Efecto inhibitorio del dietilestilbestrol sobre aislamientos clínicos de Candida albicans sensibles y resistentes a los azoles

BackgroundCandida albicans is a microorganism frequently involved in several infections; the patient's oral cavity, caries niches or periodontal disease can sometimes be the reservoir.. The fungal resistance to the available treatments, among other reasons, has led to the search for new antifungal alternatives.AimsTo carry out a comparative study of the in vitro effects of diethylstilboestrol (DES) and fluconazole (FLZ) on the growth of clinical strains of C. albicans.MethodsSeven strains of C. albicans were used: a) one FLZ-sensitive culture collection strain, ATCC 90028 (ATCC); b) four oral isolates from four oncological patients with periodontal disease (period 8, 9, 10, and 11); and c) two oral isolates from an AIDS patient with oropharyngeal candidiasis: one FLZ- sensitive (2-76), and another FLZ- resistant (12-99). The MIC was evaluated by standard spectrophotometric techniques using the CLSI (M27-A3) guidelines. The inhibitory concentration 50% (IC₅₀) was calculated using functional analysis with the Graph Pad software.ResultsDES inhibited the growth of all C. albicans strains, whether sensitive or resistant to FLZ. Experimental data fitted non-linear functions of inhibitor concentration versus response. Minimum inhibitory concentrations (MIC) for DES and FLZ were as follows: 28.18 µg/ml and 4.90 µg/ml (ATCC); 17.16 µg/ml and 3.14 µg/ml (period); 27.64 µg/ml and 4.22 µg/ml (2-76); 6.16 µg/ml and 438.19 µg/ml (12-99), respectively.ConclusionsDES showed antifungal activity on all clinical C. albicans strains isolated from patients with dental and medical diseases. It showed the highest potency on the FLZ-resistant isolate.     

Activity of antifungal agents alone and in combination against echinocandin-susceptible and -resistant Candida parapsilosis strains

Background

Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options.

Hepatic effects of long‐term tamoxifen administration to cycling female rats

The metabolic implications of tamoxifen (TAM) used as preventive therapy of young premenopausal women with high risk of breast cancer is unknown. To unravel this problem, an animal model of long‐term TAM administration to cycling young adult female rats was used to evaluate its effects in the liver. Body weight and food consumption were monitored, and at the end of the study, both parameters were lower in TAM‐treated rats. Biochemical measurements showed that the TAM administration induced alterations in serum levels of liver enzymes when compared with control rats at different stages of the estrous cycle. In TAM‐treated rats, lower glycogen storage was observed in hepatocytes close to the portal areas and pericentrolobular cells had a higher concentration of glycogen. Liver sections of TAM‐treated rats presented mild steatosis—a high percentage of area occupied by lipid droplets in the hepatocytes. These results point to metabolic changes upon long‐term TAM therapy.     

Different ways to die in a changing world: Consequences of climate change for tree species performance and survival through an ecophysiological perspective

Anthropogenic activities such as uncontrolled deforestation and increasing greenhouse gas emissions are responsible for triggering a series of environmental imbalances that affect the Earth's complex climate dynamics. As a consequence of these changes, several climate models forecast an intensification of extreme weather events over the upcoming decades, including heat waves and increasingly severe drought and flood episodes. The occurrence of such extreme weather will prompt profound changes in several plant communities, resulting in massive forest dieback events that can trigger a massive loss of biodiversity in several biomes worldwide. Despite the gravity of the situation, our knowledge regarding how extreme weather events can undermine the performance, survival, and distribution of forest species remains very fragmented. Therefore, the present review aimed to provide a broad and integrated perspective of the main biochemical, physiological, and morpho‐anatomical disorders that may compromise the performance and survival of forest species exposed to climate change factors, particularly drought, flooding, and global warming. In addition, we also discuss the controversial effects of high CO₂ concentrations in enhancing plant growth and reducing the deleterious effects of some extreme climatic events. We conclude with a discussion about the possible effects that the factors associated with the climate change might have on species distribution and forest composition.     

Forest Fragmentation Reduces Seed Dispersal of Duckeodendron cestroides, a Central Amazon Endemic

Fragmentation that alters mutualistic relationships between plants and frugivorous animals may reduce the seed dispersal of trees. We examined the effects of forest fragmentation on the distributions of seeds and seedlings of a Central Amazon endemic tree, Duckeodendron cestroides . In the dry seasons of 2002–2004, seeds and first-year seedlings were counted within wedge-shaped transects centered around Duckeodendron adults in fragments and nearby continuous forests at the Biological Dynamics of Forest Fragmentation Project. Analyses showed that fragmentation reduced seed dispersal quantity and quality. The percent and distance of dispersed seeds were both twice as great in continuous forest as in fragments. The distances of each tree's five furthest dispersed seeds were three times greater in continuous forest than fragments. Over the 3-yr study, 20 times more seeds were dispersed more than 10 m from parent crowns in continuous forest than fragments. A regression analysis showed more dispersed seeds at all distances in continuous forest than fragments. Dispersal differences were strong in 2002 and 2004, years of large fruit crops, but weak or absent in 2003, when fruit production was low. As distance from parent crowns increased, the number of seedlings declined more rapidly in fragments than continuous forest. Distance-dependent mortality between the seed and seedling stages appeared to be more important in continuous forest than fragments. This research provides ample, indirect evidence demonstrating that forest fragmentation can result in the breakdown of a seed dispersal mutualism, potentially jeopardizing the reproduction of a rare, tropical tree.     

An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells

Recent studies demonstrated the importance of the mitochondrial ATP in the regulation of a novel long-chain fatty acid generation/export system in mitochondria of diabetic rat heart. In steroidogenic systems, mitochondrial ATP and intramitochondrial arachidonic acid (AA) generation are important for steroidogenesis. Here, we report that mitochondrial ATP is necessary for the generation and export of AA, steroid production and steroidogenic acute regulatory protein induction supported by cyclic 3'-5'-adenosine monophosphate in steroidogenic cells. These results demonstrate that ATP depletion affects AA export and provide new evidence of the existence of the fatty acid generation and export system involved in mitochondrial cholesterol transport.     

Towards complete sets of farnesylated and geranylgeranylated proteins

Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS) has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase) and can be queried for verification status, type of modifying enzymes (anchor type), and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins-for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs) used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain-containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for the selective farnesylation of targets with an evolutionary conserved modification site.