Ocular surface involvement in patients with neurofibromatosis type 1 syndrome.

PURPOSE: The aim of this study is to evaluate ocular surface morphological and functional changes in patients with neurofibromatosis type 1 (NF1). METHODS: Twenty-eight patients with NF1 and 14 healthy subjects were included in this study. All participants underwent a medical history collection, a complete ophthalmological examination including slit lamp exam and assessment of best-corrected visual acuity (BCVA), corneal sensitivity, and lacrimal function (Schirmer test and fluorescein tear break-up time test). Corneal nerves' morphology and endothelial cells density were evaluated by in vivo corneal confocal microscopy (IVCM). Tear and conjunctiva epithelium samples were collected to evaluate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) tear levels and conjunctival expression of their receptors TrkA and p75NTR. RESULTS: Patients with NF1 showed a significant decrease of FTBUT when compared with healthy subjects (p < 0.001). Corneal sensitivity was ≤ 50 mm in 46% of NF1 patients. IVCM showed a significant increase of corneal nerve branching and of corneal endothelial cells density. No significant difference was observed between the two groups on NGF and BDNF tear levels and conjunctival expression of their receptors. CONCLUSION: This study demonstrated the presence of ocular surface changes in NF-1 patients including decrease of tear stability and of corneal sensitivity. Patients with NF1 also showed changes of corneal endothelial cells' density.

Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.

OBJECTIVE: The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders. METHODS: A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. RESULTS: Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). CONCLUSIONS: The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism.

This study was designed to investigate the molecular effects of diphenyl diselenide ((PhSe)2) on cholesterol metabolism in HepG2 cell line in a dose-dependent manner. The protein levels of both total and phosphorylated 3- hydroxy-3-methylglutaryl coenzyme A reductase (HMGR and P-HMGR), low-density lipoprotein receptors (LDLr) and the proteins involved in their regulatory network were analyzed by Western blotting, and the effect of (PhSe)2 on HMGR activity was measured. Additionally, we also evaluated the effects of this compound on glucose transporter type 4 (GLUT4) translocation using fluorescence microscopy in L6 skeletal muscle cell line. Results demonstrated that (PhSe)2 increased P-HMGR, HMGR, and LDLr protein levels as well as simvastatin treatment, which was used as positive control, without directly affecting HMGR activity. We observed that both long- and short-term HMGR regulation mechanisms are involved in the effects of (PhSe)2, as this compound was able to augment Sterol regulatory element binding proteins (SREBP)-1 and Insulin induced gene (Insig)1 protein levels, and to increase AMP activated kinase (AMPK) activation state. We also found that, in L6 skeletal myotubes, 10 µM (PhSe)2 increases GLUT4 translocation through AMPK activation. Taken together, these findings suggest that (PhSe)2 can modulate the expression of some proteins involved in cholesterol and glucose cell metabolism.

Regulation of cholesterol biosynthetic pathway in different regions of the rat central nervous system.

AIM: In this study, we investigated the regulatory network of the key and rate-limiting enzyme of cholesterol biosynthetic pathway, the 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) in different brain regions, to add new insight about lipid metabolism and physiology in the central nervous system (CNS). METHODS: HMGR levels and activation state and the proteins involved in the enzyme regulatory network were analysed by Western blot in hippocampus, cortex, cerebellum and brain stem of adult male rats. RESULTS: HMGR protein level and phosphorylation state exhibit a specific pattern in each brain area analysed, according to the levels and activation state of the proteins responsible for the short- and long-term regulation of the enzyme. Moreover, low-density lipoprotein receptor expression displays a similar trend to that of HMGR. CONCLUSIONS: The obtained data indicate that cholesterol biosynthesis could be differently modulated in each brain region in adult male rat and emphasize marked differences in HMGR and low-density lipoprotein receptor regulation. The results provide new insights into the intricate network that regulates cholesterol homoeostasis in the adult CNS in connection with the regional needs of this molecule.

3-Hydroxy-3-methylglutaryl coenzyme A reductase regulation by antioxidant compounds: new therapeutic tools for hypercholesterolemia?

Oxidative stress has recently been implicated in the pathogenesis of various diseases such as diabetes and coronary artery disease whose main modifiable risk factor is the abnormal level of lipids and/or lipoproteins in the blood. Thus, the maintenance of cholesterol homeostasis together with the reduction of intracellular reactive oxygen species content could partially prevent the occurrence of atherosclerotic phenomena. Owing to the ability exerted by some antioxidants to modulate the activity and/or the protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rate-limiting enzyme of cholesterol biosynthetic pathway), their use as additional approach to the management of hypercholesterolemia should be taken into account. Here we provide an up-dated overview of the antioxidants whose ability to affect 3-hydroxy-3-methylglutaryl coenzyme A reductase either in the short- or in the long-term regulations has been reported.

Design methodology for multi-pumped discrete Raman amplifiers: case-study employing photonic crystal fibers.

This paper proposes a new design methodology for discrete multi-pumped Raman amplifier. In a multi-objective optimization scenario, in a first step the whole solution-space is inspected by a CW analytical formulation. Then, the most promising solutions are fully investigated by a rigorous numerical treatment and the Raman amplification performance is thus determined by the combination of analytical and numerical approaches. As an application of our methodology we designed an photonic crystal fiber Raman amplifier configuration which provides low ripple, high gain, clear eye opening and a low power penalty. The amplifier configuration also enables to fully compensate the dispersion introduced by a 70-km singlemode fiber in a 10 Gbit/s system. We have successfully obtained a configuration with 8.5 dB average gain over the C-band and 0.71 dB ripple with almost zero eye-penalty using only two pump lasers with relatively low pump power.

Numerical comparison between conventional dispersion compensating fibers and photonic crystal fibers as lumped Raman amplifiers.

In this paper we discuss the use of photonic crystal fibers (PCFs) as discrete devices for simultaneous wideband dispersion compensation and Raman amplification. The performance of the PCFs in terms of gain, ripple, optical signal-to-noise ratio (OSNR) and required fiber length for complete dispersion compensation is compared with conventional dispersion compensating fibers (DCFs). The main goal is to determine the minimum PCF loss beyond which its performance surpasses a state-of-the-art DCF and justifies practical use in telecommunication systems.

A new acceleration technique for the design of fibre gratings.

In this paper we propose a novel acceleration technique for the design of fibre gratings based on Genetic Algorithm (GA). It is shown that with an appropriate reformulation of the wavelength sampling scheme it is possible to design high quality optical filters with low computational effort. Our results will show that the proposed technique can reduce significantly the GA's processing time.