Edema palpebral unilateral secundario a demodicosis granulomatosa / Unilateral palpebral oedema secondary to granulomatous demodicosis

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Edema palpebral secundario a leishmaniasis cutánea / Eyelid oedema secondary to cutaneous leishmania

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The effects of fluoxetine and buspirone on self-injurious and stereotypic behavior in adult male rhesus macaques.

The effects of two serotonergic agents--fluoxetine, a serotonin (5-HT) reuptake inhibitor, and buspirone, a 5-HT 1a agonist--on rates of self-injurious and stereotypic behavior were examined in 15 adult male Macaca mulatta. All animals received a placebo for 2 weeks followed by either buspirone or fluoxetine for 12 weeks. Behavior was monitored using a focal sampling technique throughout the study and for 2 weeks post-study. Cerebrospinal fluid (CSF) samples and body weights were obtained pre-study, at the ends of placebo and treatment phases, and post-study. Fluoxetine and buspirone were significantly effective in reducing rates of self-biting during treatment weeks 1 to 8 and self-directed stereotypic behavior during weeks 5 to 12 and post-treatment. No significant effect of either treatment on hair-plucking, stereotypic pacing, saluting, or head tossing was identified. The duration of neutral behavior increased, and rates of scratching and yawning decreased in the buspirone-treated condition. In the fluoxetine-treated condition, rates of yawning, scratching, and self-directed grooming were higher overall compared with those of buspirone-treated animals, and rates of scratching increased significantly (P < 0.05) in weeks 9 to 12; these findings suggest that animals in the fluoxetine-treated condition experienced higher levels of anxiety throughout the study. In both treatment conditions, concentrations of CSF 5-HIAA (5-HT metabolite) were significantly lower (P < 0.05) than placebo concentrations. Fluoxetine and buspirone may be efficacious for treatment of self-injurious and self-directed stereotypic behavior in macaques. Further studies are required to determine the optimal dosages and treatment length.

Effect of adrenalectomy on ethanol-associated changes in lymphocyte cell numbers and subpopulations in thymus, spleen, and gut-associated lymphoid tissues.

Consumption of ethanol (ETOH) by experimental animals and human beings is associated with elevated serum levels of corticosteroids. One of the most robust findings associated with ETOH consumption is a loss of lymphocytes from thymus and spleen, as well as from peripheral lymphoid organs to include mesenteric lymph nodes and Peyer's patches, which are lymphoid organs associated with the gastrointestinal tract. To study the role of corticosteroids in loss of cells from thymus, spleen, and gut-associated lymphoid organs, adrenalectomized (ADX) or intact C57Bl/6 mice were fed a liquid diet containing ETOH (to supply 36% of calories as ETOH) or an isocaloric control diet with a pair-feeding protocol. Loss of lymphocytes from all lymphoid organs was associated closely with serum corticosterone levels in both ETOH-fed and pair-fed groups. ETOH-fed ADX animals showed much less cell loss than did ETOH-fed intact animals. However, there was still an association between ETOH consumption and cell loss when cell loss in ETOH-fed ADX animals was compared with that in ADX pair-fed and ADX chow-fed groups. In both intact and ADX animals ETOH consumption was associated with a loss of immature (CD4(+) and CD8(+)) cells from the thymus. These data lead to the suggestion that corticosteroids are responsible for most of the cell loss from thymus, spleen, mesenteric lymph nodes, and Peyer's patches in association with ETOH consumption. Some cell loss, however, is independent of corticosteroids. The data presented here also support the suggestion that cell loss from lymphoid organs could be the result of nutritional factors.

Dose response to ethanol-containing liquid diets for use in a murine model for studies of biological effects due to ethanol consumption.

Dose-response experiments were performed to establish an optimum concentration of ethanol (EtOH) in liquid diet formulations for use with a murine model (C57B1/6) of potential biological effects attributable to EtOH consumption. An optimum concentration was predetermined to be the highest EtOH concentration consumed by mice without resulting in a loss of body weight. Feeding trials were performed using EtOH concentrations that ranged from 25 to 36% ethanol-derived calories (EDC) during 7-day experiments, or 10 to 30% EDC fed during 21-day experiments. The parameters studied included body weight changes, diet consumptions, daily g EtOH kg-1 body weight, as well as differences in mononuclear cell numbers from the spleen, thymus, and bone marrow. Diet consumptions by the EtOH groups and pair-fed (PF) groups were monitored by weight rather than by volume. During either 7-day or 21-day trials, diet consumptions were lower by groups receiving diets of higher EtOH concentrations; however, daily EtOH intake was maximal by groups fed diets of 25% EDC in all experiments. These mice also gained weight, whereas mice maintained on 30% EDC did not gain weight, and mice maintained on diets of 33 or 36% EDC lost significant body weight. Body weight changes in PF groups were similar to their respective EtOH group. Changes in mononuclear cell numbers of the spleen and thymus paralleled the changes seen in body weights. In the 7-day trials, cell counts declined progressively in groups maintained on diets of high EDC (> or = 30% EDC) or their PF controls. From the 21-day trials, cell counts of both the 30% EDC group and their PF controls declined, compared with all other groups. Together, the conclusion drawn from these findings was that nutritional stress was principally responsible for the mononuclear cell depletions. This contradicts previous reports and highlights the need for strict attention to the pairfeeding paradigm to avoid masking a nutritional component of such studies through overfeeding of the PF controls. Liquid diets of 25% EDC were determined to be optimal for immunological studies using a murine model, because this concentration maximizes EtOH consumption and maintains body weight of the experimental animals.

Role of decomposition products in sodium methyldithiocarbamate-induced immunotoxicity.

Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological changes in B6C3F1 mice. The most prominent effects of SMD include a decrease in thymus weight and percentage of CD4+CD8+ thymocytes, an increase in spleen weight, an increase in the percentage of neutrophils in the blood, a decrease in the percentage of lymphocytes in the blood, and a decrease in natural killer (NK) cell activity in the spleen. The mechanism by which SMD causes these changes is unknown, and the relative importance of the parent compound and its decomposition products is not known. In addition, it is not known if these effects are unique to mice, or if other mammals are affected similarly. This prompted the present investigation of the major decomposition product of SMD, methylisothiocyanate (MITC), and two minor products, methylamine and carbon disulfide, in mice. Equimolar dosages of methylamine and carbon disulfide caused minimal immunological changes, and these changes were not characteristic of those noted for SMD. In contrast, MITC significantly decreased thymus weight and cellularity and changed peripheral white blood cell populations in a manner similar to that noted for an equimolar dosage of SMD. However, MITC did not significantly affect NK cell activity or increase spleen weight. Thus, MITC is probably responsible for some of the immunological changes noted in SMD-treated mice. The remaining changes are not produced by MITC, methylamine, or carbon disulfide. Thus, it is likely that the parent compound or a synergistic action of the parent compound with one or more of the decomposition products is responsible for these remaining changes (increased spleen weight and decreased splenic NK cell activity). Data are also presented that indicate that SMD-induced thymic atrophy occurs in rats as well as mice and that the dosage required to decrease thymus weight by 50% is lower for rats than for mice. Investigations of other mammals are needed to indicate SMD's potential as a human immunotoxicant and to compare the role of MITC in the immunotoxic effects of SMD in different species.

Rat, mouse and human neutrophils stimulated by a variety of activating agents produce much less nitrite than rodent macrophages.

The role of reactive nitrogen intermediates (RNI) in the antimicrobial activities of neutrophils from various mammalian species is unclear. However, it has been reported that rodent neutrophils possess the inducible form of nitric oxide synthase and that inflammatory neutrophils from rats produce potentially antimicrobial levels of RNI. In the present study, neutrophils from humans, rats and mice were evaluated for production of nitrite, a stable end-product of RNI. Human neutrophil preparations (> 95% neutrophils) isolated from peripheral blood were stimulated for 2-24 hr with agents known to trigger the Ca(2+)-dependent constitutive nitric oxide synthase, or to stimulate synthesis of the inducible nitric oxide synthase. Superoxide dismutase was added to some cultures to decrease the levels of superoxide, a compound reported to react with RNI and yield products other than nitrite. Even though the cells were viable and responsive to stimuli, they did not produce nitrite concentrations indicative of antimicrobial potential. Preparations of inflammatory (casein-elicited) mouse neutrophils also failed to produce high concentrations of nitrite. Inflammatory rat neutrophils (2.5 x 10(6)/ml) produced nitrite concentrations of approximately 40 microM in 24-hr cultures, but plots of nitrite production versus cell number for neutrophil and macrophage preparations indicated that contaminating macrophages could account for all the nitrite production in the neutrophil preparations. Thus, neutrophils from rats, mice and humans seem comparable in their inability to produce high levels of nitrite in response to a variety of stimuli. This suggests that in most circumstances the constitutive nitric oxide synthase known to be present in these cells is limited to the production of low levels of nitric oxide for intercellular signalling. In addition, this raises questions about the presence or functional status of inducible nitric oxide synthase in rodent neutrophils.

Disparate effects of representative dithiocarbamates on selected immunological parameters in vivo and cell survival in vitro in female B6C3F1 mice.

Recent studies indicate that sodium methyldithiocarbamate is immunotoxic. Major effects of this compound in female B6C3F1 mice include decreased thymus weight, increased spleen weight, and decreased natural killer (NK) cell activity. The effects of other dithiocarbamates on these parameters are not known, and the immunotoxic potential of this important class of compounds is uncertain. In the present study, the effects of sodium methyldithiocarbamate (SMD), sodium diethyldithiocarbamate (DEDTC), and disodium ethylene-bis(dithiocarbamate)(EBD) on thymus weight, spleen weight, and NK cell activity were compared in female B6C3F1 mice. SMD caused significant loss of thymic weight following oral administration at 200, 225, or 300 mg/kg/d for 7 d and caused significant suppression of splenic NK cell activity at doses of 150, 225, or 300 mg/kg/d for 7 d. In contrast, a dose of 1000 mg/kg/d of DEDTC was required to decrease significantly thymus weight or increase spleen weight, and the only significant change produced by EBD was a slight increase in spleen weight at a dose of 675 mg/kg/d. EBD and DEDTC did not affect NK cell activity at any dose tested. Dithiocarbamates are known to be cytotoxic for a variety of cell types, and it seemed possible that SMD might be more potent in vivo than EBD or DEDTC because it was more cytotoxic than these compounds. However, direct measurement of the cytotoxicity of all three compounds toward splenocytes and thymocytes in vitro demonstrated that SMD and EBD are approximately equally potent (EC50 from 6.1 to 10.5 microM), whereas DEDTC is much more potent (EC50 from 0.13 to 0.15 microM). Of the three compounds examined in this study, only SMD affected thymus weight, spleen weight, and splenic NK cell activity in vivo. Thus, this pattern of immunological effects is not produced by all dithiocarbamates. In addition, the data demonstrate that differences in the potency of SMD, DEDTC, and EBD in vivo do not correlate with their relative cytotoxic potencies in vitro.

Evaluation of nitrite production by human monocyte-derived macrophages.

Reactive nitrogen intermediates are important in the anti-tumor and anti-microbial activities of rodent macrophages, but it is not known whether this is the case for human macrophages. In the present study, nitrite concentrations in vitro were used as an indicator of reactive nitrogen intermediate production by mouse, rat, and human macrophages. Human macrophages derived by culturing peripheral blood monocytes did not consistently produce detectable nitrite levels in response to any stimulus examined. Human macrophages were viable and metabolically active as indicated by the MTT assay, and their respiratory burst response to phorbol myristate acetate was increased following incubation with Interferon-gamma, as expected for typical macrophages. In contrast, rat or mouse peritoneal macrophages produced nitrite concentrations of approximately 20-100 microM in response to lipopolysaccharide, Interferon-gamma, or both. These results demonstrate substantial differences in the production of nitrites by rodent and human macrophages. Because of the heterogeneity among macrophage populations, these findings may not be applicable to all human macrophage populations, but they suggest a need for caution in extrapolating from rodent studies regarding the role of reactive nitrogen intermediates in anti-tumor or anti-microbial functions of human macrophages.