Elevated serum and hepatic tyrosine aminotransferase in voles chronically infected with Trypanosoma brucei gambiense.

Chronic infections of voles (Microtus montanus) with Trypanosoma brucei gambiense result in marked elevations in both serum and hepatic tyrosine aminotransferase. Serum enzyme levels correlate poorly with hepatic levels but well with parasitemia. Because the trypanosome itself contains high levels of this same enzyme, it is hypothesized that lysis of extravascular parasites, possibly due to agglutination by variant-specific antibody, releases parasite enzymes into host tissues, resulting in the observed increase in serum enzyme levels. The possible role of increased tyrosine transamination in the behavioral syndrome of trypanosome-infected voles is considered.     

Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing

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Control techniques for Culicoides biting midges and their application in the U.K. and northwestern Palaearctic

The recent emergence of bluetongue virus (Reoviridae: Orbivirus) (BTV) in northern Europe, for the first time in recorded history, has led to an urgent need for methods to control the disease caused by this virus and the midges that spread it. This paper reviews various methods of vector control that have been employed elsewhere and assesses their likely efficacy for controlling vectors of BTV in northern Europe. Methods of controlling Culicoides spp. (Diptera: Ceratopogonidae) have included: (a) application of insecticides and pathogens to habitats where larvae develop; (b) environmental interventions to remove larval breeding sites; (c) controlling adult midges by treating either resting sites, such as animal housing, or host animals with insecticides; (d) housing livestock in screened buildings, and (e) using repellents or host kairomones to lure and kill adult midges. The major vectors of BTV in northern Europe are species from the Culicoides obsoletus (Meigen) and Culicoides pulicaris (L.) groups, for which there are scant data on breeding habits, resting behaviour and host-oriented responses. Consequently, there is little information on which to base a rational strategy for controlling midges or for predicting the likely impact of interventions. However, data extrapolated from the results of vector control operations conducted elsewhere, combined with some assessment of how acceptable or not different methods may be within northern Europe, indicate that the treatment of livestock and animal housing with pyrethroids, the use of midge-proofed stabling for viraemic or high-value animals and the promotion of good farm practice to at least partially eliminate local breeding sites are the best options currently available. Research to assess and improve the efficacy of these methods is required and, in the longer term, efforts should be made to develop better bait systems for monitoring and, possibly, controlling midges. All these studies will need better methods of analysing the ecology and behaviour of midges in the field than are currently in use. The paucity of control options and basic knowledge serve to warn us that we must be better prepared for the possible emergence of other midge-borne diseases, particularly African horse sickness.     

Reduction in Brain Glucose Utilization Rate after Tryptophol (3-Indole Ethanol) Treatment

Abstract: 3-Indole ethanol has been recently identified as the hypnotic agent in trypanosomal sleeping sickness, and because it is formed in vivo after ethanol or disulfiram treatment, it is also associated with the study of alcoholism. When administered intraperitoneally to rats (250 mg/kg) tryptophol induced a sleep-like state that lasted less than an hour (no righting reflex was apparent 2 min after injection, but it returned at 11 min in bovine serum albumin solution, and 47 min in 40% ethanol solution). In ethanol solutions, tryptophol reduced brain cortical glucose utilization by 55% to the basal brain metabolic rate, and this effect lasted less than 1 h. Synergistic effects of tryptophol and ethanol were suggested by the observation that in albumin solution, tryptophol reduced brain glucose utilization by 35%, but a normal rate was not observed until 2 h postinjection.     

Vector competence of Glossina palpalis gambiensis for Trypanosoma brucei s.l. and genetic diversity of the symbiont Sodalis glossinidius

Tsetse flies transmit African trypanosomes, responsible for sleeping sickness in humans and nagana in animals. This disease affects many people with considerable impact on public health and economy in sub-Saharan Africa, whereas trypanosomes' resistance to drugs is rising. The symbiont Sodalis glossinidius is considered to play a role in the ability of the fly to acquire trypanosomes. Different species of Glossina were shown to harbor genetically distinct populations of S. glossinidius. We therefore investigated whether vector competence for a given trypanosome species could be linked to the presence of specific genotypes of S. glossinidius. Glossina palpalis gambiensis individuals were fed on blood infected either with Trypanosoma brucei gambiense or Trypanosoma brucei brucei. The genetic diversity of S. glossinidius strains isolated from infected and noninfected dissected flies was investigated using amplified fragment length polymorphism markers. Correspondence between occurrence of these markers and parasite establishment was analyzed using multivariate analysis. Sodalis glossinidius strains isolated from T. brucei gambiense-infected flies clustered differently than that isolated from T. brucei brucei-infected individuals. The ability of T. brucei gambiense and T. brucei brucei to establish in G. palpalis gambiensis insect midgut is statistically linked to the presence of specific genotypes of S. glossinidius. This could explain variations in Glossina vector competence in the wild. Then, assessment of the prevalence of specific S. glossinidius genotypes could lead to novel risk management strategies.     

低氧低二氧化碳对大鼠脑血流的调节作用

低氧下脑血流与急性高原病有关,许多研究已证明,低氧不适应者的ＣＢＦ明显高于低氧适应者,而高原世居者则低于海平正常值。低氧下低动脉血二氧化碳分压有对抗低氧扩血管及降低ＣＢＦ的作用。因此研究低氧下低ＰａＣＯ２对ＣＢＦ的调节作用对于研究急性高原病的防治及其机理分析具有重要意义。本项研究目的：（１）揭示低氧下低ＰａＣＯ２与ＣＢＦ之间的关系;（２）通过增加通气量使ＰａＣＯ２下降至合适水平,以保护脑血流维持在     

Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas’ disease, and leishmaniasis

Summary. Trypanosomatids depend on spermidine for growth and survival. Consequently, enzymes involved in spermidine synthesis and utilization, i.e. arginase, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC), spermidine synthase, trypanothione synthetase (TryS), and trypanothione reductase (TryR), are promising targets for drug development. The ODC inhibitor α-difluoromethylornithine (DFMO) is about to become a first-line drug against human late-stage gambiense sleeping sickness. Another ODC inhibitor, 3-aminooxy-1-aminopropane (APA), is considerably more effective than DFMO against Leishmania promastigotes and amastigotes multiplying in macrophages. AdoMetDC inhibitors can cure animals infected with isolates from patients with rhodesiense sleeping sickness and leishmaniasis, but have not been tested on humans. The antiparasitic effects of inhibitors of polyamine and trypanothione formation, reviewed here, emphasize the relevance of these enzymes as drug targets. By taking advantage of the differences in enzyme structure between parasite and host, it should be possible to design new drugs that can selectively kill the parasites.     

IL-10 is up regulated in early and transitional stages in vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense

IL-10 has been suggested as a possible parameter for human African trypanosomiasis stage determination. However, conclusive experimental studies have not been carried out to evaluate this, which is a prerequisite before a potential test can be validated in humans for diagnostic purposes. We used the vervet monkey model of trypanosomiasis to scrutinize IL-10 in blood and cerebrospinal fluid (CSF). Five adult males were experimentally infected with T. b. rhodesiense. The infected animals became anemic and exhibited weight loss. Parasitemia was patent after 3 days and fluctuated around 3.7 × 10⁷ trypanosomes/ml throughout the experimental period. The total CSF white cell counts increased from pre-infection means around 3 cells/μl to a peak of 30 cells/μl, 42 days post-infection (DPI). IL-10 was not detectable (< 2 pg/ml) in serum prior to infection. IL-10 serum concentrations increased to 273 pg/ml 10 DPI coinciding with the first peak of parasitemia. Thereafter the levels declined to a mean value of 77 pg/ml 34 DPI followed by a significant rise to a second peak of 304 pg/ml (p < 0.008) 42 DPI. There was no detectable IL-10 in CSF. IL-10 synthesis is thus stimulated both in the early and transitional stages of experimental trypanosomiasis. That IL-10 is produced in early stage disease is an interesting finding unlikely to be detected in humans where it is difficult to determine the exact time of infection. The IL-10 peak observed on day 42 of infection might indicate onset of parasite neuroinvasion coinciding with a peak in white blood cell counts in the blood and CSF.     

Autotoxic potential of cucurbit crops

Soil sickness is often observed in cucurbit crops such as Citrullus lanatus, Cucumis melo and Cucumis sativus, but not in cucurbit crops such as Cucurbita moschata, Lagenaria leucantha and Luffa cylindrica. Results showed that root aqueous extracts of Citrullus lanatus, Cucumis melo and Cucumis sativus were autotoxic, but those of Cucurbita moschata, Momordica charantia and Luffa cylindrica were less autotoxic to the radicle elongation of respective species. Plant growth of Citrullus lanatus, Cucumis melo and Cucumis sativus were greatly inhibited by autotoxic substances released from powered root tissue at a rate of 1 g per seedling. Root exudates of Citrullus lanatus, Cucumis melo and Cucumis sativus were autotoxic to radicle elongation and seedling growth of respective species. However, root exudates of Citrullus lanatus did not inhibit radicle elongation of Cucurbita ficifolia, which is commonly used as rootstock for the grafting of Citrullus lanatus, Cucumis melo and Cucumis sativus to decrease soil-borne diseases in commercial production. It seems possible to overcome autotoxicity in cucurbit crops by grafting on Cucurbita ficifolia. This revised version was published online in June 2006 with corrections to the Cover Date.