The present study was designed to determine the effects of physical training on the development of cancer induced by the injection of Ehrlich tumor cells in mice. Male Swiss mice were subjected to a swim training protocol (5 days/wk for 6 wk, 1 h at 50% of maximal capacity-trained groups) or remained sedentary in their cages (sedentary groups). The inoculation of Ehrlich tumor cells was performed at the end of the fourth week, and animals were killed after 6 wk of training. Heart and solid tumor weights were recorded, and tumor volumes were calculated. Portions of the tumors were used for the evaluation of macrophages and neutrophil accumulation or fixed in neutral 10% buffered formalin for histological analysis. The tumor volume and weight were, respectively, approximately 270% and 280% greater in sedentary mice than in trained mice. Macrophage infiltration in the tumor tissue was significantly lower in trained mice (0.65 +/- 0.16 vs. 1.78 +/- 0.43 macrophages x 10(3) in the sedentary group). Moreover, neutrophil accumulation in tumors was slightly reduced after exercise training, and the amount of tumor cells was reduced in trained mice. Exercise capacity was substantially increased in trained mice, as determined by a 440% increase in the exercise time at 50% of maximal capacity. In summary, swim training retarded the development of Ehrlich tumors in mice, accompanied by a reduction in macrophage infiltration and neutrophil accumulation. These findings provide conceptual support for clinical observations that controlled physical activities may be a therapeutically important approach to preventing cancer progression and may improve the outcome of cancer treatment.
The spiny rat (Proechimys guyannensis) is a neotropical rodent that is used in biomedical research, particularly research related to chronic resistance to epilepsy and infectious diseases. To our knowledge, there are few reports concerning the reproductive biology of this species. Therefore, besides providing basic biometric and morphometric data, in the present study we investigated testis function and spermatogenesis in adult spiny rats. The mean testis weight and gonadosomatic index obtained were 1.63 ± 0.2 g and 1.15 ± 0.1% respectively. Based on the development of the acrosomic system, 12 stages of the seminiferous epithelium cycle were characterized. Stages VI and VII presented the highest frequencies (~17-19%), whilst stages II to V showed the lowest frequencies (~2-4%). The most advanced germ cell types labelled at 1 h or 20 days after BrdU injections were respectively preleptotene/leptotene spermatocytes at stage VII and elongated spermatids at stage III. The mean duration of one cycle was 7.5 ± 0.01 days and the entire spermatogenic process lasted 33.7 ± 0.06 days (~4.5 cycles). The seminiferous tubules (ST) occupied ~96 ± 1% of the testis parenchyma, whereas Leydig cells comprised only 1.5 ± 0.4%. The number of Sertoli cells (SC) per testis gram and the SC efficiency (spermatids/SC) were respectively 78 × 106 ± 11 × 106 and 7.9 ± 1. The daily sperm production per testis gram (spermatogenic efficiency; daily sperm production (DSP)/g/testis) was 78 × 106 ± 8 × 106. To our knowledge, this spermatogenic efficiency is among the highest found for mammals investigated to date and is probably related to the very short duration of spermatogenesis and the very high ST percentage and SC number obtained for this species.
To assess the importance of carbohydrate moieties to the antiangiogenic activity of plasminogen fragments, we cloned the fragment corresponding to amino acids Val 79 to Thr 346 (Kint3-4) that presents the three glycosylation sites. The activity of glycosylated and unglycosylated Kint3-4 was tested in murine sponge implant model. We observed a significant decrease in the neovascularization on the sponge after treatment with Kint3-4 by histological examination and determination of the hemoglobin levels. The effects were more intense with the glycosylated than the unglycosylated protein. Technecium-labeled red blood cells confirmed the inhibition of cell infiltration in the implanted sponge. Studies using melanoma B16F1 implanted in a mouse demonstrated that treatment with glycosylated Kint3-4 (0.15 nmol ⁄ 48 h) during 14 days suppresses tumor growth by 80%. The vascular endothelial growth factor mRNA levels on the tumor were reduced after treatment. Kint3-4 is a potent plasminogen fragment that has been found to inhibit tumor growth. (Cancer Sci 2010; 101: 453-459) T he vasculature is an important organ. Angiogenesis, the formation of new blood vessels from pre-existing capillaries, is a fundamental and complex process involved in reproduction, cellular development, and pathological events, such as inflammation, diabetic retinopathy, endometriosis, adiposity, and cancer.(1,2) During tumor growth and chronic inflammation, neovascularization is required for the provision of nutrients and oxygen and to mobilize host cells, such as leukocytes. (3,4) The new vascular network demands an extensive interplay between cells, soluble factors, and extracellular components, and is tightly regulated by the expression of angiogenic and angiostatic factors.(5,6) A wide range of molecules mediates angiogenesis by acting directly or indirectly on endothelial cells via accessory cells, such as polymorphonuclear leukocytes.(7-9) Among these molecules are fragments of the plasmatic glycoprotein plasminogen, which have different angiostatic activity. Plasminogen presents five segments that, because of their specific structure, were designated as kringles (K1-K5). The antiproliferative activity of plasminogen is shared by K1, K2, K3, and K4 being the most potent angiostatin (K1-4 corresponding to amino acids Cys 84 -Cys 435 ), followed by K2-3. (10,11) The sequence numbering of plasminogen starts with Glu 1 of the mature protein or Glu 20 for human plasminogen when including signal peptide. K2 and K3 individually or in combination exhibit weak activity when compared with K2-3, and a combination of K1-3 and K4 resulted in the same activity level of K1-4.(11) It was also observed that the most potent inhibitor of endothelial cell angiogenesis of is K1-3 (amino acids Cys 84 -Cys 333 of plasminogen). (12) These results show that proteolytic processing with the exposure of antiangiogenic sites, kringle conformation, interkringle interaction, and carbohydrate moieties can alter efficiency and function. Despite the anti-angiogenic activity...
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ABSTRACT. The factors related to cannibalistic behavior of dams in a Wistar rat colony are identified and analyzed. The maternal genetic effects were tested as a random effect by the method of generalized linear models. The season at parturition, the dam´s age at parturition and the density of the room at parturition were tested as fixed effects, whereas the litter size at birth was tested as a co-variable. The genetic effect of the dam was significant for the number of cannibalized pups. Although the season at parturition, the dam´s age and room density on the day of parturition were not individually significant (p > 0.05), most of the interactions between the variation sources were significant (p < 0.05). Cannibalism occurred mostly in dams aged over 241 days, with parturition during spring. So that occurrences of cannibalism could be avoided, dams with the smallest number of cannibalized pups should be selected, coupled to dams younger than 241 days, breeding during spring. The above strategies may reduce the number of couples in the vivarium and increase their production efficiency.Keywords: laboratory animals, maternal behavior, infanticide, rodents.Efeito do ambiente e da matriz sobre o canibalismo em filhotes de ratos Wistar RESUMO. O objetivo deste estudo foi identificar os fatores relacionados ao comportamento de canibalismo das fêmeas em uma colônia de ratos Wistar. Os efeitos genéticos maternos foram testados como efeito aleatório usando o método dos modelos lineares generalizados. A estação do parto, a idade da fêmea ao parto e a densidade da sala ao parto foram testados como efeitos fixos e o tamanho da ninhada ao nascimento foi testado como covariável. O efeito genético da matriz foi significativo para o número de filhotes canibalizados. A estação do ano ao parto, a idade da matriz e a densidade da sala no dia do parto quando testados separadamente não foram significativos (p > 0,05), porém, a maioria das interações entre estas fontes de variação foram significativas (p < 0,05). O canibalismo ocorreu em maior frequência em fêmeas com idade superior a 241 dias durante a primavera. Para evitar o canibalismo na população estudada, recomenda-se a seleção de fêmeas com menor número de filhotes canibalizados e a maior utilização de matrizes com idade inferior a 241 dias durante a primavera. Estas estratégias podem promover a redução do número de casais necessários no biotério e aumentar sua eficiência reprodutiva.Palavras-chave: animais de laboratório, comportamento materno, infanticídio, roedores.
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