The Effect of Ascorbic Acid on Mancozeb-Induced Toxicity in Rat Thymocytes.

Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defence systems in cells. The effect of mancozeb on the cells of a primary lymphoid organ has not been studied. In the present study, the effects of mancozeb (0.2, 2 and 5 µg/ml) or mancozeb+ascorbic acid (100 µg/ml), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 µg/ml of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 µg/ml of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.

The role of gut hormones in appetite regulation (review).

Eating process is an aggregate of complex and different forms of behavior. Its regulation is based on energy homeostasis and appetite control which includes two components: the homeostatic and the hedonistic control. Important signals in appetite regulation are gut-derived hormones. They are produced by enteroendocrine cells in response to nutrient and energy intake, and achieve their effects by influencing brain structures involved in food intake regulation. The key brain structure involved in this process is the hypothalamus. Gut hormones reach the hypothalamus from the circulation or by the vagal nerve via the nucleus of the solitary tract. Among gut peptides, ghrelin is the only orexigenic hormone, leading to an increase in food intake and body weight. All others, such as cholecystokinin, glucagon like peptide-1, oxyntomodulin, peptide tyrosine tyrosine or pancreatic polypeptide, are anorexigenic, leading to decrease in food intake. Also, gut-derived endocannabinoids exert orexigenic effect on appetite. Keeping in mind the growing problem of obesity, the crucial issue when considering gut derived peptides is to understand their mechanisms of acting because of potential role in clinical therapy, and discovering long-lasting gut peptides or their analogues, with no or minimal side effects.

A case of chronic myeloid leukemia without Ph1 translocation.

A case of chronic myeloid leukemia (CML) with a short survival (11 months) is described. Cytogenetic peculiarities of the bone marrow cells analyzed by G-banding consisted of a Ph1 chromosome with no translocation and a translocation t(5;13). Hematological characteristics were marked leukocytosis and massive splenomegaly. After treatment with busulfan complete hematological remission was achieved, followed by the appearance of a normal clone. However, 6 months later the patient entered the blastic crisis and a hyperdiploid clone appeared. The usual chemotherapy was given, but the patient responded only partially and died with a prevalence of pathologic myeloblasts in the bone marrow, corresponding to progression of the hyperdiploid clone.