed.
13024 Esseiva, A.C., Maréchal-Drouard, L., Cosset, A. & Schneider, A., 2004. The T-Stem determines the cytosolic or mitochondrial localization of trypanosomal tRNAsMet. Molecular Biology of the Cell, 15 (6): 2750-2757.
Schneider: Department of Biology/Zoology, University of Fribourg, CH-1700 Fribourg, Switzerland. [[email protected]]
13025 Flohé, L., 2004. The trypanothione system. Free Radical Biology and Medicine, 36 (Suppl.): S14.
Flohé: MOLISA GmbH, UniversitätsplatzZ, D-39106 Magdeburg, Germany.
13026 Franck, X., Fournet, A., Prina, E., Mahieux, R., Hocquemiller, R. & Figadère, B., 2004. Biological evaluation of substituted quinolines. Bioorganic and Medicinal Chemistry Letters, 14 (14): 3635-3638.
Figadère: Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université de Paris-Sud, rue J.B. Clément, 92296 Châtenay-Malabry, France. [[email protected]]
13028 Gadelha, C., LeBowitz, J.H., Manning, J., Seebeck, T. & Gull, K., 2004. Relationships between the major kinetoplastid paraflagellar rod proteins: a consolidating nomenclature. Molecular and Biochemical Parasitology, 136 (1): 113-115.
Gull: Sir Willian Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. [[email protected]]
Proposals are made for a nomenclature for major kinetoplast paraflagellar rod (PFR) proteins so as to avoid confusing or misleading annotation.
13029 Garcia-Salcedo, J.A., Perez-Morga, D., Gijon, P., Dilbeck, V., Pays, E. & Nolan, D.P., 2004. A differential role for actin during the life cycle of Trypanosoma brucei. EMBO Journal, 23 (4): 780-789.
Garcia-Salcedo: Laboratory of Molecular Parasitology, ULB-Institute of Molecular Biology and Medicine, Gosselies, Belgium. [[email protected]]
13030 Ghedin, E., Bringaud, F., Peterson, J., Myler, P., Berriman, M., Ivens, A., Andersson, B., Bontempi, E., Eisen, J., Angiuoli, S., Wanless, D., Von Arx, A., Murphy, L., Lennard, N., Salzberg, S., Adams, M.D., White, O., Hall, N., Stuart, K., Fraser, C.M. & El-Sayed, N.M.A., 2004. Gene synteny and evolution of genome architecture in trypanosomatids. Molecular and Biochemical Parasitology, 134 (2): 183-191.
El-Sayed: Parasite Genomics, The Institute for Genomic Research, 9712 Medical Center Dr., Rockville, MD 20850, USA. [[email protected]]
The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.
13031 Hammarton, T.C., Engstler, M. & Mottram, J.C., 2004. The Trypanosoma brucei cyclin, CYC2, is required for cell cycle progression through G(1) phase and for maintenance of procyclic form cell morphology. Journal of Biological Chemistry, 279 (23): 24757-24764.
Mottram: Wellcome Centre for Molecular Parasitology, the Anderson College, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK. [[email protected]]
13032 He, C.Y., Ho, H.H., Malsam, J., Chalouni, C., West, C.M., Ullu, E., Toomre, D. & Warren, G., 2004. Golgi duplication in Trypanosoma brucei. Journal of Cell Biology, 165 (3): 313-321.
Warren: Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar St., PO Box 208002, New Haven, CT 06520-8002, USA. [[email protected]]
13033 Hitchcock, R.A., Zeiner, G.M., Sturm, N.R. & Campbell, D.A., 2004. The 3´ termini of small RNAs in Trypanosoma brucei. FEMS Microbiology Letters, 236 (1): 73-78.
Sturm: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, 4825 Molecular Sciences Building, 609 Charles E. Young Drive, Los Angeles, CA 90095-1489, USA. [[email protected]]
13034 Horn, D., 2004. The molecular control of antigenic variation in Trypanosoma brucei. Current Molecular Medicine, 4 (6): 563-576.
Horn: Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. [[email protected]]
13035 Hung, C.H., Qiao, X.G., Lee, P.T. & Lee, M.G.S., 2004. Clathrin-dependent targeting of receptors to the flagellar pocket of procyclic-form Trypanosoma brucei. Eukaryotic Cell, 3 (4): 1004-1014.
Lee: Department of Pathology, New York University School of Medicine, 550First Avenue, New Yrk, NY 10016, USA. [[email protected]]
13036 Irsch, T., & Krauth-Siegel, R.L., 2004. Glyoxalase II of African trypanosomes is trypanothione-dependent. Journal of Biological Chemistry, 279 (21): 22209-22217.
Kraut-Siegel: Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany. [[email protected]]
13037 Ismail, M.A., Brun, R., Easterbrook, J.D., Tanious, F.A., Wilson, W.D. & Boykin, D.W., 2003. Synthesis and antiprotozoal activity of aza-analogues of furamidine. Journal of Medicinal Chemistry, 46 (22): 4761-4769.
Boykin: Department of Chemistry, Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303-3083, USA. [see also http://pubs.acs.org]
13038 Jiang, D.W., Werbovetz, K.A., Varadhachary, A., Cole, R.N. & Englund, P.T., 2004. Purification and identification of a fatty acyl-CoA synthetase from Trypanosoma brucei. Molecular and Biochemical Parasitology, 135 (1): 149-152.
Englund: Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21205, USA. [[email protected]]
13039 Kitani, H., Yagi, Y., Naessens, J., Sekikawa, K. & Iraqi, F., 2004. The secretion of acute phase proteins and inflammatory cytokines during Trypanosoma congolense infection is not affected by the absence of the TNF-a gene. Acta Tropica, 92 (1): 35-42
Naessens: International Livestock Research Institute, Genetic Resistance to Disease, POB 30709, Nairobi, Kenya. [[email protected]]
13040 Krauth-Siegel, R.L. & Schmidt, H. 2002. Trypanothione and tryparedoxin in ribonucleotide reduction. [T. brucei] Methods in Enzymology, 347, Protein Sensors and Reactive Oxygen Species. Part A. Selenoproteins and Thioredoxin: 259-266.
Kraut-Siegel: Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany. [[email protected]]
13041 Kubata, B.K., Duszenko, M., Kabututu, Z., Rawer, M., Szallies, A., Inui, T. Urade, Y. & Hayaishi, O., 2002. Enzymatic formation of prostaglandin D2, E2, and F2a in the parasitic protozoan Trypanosoma brucei. Oxygen and Life: Oxygenases, Oxidase and Lipid Mediators. 2002. p. 461-466. Elsevier Science BV, Amsterdam.
Kubata: Department of Molecular Behavioural Biology, Osaka Bioscience Institute, Furuedai, Suita, Osaka 565-0874, Japan. [[email protected]]
13042 Landfear, S.M., Ullman, B., Carter, N.S. & Sanchez, M.A., 2004. Nucleoside and nucleobase transporters in parasitic protozoa. Eukaryotic Cell, 3 (2): 245-254.
Landfear: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road., Portland, OR 97239-3098, USA. [[email protected]]
13043 Leal, S., Acosta-Serrano, A., Morris, J. & Cross, G.A.M., 2004. Transposon mutagenesis of Trypanosoma brucei identifies glycosylation mutants resistant to concanavalin A. Journal of Biological Chemistry, 279 (28): 28979-28988.
Cross: Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA. [[email protected]]
13044 Lepesheva, G., Nes, D., Zhou, W.X., George, H. & Waterman, M., 2004. Substrate preference of CYP51 from Trypanosoma brucei may reflect specificity of sterol biosynthesis in Kinetoplastida. FASEB Journal, 18 (8 Suppl.): C178.
Lepesheva: Department of Biochemistry, Vanderbilt University School of Medicine, 622 Robinson Research Building, 23rd and Pierce Avenues, Nashville, TN 37232-0146, USA.
13045 Lepesheva, G.I., Nes, W.D., Zhou, W.X., Hill, G.C. & Waterman, M.R., 2004. CYP51 from Trypanosoma brucei is obtusifoliol-specific. Biochemistry, 43 (33): 10789-10799.
Lepesheva: Department of Biochemistry, Vanderbilt University School of Medicine, 622 Robinson Research Building, 23rd and Pierce Avenues, Nashville, TN 37232-0146, USA.
13046 Liu Qing, Liang XueHai, Uliel, S., Belahcen, M., Unger, R. & Michaeli, S., 2004. Identification and functional characterization of Lsm proteins in Trypanosoma brucei. Journal of Biological Chemistry, 279 (18): 18210-18219.
Michaeli: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel. [[email protected]]
13047 Lun, Z.-R., Li, A.-X., Chen, X.-G., Lu, L.-X. & Zhu, X.-Q., 2004. Molecular profiles of Trypanosoma brucei, T. evansi and T. equiperdum stocks revealed by the random amplified polymorphic DNA method. Parasitology Research, 92 (4): 335-340.
Lun: Center for Parasitic Organisms, School of Life Sciences, Zhongshan University, Guangzhou 510275, People’s Republic of China. [[email protected]]
13048 Luo, S.H., Rohloff, P., Cox, J., Uyemura, S.A. & Docampo, R., 2004. Trypanosoma brucei plasma membrane-type Ca2+-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca2+-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca2+ homeostasis and growth. Journal of Biological Chemistry, 279 (14): 14427-14439.
Docampo: Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana IL 61802, USA. [[email protected]]
13049 Masocha, W., Robertson, B., Rottenberg, M.E., Mhlanga, J., Sorokin, L. & Kristensson, K., 2004. Cerebral vessel laminins and IFN-g define Trypanosoma brucei brucei penetration of the blood-brain barrier. Journal of Clinical Investigation, 114 (5): 689-694.
Kristensson: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-17177 Stockholm, Sweden. [[email protected]]
13050 McCulloch, R., 2004. Antigenic variation in African trypanosomes: monitoring progress. Trends in Parasitology, 20 (3): 117-121.
McCulloch: Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, G11 6NU, UK. [[email protected]]
Antigenic variation is central to the success of African trypanosomes and other eukaryotic, bacterial and viral pathogens. Our understanding of the control and execution of this immune evasion strategy in trypanosomes is incomplete, despite the molecular basis of antigenic variation being first described over twenty years ago. Recent research progress in this field is highlighted and some unresolved questions raised.
13051 McKean, P.G., Baines, A., Vaughan, S. & Gull, K., 2003. g-Tubulin functions in the nucleation of a discrete subset of microtubules in the eukaryotic flagellum. Current Biology, 13 (7): 598-602.
Gull: Department of Biological Sciences, Lancaster University, Lancaster, Lancashire LA1 4YQ, UK. [[email protected]]
13052 Melville, S.E., Majiwa, P.A.O. & Tait A., 2004. The African trypanosome genome. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 39-57.
Melville: Department of Pathology, Division of Microbiology and Parasitology, University of Cambridge, Cambridge, UK.
There is a genome within the nucleus of African trypanosomes, and another in the kinetoplast. Genomics is regarded as an enabling technology which should generate meaningful research and advances in diagnostic tools and new drug targets. Funding is available to finish the sequencing of the Trypanosoma brucei genome to a high degree of accuracy. The broad aim is to describe all the genes in one particular cloned stock of T. brucei, in terms of structure, DNA sequence and organization along the chromosomes. Using new methods of separation, three classes of chromosomes have been defined: large megabase chromosomes, intermediate chromosomes and mini-chromosomes. Most of the nuclear genome is made up of megabase chromosomes, and include housekeeping genes dealing with the basic activities of the cell. The mini-chromosomes may be for storing unexpressed variable surface glycoprotein (VSG) genes. The intermediate chromosomes may number one to five, depending on the stock; further genomic information will throw light in the functions of this group. The karyotype of megabase chromosomes is essentially diploid, but at least some VSG genes are haploid. Some size polymorphism is found in homologous chromosomes; despite this, faithful segregation of chromosomes at mitosis and crossing over can take place. Closer study of specific genes has proceeded well before the full elucidation of the genome. Trypanosoma brucei is expected to show evidence for some 8000 unique nuclear transcripts; to date over 3000 have been identified. Approximately 48 percent of ESTs (expressed sequence tags) clearly correspond to known proteins recorded from other organisms and the function of these is often understood. The remaining 52 percent have no such homologues. Discovering genes may be assisted by the random sequencing of short fragments of genomic DNA, creating genome survey sequences: this method can give a rapid means of identifying genes or even parts of genes that are homologous with genes already described for other organisms. The kinetoplast genome and progress in understanding its peculiar organization and replication are described. The likely benefits accruing from detailed knowledge of the full genome are discussed. Completion of work on T. brucei will greatly assist the study of other Trypanosoma genomes such as the animal infective species T. congolense and T. vivax, as well as T. b. gambiense, although these will not be carried through to the same degree of completeness. A guide to the relevant gene databases is given.
13053 Morgan, G.W., Goulding, D. & Field, M.C., 2004. The single dynamin-like protein of Trypanosoma brucei regulates mitochondrial division and is not required for endocytosis. Journal of Biological Chemistry, 279 (11): 10692-10701.
Field: Wellcome Trust Laboratories for Molecular Parasitology, Department of Biological Sciences, Imperial College, Exhibition Road, London SW7 2AY, UK. [[email protected]]
13054 Motyka, S.A. & Englund, P.T., 2004. RNA interference for analysis of gene function in trypanosomatids. Current Opinion in Microbiology, 7 (4): 362-368.
Englund: Department of Biological Chemistry, John Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA. [[email protected]]
13055 Navid, A. & Ortoleva, P.J., 2004. Simulated complex dynamics of glycolysis in the protozoan parasite Trypanosoma brucei. Journal of Theoretical Biology, 228 (4): 449-458.
Ortoleva: Department of Chemistry, College of Arts and Science, Chemistry Building, Indiana University, Bloomington, IN 47405-4001, USA. [[email protected]]
13056 Ndao, M., Magnus, E., Büscher, P. & Geerts, S., 2004. Trypanosoma vivax: a simplified protocol for in vivo growth, isolation and cryopreservation. Parasite, 11 (1): 103-106.
Ndao: National Reference Centre for Parasitology, Montreal General Hospital Research Institute, R3-107, 1625 Pine Avenue West, Montreal, QC, H3G 1A4, Canada. [[email protected]]
13057 Nguewa, P.A., Fuertes, M.A., Valladares, B., Alonso, C. & Pérez, J.M., 2004. Programmed cell death in trypanosomatids: a way to maximize their biological fitness? Trends in Parasitology, 20 (8): 375-380.
Pérez: Departamento de Parasitologia, Facultad de Farmacia, Universidad de la Laguna, 38071, La Laguna, Tenerife, Spain. [[email protected]]
Programmed cell death (PCD) is a biochemical process that plays an essential role in the development of multicellular organisms. However, accumulating evidence indicates that PCD is also present in single-celled eukaryotes. Thus, trypanosomatids might be endowed with a PCD mechanism that is derived from ancestral death machinery. PCD in trypanosomatids could be a process without a defined function, inherited through eukaryotic cell evolution, which might be triggered in response to diverse stimuli and stress conditions. However, recent observations suggest that PCD might be used by trypanosomatids to maximize their biological fitness. Therefore, PCD could represent a potential pharmacological target for protozoan control.
13058 Nishimura, K., Hamashita, K., Okamoto, Y., Kawahara, F., Ihara, H., Kozaki, S., Ohnishi, Y. & Yamasaki, S., 2004. Differential effects of interferon-g on production of trypanosome-derived lymphocyte-triggering factor by Trypanosoma brucei gambiense and Trypanosoma brucei brucei. Journal of Parasitology, 90 (4): 740-745.
Nishimura: Division of Veterinary Science, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, 1-1, Gakuencho, Sakai, Osaka 599-8531, Japan. [[email protected]]
13059 Nolan, D.P., Garcia-Salcedo, J.A., Vanhamme, L. & Pays, E., 2004. Communication in trypanosomatids. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 59-75.
Nolan: Department of Biochemistry, Trinity College, Dublin 2, Ireland.
The parasitic trypanosomatids have to respond to major changes in their environment during the life cycle. Survival and appropriate response depends on efficient sensing mechanisms and signalling pathways. The present review covers interactions with host components involving macromolecules and surface receptors, with emphasis on the transferrin receptor, receptors for lipoproteins, receptors for serum trypanolytic factors, and receptors involved in sensing host growth factors and cytokines. The peculiar micro-environment of the flagellar pocket in which there is a very high turnover rate of membrane is described. The proteins, pathways and molecules involved in communication are discussed, covering especially adenylate cyclases, current ideas on signal transduction pathways, and the glycosylphosphoinositol-specific phospholipase C. Further descriptions cover acylation-dependent membrane targeting, GPI anchors as signalling molecules, and the role of Ca2+. Virulence factors affecting host-parasite interactions are discussed. Control of the cell cycle and differentiation are seen from the standpoint of reprogramming of gene expression, and the inverse relation between growth and the efficiency of differentiation. A detailed chart explaining current ideas on the control of gene expression in T. brucei is presented. The outlook for the future in these studies is reviewed.
13060 Nyarko, E., Hara, T., Grab, D.J., Habib, A., Kim, Y., Nikolskaia, O., Fukuma, T. & Tabata, M., 2004. In vitro toxicity of palladium(II) and gold(III) porphyrins and their aqueous metal ion counterparts on Trypanosoma brucei brucei growth. Chemico-Biological Interactions, 148 (1-2): 19-25.
Fukuma: Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
13061 Overath, P. & Engstler, M., 2004. Endocytosis, membrane recycling and sorting of GPI-anchored proteins: Trypanosoma brucei as a model system. Molecular Microbiology, 53 (3): 735-744.
Engstler: Universität Tübingen, Interfakultäres Institut für Zellbiologie, Abtailung Immunologie, Auf der Morgenstelle 15, D-72076 Tübingen, Germany. [[email protected]]
13062 Parsons, M., 2004. Glycosomes: parasites and the divergence of peroxisomal purpose. Molecular Microbiology, 53 (3): 717-724.
Parsons: Seattle Biomedical Research Institute, 307 Westlake, Seattle, WA, 98109, USA. [[email protected]]
Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome.
13063 Paul, K.S., Bacchi, C.J. & Englund, P.T., 2004. Multiple triclosan targets in Trypanosoma brucei. Eukaryotic Cell, 3 (4): 855-861.
Englund: Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA. [[email protected]]
13064 Pays, E., Vanhamme, L. & Pérez-Morga, D., 2004. Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries. Current Opinion in Microbiology, 7 (4): 369-374.
Pays: Laboratory of Molecular Parasitology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B6041 Gosselies, Belgium. [[email protected]]
13065 Podlipaev, S.A., Sturm, N.R., Fiala, I., Fernanades, O., Westenberger, S.J., Dollet, M., Campbell, D.A. & Lukeš, J., 2004. Diversity of insect trypanosomatids assessed from the spliced leader RNA and 5S rRNA genes and intergenic regions. Journal of Eukaryotic Microbiology, 51 (3): 283-290.
Lukeš: Institute of Parasitology, Czech Academy of Sciences, Ceské Budejovice, Czech Republic. [[email protected]]
13066 Pullen, T.J., Ginger, M.L., Gaskell, S.J. & Gull, K., 2004. Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a eukaryotic flagellum. Molecular Biology of the Cell, 15 (7): 3257-3265.
Gull: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. [[email protected]]
13067 Sanchez, M.A., Drutman, S., van Ampting, M., Matthews, K. & Landfear, S.M., 2004. A novel purine nucleoside transporter whose expression is up-regulated in the short stumpy form of the Trypanosoma brucei life cycle. Molecular and Biochemical Parasitology, 136 (2): 265-272.
Sanchez: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L 220, Portland, OR 97239, USA. [[email protected]]
13068 Saravanamuthu, A., Vickers, T.J., Bond, C.S., Peterson, M.R., Hunter, W.N. & Fairlamb, A.H., 2004. Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase - A template for drug design. Journal of Biological Chemistry, 279 (28): 29493-29500.
Fairlamb: Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
13069 Seebeck, T., Schaub, R. & Johner, A., 2004. cAMP signalling in the kinetoplastid protozoa. Current Molecular Medicine, 4 (6): 585-599.
Seebeck: Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland. [[email protected]]
13070 Sheader, K., te Vruchte, D. & Rudenko, G., 2004. Bloodstream form-specific up-regulation of silent VSG expression sites and procyclin in Trypanosoma brucei after inhibition of DNA synthesis or DNA damage. Journal of Biological Chemistry, 279 (14): 13363-13374.
Rudenko: The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. [[email protected]]
13071 Shlomai, J., 2004. The structure and replication of kinetoplast DNA. Current Molecular Medicine, 4 (6): 623-647.
Shlomai: Department of Parasitology, The Kuvin Center for the Study of Infectious and Tropical Diseases, Hebrew University Jerusalem - Hadassah Medical Scool, Jerusalem 91120, Israel. [[email protected]]
13072 Stevens J.R. & Brisse S., 2004. Systematics of trypanosomes of medical and veterinary importance. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 1-23.
Stevens: Hatherley Laboratories, Department of Biological Sciences, University of Exeter, Exeter, UK.
The chapter focusses on new evidence, in part derived from molecular biology, bearing on the systematic position and evolutionary relationships of the trypanosomes of medical and veterinary importance. A phylogenetic tree based on 18S SSU ribosomal RNA gene sequences covering these forms is presented. Each subgenus is treated in respect of species content, morphology, host range, pathogenicity, and biochemical and molecular characterization. A review of contemporary taxonomy concludes that the species content of the subgenus Schizotrypanum has been the most altered by the impact of recent phylogenetic studies and deserves yet closer attention with a view to possible subdivision later. The intraspecific taxonomy of Trypanosoma congolense also requires further study.
13073 Suzuki, T., Nihei, C.I., Yabu, Y., Hashimoto, T., Suzuki, M., Yoshida, A., Nagai, K., Hosokawa, T., Minagawa, N., Suzuki, S., Kita, K. & Ohta, N., 2004. Molecular cloning and characterization of Trypanosoma vivax alternative oxidase (AOX) gene, a target of the trypanocide ascofuranone. Parasitology International, 53 (3): 235-245.
Suzuki: Department of Molecular Parasitology, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601, Japan. [[email protected]]
13074 Trujillo, M., Budde, H., Piñeyro, M.D., Stehr, M., Robello, C., Flohé, L. & Radi, R., 2004. Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxynitrite via oxidation of fast reacting thiols. Journal of Biological Chemistry, 279 (33): 34175-34182.
Radi: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Avda. Gral. Flores 2125, 11800 Montevideo, Uruguay. [[email protected]]
13075 Tu, X.M. & Wang, C.C., 2004. The involvement of two cdc2-related kinases (CRKs) in Trypanosoma brucei cell cycle regulation and the distinctive stage-specific phenotypes caused by CRK3 depletion. Journal of Biological Chemistry, 279 (19): 20519-20528.
Wang: Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-2280, USA. [[email protected]]
13076 Uemura, A., Watarai, S., Kushi, Y., Kasama, T., Ohnishi, Y. & Kodama, H., 2004. Isolation and characterization of gangliosides from Trypanosoma brucei. Journal of Parasitology, 90 (1): 123-127.
Watarai: Laboratory of Veterinary Immunology, Division of Veterinary Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan. [[email protected]]
13077 Uliel, S., Liang, X.H., Unger, R. & Michaeli, S., 2004. Small nucleolar RNAs that guide modification in trypanosomatids: repertoire, targets, genome organisation, and unique functions. International Journal for Parasitology, 34 (4): 445-454.
Michaeli: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel. [[email protected]]
13078 Ullu, E., Tschudi, C. & Chakraborty, T., 2004. RNA interference in protozoan parasites. Cellular Microbiology, 6 (6): 509-519.
Ullu: Department of Internal Medicine, Yale Medical School, BCMM 136D, 295 Congress Avenue, Box 9812, New Haven, CT 06536-8012, USA. [[email protected]]
13079 Uzcanga, G.L., Perrone, T., Noda, J.A., Pérez-Pazos, J., Medina, R., Hoebeke, J. & Bubis, J., 2004. Variant surface glycoprotein from Trypanosoma evansi is partially responsible for the cross-reaction between Trypanosoma evansi and Trypanosoma vivax. Biochemistry, 43 (3): 595-606.
Bubis: Departamento de Biología Celular, Universidad Simón Bolívar, Caracas, Venezuela. [[email protected]]
13080 Vassella, E., Probst, M., Schneider, A., Studer, E., Renggli, C.K. & Roditi, I., 2004. Expression of a major surface protein of Trypanosoma brucei insect forms is controlled by the activity of mitochondrial enzymes. Molecular Biology of the Cell, 15 (9): 3986-3993.
Vassella: Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland. [[email protected]]
13081 Vaughan, S. & Gull, K., 2003. The trypanosome flagellum. Journal of Cell Science, 116 (5): 757-759.
Gull: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. [[email protected]]
Stages in the duplication of the trypanosome flagellum are described: these are the preliminaries to full cell division. The flagellum is seen as a contributor to pathogenesis in the host, to motility of the cell and its surface molecules, to recognition of the environment, and to the attachment of the parasite at critical stages of the life cycle. The trypanosome is presented as an ideal model organism for the study of eukaryotic flagella and cilia in general.
13082 Versées, W., Loverix, S., Vandemeulebroucke, A., Geerlings, P. & Steyaert, J., 2004. Leaving group activation by aromatic stacking: an alternative to general acid catalysis. Journal of Molecular Biology, 338 (1): 1-6.
Versées: Laboratorium voor Ultrastructuur, Instituut voor Moleculaire Biologie, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. [[email protected]]
13083 Vickers, T.J. & Fairlamb, A.H., 2004. Trypanothione S-transferase activity in a trypanosomatid ribosomal elongation factor 1B. Journal of Biological Chemistry, 279 (26): 27246-27256.
Fairlamb: Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. [[email protected]]
13084 Werbovetz, K.A., Sackett, D.L., Delfín, D., Bhattacharya, G., Salem, M., Obrzut, T., Rattendi, D. & Bacchi, C., 2003. Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide (GB-II-5) against kinetoplastid parasites. Molecular Pharmacology, 64 (6): 1325-1333.
Werbovetz: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA.
[mailto: [email protected]]
13085 Wickstead, B., Ersfeld, K. & Gull, K., 2004. The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes. Genome Research, 14 (6): 1014-1024.
Gull: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. [[email protected]]
13086 Zeiner, G. M., Foldynová, S., Sturm, N.R., Lukeš, J. & Campbell, D.A., 2004. SmD1 is required for spliced leader RNA biogenesis. Eukaryotic Cell, 3 (1): 241-244.
Campbell: Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, 609 Charles E. Young Drive East, Los Angeles, CA 90095-1489, USA. [[email protected]]
