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CLX (celecoxib) is a highly hydrophobic non-steroidal anti-inflammatory drug with high plasma protein binding. We describe here the encapsulation of CLX in MLVs (multilamellar vesicles) composed of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) and variable amounts of cholesterol. The effects of cholesterol content on liposome size, percentage drug loading and in vitro drug release profiles were investigated. Differential scanning calorimetry and FTIR (Fourier-transform infrared) spectroscopy were used to determine molecular interactions between CLX, cholesterol and DSPC. The phase transition temperature (Tm) of vesicles was reduced in a synergistic manner in the presence of both CLX and cholesterol. Encapsulation efficiency, loading and release of CLX decreased with increasing cholesterol content. FTIR results indicated that this decrease was due to a competition between CLX and cholesterol for the co-operativity region of the phospholipids. In the presence of cholesterol, CLX was pushed further into the hydrophobic core of the bilayer. However, MLVs prepared with DSPC only (without cholesterol) exhibited the lowest ability for drug retention after 72 h. Our results indicated that CLX, without the requirement of modifications to enhance solubilization, can be encapsulated and released from liposomal formulations. This method of drug delivery may be used to circumvent the low bioavailability and systemic side effects of oral CLX formulations.

Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. 15-Lipoxygenase-1 (15-LO-1), a member of the inflammatory eicosanoid pathway, oxidatively metabolizes linoleic acid and its expression is repressed in CRC. In this study, we investigated the hypothesis that the lack of 15-LO-1 expression in CRC cells might contribute to tumorigenesis. Therefore we introduced 15-LO-1 into HCT-116 and HT-29 cells that do not have detectable levels of 15-LO-1. Our data indicate that expression of 15-LO-1 significantly decreased cell proliferation and increased apoptosis. In addition, we observed a reduction in adhesion to fibronectin, anchorage-independent growth on soft agar, cellular motility and ability to heal a scratch wound, and migratory and invasive capacity across Matrigel. 15-LO-1 expression also reduced the expression of metastasis associated protein-1, a part of the nucleosome remodeling and histone deacetylase silencing complex. We propose that 15-LO-1 expression in CRC might contribute to the inhibition of metastatic capacity in vitro and can be exploited for therapeutic purposes. (Cancer Sci 2009;100: 2283-2291).

Classical dynamics calculations were made to describe the desorption induced following the excitation of a molecule to a repulsive, dissociating state, a process of interest in electronically stimulated desorption. Yields of ejected atoms/molecules versus depth of excitation were calculated for a solid sample of oxygen molecules and energy spectra of the ejecta were calculated. The relaxation of the repulsive state produces a collision sequence resulting in ejection with an efficiency slightly smaller than that for an amorphous atomic argon solid due to energy transfer to vibrational excitation.

Simulation de l'ejection rapide a partir d'un solide amorphe faiblement lie aux densites d'excitation elevees, a l'aide de la dynamique moleculaire afin de comprendre l'ejection d'un volume du materiau par des ions lourds rapides. Calcul de l'ejection des molecules diatomiques d'un solide comme reponse a une grande quantite d'energie deposee dans l'excitation vibrationnelle de ces molecules a l'interieur d'un petit cylindre: la «trace» des ions incidents. Les calculs sont effectues pour deux modes de l'excitation vibrationnelle et pour des echantillons ayant des geometries, des densites numeriques, des energies de cohesion, des epaisseurs, et des conditions aux limites differentes

Diabetic Retinopathy and Age related Macular Degeneration are two major retinal diseases which are creating serious concern in today’s age. Detection of preliminary signs of abnormalities due to these diseases is hard and time consuming for the ophthalmologists as the abnormal objects are very fine and small in size. As early detection of abnormalities can prevent permanent vision loss, a semi automated system is developed to detect the affected portion of retina and is tested with some retinal images. A training image set is used to train a support vector machine classifier. A test image set is given to the classifier for automatic detection of disease type. Efficiency of the classifier is tested comparing the actual value and predicted value by the classifier.

To study abnormalities in liver associated enzymes and histology in AIDS patients with common infections like hepatotrophic viruses and mycobacteria. 30 cases of HIV/AIDS were studied for any significant pattern emerging. The male:female ratio was 4.26:1, occupation being long-distance truck drivers (30%); migrant goldsmiths (27%); migrant labourers (24%). Duration of illness from onset was within three months (46%) and the maximum duration was 26 months (2%). The most common presentation was fever (90%), weakness (79%), weight loss (62%) and diarrhoea (62%). The CD4 cell count was between 200-500/microL (33%). LFT showed hyperglobulinemia in patients having CD4 cell count500/microL. Rise of alkaline phosphatase was seen in 63% with CD4 cell count200/microL. 66.6% had HBsAg reactivity, 33.3% had positive anti-HCV antibody and 50% had abnormal liver histology. One third of these had systemic opportunistic infections like tuberculosis. No correlation could be made between hepatic histology and LFT.

Cadmium (Cd2+) is a known carcinogen that inactivates the DNA mismatch repair (MMR) pathway. In this study, we have tested the effect of Cd2+ exposure on the enzymatic activity of the mismatch binding complex MSH2-MSH6. Our results indicate that Cd2+ is highly inhibitory to the ATP binding and hydrolysis activities of MSH2-MSH6, and less inhibitory to its DNA mismatch binding activity. The inhibition of the ATPase activity appears to be dose and exposure time dependent. However, the inhibition of the ATPase activity by Cd2+ is prevented by cysteine and histidine, suggesting that these residues are essential for the ATPase activity and are targeted by Cd2+. A comparison of the mechanism of inhibition with N-ethyl maleimide, a sulfhydryl group inhibitor, indicates that this inhibition does not occur through direct inactivation of sulfhydryl groups. Zinc (Zn2+) does not overcome the direct inhibitory effect of Cd2+ on the MSH2-MSH6 ATPase activity in vitro. However, the increase in the mutator phenotype of yeast cells exposed to Cd2+ was prevented by excess Zn2+, probably by blocking the entry of Cd2+ into the cell. We conclude that the inhibition of MMR by Cd2+ is through the inactivation of the ATPase activity of the MSH2-MSH6 heterodimer, resulting in a dominant negative effect and causing a mutator phenotype.

The similarity between the two-body tau decay into the pion and the neutrino and the pion decay into the muon and neutrino suggests the possibility of radiative tau decays (tau..--> pi nu../sub tau/..gamma.. and tau..-->..rho..nu../sub tau/..gamma..) analogous to radiative pion decay. These three-body decays can provide a means for determining the tau-neutrino mass. The decay tau..--> pi nu../sub tau/..gamma.. is useful for determining the sign and magnitude of the structure parameter ..gamma...

Colon cancer is a major cause of morbidity and mortality throughout the world.The pathogenesis of colon cancer with respect to loss of cellular differentiation has not been clearly understood. To understand this loss in colon cancer and to differentiate the cancer cells, sodium butyrate (NaB), one of the differentiation inducer, is commonly used. NaB is produced in the colonic lumen as a consequence of bacterial fermentation of complex carbohydrates and it alters colon cancer cell morphology and reduces the cell growth and motility. Although, the differentiation process of colon cancers, which are stimulated with NaB, has been resolved at genetic level, the underlying mechanisms regarding structural and functional alterations regulating the differentiation of colon cancer cells have not been well characterized. Therefore, in this study, it was aimed to explore the NaB-induced macromolecular structural and functional changes in differentiation of colon cancer cells by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and FTIR microspectroscopy. These changes were determined from the spectral analysis of control and NaB treated colon cancer cell spectra and their chemical maps. Based on the spectral differences, cluster analysis was applied to discriminate the groups. The spectral analysis indicated the differences in saturated and unsaturated lipids, protein and nucleic acid content between the control and NaB treated cancer cells. The variation in membrane fluidity and lipid order was also determined in the NaB treated cells. Moreover, the successful discrimination between control and treated cells was obtained. The results of this study not only shed light on better understanding the loss of differentiation mechanisms in colon cancers but also strongly support the power of ATR-FTIR spectroscopy and FTIR microscopy as novel, simple, reagent-free methods for the identification of differentiated cancer cells.