Exposure to anabolic-androgenic steroids shortens life span of male mice.

Adult male laboratory mice were exposed for 6 months to a combination of four anabolic-androgenic steroids of the kinds and at the relative levels to which human athletes and body builders expose themselves. The four steroids included testosterone, two 17-alkylated steroids, and an ester, and they were given at doses that totaled either 5 or 20 times normal androgenic maintenance levels for mice. By the time the survivors were 20 months old (1 yr after the termination of steroid exposure), 52% of the mice given the high dose of steroids had died compared with 35% of the mice given the low dose and only 12% of the control mice given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice typically revealed tumors in the liver or kidney, other kinds of damage to these two organs, broadly invase lymphosarcomas, or heart damage, and usually more than one of these conditions. It can be concluded that the life span of male mice is decreased dramatically by exposing them for 6 months to the kinds and relative levels of anabolic steroids used by many athletes and body builders.

Clinical efficacy and toxicity of doxorubicin encapsulated in glutaraldehyde-treated erythrocytes administered to dogs with lymphosarcoma.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m2 of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was mot strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

Induction of human immunodeficiency virus-specific T cell responses in rhesus monkeys by synthetic peptides from gp160.

We have previously identified several synthetic peptides from conserved regions of the human immunodeficiency virus (HIV) envelope protein gp160 that have the capacity to induce broadly reactive T cell responses against gp160 in mice of several major histocompatibility complex (MHC) haplotypes. In the present investigation three rhesus monkeys were immunized with a mixture of eight synthetic peptides that are capable of inducing T cell activity in mice. Peripheral blood mononuclear cells (PBMCs) from these monkeys were monitored every 2 weeks for a period of 34 weeks for proliferative responses against individual peptides and recombinant gp160. Peripheral blood mononuclear cells from all three rhesus monkeys showed good proliferative responses with peptides 104 (aa 45-55), 111 (aa 118-130), and 63 (aa 519-543), whereas weak responses were observed with peptides 113 (aa 204-216) and 116 (aa 240-252). Two of the three rhesus monkey-derived PBMC preparations also showed good proliferative responses with peptide 61 (aa 586-598). Significant responses were not observed with peptides 105 (aa 48-61) and R15K (aa 315-329) in any of the monkeys immunized. However, PBMCs from all three monkeys showed significantly high proliferative responses with recombinant gp160, the HIV-1 envelope protein precursor. These results demonstrate that mixtures of synthetic peptides from HIV env gene product can prime gp160-specific T cell responses in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

SV7, a molecular clone of Moloney murine sarcoma virus 349, transforms vascular endothelial cells.

SV7, a progeny of Moloney murine sarcoma virus 349 cells, was molecularly cloned. SV7 induced sarcomas consisting of vascular and fibrous components. The large blood-filled vascular dilatations appeared grossly as dark red spots in the tumors and constituted up to 50% of the tumor volume. These vascular structures, ranging from small capillaries to cavernous vascular dilatations, were lined by one to several layers of neoplastic endothelial cells. Thick papillary outgrowths of the neoplastic endothelium extended into and often occluded the vessel lumens. The fibrous component consisted mostly of spindle cells and granulocytes, which provided the stroma for the vascular structures. The vascular and fibrous components appeared to have arisen independently. Lymphopenia accompanied by myeloid metaplasia was observed in the spleen of both SV7- and myeloproliferative sarcoma virus (MPSV)-infected mice. The blood of SV7-infected mice had a much higher level of circulating granulocytes than did that of MPSV-infected mice. The latter manifested a more advanced myeloid metaplasia, characterized by aggregates of myelomonocytic blast cells in the spleen.

Detection of circulating Dirofilaria immitis antigens in random source laboratory dogs: evaluation of two commercial serodiagnostic tests.

Two commercially available serodiagnostic tests for Dirofilaria immitis antigens were evaluated for sensitivity, specificity, predictive values, and reliability using serum from 110 random source dogs. Both tests were performed in two separate laboratories on serum samples randomized in five blocks of 22 samples each. Dogs were examined for microfilariae using the modified Knott's technique, and for adult parasites by necropsy. Forty-eight of the 110 dogs (43.6%) had either adult or juvenile parasites within the cardiopulmonary vasculature or microfilariae in the peripheral blood. Of those 48, 26 (54.2%) were amicrofilaremic and had cardiopulmonary parasite populations ranging from one to greater than 50. In both laboratories, both commercial tests failed to detect infection in eight of the 26 amicrofilaremic dogs. Three amicrofilaremic dogs were positive by both tests in both laboratories. Four dogs (3.6%) had microfilariae without adults. Two of those four dogs were negative by both commercial tests in both laboratories. One commercial test had 38 false negatives in one laboratory, 13 of which were also negative in the second laboratory. The other test had 21 false negatives in one laboratory and 20 in the other laboratory. Fourteen of these samples were falsely negative in both laboratories. False positives were low in both laboratories for both tests.

Efficacy of commercial vaccines for protecting guinea pigs against Bordetella bronchiseptica pneumonia.

Autogenous bacterins are recommended to protect guinea pigs (Cavia porcellus) against pneumonia due to Bordetella bronchiseptica. Bordetella vaccines are available commercially for several other animal species. The substantial antigenic cross-reactivity among Bordetella isolates from various animal species suggests that immunity resulting from use of these vaccines might protect guinea pigs. Groups of ten individually housed Hartley guinea pigs from a colony free of Bordetella were vaccinated with one of two commercial porcine B. bronchiseptica vaccines, a human DPT vaccine (which includes a Bordetella pertussis component), or an autogenous B. bronchiseptica bacterin. Twenty-one days following vaccination, the animals were challenged with an intranasal dose of 10(6) virulent B. bronchiseptica cells. The animals were euthanized and necropsied 15 days after challenge. The nares, nasopharynx, distal trachea and lungs were cultured. All nonvaccinated control animals developed acute signs of pneumonia, while none of the vaccinated animals developed clinical signs of disease or gross lesions. The frequency of B. bronchiseptica isolation from the lungs of animals in each vaccine group was reduced. However, approximately 70% of all animals in each vaccine group harbored B. bronchiseptica in the trachea, and almost all harbored B bronchiseptica in the nares and nasopharynx. The porcine vaccines appeared to afford protection against acute pulmonary disease in the guinea pig.