Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.

Avaliou-se o perfil metabólico de 40 ovinos Santa Inês, inteiros, com peso vivo médio inicial de 17±1,7kg,, submetidos à restrição alimentar seguida de realimentação em confinamento, distribuídos em quatro tratamentos: 0, 20, 40 e 60% de restrição alimentar. Dois ensaios foram desenvolvidos, um referente à restrição e outro à realimentação. Para tanto, foi utilizado delineamento experimental inteiramente ao acaso, com quatro tratamentos e 10 repetições, e distribuído em fatorial cruzado 4x3. Observou-se na fase de restrição que os níveis de fósforo foram mais altos nos animais sob restrição alimentar; o mesmo ocorrendo na fase final para as concentrações de proteínas totais (PT), albumina (Alb) e colesterol total. A gama-glutamiltransferase (GGT) decresceu de forma linear com o aumento da restrição. No segundo ensaio, verificou-se que as concentrações de PT, Alb, globulina, colesterol total, lipoproteína de alta densidade, GGT e magnésio (Mg) apresentaram diferença (P<0,05) entre os períodos de coleta. Já na restrição prévia, observou-se comportamento linear decrescente para GGT e interação tratamento versus período de coleta para a concentração de cálcio. Os níveis de restrição alimentar afetaram o metabolismo proteico e não interferiram no metabolismo energético, e a realimentação resultou em alteração no metabolismo proteico, energético e mineral.

The objective of this study was to evaluate the metabolic profile of 40 Santa Inês sheep, whole, with average weight of 17±1,7kg, submitted to food restriction followed by refeeding in confinement, distributed in four treatments: 0, 20, 40 and 60% restriction food. Two tests were developed, one for restriction and one for refeeding. In this experiment a completely randomized design was used, with four treatments and 10 repetitions, distributed in a factorial 4x3 crossover. In the constraint phase it was observed that phosphorus levels were higher in animals under food restriction, this also occurred in the final stage for of total protein (TP), albumin (Alb) and total cholesterol concentrations. The gamma-glutamyl transferase (GGT) decreased linearly with increasing restriction. On the second trial it was found that concentrations of PT, Alb, globulin, total cholesterol, high density lipoprotein, GGT and Mg were similar (P<0,05) between collection periods. In the previous restriction, a decreasing linear behavior and interaction treatment for GGT versus collection period for the concentration of calcium was observed. The levels of food restriction affect protein metabolism and did not interfere with energy metabolism, and feedback resulted in changes in protein, energy and mineral metabolism.

Apoptosis is a well-known specific process of cell death that normally occurs in physiological situations such as tissue or organ development and involution. During tumor growth there is a balance between proliferation and cell death which involves apoptotic mechanisms. In the present study genomic DNAs from 120 breast tumor biopsies were analyzed by agarose gel electrophoresis and none of them presented the fragmentation pattern characteristic of the apoptosis process. However, 33% of the 105 breast cancer patients clearly showed the apoptotic pattern when DNA from blood cells was analyzed. None of the DNAs from healthy volunteer blood cells showed any trace of apoptosis. Since the breast cancer patients were not receiving chemo- or hormone therapy, the possible relationship between blood cortisol levels and the apoptotic pattern found in patient blood cells was investigated. Using a chemoluminescence immunodetection assay, similar cortisol levels were observed in breast cancer patient sera presenting or not apoptotic blood cells and in healthy volunteer sera. Analysis of the clinical data obtained from 60 of these patients showed that patients bearing tumors of smaller size (under 20 mm) were more susceptible to the apoptotic effect in blood cells. According to the Elston grade, it was observed that 7 of 12 patients with grade III tumors (58%) presented apoptotic peripheral blood cells, in contrast to 10 of 48 patients with grade I and grade II tumors. These observations may reflect the immunosuppression characteristic of some breast cancer patients, which may contribute to tumor growth. Therefore, further studies are necessary to elucidate the factor(s) involved in such massive blood cell death.