RESUMO
Endocrine monitoring of non-human primates (NHP) via faecal metabolites of steroid hormones appears as a useful non-invasive alternative to evaluate the reproductive status of free living NHP, as well as of those kept in captivity but of difficult handling. However, validation is needed with plasma values before its application in the field. The aim of the present study was to monitor the different phases of the menstrual cycle from the new world NHP Sapajus apella and S. libidinosus. For this, hormonal and faecal plasma levels of E2, P4 and cortisol were assessed during different days of the menstrual cycle, together with colpocitology. The mean duration of the menstrual cycle according colpocitology was of 21.7 and 21.0 days for S. apella and S. libidinosus, respectively. These values were similar to those observed via plasma analysis, i.e. 22.7 and 20.3 days for S. apella and S. libidinosus, respectively. The day of plasmatic E2 peak was set as Day -1 and the estimated day of ovulation was set as Day 0 and occurred two days earlier in S. libidinosus than in S. apella females. In both species, it was observed a delay in faecal E2 peak of six days for S. apella and of 11 days for S. libidinosus when compared with the plasma peak. A maximum P4 plasma concentration was observed in the middle of luteal phase in S. apella and in S. libidinosus, both at around day 5. However, faecal P4 peaks were detected at days 9 and 8 in S. apella and S. libidinosus, respectively. Mean plasma and faecal cortisol levels were variable during all ovulatory cycle of S. apella and S. libidinosus females. Although no exact correlation was observed between plasmatic and faecal profile of steroid hormone, faecal samples were able to indicate ovarian cycle phase, being important to assess the reproductive status of the females applying a non-invasive method.
RESUMO
O interesse pelas células tronco fascina os cientistas ao redor do mundo há mais de 100 anos, como reportado nos estudos pioneiros (1877) do embriologista alemão Ernst Haeckel que mencionou sobre a formação de organismos completes a partir de poucas células originais (Ramalho-Santos & Willenbring, 2007). Ao longo dos anos, evidências foram sendo geradas de que células tronco presentes em embriões são responsáveis pela formação de todos os tecidos de um individuo adulto e que mesmo apos sua formação, estes organismos ainda possuem células tronco em seus tecidos que são capazes de se proliferarem promovendo a renovação/reposição celular.(AU)
Assuntos
Animais , Células-Tronco , Transplante de Células-Tronco/história , Técnicas Reprodutivas/veterináriaRESUMO
Cell phenotype evaluation enables better understanding of the rejection process in experimental transplantation. We studied allograft survival and the mechanisms associated with rejection in a murine model of skin transplantation in the absence of immunosuppression or after FTY720 or sirolimus (SRL) administration for 21 days. Leukocyte phenotype was evaluated in the peripheral blood, spleen, axillary lymph nodes, thymus gland, and skin graft using flow cytometry at 5 days posttransplantation. Treatment with FTY720 plus SRL increased skin allograft survival in association with lymphopenia, reduced CD11b+ and CD3+CD4+ cell percentages in the graft, decreased CD3+CD4+, CD3+CD8+, and CD11b+ cell counts in lymphoid organs, and decreased CD4+CD8+ cell count in the thymus. These results suggest that increased allograft survival in animals treated with FTY720 plus SRL is due to possible impairment of antigen presentation or recognition in the graft and secondary lymphoid organs, and decreased emigration of mature thymocytes to the periphery.
Assuntos
Imunossupressores/uso terapêutico , Propilenoglicóis/uso terapêutico , Sirolimo/uso terapêutico , Transplante de Pele/imunologia , Esfingosina/análogos & derivados , Animais , Contagem de Células , Cloridrato de Fingolimode , Citometria de Fluxo , Sobrevivência de Enxerto/imunologia , Contagem de Leucócitos , Leucócitos/citologia , Leucócitos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Fenótipo , Pele/citologia , Esfingosina/uso terapêutico , Transplante HomólogoRESUMO
In transplantation, parasite diseases are transmitted from the donor, or appear as de novo infections, or activate from a dormant insource as a consequence of immunosuppression. Clinical findings have shown that an intact immune system is crucial to prevent recurrence of Leishmania infection. We used BALB/c and C57BL/6 mice to evaluate the role of FTY720 in leishmaniasis. Mice inoculated with Leishmania (Leishmania) amazonensis were followed over 7 weeks for foot thickness measurements after initiation of FTY720 treatment. After 10 days of treatment, spleen, blood, and the foot were harvested for evaluation. BALB/c showed greater evident foot thickness than C57BL/6 mice. Oral treatment with FTY720 (1 mg/kg/d) over 10 days produced the same outcome. Increases in CD4(+) and CD8(+) T cells were observed after infection; FTY720 treatment was associated with a decrease in CD4(+) T cells only in BALB/c mice, whereas CD8(+) T cells were decreased in both mice strains. CD11b(+) expression decreased after infection with a discrete increase after FTY720 treatment. Lymphopenia was observed among all FTY720-treated mice. In conclusion, we observed that FTY720 produced no worse an outcome as monotherapy in established infections with L (L) amazonensis.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Imunossupressores/farmacologia , Leishmania mexicana , Leishmaniose Cutânea/imunologia , Propilenoglicóis/farmacologia , Esfingosina/análogos & derivados , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Cloridrato de Fingolimode , Citometria de Fluxo , Membro Posterior/efeitos dos fármacos , Membro Posterior/patologia , Leishmaniose Cutânea/patologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Esfingosina/farmacologia , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
The goal in transplantation is to obtain immunosuppressant combinations that decrease the incidence of acute and chronic rejection but cause fewer side effects. FTY720 is a new immunomodulator that prevents experimental allograft rejection without inhibiting T-cell activation. It is currently under clinical investigation for multiple sclerosis. We investigated whether FTY720 in combination with sirolimus (SRL) could cause renal toxicity in C57BL/6 mice when administered for 21 days. Serum creatinine and 24-hour urinary creatinine concentrations were assessed by enzymatic colorimetric assays. Urinary protein concentration was measured by the Bradford protein assay. Whereas serum creatinine levels were increased in FTY720 + SRL-treated animals, there were no changes in urinary volume, urinary protein levels, serum urea concentration, creatinine clearance, and kidney structure. Our findings suggested that FTY720 monotherapy for multiple sclerosis and other diseases could play an important immunomodulatory role without causing the side effects frequently observed with other transplantation regimens.
Assuntos
Creatinina/sangue , Imunossupressores/farmacologia , Propilenoglicóis/farmacologia , Sirolimo/farmacologia , Esfingosina/análogos & derivados , Animais , Creatinina/urina , Diurese/efeitos dos fármacos , Cloridrato de Fingolimode , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Transplante de Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Propilenoglicóis/efeitos adversos , Propilenoglicóis/uso terapêutico , Proteinúria , Sirolimo/uso terapêutico , Esfingosina/efeitos adversos , Esfingosina/farmacologia , Esfingosina/uso terapêuticoRESUMO
Calcineurin inhibitors such as cyclosporine (CsA) and tacrolimus (FK506) show similar efficacy to prevent rejection within the first year after organ transplantation. However, their use is limited by side effects, such as kidney damage, hypertension, new-onset diabetes, and hyperlipidemia. The consensus opinion suggests that compared with CsA, FK506 has fewer negative effects on blood pressure, serum lipids, and renal function. Nevertheless, FK506 use is associated with a higher incidence of posttransplantation diabetes mellitus. FTY720 is a new compound that has shown beneficial effects in animal models of rejection in transplantation, ischemia/reperfusion injury, autoimmune diseases, and tumor development. Our aim was to investigate whether FTY720 + tacrolimus association could provide additional immunosuppression without causing renal toxicity. FTY720 as a monotherapy or in association with FK506 was administered to C57BL/6 mice for 21 days to prevent skin graft rejection and to evaluate renal function and structure. Increased skin allograft survival in the FTY720 + FK506 group was associated with decreased cell numbers in the spleen, blood, and axillary lymph nodes. Changes in major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1) expressions in splenocytes were also found in this group. The major effects already described for FK506 (diabetes) or FTY720 (lymphopenia) were observed after 21 days administration even when the drugs were associated. FTY720 associated with FK506 caused fewer changes in kidney structure, and blood glucose levels were lower than in FK506 monotherapy.
Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Rim/fisiologia , Propilenoglicóis/uso terapêutico , Transplante de Pele/fisiologia , Esfingosina/análogos & derivados , Tacrolimo/uso terapêutico , Animais , Cloridrato de Fingolimode , Citometria de Fluxo , Rim/efeitos dos fármacos , Testes de Função Renal , Camundongos , Transplante de Pele/imunologia , Esfingosina/uso terapêutico , Transplante HomólogoRESUMO
An enzyme presenting kallikrein-like activity (designated sK1) was purified from the supernatant of Schistosoma mansoni adult worm homogenate. The enzyme cleaves bradykinin from purified rat plasma kininogen. Activity was optimal at pH 9.0 and the enzyme showed amidolytic activity, since it hydrolysed the kallikrein synthetic substrate D-Pro-Phe-Arg-p-nitroanilide. The activity of sK1 upon rat plasma kininogen was strongly inhibited by the serine proteinase inhibitors phenylmethanesulfonyl fluoride, aprotinin or soybean trypsin inhibitor, but not by ethylenediaminetetraacetic acid or sodium tetrathionate. The molecular mass of sK1, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, was 66 kDa and the pI value, estimated by analytical chromatofocusing, was 4.2. Physical and chemical properties suggest that sK1 is a serine proteinase of the kallikrein family. Evidence is presented which suggests that sK1 is a component of the tegumental surface of the parasite and the levels of its activity in the male adult worm are approximately 21 times higher than those in the female adult worm. The intravenous injection of 3 micrograms of sK1 into an anaesthetized rat induced a drastic reduction in the arterial blood pressure of the animal. This effect lasted for about 1 min, and was followed by a progressive recovery of the arterial pressure. Neither bradycardia nor cardiac arrhythmias were noticed, suggesting a peripheral vasodilation effect. The presence of sK1 on the surface of adult male worms could play an important role in the wandering capacity of coupled worms into the visceral vasculature of the host.