Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission

Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa. True babesiae (Babesia genus sensu stricto) are biologically characterized by direct development in erythrocytes and by transovarial transmission in the tick. A large number of true Babesia species have been described in various vertebrate and tick hosts. This review presents the genus then discusses specific adaptations of Babesia spp. to their hosts to achieve efficient transmission. The main adaptations lead to long-lasting interactions which result in the induction of two reservoirs: in the vertebrate host during low long-term parasitemia and throughout the life cycle of the tick host as a result of transovarial and transstadial transmission. The molecular bases of these adaptations in vertebrate hosts are partially known but few of the tick-host interaction mechanisms have been elucidated.     

Taurine-deficient dilated cardiomyopathy in a family of golden retrievers

A reversible taurine-deficient dilated cardiomyopathy occurred in five related golden retrievers. An apical systolic heart murmur was the most common physical abnormality. According to fractional shortening and end-systolic diameter on echocardiography, significant improvements (P<0.005) were recorded within 3 to 6 months of starting taurine supplementation. The dogs regained substantial systolic function, and four were weaned off all cardiac medications except taurine. This response to therapy was unusual, because canine dilated cardiomyopathy is generally progressive and fatal.     

Clinical evaluation of a nutraceutical,carprofen and meloxicam for the treatment of dogs with osteoarthritis

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.     

An index for selective toxicity of miticides to phytophagous mites and their predators based on orchard trials

Data from nine trials conducted from 1990 to 1998 in apple orchards in Nova Scotia and Quebec, Canada, were used to estimate the predator-prey selectivity of miticides and their potential compatibility with biological control of mites. The European red mite Panonychus ulmi (Koch) was the dominant and more harmful phytophagous species, followed by the apple rust mite, Aculus schlechtendali (Nalepa). Two predacious mites, the phytoseiid, Typhlodromus pyri Sheuten, and the stigmaeid, Zetzellia mali (Ewing), were often found in the orchards. We used one minus the ratio of mite-days in treated plots to those in the control plots as an index of population suppression and toxicity of the miticides. Miticides were then categorized into classes similar to those employed by the International Organization for Biological Control to rate pesticide toxicity to natural enemies of insect and mite pests. Selectivity of miticides was mostly based on toxicity to P ulmi, the major pest, versus toxicity to T pyri, the major predator, with some consideration of the two lesser species, A schlechtendali and Z mali. In most cases, our findings were in accord with other studies. Abamectin and clofentezine had favourable selectivity (more toxic to the two phytophagous mites than to T pyri). The higher recommended rate of pyridaben (450 g ha(-1)) and two rates of spirodiclofen (180 and 240 g ha(-1)) were neutral (equally toxic to pests and predators). The lower rate of pyridaben (216 g ha(-1)), dicofol, formetanate hydrochloride and propargite were unfavourably selective (more toxic to T pyri). A higher than recommended rate of pyridaben (2160 g ha(-1)) applied before bloom was disruptive--P ulmi-days after treatment were actually greater than with the untreated control. P ulmi resistance to dicofol and propargite were probable complicating factors in some of the orchard trials.     

Portal vein and aortic thromboses in a Siberian husky with ehrlichiosis and hypothyroidism

A six-year-old, neutered male Siberian husky was presented for euthanasia for end-stage liver disease. Examination of the dog raised questions regarding the severity of the condition. It had presented to the referring veterinarian with polyuria, polydipsia and weight loss. Blood tests at that time revealed elevated liver enzymes and hypoalbuminaemia. Cirrhosis was presumptively diagnosed, based on an ultrasound examination, which showed ascites with a normal liver. The dog had a history of hypothyroidism, which was controlled with levothyroxine. Physical examination revealed cachexia. A second abdominal ultrasound examination was performed and revealed portal vein and aortic thromboses. Tick titres showed a positive Ehrlichia canis titre of 1:640. Skin biopsies showed lymphoplasmacytic vasculitis. Doxycycline and aspirin treatment was initiated, and the clinical signs resolved. The authors concluded that the thrombi were primarily caused by chronic ehrlichiosis, based on the clinical findings and the response to treatment.     

Efficacy and Mechanism of Action of Marine Alkaloid 3,10-Dibromofascaplysin in Drug-Resistant Prostate Cancer Cells

Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed. Inhibition of the drug-induced JNK1/2 activation or of the basal p38 activity resulted in increased cytotoxicity of DBF, whereas an active ERK1/2 was identified to be important for anticancer activity of the alkaloid. Synergistic effects of DBF were observed in combination with PARP-inhibitor olaparib most likely due to the induction of ROS production by the marine alkaloid. In addition, DBF intensified effects of platinum-based drugs cisplatin and carboplatin, and taxane derivatives docetaxel and cabazitaxel. Finally, DBF inhibited AR-signaling and resensitized AR-V7-positive 22Rv1 prostate cancer cells to enzalutamide, presumably due to AR-V7 down-regulation. These findings propose DBF to be a promising novel drug candidate for the treatment of human PCa regardless of resistance to standard therapy.     

Effect of heat pretreatment on the yield and composition of oil extracted from corn fiber.

Previously, hexane extraction of corn fiber was reported to produce a unique and potentially valuable oil that contained high levels of several phytosterols (which have been noted for their cholesterol-lowering properties). Current studies revealed that heat treatment (over the range of 100-175 degrees C) of corn fiber in either a convection oven or a vacuum oven caused only a modest reduction in the levels of the phytosterol components. However, these same heat pretreatments caused a considerable increase (up to 10-fold) in the levels (increasing from 0.34 wt % to a maximum of 3.64 wt % gamma-tocopherol in the oil) and yields (increasing from 5.4 mg of gamma-tocopherol/100 g of corn fiber to a maximum of 52.1 mg of gamma-tocopherol/100 g of corn fiber) of gamma-tocopherol in corn fiber oil. The main differences between the convection oven and vacuum oven pretreatments were associated with the disappearance of free fatty acids and free phytosterols at the higher temperature pretreatments in the vacuum oven, probably due to the lower boiling points of these lipids. Microwave pretreatment was also effective but caused a much smaller increase in the levels of gamma-tocopherol.     

Inhibition of aflatoxin biosynthesis in Aspergillus flavus by diferuloylputrescine and p-coumaroylferuloylputrescine

A mixture of diferuloylputrescine/p-coumaroylferuloylputrescine (85:15, w/w) demonstrated inhibitory activity against aflatoxin B1 biosynthesis in Aspergillus flavus isolate AF13. Inhibition was concentration dependent, with a 50% effective dose of 30 microg of diferuloylputrescine/p-coumaroylferuloylputrescine per milliliter of medium. Aflatoxin inhibition levels of up to 93% were achieved using this conjugated polyamine material. This diconjugated polyamine mixture did not display inhibitory effects on A. flavus growth (mycelial weight) at any of the concentrations tested. A survey of hand-dissected corn (Zea mays) kernel tissues, including endosperm, germ, pericarp, and wax, revealed that the highest concentrations of these conjugated polyamines were localized in the pericarp of the seed. Analysis of a number of corn accessions did not reveal a correlation between diferuloylputrescine/ p-coumaroylferuloylputrescine concentration and resistance/susceptibility to A. flavus infection. The localization of these diconjugated polyamine components in the pericarp, which functions as a physical barrier and surrounds the internal food storage reserves, suggests a defensive role for these materials.     

Responses of Fasciola hepatica infected sheep to various infection levels

The response to Fasciola hepatica was studied in sheep infected with 5, 30, 150 metacercariae. The animals were necropsied 12 weeks post-infection (p-i) for counting and measuring flukes. Cellular and humoral responses were detected by peripheral eosinophil count, peripheral blood lymphocyte proliferation with excretory-secretory products (FhESP) and ELISA. All sheep were infected at necropsy except one sheep which was infected with 5 metacercariae. Mean parasitic intensities were 40%, 44% and 27% of the infection dose in sheep infected with 5, 30, 150 metacercariae respectively. FhESP-specific lymphocyte responses of the 3 infected groups were significantly enhanced in weeks 3 and 4 p-i (p < 0.05). The kinetics of the specific humoral response were similar for the 3 infected groups but the antibody level was significantly lower in animals infected with 5 metacercariae than in the 2 other infected groups from week 5 p-i to week 12 p-i (p < 0.05). Peripheral eosinophil count was significantly enhanced (p < 0.05) in infected groups. The numbers of peripheral eosinophils were significantly different between the 3 infected groups in week 3, 4 and 6 p-i and were related to infection level. These results confirm that sheep are highly susceptible to F. hepatica infection, even when infection pressure is very low. Peripheral eosinophilia was dependent of the infection level. The immune response was similar in sheep infected with various numbers of flukes.