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Novel Antibody Response may Explain HIV Vaccine Success. A new analysis of the AIDS vaccine trial ever to report positive results suggests that a novel antibody response led to the modest level of efficacy seen in the study. So, the RV144 vaccine trial, which involved 16,000 heterosexuals in Thailand who were at low risk of HIV infection, sparked controversy in September 2009 when researchers reported their n results. People who received the vaccine, a combination of two different preparations, had a 31% lower risk of becoming infected. Moreover, RV144 analysis did not find any correlation between neutralizing antibodies and protection. They discovered that protected people had higher level of a binding antibody that attaches to region of HIV’s surface protein called V1/V2.

    Little Action on Chronic Diseases

According to the science magazine, heads of U.N. member states will gather to discuss the growing pandemic of no communicable diseases such as cancer and diabetes. The huge successful meeting on HIV/AIDS, Tuberculosis and Malaria, but some public health experts and advocates who had high hopes for the meeting find their enthusiasm a but quashed.

	In both wealthy and poor countries, NCDs kill more people than all other diseases combined, for 63%of deaths in 2008. From the long list of chronic diseases, who identified four priorities such as cancer, diabetes, cardiovascular disease, and respiratory disease. And the four major risk factors such as smoking, unhealthy diet, lack of physical activity, and alcohol abuse
    Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors.

The fluorescent is the emission of electromagnetic radiation, especially of visible light, stimulated in a substance by the absorption of incident radiation and persisting only as long as the stimulating radiation is continued. Biochemistry mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. It emerged in several areas of human physiology. A fluorescent probe is excellent tools for their detection, with high spatial and temporal resolution. The interplay between zinc and nitric oxide in the nervous, cardiovascular, and immune systems is highlighted to illustrate the contributions of selective fluorescent probes to the study of these two important bioinorganic analyze. + zinc indicators depend on an increase or rarely a decrease in flourescence emission intensity.

         + Early fluorescent indicators employed in experiments to investigate biological mobile zinc were based on 8-substituted quinoline platforms.
          +Since then, the quinoline derivative 6-methoxy-8-p-toluenesulfonamidequinoline (TSQ) has been employed.

Ratiometric florescent sensors for mobile zinc are technique localization provide the opportunity for sophisticated experiments involving zinc quantification.

Because each ratio of emission and/or excitation intensity at two chosen wavelengths correspond to a specific concentration, ratiometric sensors can be used to determine zinc concentration in dual excitation or dual emission experiments.
A few examples compounds for selected rationmetric fluorescent probes for biological zinc called ZnIC and ZTRS.

There are two strategies in developing the small-molecule fluorescent probes for nitric oxide:

1. It is based on entirely organic probes in which an oxidation product of NO, such as N2O3, reacts with a functional group to modulate the fluorescence (95). Such probes often result in bright (typically 50–150-fold) emission enhancement in the presence of nitric oxide under aerobic conditions. (More widely used) 2. A second strategy is the use of transition metals to mediate reactivity of an emissive dye with NO. These probes can be less bright than purely organic probes Fluorescein-based sensors constitute the largest family of indicators for biological zinc. The success of these probes has relied on the stability, water solubility, brightness, and visible-light excitation/emission of the fluorescein platform. The rhodamine based allows zinc detection at longer wavelengths with a 75-fold turn-on response.

Diaminofluoresceins incorporating the o-diamine benefit from visible excitation wavelengths, thus limiting interference fromcellular autofluorescence and minimizing tissue damage during imaging under aerobic conditions
Probes based on the BODIPY framework were developed that have higher NO sensitivity than diaminofluorescein (DAF) analogs.

          + Fluorescein-based sensors constitute the largest family of indicators for biological zinc.
          +Synthetic modifications to the zinc-binding unit can improve the turn-on properties of ZP sensors by lowering the proton and zinc affinity of the probe.
          +Sensors of the ZP and the related families of sulfur-containing ZS sensors (71) and quinoline-containing QZ sensors (72) span a wide range of zinc affinities and dynamic ranges

-Based on the fact that Cu2+ reacts with NO to produce Cu1+ which lowers the energy of a quenching lone pair on the N and lowers PET quenching in the N nitrosated product; does not nee O2 -->good for imaging NO in hypoxic environment.

• CuFL1 platform based on fluorescein dye with aminoquinoline moiety to bind Cu2+

- CuFl1 reacts with NO to produce a 16 fold emission turn on; probe is sensitive to NO -Cu2+ reacts with NO to produce Cu+ --> results in 1st order dependency on [NO] -CuFL probe used for imaging NO in Raw 264.7 macrophages, SKN-SH neuroblastoma cells, gram + bacteria

• FL2E proble - modification of the FL1 platform to generate a symmetric probe

-caused by addition of ester groups on the two quinolines -upon the entry of FL2E into the cell, intracellular esterases hydrolyzes FL2E into FL2A, which cannot recross the cell membrane -FL2E have been used in Raw 264.7 macrophages, SKN-SH neuroblastoma cells, and olfactory bulb brain slices

 +The involvement of both Zn(II) and NO in a variety of neurological dysfunctions such as Alzheimer’s disease. The neurotoxic effects of both inorganic species, has sparked interest in studying two analytes in the central nervous system.

+ The treatment of hippocampal neurons with exogenous NO donors, including sodium nitroprusside or spermine NONOate, resulted in mobilization and accumulation of Zn(II) in brain tissue, as detected by TSQ fluorescence and Timm staining (139) Cardiovascular System + Increased fluorescence from Zinquin-E was observed in both the cytoplasm and nucleus (143). And NO has vasodilatory effects in the cardiovascular system, the NO/Zn(II) interplay has also been implicated in hypoxia-mediated NO biosynthesis that contributes to vasoconstriction. + PKG inhibition was observed and NO was detected byDAF-FM.Morphinemobilized intracellular Zn by the NO/cGMP/PKG pathway and inhibited a mitochondrial permeability transition pore opening by inactivation of GSK-3β. Immune System + Zinc and nitric oxide participate in processes orchestrated by the immune system to defend against pathogens. Zinc deficiency leads to impaired immune function and increased susceptibility to infection (149). + Exposure to endotoxins, such as proinflammatory cytokines and/or LPS, prompts expression of the iNOS and hence increased NO production under inflammatory conditions. In cultured murine keratinocytes during cytokine-induced inflammation, the presence of 10 μM Zn (II) decreased NO production, a result of iNOS inhibition confirmed both at the protein and mRNA levels (151).