201 research outputs found
Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer
Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general
Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury
BACKGROUND: Falls in older people have been characterized extensively in the literature, however little has been reported regarding falls in middle-aged and younger adults. The objective of this paper is to describe the perceived cause, environmental influences and resultant injuries of falls in 1497 young (20â45 years), middle-aged (46â65 years) and older (> 65 years) men and women from the Baltimore Longitudinal Study on Aging. METHODS: A descriptive study where participants completed a fall history questionnaire describing the circumstances surrounding falls in the previous two years. RESULTS: The reporting of falls increased with age from 18% in young, to 21% in middle-aged and 35% in older adults, with higher rates in women than men. Ambulation was cited as the cause of the fall most frequently in all gender and age groups. Our population reported a higher percentage of injuries (70.5%) than previous studies. The young group reported injuries most frequently to wrist/hand, knees and ankles; the middle-aged to their knees and the older group to their head and knees. Women reported a higher percentage of injuries in all age groups. CONCLUSION: This is the first study to compare falls in young, middle and older aged men and women. Significant differences were found between the three age groups with respect to number of falls, activities engaged in prior to falling, perceived causes of the fall and where they fell
Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet
<p>Abstract</p> <p>Background</p> <p>N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.</p> <p>Results</p> <p>By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.</p> <p>Conclusion</p> <p>These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.</p
Interatomic potentials and solvation parameters from protein engineering data for buried residues
Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (Hâbonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of freeâenergy differences. The set of mutants included substitutions of uncharged, inflexible, waterâinaccessible residues in αâhelices and ÎČâsheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and Hâbonds were smaller than in molecular mechanics and followed the âlike dissolves likeâ rule, as expected in condensed media but not in vacuum. The depths of modified LennardâJones potentials were â0.34, â0.12, and â0.06 kcal/mole for similar atom types (polarâpolar, aromaticâaromatic, and aliphaticâaliphatic interactions, respectively) and â0.10, â0.08, â0.06, â0.02, and nearly 0 kcal/mole for different types (sulfurâpolar, sulfurâaromatic, sulfurâaliphatic, aliphaticâaromatic, and carbonâpolar, respectively), whereas the depths of Hâbond potentials were â1.5 to â1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, â1, â21, and â66 cal/moleĂ
2 for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the waterâprotein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106915/1/111984_ftp.pd
Participatory organizational intervention for improved use of assistive devices for patient transfer: study protocol for a single-blinded cluster randomized controlled trial
Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy
Neigbourhood ethnic composition and social participation of young people in England
We analyse how neighbourhood ethnic diversity and segregation affect adolescents' social participation in England. We distinguish between participation in `purposeful activities' - such as sports and volunteering - and hanging around with friends. We suggest a novel identification strategy to address the problem of endogeneity of ethnic diversity and segregation. We find that ethnic diversity decreases hanging around, while ethnic segregation increases it. No effects are found on participation in purposeful activities
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