Regulatory cross-talk of mouse liver polyamine and methionine metabolic pathways: a systemic approach to its physiopathological consequences.

Both polyamines and methionine derivatives are nitrogen compounds directly related to the regulation of gene expression. In silico predictions and experimental evidence suggest a cross-talk between polyamine and methionine metabolism in mammalian tissues. Since liver is the major organ that controls nitrogen metabolism of the whole organism, it is the best tissue to further test this hypothesis in vivo. In this work, we studied the effects of the chronic administration of a methionine-supplemented diet (0.5% Met in drinking water for 5 months) on the liver of mice (designated as MET-mice). Metabolic and proteomic approaches were performed and the data obtained were subjected to biocomputational analysis. Results showed that a supplemental methionine intake can indeed regulate biogenic amine metabolism in an in vivo model by multiple mechanisms including metabolic regulation and specific gene demethylation. Furthermore, putative systemic effects were investigated by molecular and cellular biology methods. Among other results, altered expression levels of multiple inflammation and cell proliferation/death balance markers were found and macrophage activation was observed. Overall, the results presented here will be of interest across a variety of biomedical disciplines, including nutrition, orphan diseases, immunology and oncology.

Consórcio de manjericão (Ocimum basilicum L. ) e alface sob dois arranjos de plantas / Intercrop of basil (Ocimum basilicum L. ) and lettuce under two plant arrangements

Ocimum basilicum L. (Lamiaceae) é comercialmente utilizada como aromatizante ou condimento preparado com suas folhas verdes e aromáticas, que podem ser usadas frescas ou secas. O objetivo deste trabalho foi avaliar a produção de biomassa de manjericão sob duas ou três fileiras no canteiro, consorciado ou não com alface. O manjericão e a alface foram alocados no campo em experimento conjunto, sendo constituídos cinco tratamentos da seguinte forma: duas fileiras solteiras de manjericão (M2) espaçadas de 0,50 m; três fileiras solteiras de manjericão espaçadas de 0,33 m (M3); quatro fileiras solteiras de alface espaçadas de 0,25 m (A4); duas fileiras solteiras de manjericão consorciadas com quatro fileiras de alface (M2A4) e três fileiras de manjericão consorciada com quatro fileiras de alface (M3A4). O delineamento utilizado foi em blocos casualizados, com oito repetições. As plantas de alface foram colhidas aos 48 dias após o transplantio e as de manjericão, em duas épocas, aos 96 e 113 dias após o transplantio (DAT). O consórcio não influenciou as áreas foliares nem as produções de folhas ou inflorescências do manjericão nem de cabeças comerciais ou não-comerciais da alface. No entanto, quanto ao arranjo de plantas, na segunda época de colheita, as plantas de manjericão cultivadas sob duas fileiras tiveram maior área foliar (2.076,99 cm² planta-1) e maior massa fresca de folhas (5.012,53 kg ha-1). Considerando-se que os valores da Razão de Área Equivalente - RAE na primeira e segunda colheita do manjericão foram maiores que 1,0, conclui-se que o consórcio manjericão com alface é viável. Recomenda-se o arranjo de três fileiras de manjericão alternadas com quatro fileiras de alface, e colheita aos 96 DAT, por ter tido RAE de 2,01.

Ocimum basilicum L. (Lamiaceae) is used commercially as flavoring or seasoning that was prepared with its green and aromatic leaves, which can be used fresh or dried. The aim of this work was to evaluate yield of biomass of basil under two or three rows per plot, intercropped or not with lettuce. Basil and lettuce were planted at field in joined experiment, which established five treatments: two rows of basil in monocrop system (M2) spaced 0.50 m; three rows of basil in monocrop system spaced 0.33 m (M3); four rows of lettuce in monocrop system spaced 0.25 m (A4); two rows of basil in monocrop system and intercropped with four rows of lettuce (M2A4) and three rows of basil intercropped with four rows of lettuce (M3A4). Used design was randomized blocks with eight replications. Lettuce plants were harvested on 48 days after transplanting and basil plants were harvested in two dates, on 96 and on 113 days after transplanting (DAT). Intercrop did not influence on foliar area neither on yields of leaves of inflorescences of basil neither on commercial or non-commercial lettuce heads. Although, regarding plant arrangement, on second harvest date, basil plants that were cultivated under two rows had the greatest foliar area (2,076.99 cm² plant-1) and the greatest fresh masses of leaves (5,012.53 kg ha-1). Considering that the values of Equivalent Area Ration in the first and the second harvest of basil were higher than 1.0. It was concluded that to intercrop basil with lettuce is viable. It is recommended the arrangement of three rows of basil alternated with four rows of lettuce, with harvested at 96 DAT, because it had EAR of 2.01.

(-)-Epigallocatechin-3-gallate interferes with mast cell adhesiveness, migration and its potential to recruit monocytes.

Mast cells are multipotent effector cells of the immune system. They are able to induce and enhance angiogenesis via multiple pathways. (-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea and a putative chemopreventive agent, was reported to inhibit tumor invasion and angiogenesis, processes that are essential for tumor growth and metastasis. Using the human mast cell line HMC-1 and commercial cDNA macroarrays, we evaluated the effect of EGCG on the expression of angiogenesis-related genes. Our data show that among other effects, EGCG treatment reduces expression of two integrins (alpha5 and beta3) and a chemokine (MCP1), resulting in a lower adhesion of mast cells associated with a decreased potential to produce signals eliciting monocyte recruitment. These effects on gene expression levels are functionally validated by showing inhibitory effects in adhesion, aggregation, migration and recruitment assays.

Development of an expression macroarray for amine metabolism-related genes.

Cationic amino acids are the precursors of biogenic amines, histamine from histidine, and putrescine, spermidine and spermine from arginine/ornithine (and methionine), as well as nitric oxide. These amines play important biological roles in inter- and intracellular signaling mechanisms related to inflammation, cell proliferation and neurotransmission. Biochemical and epidemiological relationships between arginine-derived products and histamine have been reported to play important roles in physiopathological problems. In this communication, we describe the construction of an expression macroarray containing more than 30 human probes for most of the key proteins involved in biogenic amines metabolisms, as well as other inflammation- and proliferation-related probes. The array has been validated on human mast HMC-1 cells. On this model, we have got further support for an inverse correlation between polyamine and histamine synthesis previously observed on murine basophilic models. These tools should also be helpful to understand the amine roles in many other inflammatory and neoplastic pathologies.

Multicenter evaluation of efficacy, tolerability and safety of a new first-line antihypertensive drug, isradipine, in a Latin-American population.

Isradipine, a new antihypertensive dihydropyridine calcium antagonist, was evaluated for its efficacy, tolerability, and safety in 91 ambulatory patients who had mild-to-moderate hypertension. The design of the present study included a two-week wash-out period after confirmation of disease, followed by 12 weeks of active treatment with 2.5 mg isradipine twice daily. Patients were switched from other antihypertensive drugs, mainly diuretics and beta-blockers. The dose of isradipine remained virtually unchanged throughout the study and resulted in a mean decrease of 22 mm Hg in systolic blood pressure (SBP) (P less than .00001) and 19 mm Hg in diastolic blood pressure (DBP) (P less than .00001). Heart rate was unchanged (difference of -1 beats/min), as was the mean body weight of the study patients. Isradipine was generally well tolerated. Side effects were few and, when present, tended to diminish and eventually disappear during the treatment period. All of the clinical laboratory parameters tested and electrocardiograph intervals remained unchanged. In conclusion, these results indicate that isradipine is a novel drug which is highly effective and well tolerated in the treatment of mild to moderate hypertension in this group of patients.

Modulation of ventricular parasystole by extraneous depolarizations.

The ectopic cycle length of a ventricular parasystole was influenced in a predictable fashion (modulated) by nonparasystolic beats. Although the interectopic intervals were not multiples of the ectopic cycle length (as in "classical" parasystole), the diagnosis could be established because: a) nonparasystolic beats falling during the first half of the cycle produced an 8-12% shortening of the ectopic cycle length; and b) nonparasystolic beats occurring during the second half of the cycle decreased the ectopic cycle length by 9-14%. The events occurring in this case are further proof that the classical criteria for the diagnosis of parasystole have to be reevaluated.