Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema

To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.     

Gold complexes with benzimidazole derivatives: synthesis,characterization and biological studies

Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG–DTA) analyses, and FT-IR and UV–Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC₅₀ values below 5.7 μM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.     

Association between Inflammatory Infiltrates and Isolated Monosomy 22/del(22q) in Meningiomas

Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69⁺ lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69⁺, CD63⁺, CD16⁺ and CD33⁺ cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.     

Importation route of the sickle cell trait into Portugal: contribution of molecular epidemiology.

To elucidate the origin and spread of the sickle cell trait into the Portuguese population, we examined nine polymorphic DNA markers within the beta globin gene cluster defining the haplotype. The population sample included 64 sickle-cell-gene-bearing individuals from defined Portuguese-speaking white, black, and Asian Indian populations. The nature and geographic distribution of the different beta S haplotypes in Portugal suggest that the sickle cell trait has been imported twice: between the eighth and the thirteenth centuries from the Mediterranean basin (in association with the Benin haplotype) and after the fifteenth century from black Africa over an Atlantic route (Senegal and Bantu haplotypes).     

Measuring the impact of flooding on Amazonian trees: photosynthetic response models for ten species flooded by hydroelectric dams

Increasing areas of Amazonian forest are coming under flood stress due to dam construction and greater variability in river flood levels due to climate change. The physiological responses of Amazonian trees subjected to flooding are important to understand the consequences of these changes. Irradiance response curves for photosynthesis obtained from ten tropical tree species growing in flooded areas were used to fit three empirical models. The study was done in floodplains along the Uatumã River, both upstream and downstream of the Balbina Hydroelectric Dam in Brazil’s state of Amazonas (01°55′S; 59°28′W). Ten species were studied. Models compared were: non-rectangular hyperbola, rectangular hyperbola, and exponential. All models were quantitatively adequate for fitting the response of measured data on photosynthesis to irradiance for all ten species in the non-flooding and flooding periods. Considerable variation was found among the model estimates of maximum photosynthesis (P _nmax), dark respiration (R _d) and apparent quantum yield of photosynthesis (α). For photosynthesis, the two hyperbolas overestimated P _nmax while EXP presented more realistic values. For estimating R _d, RH presented the most realistic values. To avoid unrealistic value estimates of R _d, we recommend adding measured R _d values to the regressions. The results suggest that the EXP model presented the most realistic P _nmax and α values, and, in spite of less accuracy in fitting photosynthetic irradiance curves than the RH model, it can be recommended for accessing the information used in photosynthetic irradiance curves for the leaves of tropical trees growing in Amazonian floodplains or in areas that are artificially flooded by dams.     

Superoxide Dismutase Activity and Lipid Peroxidation in the Liver of Guinea Pig Infected with Leptospira interrogans

Superoxide dismutase (SOD) activity and the degree of lipid peroxidation were studied over a two week period in guinea pigs infected with Leptospira interrogans derived from wild mice. The total SOD activity in infected host liver increased by four-fold two days after infection; this was followed by a 20% decrease resulting in levels comparable to normal, uninfected liver. During the period of decreasing SOD activity after day two, the levels of TBA-reactive material (TBARS) are increased by three-fold in infected guinea pig, liver, compared to uninfected liver. The results indicate that SOD attenuates intracellular superoxide-mediated toxic effects in guinea pigs infected with L. interrogans. In addition, electron microscopy structure demonstrates correlated pathogenic shrinkage of mitochondrial and Kupffer cell structures.     

Effect of denervation on the mitotic index of the intestinal epithelium of the rat

Summary The infradiaphragmatic section of vagi nerves at the level of the diaphragm crura causes, on the third day after surgery, a reduction of the mitotic activity in the crypts of the intestinal epithelium of the rat. Moreover there is a drastic reduction in number of the goblet cells that remain concentrated at the lower third of the villi. After the third day after vagotomy there is a tendency to normality.Sympathectomy did not affect significantly the intestinal epithelium of the rat. When both surgeries were performed together, there was no additive effect.