Usual or unusual presentations of Dirofilaria repens in two sibling dogs: a case report

This study describes two different manifestations of Dirofilaria repens infection in sibling dogs with microfilaremia. Dog 1, asymptomatic, harbored a gravid female of D. repens on the parietal layer of tunica vaginalis of one testicle and showed a marked circulating eosinophilia (3.3·103/μL). Both testicles were normal in shape and size without any gross lesions. Dog 2 had a pyotraumatic dermatitis. The cases were confirmed by PCR and sequencing. The sequences obtained showed 100% identity with those of D. repens isolated from human scrotum in Croatia. The treatment with moxidectin 2.5% and imidacloprid 10%/kg was effective in eliminating microfilariae after just one application, as demonstrated by negative modified Knott’s tests and PCR analyses of blood samples. This status was maintained during the post-treatment observation period. The classical localization of D. repens in dogs is in subcutaneous tissues, within nodules or free; however, it can also occur with some frequency in testicles, as described in humans. The infection can be associated with circulating eosinophilia or pyotraumatic dermatitis, as reported in this study. Thus, in endemic areas, it is advisable to carefully inspect the removed testicles at neutering since parasite localization can take place without any macroscopic changes. Moreover, in the case of circulating eosinophilia or pyotraumatic dermatitis, investigations should include modified Knott’s test and PCR to ensure that D. repens is not the cause of these alterations. Rapid and sensitive tests for the early detection of infected animals would help to prevent or limit the spread of this zoonosis

An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung metastasis

Toxicolog

Do Stress Responses Promote Leukemia Progression? An Animal Study Suggesting a Role for Epinephrine and Prostaglandin-E2 through Reduced NK Activity

In leukemia patients, stress and anxiety were suggested to predict poorer prognosis. Oncological patients experience ample physiological and psychological stress, potentially leading to increased secretion of stress factors, including epinephrine, corticosteroids, and prostaglandins. Here we tested whether environmental stress and these stress factors impact survival of leukemia-challenged rats, and studied mediating mechanisms. F344 rats were administered with a miniscule dose of 60 CRNK-16 leukemia cells, and were subjected to intermittent forced swim stress or to administration of physiologically relevant doses of epinephrine, prostaglandin-E2 or corticosterone. Stress and each stress factor, and/or their combinations, doubled mortality rates when acutely applied simultaneously with, or two or six days after tumor challenge. Acute administration of the β-adrenergic blocker nadolol diminished the effects of environmental stress, without affecting baseline survival rates. Prolonged β-adrenergic blockade or COX inhibition (using etodolac) also increased baseline survival rates, possibly by blocking tumor-related or normal levels of catecholamines and prostaglandins. Searching for mediating mechanisms, we found that each of the stress factors transiently suppressed NK activity against CRNK-16 and YAC-1 lines on a per NK basis. In contrast, the direct effects of stress factors on CRNK-16 proliferation, vitality, and VEGF secretion could not explain or even contradicted the in vivo survival findings. Overall, it seems that environmental stress, epinephrine, and prostaglandins promote leukemia progression in rats, potentially through suppressing cell mediated immunity. Thus, patients with hematological malignancies, which often exhibit diminished NK activity, may benefit from extended β-blockade and COX inhibition

In vivo reactivity of mouse natural killer (NK) cells against normal bone marrow cells

An in vivo role for mouse natural killer (NK) cells in the rapid rejection of transplantable tumors has been previously demonstrated, using an assay of elimination of [125I]iododeoxyuridine-labeled tumor cells from the lungs and other organs. We have now used the same technique to examine the role of NK cells in vivo clearance of syngeneic or allogeneic bone marrow cells from normal mice. The degree of clearance from the lungs or liver, at 4 hr after intravenous inoculation of radiolabeled bone marrow cells, correlated with the levels of NK activity in the recipients. Young CBA mice, with high NK activity, showed substantially more clearance of bone marrow cells than SJL mice, with low NK activity. Within the same strain, mice at 7 weeks of age had higher in vivo as well as in vitro reactivity than did 30-week-old mice. These differences were seen with syngeneic bone marrow cells, but there was stronger in vivo reactivity against parental cells by F1 hybrid recipients. Depression of NK activity by pretreatment of mice with cyclophosphamide, silica, or carrageenan also caused decreased clearance of syngeneic or parental bone marrow cells. Conversely, augmentation of NK activity by pretreatment of the mice with polyinosine:polycytidine resulted in increased in vivo clearance. These results indicate that NK cells may be involved in the in vivo control of growth of some normal cells as well as of some tumor cells

Suppression of natural killer (NK) activity by splenic adherent cells of low NK-reactive mice

Adherent cells with the ability to inhibit NK activity were found in the spleens of young 8-week-old SJL/J mice. Such suppressor cells were also found in the spleens of other low-NK-reactive strains, but not in the spleen of age-matched high-NK-reactive strains. These suppressor cells had the characteristics of macrophages, since they were plastic- and nylon-adherent, phagocytosed latex and iron particles, and were resistant to treatment with anti-Thy-1.2 serum plus complement. Their inhibitory activity appeared to be due to their production and/or release of soluble suppressive factor(s). Their suppressor activity was similar to that of pyran copolymer-activated macrophages which were previously shown to be suppressive for cytotoxicity by NK cells. The authors suggest here that macrophages may be involved in the physiological regulation of NK activity and may contribute to the low NK activity in some strains of mice

Suppression of activity of mouse natural killer (nk) cells by activated macrophages from mice treated with pyran copolymer.

Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic-adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran-treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors