Clinical applications of NGF in ocular diseases

Nerve Growth Factor (NGF) and its receptors TrkA and p75 are expressed in physiological states in the anterior and posterior segments of the human eye, where they exert several tissue-specific functions. The roles played by NGF in the homeostasis of the eye and in vision are, therefore, crucial and have been widely investigated both in vitro and in vivo, with growing evidence of an NGF-pathway alteration in several ocular diseases. In this review we describe the functions of NGF in health and diseases states of the eye, and discuss the potential therapeutic effectiveness of NGF in preliminary clinical reports performed in severe ocular diseases unresponsive to any standard treatment. In fact, pharmacodynamic studies showing that NGF administered topically on the ocular surface affects not only the ocular surface but is also able to reach the retina, optic nerve and brain, recently opened new perspectives for the treatment of challenging ocular surface diseases, optic nerve diseases, and degenerative diseases of the retina currently lacking an effective therapy.     

Soil and forest structure in the Colombian Amazon

Forests structural differences could result of environmental variations at different scales. Because soils are an important component of plant's environment, it is possible that edaphic and structural variables are associated and that, in consequence, spatial autocorrelation occurs. This paper aims to answer two questions: (1) are structural and edaphic variables associated at local scale in a terra firme forest of Colombian Amazonia? and (2) are these variables regionalized at the scale of work? To answer these questions we analyzed the data of a 6ha plot established in a terra firme forest of the Amacayacu National Park. Structural variables included basal area and density of large trees (diameter > or = 10cm) (Gdos and Ndos), basal area and density of understory individuals (diameter < 10cm) (Gsot and Nsot) and number of species of large trees (sp). Edaphic variables included were pH, organic matter, P, Mg, Ca, K, Al, sand, silt and clay. Structural and edaphic variables were reduced through a principal component analysis (PCA); then, the association between edaphic and structural components from PCA was evaluated by multiple regressions. The existence of regionalization of these variables was studied through isotropic variograms, and autocorrelated variables were spatially mapped. PCA found two significant components for structure, corresponding to the structure of large trees (G, Gdos, Ndos and sp) and of small trees (N, Nsot and Gsot), which explained 43.9% and 36.2% of total variance, respectively. Four components were identified for edaphic variables, which globally explained 81.9% of total variance and basically represent drainage and soil fertility. Regression analyses were significant (p < 0.05) and showed that the structure of both large and small trees is associated with greater sand contents and low soil fertility, though they explained a low proportion of total variability (R2 was 4.9% and 16.5% for the structure of large trees and small tress, respectively). Variables with spatial autocorrelation were the structure of small trees, Al, silt, and sand. Among them, Nsot and sand content showed similar patterns of spatial distribution inside the plot.     

Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus constriction to oxygen in mice

The fetal ductus arteriosus (DA) contracts to oxygen, and this feature, maturing through gestation, is considered important for its closure at birth. We have previously obtained evidence of the involvement of cytochrome P-450, possibly of the 3A subfamily (CYP3A), in oxygen sensing and have also identified endothelin (ET)-1 as the attendant effector for the contraction. Here, we examined comparatively wild-type (WT) and CYP3A-null (Cyp3a(-/-)) mice for direct validation of this concept. We found that the CYP3A subfamily is represented only by CYP3A13 in the WT DA. CYP3A13 was also detected in the DA by immunofluorescence microscopy, being primarily colocalized with the endoplasmic reticulum in both endothelial and muscle cells. However, a distinct signal was also evident in the plasma membrane. Isolated DAs from term WT animals developed a sustained contraction to oxygen with transient contractions superimposed. Conversely, no tonic response occurred in Cyp3a(-/-) DAs, whereas the phasic response persisted unabated. Oxygen did not contract the preterm WT DA but caused a full-fledged contraction after retinoic acid (RA) treatment. RA also promoted an oxygen contraction in the Cyp3a(-/-) DA. However, responses of RA-treated WT and Cyp3a(-/-) mice differed in that only the former abated with ET-1 suppression. This implies the existence of an alternative target for RA responsible for the oxygen-induced contraction in the absence of CYP3A13. In vivo, the DA was constricted in WT and Cyp3a(-/-) newborns, although with a tendency to be less narrowed in the mutant. We conclude that oxygen acts primarily through the complex CYP3A13 (sensor)/ET-1 (effector) and, in an accessory way, directly onto ET-1. However, even in the absence of CYP3A13, the DA may close postnatally thanks to the contribution of ET-1 and the likely involvement of compensating mechanism(s) identifiable with an alternative oxygen-sensing system and/or the withdrawal of relaxing influence(s) operating prenatally.     

Effect of ACE inhibition on glomerular permselectivity and tubular albumin concentration in the renal ablation model

Despite the central role of tubular plasma proteins that characterize progressive kidney diseases, protein concentrations along the nephron in pathological conditions have not been quantified so far. We combined experimental techniques and theoretical analysis to estimate glomerular and tubular levels of albumin in the experimental model of 5/6 nephrectomy (Nx) in the rat, with or without angiotensin-converting enzyme (ACE) inhibition. We measured glomerular permselectivity by clearance of fluorescent Ficoll and albumin and used theoretical analysis to estimate tubular albumin. As expected, 5/6 Nx induced an elevation of the fractional clearance of the largest Ficoll molecules (radii >56 ?, P < 0.05), increasing the importance of the shunt pathway of the glomerular membrane and the albumin excretion rate (119 ± 41 vs. 0.6 ± 0.2 mg/24 h, P < 0.01). ACE inhibition normalized glomerular permselectivity and urinary albumin (0.5 ± 0.3 mg/24 h). Theoretical analysis indicates that with 5/6 Nx, an increased albumin filtration overcomes proximal tubule reabsorption, with a massive increase in average albumin concentration along the tubule, reaching the highest value of >2,500 μg/ml at the end of the collecting duct. ACE inhibition improved glomerular permselectivity, limiting albumin filtration under proximal tubule reabsorption capacity, with low albumin concentration along the entire nephron, averaging <13 μg/ml at the end of the collecting duct. These results reinforce our understanding of the mechanisms of renal disease progression and the effects of angiotensin II antagonism. They also suggest that evaluation of tubular protein concentration levels could help to identify patients at risk of kidney disease progression and to improve clinical management.     

Literature review of acoustic and ultrasonic tomography in standing trees

Key message

High-resolution imaging is possible if high-frequency sensors are used together with a signal-processing and inversion algorithm that is well suited to a low signal-to-noise ratio and the effect of wood anisotropy.

Abstract

Wood is a biological growth medium, and given that standing trees adapt themselves in their growth to environmental conditions, their material properties vary with age. These changes result in variations that are far more complex than anisotropy. Wood quality and intraspecific variability can thus be studied to gain an understanding of the development mechanisms of trees, and this can be useful for clonal selection and the management of tree communities. A number of techniques are available to determine wood properties in standing trees, but the signal-processing approaches currently used are not always robust and do not always provide the image resolution needed in the particular cases of acoustic or ultrasonic tomography. This review paper thus aims to present important aspects that should be taken into account when using tomography techniques and addresses a number of open problems. A brief review of current non-destructive wood imaging techniques is initially presented followed by a comparison of the protocols, methods and models used in acoustic and ultrasonic tomography. The devices cited were studied in terms of measurement systems and signal processing. The analysis aimed to highlight and analyze the advantages and disadvantages of each device and describe challenges and trends. The effect of various parameters is discussed: frequency, signal-to-noise ratio, number of sensors and inversion algorithm. General conclusions are then drawn in relation to future signal-processing work in the acoustic and ultrasonic tomography of standing trees.     

Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: Role of oxidative stress

Background

Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes.

Methods

Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35 mg/kg, i.p.) (control + L and fructose + L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration.

Results

Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91^phox and p22^phox) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration.

Conclusions

Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration.

General significance

Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes.