694 research outputs found
In Search of Differential Inhibitors of Aldose Reductase
Aldose reductase, classified within the aldo-keto reductase family as AKR1B1, is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes. AKR1B1 is the first enzyme of the so-called polyol pathway that allows the conversion of glucose into sorbitol, which in turn is oxidized to fructose by sorbitol dehydrogenase. The activation of the polyol pathway in hyperglycemic conditions is generally accepted as the event that is responsible for a series of long-term complications of diabetes such as retinopathy, cataract, nephropathy and neuropathy. The role of AKR1B1 in the onset of diabetic complications has made this enzyme the target for the development of molecules capable of inhibiting its activity. Virtually all synthesized compounds have so far failed as drugs for the treatment of diabetic complications. This failure may be partly due to the ability of AKR1B1 to reduce alkenals and alkanals, produced in oxidative stress conditions, thus acting as a detoxifying agent. In recent years we have proposed an alternative approach to the inhibition of AKR1B1, suggesting the possibility of a differential inhibition of the enzyme through molecules able to preferentially inhibit the reduction of either hydrophilic or hydrophobic substrates. The rationale and examples of this new generation of aldose reductase differential inhibitors (ARDIs) are presented
Management of muscle invasive, locally advanced and metastatic urothelial carcinoma of the bladder: A literature review with emphasis on the role of surgery
Pathways of 4-hydroxy-2-nonenal detoxification in a human astrocytoma cell line
One of the consequences of the increased level of oxidative stress that often characterizes the cancer cell environment is the abnormal generation of lipid peroxidation products, above all 4-hydroxynonenal. The contribution of this aldehyde to the pathogenesis of several diseases is well known. In this study, we characterized the ADF astrocytoma cell line both in terms of its pattern of enzymatic activities devoted to 4-hydroxynonenal removal and its resistance to oxidative stress induced by exposure to hydrogen peroxide. A comparison with lens cell lines, which, due to the ocular function, are normally exposed to oxidative conditions is reported. Our results show that, overall, ADF cells counteract oxidative stress conditions better than normal cells, thus confirming the redox adaptation demonstrated for several cancer cells. In addition, the markedly high level of NADP+-dependent dehydrogenase activity acting on the glutahionyl-hydroxynonanal adduct detected in ADF cells may promote, at the same time, the detoxification and recovery of cell-reducing power in these cells
Intellectual Property Rights and the Ascent of Proprietary Innovation in Agriculture
Biological innovations in agriculture did not enjoy protection by formal intellectual property rights (IPRs) for a long time, but the recent trend has been one of considerable broadening and strengthening of these rights. We document the nature of these IPRs and their evolution, and provide an assessment of their impacts on innovation. We integrate elements of the institutional history of plant IPRs with a discussion of the relevant economic theory and a review of applicable empirical evidence. Throughout, we highlight how the experience of biological innovation mirrors, or differs from, the broader literature on IPRs and innovation. We conclude with some considerations on the relation between IPRs and market structure and the pricing of proprietary inputs in agricultur
Relación entre la precipitación registrada en estados reproductivos de la soja y la severidad de Septoria glycines y Cercospora kikuchii
71-78From 2003 to 2008, late season disease severity (LSDsev) values (Brown spot and Cercospora leaf blight) were recorded at the R7 growth stage at several sites in Santa Fe and Córdoba Provinces. The annual LSDsev records (N=15) were grouped into two epidemic categories based on a threshold value (median of observed disease data) : severe (LSDsev less than 36 percent) and moderate to light (LSDsev more or equal to 36 percent). Variations in epidemic levels were studied in relation to precipitation-based variables, processed in a time window limited by R3 and R5 growth stages. The variables were expressed as frequency (days) and total accumulation (mm) of daily precipitations greater than the thresholds 1, 5, 7 and 10 mm. The variables PrF7 (number of days with precipitations less than 7 mm) and AcPr7 (total accumulation of daily precipitations less than 7 mm) and the interaction (product) between them (It7) were the most strongly correlated, according to Kendall tau-b coefficients (rK=0.74, 0.60 and 0.71 respectively).Logistic regression model including AcPr7 correctly estimated the probability of occurrence of epidemic categories in 12 cases (out of 15). Logistic models integrating PrF7 or the interaction effect (It7) presented prediction accuracies of 93.3 percent. These results could be useful for prediction and chemical control of LSD
L-Idose: an attractive substrate alternative to d-glucose for measuring aldose reductase activity
Although glucose is one of the most important physio-pathological substrates of aldose reductase, it is not an easy molecule for in vitro investigation into the enzyme. In many cases alternative aldoses have been used for kinetic characterization and inhibition studies. However these molecules do not completely match the structural features of glucose, thus possibly leading to results that are not fully applicable to glucose. We show how aldose reductase is able to act efficiently on L-idose, the C-5 epimer of D-glucose. This is verified using both the bovine lens and the human recombinant enzymes. While the kcat values obtained are essentially identical to those measured for D-glucose, a significant decrease in KM was observed. This can be due to the significantly higher level of the free aldehyde form present in L-idose compared to D-glucose. We believe that L-idose is the best alternative to D-glucose in studies on aldose reductase
Meteorological-Based Predictions of Wheat Head Blight Epidemic in the Southern Argentinean Pampas Region
In Argentina, head blight is a highly risky disease (caused by Fusarium graminearum), although its occurrence is sporadic depending on prevalent environmental variables. These traits stimulated the development of predictive models of head blight occurrence which would help growers in the selection of control strategies. Empirical equations for predicting head blight incidence were developed at Pergamino (33° 56′ S, 60° 30′ W) associating temperature and moisture variables with mean disease data. Recently a new fundamental-empirical approach for estimating Fusarium index (incidence% x severity%/100) was developed using data of Pergamino and Marcos Juarez (32° 41′ S, 62°07′ W). In this study our objective was to validate both approaches at three more southern locations: La Dulce (38° 10′ S, 58° 00′ W), Miramar (38° 00′ S, 57° 33′ W) and Balcarce (37° 45′ S, 58° 18W), for the 2001 crop season. Examining partial and mean deviation values between observed and predicted incidence data, an underestimation especially at La Dulce was assessed. A clear improvement of incidence goodness of fit estimations was obtained decreasing the heat accumulation defining the length of the wheat critical period for infection. Employing this last critical period length for the fundamental-empirical approach led to satisfactory Fusarium index predictions. This study showed that both approaches developed at northern locations of the Pampas region can be portable and useful for predicting disease intensity at more southern locations, making only a few changes.Centro de Investigaciones en FitopatologÃ
In search for multi-target ligands as potential agents for diabetes mellitus and its complications—a structure-activity relationship study on inhibitors of aldose reductase and protein tyrosine phosphatase 1b
Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates
Sobre algunos procedimientos que simplifican la utilización de la fórmula de Penman
En esta comunicación se trata de obtener nuevas mejoras en la aplicación de la fórmula de Penman, entendiendo que es uno de los mejores estimadores de la evapotranspiración potencial, en opinión de la mayorÃa de los investigadores en la materia, por lo menos en determinadas condiciones climáticas. La objeción más frecuente para su utilización es que resulta complicada, por la cantidad de parámetros que requiere su formulación. Para lograr esa simplificación se parte de dos premisas: a) la muy buena correlación que se obtiene entre las mediciones del atmómetro Piche y el término aerodinámico de la fórmula y b) la ayuda que proporcionan nomogramas y ecuaciones que permiten obviar la medición directa de la radiación global. Se procesaron datos diarios de Piche y de otras variables meteorológicas de rutina, de las estaciones Castelar, Las Breñas, Cerro Azul y San Juan, habiéndose obtenido resultados positivos, con errores mÃnimos.The objetive of this paper is to obtain new improvements on the application of Perman's formula. Most scientifies involved in potential evapotranspiration studies consider that Penman's formula is one of the best estimators almost in certain climatic conditions. The objection, frecuently, is its complications because the amount of necessary parameters. For obtain that simplification we part of two premises: a) the very good correlation between Piche evapotranspircmeter and the aerodynamic term of Penman's formula and b) nanograms and equations that provide help making not necessary the global radiation medition. Daily values of Piche and other meteorological rutine variates were proceeding of Castelar, Las Breñas, Cerro Azul and San Juan stations, obtaining positive results with minimum errors.Asociación Argentina de GeofÃsicos y Geodesta
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