Detection of high antibodies titers against rat leukemia virus in an outbreak of reproductive disorders and lymphomas in Wistar rats.

Young female Wistar rats from a specific pathogen free breeding colony presented an outbreak of infertility along with neurological symptoms and malignant lymphomas. We evaluated the presence and the potential role of the rat leukemia virus (RaLV) in the disease because these clinical signs could be compatible with a retrovirus. RaLV is a mammalian type C endogenous retrovirus initially isolated from in vitro Sprague-Dawley rat embryo cultures. There are no reports of clinical disease in rats associated with this virus, and little is known about its interaction with the host. Using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, we studied the synthesis of the viral particles and the development of an immune response against the virus in this rat colony. The results showed that healthy and diseased Wistar rats synthetized viral RNA but only diseased animals developed a detectable immune response against RaLV envelop protein. Furthermore, rats with lymphomas tended to have higher titers of antibodies against RaLV epitopes than those with infertility or neurological symptoms. The results suggest that increases in the RaLV infectious particle loads could be involved in the development of lymphomas in young rats. The potential causes of RaLV reactivation are discussed.

Hematological and biochemical profiles of canine CD45- T lymphomas are different from other immunophenotypes.

BACKGROUND: Canine multicentric lymphomas are lymphoproliferative malignancies that have increased in recent decades. The patient's treatment and prognosis are determined by the grade, histological type, and lymphoma immunophenotyping. AIM: To investigate the paraclinical signs and survival time in canines with different lymphoma immunophenotypes. METHODS: Over 2 and a half years, 47 untreated dogs were diagnosed with multicentric lymphoma at the Veterinary School Hospital of Uruguay. The disease was clinically and cytologically diagnosed, and immunophenotyping was determined by flow cytometry. After the immunophenotyping, most of the patients were grouped into the following: B (LB), T aggressive (LTCD45+), or T-zone lymphoma (LTCD45-). The patients' haematological values, calcemia, lactate dehydrogenase (LDH) levels, and plasmatic electrophoretic profiles were all determined immediately after that. RESULTS: Of all canine lymphomas, 55.3% were B, 31.9% were LTCD45+, and 10.6% were TCD45-. Only 2.2% were classified as nonB/nonT, and survival time differed between groups. Patients with LTCD45- lymphomas had a mean life span of 641 days after diagnosis, followed by LB (166 days) and LTCD45+ (62 days). Red blood cell count, hematocrit, and hemoglobin levels did not differ between groups. However, the LTCD45- group had significantly higher lymphocyte levels than the LTCD45+ and LB groups (p = 0.01 and 0.006, respectively). Levels of albumin, alpha-1, and alpha-2 globulins did not differ between groups. On the other hand, gamma globulins levels in the LTCD45- were higher than in the other lymphoma groups. The presence of hypercalcemia and high plasma LDH levels were associated with patient severity. Only the TCD45+ group had hypercalcemia although both the LB and TCD45+ groups had elevations in LDH activity. Interestingly, there was a direct relationship between high LDH values (greater than 500 IU/l) and lower survival in TCD45+ lymphomas. CONCLUSION: Survival time and hematological and biochemical patterns differed among canine lymphomas immunophenotypes. Patients of LTCD45- phenotype showed higher lymphocyte counts and gamma globulin levels and more prolonged survival. Serum LDH activity may provide additional prognostic information in high-grade T-cell lymphoma.

Hematobin is a novel immunomodulatory protein from the saliva of the horn fly Haematobia irritans that inhibits the inflammatory response in murine macrophages.

BACKGROUND: The horn fly Haematobia irritans is a blood-sucking ectoparasite responsible for substantial economic loss of livestock. Like other hematophagous arthropods species, the successful blood-feeding of H. irritans is highly dependent on the modulation of the host's hemostasis and immune system. Here, we evaluated the biological activity of hematobin (HTB), a protein recently identified in the H. irritans saliva, on macrophage biology. The goal was to understand the putative interactions between the components of H. irritans saliva and the early host immune responses. RESULTS: Thioglycolate-elicited peritoneal macrophages from BALB/c mice were stimulated by lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) in the presence or absence of recombinant HTB. The presence of the salivary protein in the cultures inhibited nitric oxide production and decreased the inducible nitric oxide synthase (iNOS) expression induced by LPS plus IFN-γ. The tumor necrosis factor-α (TNF-α) and interleukin-12p40 (IL-12p40) levels were also reduced in the macrophages pre-incubated with HTB; these findings correlated to the decreased NF-κB expression. The biological activities described here were not associated with changes in annexin V binding to macrophages suggesting that HTB does not induce cell death. In addition, the activity of HTB seems to be specific to macrophages because no changes were observed in lymphocyte proliferation or cytokine production. CONCLUSIONS: We describe here the first bioactive salivary protein of H. irritans. We characterized its ability to modulate macrophage inflammatory response, and the results can help explain how horn flies modulate the host immune system to feed on blood.

Genetic toxicology and preliminary in vivo studies of nitric oxide donor tocopherol analogs as potential new class of antiatherogenic agents.

Nitric oxide donor tocopherol analogs were found to be incorporated in low-density lipoprotein to release nitric oxide into the hydrophobic core of the lipoprotein, thus inhibiting lipid oxidation processes associated with atheroma plaque formation. Previously, we studied their cytotoxicity against human and murine macrophages as first selection for in vivo studies. Herein, we examined both the in vitro mutagenic and DNA-damage effects of selected compounds to further evaluate drug potential. While the compounds of interest were nongenotoxics in both experimental tests (Ames and alkaline comet), one of the potential blood metabolites exhibited genotoxicity (alkaline comet test), and the furazan derivative was mutagenic (Ames test). Two selected (nitrooxy and furoxan) compounds were studied in long- and short-term in vivo treatment, and in these conditions, animal toxicity was not evidenced, suggesting the possibility of these compounds as potential antiatherogenic drugs.

An insect growth inhibitor--lufenuron--enhances albendazole activity against hydatid cyst.

The aim of this work was to evaluate the potential of lufenuron, a benzylphenylurea with ability to interfere with the formation of insect exoskeleton, as a therapeutic drug for larval echinococcosis (hydatid disease). For this purpose lufenuron, alone or in combination with albendazole, was administered to CD1 mice bearing Echinococcus granulosus hydatid cysts in the peritoneal cavity. Neither of the drugs alone was able to exert parasiticidal effects. However, in combination with albendazole, lufenuron reduced the growth of cysts (30-40% in cyst diameter respect to control, p<0.05). This effect was associated with ultrastructural alterations of the hydatid cyst wall and a reduction of the content of myo-inositol-hexakisphosphate, the major component of the electron dense granules of the laminated layer. Overall, this work provides evidence that lufenuron could represent a useful compound for the use in chemotherapy against larval echinococcosis, by enhancing albendazole parasiticidal activity.

Echinococcus granulosus: the establishment of the metacestode is associated with control of complement-mediated early inflammation.

In this work we studied the evolution of early inflammation, complement activation and parasite survival/death along the establishment phase of Echinococcus granulosus metacestode. Using a chamber model of infection in mice, we examined cell infiltration and C3 deposition on individual parasites during their development from protoscoleces to cystic forms. We found that the intensity of the initial inflammation decreased around undamaged but not around damaged parasites: at 43dpi undamaged parasites were mostly associated with poor/mild inflammation while damaged parasites with a strong inflammation. In addition, whereas complement activation participated in the induction of early inflammation, the deposition of C3 on undamaged parasites progressively diminished. Interestingly, we observed some parasites in pre-cystic stage with no/poor C3 deposition at 3dpi. Overall, these results indicated that the establishment and survival of the hydatid cyst is associated with the control of complement and, consequently, of local inflammation at the initial phases of infection.