An experimental model for canine visceral leishmaniasis

Seven mixed-breed dogs were challenged with either promastigotes or amastigotes of Leishmania donovani infantum strains recently isolated from naturally infected dogs. Different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. Anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and Western blotting on crude antigen. Western blotting on two pure parasite proteins, dp72 and gp70-2, was also done. Mitogenic and antigen-specific stimulation of peripheral blood lymphocytes was monitored; and the haematological, clinical and parasitological parameters measured. Dogs challenged with amastigotes exhibited a more pronounced humoral response to leishmanial antigens. Only in one case was strong antigen-specific proliferation detected. Clinical signs of disease, including hypergammaglobulinaemia, enlarged lymph nodes and the presence of parasites, were also more apparent in the dogs challenged with amastigotes. None of the seven dogs died. Serum antibodies to leishmanial antigens were apparent between 1.5 to 3 months following challenge and correlated with the appearance of enlarged lymph nodes, hypergammaglobulinaemia and the presence of parasites in tissue biopsies. Serum antibodies remained chronically high in these dogs throughout the period of the study. Only one dog (1/3) challenged intravenously with promastigotes and the dog challenged intradermally with amastigotes produced transient antibody responses to leishmanial antigen.     

Chronic Morpholine Exposure of Rats

Chronic Morpholine Exposure of Rats. HARBISON, R. D., MARINO,D. J., CONAWAY, C. C., RUBIN, L. F., AND GANDY, J. (1989). FundamAppl. Toxicol. 12,491–507. The chronic toxicity and carcinogenicpotential of morpholine were evaluated in 60 Sprague-Dawleyrats/sex/group receiving morpholine at mean inhalation exposureconcentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week,for 104 weeks. Survival, body weight gains, organ weights, hematology,and clinical chemistries were normal in exposed groups and comparableto those of the control animals. The incidences of palpabletissue masses and of histologically confirmed neoplasia werecomparable among all groups, including the control groups, andwere typical of the strain and age of the rats tested. In-lifeclinical examinations revealed increased incidences of irritationaround the eyes and nares, chromadacryorrhea, and urine stainson the fur, predominately in high-dose animals. Morpholine exposurewas associated with corneal irritation seen by ophthalmoscopicexamination and confirmed microscopically as keratitis limitedto the highest exposure group. Irritation of the maxillary andnasoturbinates as indicated by infiltration of neutrophils,focal squamous metaplasia of the turbinate epithelium, and necrosisof the turbinate bone was observed in high-dose animals. Therefore,chronic exposure of rats to morpholine for 2 years at concentrationsof 150 ppm or less revealed no carcinogenic potential or chronicsystemic toxicity. Consistent with its known irritating properties,morpholine produced only local irritation, which was limitedalmost exclusively to high-dose animals.     

Subchronic and Chronic Inhalation Toxicity of Antimony Trioxide in the Rat

Fischer 344 rats were exposed by inhalation to Sb₂O₃ (antimonytrioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and23.46 mg/m³ for 6 hr/day, 5 days/week for 13 weeks followedby a 27-week observation period. Subsequently, an inhalationon-cogenicity study was conducted at exposure levels of 0, 0.06,0.51, and 4.50 mg/m³ for 12 months followed by a 12-month observationperiod. The Sb₂O₃ in the subchronic study had a mass medianaerodynamic diameter (MMAD) of 3.05 ± 0.21 microns (mean± SD) with a geometric standard deviation (GSD) of 1.57± 0.06. In the chronic study, the MMAD was 3.76 ±0.84 and the GSD was 1.79 ± 0.32. Except for the eyes,no adverse clinical observations were attributed to Sb₂O₃ ineither study. In the subchronic study, corneal irregularitieswere seen after about 2 weeks of exposure and did not abateduring the observation period. In the chronic study, ophthalmoscopicevaluation at 24 months revealed a dose-related increase incataracts of 11, 24, 28, and 32% (both sexes combined) for eachgroup, respectively. Body weights were significantly lower (6%)than the control group's weights in the 23.46 mg/m³ males inthe subchronic study. These rats did not recover this weightduring the 27-week observation period. Body weights of the femalesin both studies and males in the chronic study were unaffected.There were no Sb₂O₃ effects on clinical chemistry or he-matologyin either study. Mean absolute and relative lung weights weresignificantly increased in the 4.92 and 23.46 mg/m³ groups inthe subchronic study. The 23.46 mg/m³ group's lung weights didnot recover to control levels during the 27-week observationperiod. Lung weights for rats in the chronic study were unaffected.Microscopic changes in the lungs in the subchronic and chronicstudy were limited to subacute-chronic interstitial inflammation,increased numbers of alveolar-in-traalveolar macrophages, foreignmaterial in the alveolar-in-traalveolar macrophages in the peribronchialand perivascular (chronic study only) lymphoid aggregates andin the peribronchial lymph nodes, granulomatous inflammation/granulomas,and fibrosis. In the chronic study, any observed neoplasms occurredwith comparable incidence among all groups and were within thehistorical range for controls. Clearance of Sb₂O₃ from the lungwas burden dependent and was reduced by 80/ in the 4.50 mg/m³group in the chronic study. The previously reported studies,which found Sb₂O₃ to be a carcinogen, were run at higher lungburdens. Under the exposure conditions of the current study,Sb₂O₃ was not a carcinogen.     

EFFECT OF RETINOIC ACID IN PSORIASIS, II

Summary.— Clinical and histological features and mitotic counts have been studied in the lesions of 11 patients with psoriasis who were treated with topically applied retinoic acid ointment for a period of 3 months.
Serial biopsies were taken at monthly intervals from treated lesions in all 11 patients and from lesions treated with the unmedicated ointment base in 9.
There was no significant difference between treated and placebo groups regarding any of the parameters studied. Irritant effects of the retinoic acid were prominent in 7 patients.
The significance of these results is discussed in the light of the known mechanism of action of retinoic acid.     

Protective immunity in the rat model of congenital toxoplasmosis and the potential of excreted-secreted antigens as vaccine components

Toxoplasma infection is a major cause of severe foetal pathology both in humans and in domestic animals, particularly sheep. We have previously reported the development of an experimental model to study congenital toxoplasmosis in the rat. Here we demonstrate that, as in humans, total protection against congenital toxoplasmosis can be achieved regardless of the strain of Toxoplasma gondii used to infect rats, or when initial and challenge infections were carried out with different strains. Chronic infection is associated with a highly specific immunity that involves both B-and T-cell responses beginning at day 10 postinfection. The antibody isotype analysis revealed that whereas immunoglobulin (Ig)G2b is the major elicited isotype, no IgG1 antibodies are detected. T cell proliferation was assayed using crude Toxoplasma extracts or excretory-secretory antigens (ESA). The analysis of T cell supernatants showed the specific secretion of both interleukin-2 and interferon-gamma by activated T cells. Immunization of rats before pregnancy with either crude Toxoplasma extracts or with ESA elicited a B cell response that included antibodies of the IgG1 isotype and conferred on the newborns high levels of protection. Preliminary experiments of immunization using two HPLC-purified ESA, GRA2 and GRA5, conferred, a significant protection although to a lesser extent. This experimental model represents an attractive model for the identification of future vaccine candidates against congenital toxoplasmosis.     

The cell cycle in psoriasis

The cell cycle has been determined in eight in-patients with psoriasis. The cell cycle time for the germinative cell compartment has been found to be 91 h, and the turnover time for the epidermal compartment, beneath the keratin layer to be 120 h (5 days). The duration of the S phase (DNA synthesis) has been found to be 10 h, and that for mitosis 30 min. If it is accepted that the turnover time for the keratin layer is 2 days, then the turnover time for the epidermis in psoriasis is 7 days, and not 3–4 days as previously described.     

GASTROCAMERA STUDIES IN ROSACEA

SUMMARY.— Ten patients with rosacea were examined with the gastro-camera. No abnormality of the gastric mucosa was found. Gastric biopsy in 5 of the patients showed no histological abnormality and histochemically the succinic dehydrogenase content of the parietal cells was also normal.