Genetic and seasonal variations of Trypanosoma theileri and the association of Trypanosoma theileri infection with dairy cattle productivity in Northern Japan.

Trypanosoma theileri is considered a non- or low-pathogenic trypanosome that generally causes latent infection in apparently healthy cattle; however, T. theileri propagates in the bloodstream and may cause clinical disease in pregnant animals or co-infection with bovine leukemia virus or Theileria orientalis. In the current study, a monthly survey of T. theileri infection over one year was carried out in a research dairy farm in Hokkaido, Japan to determine the 1) seasonal variations in the prevalence, 2) genetic characterization of T. theileri, and 3) associations of milk and blood parameters in dairy cattle with T. theileri infection, including data of metabolic profile tests and dairy herd performance tests, using linear mixed models. We found that 1) the prevalence of T. theileri infection was significantly higher in summer and winter than in other seasons; 2) T. theileri possibly showed genetic diversity in Eastern Hokkaido; and 3) T. theileri infection was associated with significantly lower levels of blood urea nitrogen, milk protein, and solids-not-fat, which are caused by a low rumen fermentation level. This is the first study to report the negative impact of T. theileri infection in dairy cattle, and our study indicates that control of T. theileri infection can improve the productivity of dairy cattle.

Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity.

As a relatively successful pathogen, several parasites can establish long-term infection in host. This "harmonious symbiosis" status relies on the "precise" manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.

Infection with Trypanosoma lewisi or Trypanosoma musculi may promote the spread of Toxoplasma gondii.

Toxoplasma gondii can infect almost all warm-blooded vertebrates with pathogensis being largely influenced by the host immune status. As important epidemiological hosts, rodents are globally distributed and are also commonly found infected with haemoflagellates, such as those in the genus Trypanosoma. We here address whether and how co-infection with trypanosomes can influence T. gondii infection in laboratory models. Rats of five strains, co-infected with T. lewisi and mice of four strains, co-infected with T. musculi, were found to be more or less susceptible to T. gondii infection, respectively, with corresponding increased or decreased brain cyst burdens. Downregulation of iNOS expression and decreased NO production or reverse were observed in the peritoneal macrophages of rats or mice, infected with trypanosomes, respectively. Trypanosoma lewisi and T. musculi can modulate host immune responses, either by enhancement or suppression and influence the outcome of Toxoplasma infection.

Curcumin pre-treatment modulate the activities of adenine nucleotide and nucleoside degradation enzymes in lymphocyte of rats infected with Trypanosoma evansi.

This study aimed to evaluate nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities in lymphocytes from rats supplemented or not with curcumin 30 days prior to experimental infection with Trypanosoma evansi. Thirty-two adult male Wistar rats were divided in four groups. The pre-infection group 20 (PreI20) received orally 20 mg/kg of curcumin and pre-infection group 60 (PreI60) received orally 60 mg/kg of curcumin for 30 days prior inoculation with T. evansi. The infected e non-infected control groups received only oral vehicle for 30 days. Trypanosoma evansi infected groups were inoculated intraperitoneally with 0.2 ml of blood with 1 × 106 parasites. After inoculation the treatment of the groups continued until the day of euthanasia (15 days). The results showed that curcumin pre-treatment, with both doses, reduced (P < .05) NTPDase and increased (P < .05) ADA activity in lymphocytes of treated groups when compared to untreated and infected animals (control). The results of this study support the evidence that the regulation of ATP and adenosine levels by NTPDase and ADA activities appear to be important to modulate the immune response in T. evansi infection, once the treatment with curcumin maintained the NTPDase activity reduced and enhanced ADA activity in lymphocytes. It is possible to conclude that the use of curcumin prior to infection with T. evansi induces immunomodulatory effects, favoring the response against the parasite.

A new landscape of host-protozoa interactions involving the extracellular vesicles world.

Extracellular vesicles (EVs) are released by a wide number of cells including blood cells, immune system cells, tumour cells, adult and embryonic stem cells. EVs are a heterogeneous group of vesicles (~30-1000 nm) including microvesicles and exosomes. The physiological release of EVs represents a normal state of the cell, raising a metabolic equilibrium between catabolic and anabolic processes. Moreover, when the cells are submitted to stress with different inducers or in pathological situations (malignancies, chronic diseases, infectious diseases.), they respond with an intense and dynamic release of EVs. The EVs released from stimulated cells vs those that are released constitutively may themselves differ, both physically and in their cargo. EVs contain protein, lipids, nucleic acids and biomolecules that can alter cell phenotypes or modulate neighbouring cells. In this review, we have summarized findings involving EVs in certain protozoan diseases. We have commented on strategies to study the communicative roles of EVs during host-pathogen interaction and hypothesized on the use of EVs for diagnostic, preventative and therapeutic purposes in infectious diseases. This kind of communication could modulate the innate immune system and reformulate concepts in parasitism. Moreover, the information provided within EVs could produce alternatives in translational medicine.

Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor-Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog.

Arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. We report that arginase expression and activity were induced in macrophages during mouse infection by Trypanosoma musculi, a natural parasite of this host. This induction was reproduced in vitro by excreted/secreted factors of the parasite. A mAb directed to TbKHC1, an orphan kinesin H chain from Trypanosoma brucei, inhibited T. musculi excreted/secreted factor-mediated arginase induction. Anti-TbKHC1 Ab also inhibited T. musculi growth, both in vitro and in vivo. Induction of arginase activity and parasite growth involved C-type lectin receptors, because mannose injection decreased arginase activity induction and parasite load in vitro and in vivo. Accordingly, the parasite load was reduced in mice lacking mannose receptor C-type 1. The T. musculi KHC1 homolog showed high similarity with TbKHC1. Bioinformatics analysis revealed the presence of homologs of this gene in other trypanosomes, including pathogens for humans and animals. Host metabolism dysregulation represents an effective parasite mechanism to hamper the host immune response and modify host molecule production to favor parasite invasion and growth. Thus, this orphan kinesin plays an important role in promoting trypanosome infection, and its neutralization or the lock of its partner host molecules offers promising approaches to increasing resistance to infection and new developments in vaccination against trypanosomiasis.

Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.

Eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. Protein S-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (PAT) and can be removed by lysosomal palmitoyl-protein thioesterase (PPT) or cytosolic acyl-protein thioesterase (APT). In addition to anchoring proteins to intracellular membranes, functions of dynamic palmitoylation include - targeting proteins to specific intracellular compartments via trafficking pathways, regulating the cycling of proteins between membranes, modulating protein function and regulating protein stability. Recent studies in the eukaryotic parasites - Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei, Cryptococcus neoformans and Giardia lamblia - have identified large families of PATs and palmitoylated proteins. Many palmitoylated proteins are important for diverse aspects of pathogenesis, including differentiation into infective life cycle stages, biogenesis and tethering of secretory organelles, assembling the machinery powering motility and targeting virulence factors to the plasma membrane. This review aims to summarize our current knowledge of palmitoylation in eukaryotic parasites, highlighting five exemplary mechanisms of parasite virulence dependent on palmitoylation.

Vertical transmission of Trypanosoma evansi in experimentally infected rats.

Many reproductive problems has been described in male and female animals infected by Trypanosoma evansi. Thus, the aim of this study was to evaluate the occurrence of vertical (Experiment I) and venereal (Experiment II) transmission of T. evansi in rats experimentally infected. In the experiment I, eight female Wistar rats were used: three animals as negative controls, and five rats were infected by T. evansi on day ten of gestation. Out of these eight females, half puppies were used for molecular analysis (polymerase chain reaction - PCR) for T. evansi. Two infected females showed delivery problems, such as stillbirth, and fetal death that also led to female death. Three female rats infected had normal delivery of stunted offspring at term that died 2 days after birth. Rats from the control group had normal delivery of healthy offspring. T. evansi PCR was positive for 80% (12/15) of pups in the infected group. For the experiment II, five male rats were infected by T. evansi, and monitored by blood smears to check the parasitemia level. When the male rats showed parasitemia between 2 and 5 parasites per field, they were individually housed with one female adult rat. After approximately 21 days, the females delivered their offspring. Blood sample was collected from the females for blood smears and T. evansi PCR tests, which revealed negative results. Therefore, we were able to prove the occurrence of transplacental transmission of T. evansi and its negative effect on female rats and their offspring.

Flagellar antigen based CI-ELISA for sero-surveillance of surra.

Trypanosoma evansi causes a disease known as 'surra' in wide range of domesticated and wild animals including cattle, buffaloes, horses, camels etc. The disease is transmitted through the bites of haematophagous tabanid flies and is characterized by undulating fever, chronic progressive weakness, and hypoglycemia leading to low productivity in animals. In the present study, monoclonal antibodies (MAbs) have been produced (IgG3 sub-type) against purified flagellar (FLA) protein of T. evansi and its immunoreactivity was evaluated by serological tests. MAb and purified protein were then exploited in the development of CI-ELISA and the diagnostic potentiality of the new ELISA test has been evaluated using 1230 sera samples from field animals including cattle, buffaloes, camels, horses and donkeys. The statistical analysis of the data showed optimum combination of sensitivity and specificity at 95.8 and 94.4, respectively. The positive-negative cut off percentage inhibition (PI) value was found to be >55, with a Cohen's Kappa value of 0.83. The study showed that the new assay has potential for application in sero-diagnosis as well as sero-surveillance of surra.

Molecular and functional characterization of goldfish (Carassius auratus L.) Serum Amyloid A.

Quantitative expression analysis of goldfish SAA revealed the highest mRNA levels in the kidney, spleen and intestine with lower mRNA levels in muscle and liver. Goldfish SAA was differentially expressed in goldfish immune cells with highest mRNA levels observed in neutrophils. To functionally assess goldfish SAA, recombinant protein (rgSAA) was generated by prokaryotic expression and functionally characterized. Monocytes and macrophages treated with rgSAA exhibited differential gene expression of pro-inflammatory and anti-inflammatory cytokines. rgSAA induced gene expression of both pro-inflammatory (TNFα1, TNFα2) and anti-inflammatory cytokines (IL-10, TGFß) in monocytes. rgSAA induced IL-1ß1 and SAA gene expression in macrophages. rgSAA was chemotactic to macrophages and neutrophils, but not monocytes. rgSAA did not affect respiratory burst induced by heat-killed Aeromonas salmonicida. rgSAA treatment of macrophages down-regulated their production of nitric oxide. rgSAA exhibited antibacterial properties against Escherichia coli in a concentration dependent manner.

Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi: Immunological, physiological, molecular and structural evidences.

In higher eukaryotes, the sarco-endoplasmic reticulum (ER) Ca(2+)-ATPase (SERCA) is characterized for its high sensitivity to low concentrations of thapsigargin (TG), a very specific inhibitor. In contrast, SERCA-like enzymes with different sensitivities to TG have been reported in trypanosomatids. Here, we characterized a SERCA-like enzyme from Trypanosoma evansi and evaluated its interaction with TG. Confocal fluorescence microscopy using BODIPY FL TG and specific anti-SERCA antibodies localized the T. evansi SERCA-like enzyme in the ER and confirmed its direct interaction with TG. Moreover, the use of either 1 µM TG or 25 µM 2',5'-di (tert-butyl)-1,4-benzohydroquinone prevented the reuptake of Ca(2+) and consequently produced a small increase in the parasite cytosolic calcium concentration in a calcium-free medium, which was released from the ER pool. A 3035 bp-sequence coding for a protein with an estimated molecular mass of 110.2 kDa was cloned from T. evansi. The corresponding gene product contained all the invariant residues and conserved motifs found in other P-type ATPases but lacked the calmodulin binding site. Modeling of the three-dimensional structure of the parasite enzyme revealed that the amino acid changes found in the TG-SERCA binding pocket do not compromise the interaction between the enzyme and the inhibitor. Therefore, we concluded that T. evansi possesses a SERCA-like protein that is inhibited by TG.

Dose finding of 3'deoxyadenosine and deoxycoformycin for the treatment of Trypanosoma evansi infection: An effective and nontoxic dose.

The aim of this study was to evaluate the therapeutic efficacy and safety of using 3'deoxyadenosine (Cordycepin - adenosine analogue) combined with deoxycoformycin (Pentostatin - an adenosine deaminase inhibitor) in mice infected with Trypanosoma evansi. We show that the combination of Cordycepin (2.0 mg kg(-1)) and Pentostatin (0.2, 0.5, 1.0, 2.0 mg kg(1)) is effective in the clearance of T. evansi, although at the higher concentrations of Pentostatin 2 mg kg(-1) some toxicity was observed in the liver and kidney. Since the Cordycepin 2.0 mg kg(-1) and Pentostatin 0.2 mg kg(-1) combination was effective and had low toxicity, we recommend this as a therapeutic option for a T. evansi mouse model.

Relationship between behavioral alterations and activities of adenylate kinase and creatine kinase in brain of rats infected by Trypanosoma evansi.

The aim of this study was to investigate the behavioral assessment and activities of important enzymes involved in the phosphoryl transfer network in rat brains that were experimentally infected with Trypanosoma evansi. Behavioral assessment (cognitive performance), pro-inflammatory cytokines in serum and activities of adenylate kinase (AK), pyruvate kinase (PK), and creatine kinase (CK) in brain were evaluated at 5 and 15 days post-infection (PI). Here we demonstrate a cognitive impairment in the rats infected with T. evansi. At 5 and 15 days PI, a memory deficit and a depressant activity were demonstrated by an inhibition avoidance test and increase in the immobility time in a tail suspension test, respectively. On day 5 PI, a decrease in the CK activity and an increase in the AK activity were observed. On day 15 PI, an increase in the CK activity and a decrease in the AK activity were observed. Considering the importance of energy metabolism for brain functioning, it is possible that the changes in the activity of enzymes involved in the cerebral phosphotransfer network and an increase in the proinflammatory cytokines (TNF and IFN) may be involved at least in part in the cognitive impairment in infected rats with T. evansi.

Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI / Associação entre a Relação Neutrófilos/Linfócitos e o Grau de Isquemia Eletrocardiográfica no IAMEST

Background: Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. Objective: To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. Methods: Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). Results: Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p < 0.001). Conclusion: We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores. .

Fundamento: A relação neutrófilos/linfócitos (N/L) tem sido descrita como boa preditora de eventos cardiovasculares adversos futuros em pacientes com infarto agudo do miocárdio com elevação do segmento ST (IAMEST). Mudanças na porção terminal do complexo QRS também têm sido associadas a eventos adversos após IAMEST. Objetivo: Investigar a associação entre o grau de isquemia no ECG e a relação N/L em pacientes com IAMEST para determinar fatores de risco convencionais adicionais na estratificação precoce de risco. Métodos: Pacientes com IAMEST foram investigados. O grau de isquemia foi analisado a partir do ECG obtido à admissão. A contagem de leucócitos e seus subtipos foi realizada a partir de hemograma automatizado. De acordo com o grau de isquemia presente no ECG de admissão, os pacientes foram classificados em dois grupos, isquemia grau 2 (IG2) e isquemia grau 3 (IG3). Resultados: Pacientes com IG3 apresentaram valores médios significativamente menores de fração de ejeção do ventrículo esquerdo do que os pacientes com IG2 (44,58 ± 7,23 versus 48,44 ± 7,61; p = 0,001). Como esperado, a taxa de mortalidade intra-hospitalar aumentou proporcionalmente com o aumento no grau de isquemia (p = 0,036). Houve diferenças significativas nas porcentagens de linfócitos (p = 0,010) e de neutrófilos (p = 0,004) e, portanto, a relação N/L diferiu significativamente entre pacientes com IG2 e IG3 (p < 0,001). À análise de regressão logística multivariada, apenas a relação N/L emergiu como variável independente com efeito significativo sobre o grau de isquemia no ECG (odds ratio = 1,254; intervalo de confiança de 95% 1,120-1,403; p < 0,001). Conclusão: Nós encontramos uma associação entre IG3 e relação N/L aumentada em pacientes com IAMEST. Acreditamos que esta associação possa oferecer um valor prognóstico adicional para estratificação de risco em pacientes com IAMEST quando usado em combinação com escores de risco padronizados. .

Trypanosoma evansi infection impairs memory, increases anxiety behaviour and alters neurochemical parameters in rats.

The aim of this study was to investigate neurochemical and enzymatic changes in rats infected with Trypanosoma evansi, and their interference in the cognitive parameters. Behavioural assessment (assessment of cognitive performance), evaluation of cerebral L-[3H]glutamate uptake, acetylcholinesterase (AChE) activity and Ca+2 and Na+, K+-ATPase activity were evaluated at 5 and 30 days post infection (dpi). This study demonstrates a cognitive impairment in rats infected with T. evansi. At 5 dpi memory deficit was demonstrated by an inhibitory avoidance test. With the chronicity of the disease (30 dpi) animals showed anxiety symptoms. It is possible the inhibition of cerebral Na+, K+-ATPase activity, AChE and synaptosomal glutamate uptake are involved in cognitive impairment in infected rats by T. evansi. The understanding of cerebral host­parasite relationship may shed some light on the cryptic symptoms of animals and possibly human infection where patients often present with other central nervous system (CNS) disorders.

The origin recognition complex in human diseases.

ORC (origin recognition complex) serves as the initiator for the assembly of the pre-RC (pre-replication complex) and the subsequent DNA replication. Together with many of its non-replication functions, ORC is a pivotal regulator of various cellular processes. Notably, a number of reports connect ORC to numerous human diseases, including MGS (Meier-Gorlin syndrome), EBV (Epstein-Barr virus)-infected diseases, American trypanosomiasis and African trypanosomiasis. However, much of the underlying molecular mechanism remains unclear. In those genetic diseases, mutations in ORC alter its function and lead to the dysregulated phenotypes; whereas in some pathogen-induced symptoms, host ORC and archaeal-like ORC are exploited by these organisms to maintain their own genomes. In this review, I provide detailed examples of ORC-related human diseases, and summarize the current findings on how ORC is involved and/or dysregulated. I further discuss how these discoveries can be generalized as model systems, which can then be applied to elucidating other related diseases and revealing potential targets for developing effective therapies.

Hyperlipidaemia in trypanosomiasis of naturally infected horses: possible cachexia-anorexia syndrome?

Trypanosomiasis caused by Trypanosoma evansi commonly produces wasting disease with signs of emaciation and cachexia mainly at the end stage. The present study was conducted to explore the possible hyperlipaemia or hyperlipidaemia and its association with cachexia-anorexia in equine trypanosomiasis. Out of the fifteen confirmed animals, none of the plasma sample was opaque. There was a significant increase in plasma triglyceride, total cholesterol and blood urea nitrogen and a highly significant increase in low-density lipoprotein (LDL) levels. A mild increase in high-density lipoprotein (HDL) and very low-density lipoprotein levels were observed, while the relative percentage of HDL and LDL was altered with high significance. A moderate increase in triglyceride and highly significant increase in LDL might be the reasons for retention of appetite and lipolysis. Possible protein breakdown and presence of lipolysis might be the reasons for cachexia in equine trypanosomiasis.

Influence of Trypanosoma evansi in adenine nucleotides and nucleoside concentration in serum and cerebral cortex of infected rats.

This study aimed to evaluate the adenine nucleotides and nucleoside concentration in serum and cerebral cortex of rats infected with Trypanosma evansi. Each rat was intraperitoneally infected with 1 × 10(6) trypomastigotes suspended in cryopreserved blood (Group A; n = 18). Twelve animals were used as controls (Group B). The infected animals were monitored daily by blood smears. At days 4 and 20 post-infection (PI) it was collected serum and cerebral cortex to measure the levels of ATP, ADP, AMP and adenosine by high performance liquid chromatography (HPLC). In serum there was a significant (P < 0.05) increase in the ATP, AMP and adenosine concentrations at days 4 and 20 PI in infected rats when compared to not-infected. Furthermore, in the cerebral cortex it was observed a significant (P < 0.05) increase in the concentrations of ATP, AMP and decreased adenosine levels at day 4 PI. At day 20 PI it was only observed an increase in the AMP and adenosine concentrations in cerebral cortex of infected rats when compared to not-infected. It was not observed any difference in ADP concentration in serum and brain at days 4 and 20 PI. No change was observed histologically in the cerebral cortex of infected animals. The results allow us to conclude that infection with T. evansi in rats causes an increase in the concentrations of ATP, AMP and adenosine in serum and cerebral cortex the time periods evaluated. These alterations occurred as a result of T. evansi infection which involves neurotransmission, neuromodulation and immune response impairment confirm the importance of the purinergic system in this pathology.

The acute and sub-chronic exposures of goldfish to naphthenic acids induce different host defense responses.

Naphthenic acids (NAs) are believed to be the major toxic component in oil sands process-affected water (OSPW) produced by the oil sands mining industry in Northern Alberta, Canada. We recently reported that oral exposure to NAs alters mammalian immune responses, but the effect of OSPW or NAs on the immune mechanisms of aquatic organisms has not been fully elucidated. We analyzed the effects of acute and sub-chronic NAs exposures on goldfish immune responses by measuring the expression of three pro-inflammatory cytokine genes, antimicrobial functions of macrophages, and host defense after challenge with a protozoan pathogen (Trypanosoma carassii). One week after NAs exposure, fish exhibited increased expression of pro-inflammatory cytokines (IFNγ, IL-1ß1, TNF-α2) in the gills, kidney and spleen. Primary macrophages from fish exposed to NAs for one week, exhibited increased production of nitric oxide and reactive oxygen intermediates. Goldfish exposed for one week to 20 mg/L NAs were more resistant to infection by T. carassii. In contrast, sub-chronic exposure of goldfish (12 weeks) to NAs resulted in decreased expression of pro-inflammatory cytokines in the gills, kidney and spleen. The sub-chronic exposure to NAs reduced the ability of goldfish to control the T. carassii infection, exemplified by a drastic increase in fish mortality and increased blood parasite loads. This is the first report analyzing the effects of OSPW contaminants on the immune system of aquatic vertebrates. We believe that the bioassays depicted in this work will be valuable tools for analyzing the efficacy of OSPW remediation techniques and assessment of diverse environmental pollutants.

The role of melatonin in parasite biology.

Regarded as the circadian hormone in mammals, melatonin is a highly conserved molecule, present in nearly all species. In this review, we discuss the role of this indolamine and its precursors in the cell biology of parasites and the role of the molecule in the physiology of the host. In Plasmodium, melatonin can modulate intracellular concentrations of calcium and cAMP, which in turn can regulate kinase activity and cell cycle. In Trypanosoma infections, modulation of the immune system by melatonin is extremely important in controlling the parasite population. Melatonin also contributes to the inflammatory response to Toxoplasma gondii infection. Thus, there are a number of unique adaptations involving intricate connections between melatonin and the biology of the parasite-host relationship.