Alzheimer's Disease Risk and Progression: The Role of Nutritional Supplements and their Effect on Drug Therapy Outcome.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly population. Despite significant advancements in understanding the genetic and molecular basis of AD, the pathology still lacks treatments that can slow down or reverse the progression of cognitive deterioration. Recently, the relationship between nutrient deficiency and dementia onset has been highlighted. AD is in fact a multifactorial pathology, so that a multi-target approach using combinations of micronutrients and drugs could have beneficial effects on cognitive function in neurodegenerative brain disorders leading to synaptic degeneration. Primarily, this review examines the most recent literature regarding the effects of nutrition on the risk/progression of the disease, focusing attention mostly on antioxidants agents, polyunsaturated fatty acids and metals. Secondly, it aims to figure out if nutritional supplements might have beneficial effects on drug therapy outcome. Even if nutritional supplements showed contrasting evidence of a likely effect of decreasing the risk of AD onset that could be studied more deeply in other clinical trials, no convincing data are present about their usefulness in combination with drug therapies and their effectiveness in slowing down the disease progression.

In vitro effects of resveratrol on oxidative stress in diabetic platelets.

To evaluate the in vitro effects of resveratrol (RSV) incubation on platelets from compensated and decompensated diabetic patients in order to use it as an adjuvant therapy. The study was performed on 77 diabetic patients and divided into two phases: 29 compensated and 48 decompensated diabetic platelets were analyzed at recruitment (T0) and after in vitro RSV incubation (20 µg/ml) for 3 h at 37 °C (T1). Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes TMA-DPH and DPH were determined. In vitro RSV incubation counteracts oxidative damage associated with diabetes and its complications; it is able to improve platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it enhances antioxidant systems' functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels in both compensated and decompensated patients. Such platelet functionality enhancement suggests a new method of secondary prevention of complications associated with platelet dysfunction. Being free from one of the major risks associated with many antidiabetic agents, it can be assumed that RSV utilization in the diabetic diet may have a preventive and protective role in the progression of diabetic oxidative damage.

Spatially resolved analysis of Kα x-ray emission from plasmas induced by a femtosecond weakly relativistic laser pulse at various polarizations.

Spatially resolved K-shell spectroscopy is used here to investigate the interaction of an ultrashort laser pulse (λ=800 nm, τ=40 fs) with a Ti foil under intense irradiation (Iλ(2)=2×10(18)Wµm(2)cm(-2)) and the following fast electron generation and transport into the target. The effect of laser pulse polarization (p, s, and circular) on the Kα yield and line shape is probed. The radial structure of intensity and width of the lines, obtained by a discretized Abel deconvolution algorithm, suggests an annular distribution of both the hot electron propagation into the target and the target temperature. An accurate modeling of Kα line shapes was performed, revealing temperature gradients, going from a few eV up to 15-20 eV, depending on the pulse polarization. Results are discussed in terms of mechanisms of hot electron generation and of their transport through the preplasma in front of the target.

Research advances in plant-made flavivirus antigens.

Outbreaks of flaviviruses such as dengue (DV), yellow fever (YFV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV) and West Nile (WNV) affect numerous countries around the world. The fast spread of these viruses is the result of increases in the human population, rapid urbanisation and globalisation. While vector control is an important preventive measure against vector-borne diseases, it has failed to prevent the spread of these diseases, particularly in developing countries where the implementation of control measures is intermittent. As antiviral drugs against flaviviruses are not yet available, vaccination remains the most important tool for prevention. Although human vaccines for YFV, TBEV and JEV are available, on-going vaccination efforts are insufficient to prevent infection. No vaccines against DENV and WNV are available. Research advances have provided important tools for flavivirus vaccine development, such as the use of plants as a recombinant antigen production platform. This review summarises the research efforts in this area and highlights why a plant system is considered a necessary alternative production platform for high-tech subunit vaccines.

Directional bremsstrahlung from a Ti laser-produced x-ray source at relativistic intensities in the 3-12 keV range.

Front and rear side x-ray emission from thin titanium foils irradiated by ultraintense laser pulses at intensities up to ≈5 × 10(19) W/cm2 was measured using a high-resolution imaging system. Significant differences in intensity, dimension, and spectrum between front and rear side emission intensity in the 3-12 keV photon energy range was found even for 5 µm thin Ti foils. Simulations and analysis of space-resolved spectra explain this behavior in terms of directional bremsstrahlung emission from fast electrons generated during the interaction process.

Tracking propagation of ultrashort intense laser pulses in gases via probing of ionization.

We use optical interferometry to study the propagation of femtosecond laser pulses in gases. We show the measurements of propagation in a nitrogen gas jet and we compare the results with propagation in He under the same irradiation conditions. We find that in the case of nitrogen, the detailed temporal structure of the laser pulse can be tracked and visualized by measuring the phase and the resulting electron-density map. A dramatically different behavior occurs in He gas jets, where no details of the temporal structure of the laser pulse are visible. These observations are explained in terms of the ionization dynamics of nitrogen compared to helium. These circumstances make N2 gas sensitive to variations in the electric field and, therefore, allow the laser-pulse temporal and spatial structures to be visualized in detail.

Intense gamma-ray source in the giant-dipole-resonance range driven by 10-TW laser pulses.

A gamma-ray source with an intense component around the giant dipole resonance for photonuclear absorption has been obtained via bremsstrahlung of electron bunches driven by a 10-TW tabletop laser. 3D particle-in-cell simulation proves the achievement of a nonlinear regime leading to efficient acceleration of several sequential electron bunches per each laser pulse. The rate of the gamma-ray yield in the giant dipole resonance region (8

Novel x-ray multispectral imaging of ultraintense laser plasmas by a single-photon charge coupled device based pinhole camera.

Spectrally resolved two-dimensional imaging of ultrashort laser-produced plasmas is described, obtained by means of an advanced technique. The technique has been tested with microplasmas produced by ultrashort relativistic laser pulses. The technique is based on the use of a pinhole camera equipped with a charge coupled device detector operating in the single-photon regime. The spectral resolution is about 150 eV in the 4-10 keV range, and images in any selected photon energy range have a spatial resolution of 5 microm. The potential of the technique to study fast electron propagation in ultraintense laser interaction with multilayer targets is discussed and some preliminary results are shown.

Femtosecond interferometry of propagation of a laminar ionization front in a gas.

We use optical interferometry to investigate ultrafast ionization induced by an intense, ultrashort laser pulse propagating in a helium gas. Besides standard phase shift information, our interferograms show a localized region of fringe visibility depletion (FVD) that moves along the laser propagation axis at luminal velocity. We find that such a loss of visibility can be quantitatively explained by the ultrafast change of refractive index due to the field ionization of the gas in the laser pulse width. We demonstrate that by combining the post facto phase shift distribution with the probe pulse transit effect in the ionizing region, the analysis of the observed FVD yields significant information on the ultrafast dynamics of propagation of the ionization front in the gas.

Vitamin D and diabetes.

Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form-1alpha,25-dihydroxyvitamin D3-have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1alpha,25-dihydroxyvitamin D3, or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.

NOD macrophages produce high levels of inflammatory cytokines upon encounter of apoptotic or necrotic cells.

During the development of type 1 diabetes, pancreatic beta-cells are subject to an immune attack, leading to their apoptotic or necrotic cell death. Apoptotic beta-cells are also present during periods of tissue remodeling, such as in early life. Macrophages should clear apoptotic cells silently without production of pro-inflammatory cytokines. The aim of the present study was to investigate the cytokine pattern of NOD macrophages exposed to apoptotic or necrotic cells in vitro. In contrast to the limited response of macrophages from C57BL/6 or NOR mice, NOD macrophages reacted aberrantly to both necrotic and apoptotic cells, with secretion of inappropriately high amounts of IL1beta and TNFalpha. Further exploration of the macrophage behavior showed an excessive response of NOD macrophages when exposed to LPS (high iNOS and IL12p40 levels), accompanied by hyper-activation of NF-kappaB(p65). In contrast, NOD macrophages failed to up-regulate IL1beta and IL12p40 in response to IFNgamma. This failure correlated with low protein levels and a low phosphorylation state of STAT1alpha. We conclude that NOD macrophages have severely aberrant cytokine expression patterns that could contribute to the initiation or continuation of an immune attack towards the pancreatic beta-cells and thus onset and progression of type 1 diabetes.

Removal of azinphos methyl by alfalfa plants (Medicago sativa L.) in a soil-free system.

The objective of this study was to investigate the removal of azinphos methyl assisted by alfalfa plants, with special emphasis on the effects of this compound on some plant's physiological parameters. Hydroponic cultures of alfalfa (Medicago sativa L., var Romagnola) were employed as a model system. These cultures were exposed to a nutrient medium containing 10 mg/l of azinphos methyl. A first-order kinetic approach was used to describe the removal of azinphos methyl from the solution. After 20 days of culture, the initial amount of azinphos methyl was reduced to non-detectable levels in the presence of plants. In the absence of plants, 20% of azinphos methyl remained in the solution after 30 days of treatment. The half-life of the pesticide was reduced from 10.8 to 3.4 days in the presence of plants. The growth index of alfalfa plants exposed to azinphos methyl was negatively affected. Chlorophyll contents were reduced after 24 h of treatment and thereafter the levels were comparable to that of control plants. The peroxidase activity of alfalfa roots was not affected by the presence of azinphos methyl. In conclusion, alfalfa plants were able to survive when exposed to an effective concentration of 10 mg/l of azinphos methyl in the root zone, with some alterations on their physiological parameters.

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice.

AIMS/HYPOTHESIS: 1,25-dihydroxyvitamin D(3), the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D deficiency in early life. METHODS: Breeding pairs of NOD mice, as well as their offspring (test mice), were kept in surroundings devoid of ultraviolet light and were fed a vitamin D-depleted diet for 100 days. Mice were followed for 250 days. RESULTS: At 250 days, 35% (12/35) male and 66% (22/33) female vitamin D-deficient mice were diabetic compared to 15% (6/40, p=0.05) and 45% (13/29, p<0.01) of the control mice. At 100 days no difference in insulitis was seen, but more vitamin D-deficient mice were glucose intolerant. Higher IL1 expression was detected in islets of vitamin D-deficient mice and their peritoneal macrophages had an aberrant cytokine profile (low IL1 and IL6, high IL15). Thymus and lymph nodes of vitamin D-deficient mice contained less CD4(+)CD62L(+) cells. CONCLUSION/INTERPRETATION: Vitamin D status increases the expression of Type 1 diabetes in NOD mice. Our data in NOD mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk.

The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression.

Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is becoming a widely used method to quantify cytokines from cells, tissues, or tissue biopsies. The method allows for the direct detection of PCR product during the exponential phase of the reaction, combining amplification and detection in a single step. Using TaqMan chemistry (Applied Biosystems, Foster City, CA) and the ABI Prism 7700 Sequence Detection System (Applied Biosystems), we validated a large panel of murine and human cytokines, as we as other factors playing a role in the immune system, such a chemokines and apoptotic markers. Although the method allows fast, sensitive, and accurate quantification, different control assays are necessary for the method to be reliable. By construction of complementary DNA (cDNA) plasmid clones, standard curves are generated that allow direct quantification of every unknown sample. Furthermore, the choice of a reliable housekeeping gene is very important. Finally, co-amplification of contaminating genomic DNA is avoided by designing sets of primers located in different exons or or intron-exon junctions. In conclusion, the real-time RT-PCF technique is very accurate and sensitive, allows high through put, and can be performed on very small samples. The development of real-time RT-PCR has resulted in an exponential increase in its use over the last couple of years, and the method has undoubtedly become the standard for quantifying cytokine patterns, clarifying many functional properties of immune cells and their associated diseases.

Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents.

AIMS/HYPOTHESIS: High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents in the prevention of PNF after xenogeneic islet transplantation. METHODS: Spontaneously diabetic NOD mice were transplanted with 300 rat islets. Animals were treated with acetylsalicylic acid (AsA), rofecoxib, TGF-beta or IL-1 receptor antagonist (IL-1ra). Intra-graft expression of inflammation-related molecules was measured by real time PCR 8 h post-transplantation. At the same time point, plasma nitrite levels were measured. RESULTS: Xenogeneic islets transplanted in control spontaneously diabetic mice resulted in PNF in 16 out of 38 mice (42%). Initial graft loss was not altered by administration of rofecoxib (30%) or TGF-beta (25%). AsA reduced the rate of rapid graft loss to 8% ( p<0.05 vs controls) and administration of IL-1ra even totally prevented PNF (0%, p<0.05 vs controls). Furthermore, all therapies prolonged the mean survival time of xenogeneic islet grafts. The inhibition of PNF by AsA was associated with decreased intra-islet levels of inflammation-related molecules (IL-1, TNF-alpha, iNOS, COX-2) and chemokines (MCP-1 and MIP-3alpha). Finally, also a diminished production of systemic nitrite levels was observed in AsA- and IL-1ra-treated islet recipients. CONCLUSIONS/INTERPRETATION: These data show that treatment with AsA or IL-1ra prevents PNF after islet transplantation in spontaneously diabetic NOD mice. Moreover, the involvement of non-specific inflammation is recognized in xenogeneic islet PNF in spontaneously diabetic NOD mice.

Atividade antibacteriana em alguns extratos de vegetais do semi-árido brasileiro

Espécies nativas ou endêmicas do semi-árido brasileiro foram investigadas com o intuito de se descobrir novas drogas antimicrobianas. Os ensaios foram realizados contra cepas padrões de Staphylococcus aureus e Escherichia coli através do método de difusão em disco. Dos 137 extratos de vegetais avaliados, sete apresentaram atividade significativa contra o Staphylococcus aureus. Os extratos ativos foram preparados a partir de espécies pertencentes às famílias Leguminosae e Rutaceae e serão futuramente fracionados com o intuito de se chegar às moléculas ativas.

Species native or endemic of the Brazilian semi-arid were investigated with the intention of discovering new antibacterial drugs. The rehearsals were accomplished against standard strains of Staphylococcus aureus and Escherichia coli through the diffusion method in disk. Of the 137 extracts of appraised vegetables, seven presented significant activity against the Staphylococcus aureus. The active extracts were prepared starting from species belonging to the Leguminosae and Rutaceae families and they will be fractional hereafter with the intention of arriving to the active molecules.

Hairy roots of Brugmansia candida that grow without agitation: biotechnological implications.

Hairy roots of Brugmansia candida that grew without agitation were obtained. Kinetics of growth and production of the tropane alkaloids scopolamine and hyoscyamine, with and without agitation, were studied. The exponential growth rate was higher in the roots that were exposed to shaking (0.13 d(-1)) than in the nonagitated ones (0.09 d(-1)). The specific production and the levels per flask of both alkaloids were enhanced without shaking. The use of these roots in large-scale productions could be economically advantageous. It remains to be seen if the data obtained in shake flasks can be extrapolated to large-scale bioreactors.

High-energy electron beam production by femtosecond laser interactions with exploding-foil plasmas.

The interaction of an ultraintense, 30-fs laser pulse with a preformed plasma was investigated as a method of producing a beam of high-energy electrons. We used thin foil targets that are exploded by the laser amplified spontaneous emission preceding the main pulse. Optical diagnostics show that the main pulse interacts with a plasma whose density is well below the critical density. By varying the foil thickness, we were able to obtain a substantial emission of electrons in a narrow cone along the laser direction with a typical energy well above the laser ponderomotive potential. These results are explained in terms of wake-field acceleration.

Occurrence of cadaverine in hairy roots of Brugmansia candida.

The polyamine, cadaverine, was detected in transformed root cultures of Brugmansia candida (syn. Datura candida), a Solanaceae which produces the tropane alkaloids scopolamine and hyoscyamine. To the best of our knowledge, this is the first time that the existence of this uncommon polyamine has been detected in a Datura species. Cadaverine, however, could not be found in the whole plant. The occurrence of cadaverine in hairy roots could be a consequence of either the transformation or a response to stress. Also, cadaverine could be participating in other secondary pathways rather than to the tropane alkaloids. The common polyamines, putrescine, spermidine and spermine were also observed.

Analyzing laser plasma interferograms with a continuous wavelet transform ridge extraction technique: the method.

Laser plasma interferograms are currently analyzed by extraction of the phase-shift map with fast Fourier transform (FFT) techniques [Appl. Opt. 18, 3101 (1985)]. This methodology works well when interferograms are only marginally affected by noise and reduction of fringe visibility, but it can fail to produce accurate phase-shift maps when low-quality images are dealt with. We present a novel procedure for a phase-shift map computation that makes extensive use of the ridge extraction in the continuous wavelet transform (CWT) framework. The CWT tool is flexible because of the wide adaptability of the analyzing basis, and it can be accurate because of the intrinsic noise reduction in the ridge extraction. A comparative analysis of the accuracy performances of the new tool and the FFT-based one shows that the CWT-based tool produces phase maps considerably less noisy and that it can better resolve local inhomogeneties.