Metformin inhibits inflammatory angiogenesis in a murine sponge model.

To investigate the effects of metformin on angiogenesis, on inflammatory cell accumulation and on production of endogenous cytokines in sponge implant in mice. Polyester-polyurethane sponges were implanted in Swiss mice and metformin (40 or 400mg/kg/day) was given orally for six days. The implants collected at day 7 postimplantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) e collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant. A regulatory function of metformin on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of metformin.

Estudo comparativo da cinética de degradação ruminal de forragens tropicais em bovinos e ovinos / Comparative study of ruminal degradation kinetics of tropical forages in cattle and sheep

Estimaram-se os parâmetros da cinética de degradação ruminal in situ da fibra em detergente neutro (DgFDN) da cana-de-açúcar e das silagens de capim-elefante, de milho e de sorgo em diferentes tempos de incubação, tamanhos de partícula (1 e 2mm) e espécies (ovinos e bovinos). A DgFDN foi obtida nos tempos de incubação: 3, 6, 12, 24, 36, 48, 72, 96, 120, 144 e 240 horas. A avaliação dos tamanhos de partículas e das espécies na degradabilidade foi realizada pelo teste de identidade de modelos de regressão não linear e interpretada pela análise de fatores. As taxas de degradação da FDN (k d) também foram estimadas, matematicamente, utilizando-se apenas de dois tempos de incubação in situ (tempos 6 e 24h ou 6 e 36h). Os valores de k d estimados em 2 tempos ou 11 tempos de incubação foram comparados pelo teste t com arranjo em pares. Os valores de k d estimados com dois tempos de incubação, quando comparados com os valores obtidos em vários tempos de incubação mostraram-se similares (P>0,05). Em estudos da cinética de degradação ruminal in situ da FDN, ovinos não devem ser considerados modelos experimentais para bovinos, mas o tamanho de partícula do alimento incubado, de 1 ou 2mm, tem pouca influência nos parâmetros de degradação ruminal.

The neutral detergent fiber degradability (NDFd) of sugar-cane, and elephantgrass, corn, and sorghum silages were predicted by in situ method, with different time points, sample grind sizes (1 and 2mm) and animal species (sheep and cattle). The feedstuffs were incubated at 3, 6, 12, 24, 36, 48, 72, 96, 120, 144, 240 hours. The effects of sample grind sizes and of the species in NDFd were analyzed through the test of identity of non-linear regression models and interpreted by factor analysis. The rates of degradation of NDF (k d) were also estimated for two times of incubation in situ (times 6 and 24h or 6 and 36h), and they were compared to the k d values estimated at the in situ trial, through the t statistical test. The k d values estimated by different time points and predicted by in situ incubation times were similar (P>0.05). There is little interference of particle size in degradation parameters, and the NDF degradation in situ trials in sheep can not be used as an experimental model for cattle.

Group selection models in prebiotic evolution.

The evolution of enzyme production is studied analytically using ideas of the group selection theory for the evolution of altruistic behavior. In particular, we argue that the mathematical formulation of Wilson's structured deme model [The Evolution of Populations and Communities (Benjamin-Cumings, Menlo Park, 1980)] is a mean-field approach in which the actual environment that a particular individual experiences is replaced by an average environment. That formalism is further developed so as to avoid the mean-field approximation and then applied to the problem of enzyme production in the prebiotic context, where the enzyme producer molecules play the altruists role while the molecules that benefit from the catalyst without paying its production cost play the nonaltruists role. The effects of synergism (i.e., division of labor) as well as of mutations are also considered and the results of the equilibrium analysis are summarized in phase diagrams showing the regions of the space of parameters where the altruistic, nonaltruistic, and the coexistence regimes are stable. In general, those regions are delimitated by discontinuous transition lines which end at critical points.

Error propagation in the hypercycle.

We study analytically the steady-state regime of a network of n error-prone self-replicating templates forming an asymmetric hypercycle and its error tail. We show that the existence of a master template with a higher noncatalyzed self-replicative productivity a than the error tail ensures the stability of chains in which m < n-1 templates coexist with the master species. The stability of these chains against the error tail is guaranteed for catalytic coupling strengths K on the order of a. We find that the hypercycle becomes more stable than the chains only if K is on the order of a2. Furthermore, we show that the minimal replication accuracy per template needed to maintain the hypercycle, the so-called error threshold, vanishes as square root of n/K for large K and N < or = 4.