Drug and Alcohol Rehabilitation: Comparison of Two High-Throughput Assays for Quantification of Adenovirus Type 5 Neutralizing Antibodies in a Population of Donors in China.

Comparison of two high-throughput assays for quantification of adenovirus type 5 neutralizing antibodies in a population of donors in china.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2012; 7(5): e37532
Liu Q, Nie J, Huang W, Meng S, Yuan B, Gao D, Xu X, Wang Y

The presence of various levels of Adenovirus serotype 5 neutralizing antibodies (Ad5NAb) is thought to contribute to the inconsistent clinical results obtained from vaccination and gene therapy studies. Currently, two platforms based on high-throughput technology are available for Ad5NAb quantification, chemiluminescence- and fluorescence-based assays. The aim of this study was to compare the results of two assays in the seroepidemiology of Ad5NAb in a local population of donors.The fluorescence-based neutralizing antibody detection test (FRNT) using recombinant Ad5-EGFP virus and the chemiluminescence-based neutralizing antibody test (CLNT) using Ad5-Fluc were developed and standardized for detecting the presence of Ad5NAb in serum samples from the population of donors in Beijing and Anhui provinces, China. First, the overall percentage of people positive for Ad5NAb performed by CLNT was higher than that obtained by FRNT (85.4 vs 69.9%, p<0.001). There was an 84.5% concordance between the two assays for the 206 samples tested (144 positive in both assays and 30 negative in both assays). All 32 discordant sera were CLNT-positive/FRNT-negative and were confirmed positive by western blot. Secondly, for all 144 sera positive by both assays, the two assays showed high correlation (r?=?0.94, p<0.001) and close agreement (mean difference: 0.395 log(10), 95% CI: -0.054 log(10) to 0.845 log(10)). Finally, it was found by both assays that there was no significant difference observed for titer or prevalence by gender (p?=?0.503 vs 0.818, for two assays); however, age range (p?=?0.049 vs 0.010) and geographic origin (p?=?0.007 vs 0.011) were correlated with Ad5NAb prevalence in northern regions of China.The CLNT assay was relatively more simple and had higher sensitivity than the FRNT assay for determining Ad5NAb titers. It is strongly suggested that the CLNT assay be used for future epidemiological studies of Ad5NAb in other localities. HubMed – drug


Thermodynamics of aryl-dihydroxyphenyl-thiadiazole binding to human hsp90.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2012; 7(5): e36899
Kazlauskas E, Petrikait? V, Michailovien? V, Revuckien? J, Matulien? J, Grinius L, Matulis D

The design of specific inhibitors against the Hsp90 chaperone and other enzyme relies on the detailed and correct understanding of both the thermodynamics of inhibitor binding and the structural features of the protein-inhibitor complex. Here we present a detailed thermodynamic study of binding of aryl-dihydroxyphenyl-thiadiazole inhibitor series to recombinant human Hsp90 alpha isozyme. The inhibitors are highly potent, with the intrinsic K(d) approximately equal to 1 nM as determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Dissection of protonation contributions yielded the intrinsic thermodynamic parameters of binding, such as enthalpy, entropy, Gibbs free energy, and the heat capacity. The differences in binding thermodynamic parameters between the series of inhibitors revealed contributions of the functional groups, thus providing insight into molecular reasons for improved or diminished binding efficiency. The inhibitor binding to Hsp90 alpha primarily depended on a large favorable enthalpic contribution combined with the smaller favorable entropic contribution, thus suggesting that their binding was both enthalpically and entropically optimized. The enthalpy-entropy compensation phenomenon was highly evident when comparing the inhibitor binding enthalpies and entropies. This study illustrates how detailed thermodynamic analysis helps to understand energetic reasons for the binding efficiency and develop more potent inhibitors that could be applied for therapeutic use as Hsp90 inhibitors.
HubMed – drug


Construction and operation of a microrobot based on magnetotactic bacteria in a microfluidic chip.

Filed under: Drug and Alcohol Rehabilitation

Biomicrofluidics. 2012 Jun; 6(2): 24107-2410712
Ma Q, Chen C, Wei S, Chen C, Wu LF, Song T

Magnetotactic bacteria (MTB) are capable of swimming along magnetic field lines. This unique feature renders them suitable in the development of magnetic-guided, auto-propelled microrobots to serve in target molecule separation and detection, drug delivery, or target cell screening in a microfluidic chip. The biotechnology to couple these bacteria with functional loads to form microrobots is the critical point in its application. Although an immunoreaction approach to attach functional loads to intact MTB was suggested, details on its realization were hardly mentioned. In the current paper, MTB-microrobots were constructed by attaching 2??m diameter microbeads to marine magnetotactic ovoid MO-1 cells through immunoreactions. These microrobots were controlled using a special control and tracking system. Experimental results prove that the attachment efficiency can be improved to ?30% via an immunoreaction. The motility of the bacteria attached with different number of loads was also assessed. The results show that MTB can transport one load at a velocity of ?21??m/s and still move and survive for over 30?min. The control and tracking system is fully capable of directing and monitoring the movement of the MTB-microrobots. The rotating magnetic fields can stop the microrobots by trapping them as they swim within a circular field with a controllable size. The system has potential use in chemical analyses and medical diagnoses using biochips as well as in nano/microscale transport.
HubMed – drug


A microfluidic platform for controlled biochemical stimulation of twin neuronal networks.

Filed under: Drug and Alcohol Rehabilitation

Biomicrofluidics. 2012 Jun; 6(2): 24106-2410610
Biffi E, Piraino F, Pedrocchi A, Fiore GB, Ferrigno G, Redaelli A, Menegon A, Rasponi M

Spatially and temporally resolved delivery of soluble factors is a key feature for pharmacological applications. In this framework, microfluidics coupled to multisite electrophysiology offers great advantages in neuropharmacology and toxicology. In this work, a microfluidic device for biochemical stimulation of neuronal networks was developed. A micro-chamber for cell culturing, previously developed and tested for long term neuronal growth by our group, was provided with a thin wall, which partially divided the cell culture region in two sub-compartments. The device was reversibly coupled to a flat micro electrode array and used to culture primary neurons in the same microenvironment. We demonstrated that the two fluidically connected compartments were able to originate two parallel neuronal networks with similar electrophysiological activity but functionally independent. Furthermore, the device allowed to connect the outlet port to a syringe pump and to transform the static culture chamber in a perfused one. At 14 days invitro, sub-networks were independently stimulated with a test molecule, tetrodotoxin, a neurotoxin known to block action potentials, by means of continuous delivery. Electrical activity recordings proved the ability of the device configuration to selectively stimulate each neuronal network individually. The proposed microfluidic approach represents an innovative methodology to perform biological, pharmacological, and electrophysiological experiments on neuronal networks. Indeed, it allows for controlled delivery of substances to cells, and it overcomes the limitations due to standard drug stimulation techniques. Finally, the twin network configuration reduces biological variability, which has important outcomes on pharmacological and drug screening.
HubMed – drug



Equine Therapy for Drug and Alcohol Addiciton in Tucson Arizona – www.cottonwooddetucson.com Cottonwood de Tucson’s Equine Therapy program Among a variety of holistic treaments, the equine therapy program at Cottonwood de Tucson, a drug and alcohol rehabilitation center in Tucson, Arizona works with each patient to help explore boundaries, intimacy issues as well as mirror behaviorial patterns. While working with the horses patients experience an awareness of their own emotional state reflected in the horses actions. The horses experience the present moment with no motives or judgments and working with them patients can process perceived fear of rejection. Horse-assisted therapy demands a level of authenticity from the patient. Working with the horses can provide a rich opportunity to discover inner demons and inner strenghts. Cottonwood de Tucson Addiction Rehab Cottonwood de Tucson


Council, residents oppose drug rehab facility

Filed under: Drug and Alcohol Rehabilitation

The Town of Loomis is joining with residents to oppose a drug and alcohol recovery facility in a home on a private driveway off Wells Avenue. At residents' request, Town Council took up the matter on their May 8 agenda. According to Town Manager Rick …
Read more on Loomis News


The Good Guys and Bad Guys That I've Been: Paul Williams on 'Paul Williams

Filed under: Drug and Alcohol Rehabilitation

And after badly derailing his career with drug and alcohol abuse, he is now proudly 22 years sober. And yet, the nonfiction feature “Paul Williams Still Alive,” directed by Stephen Kessler, is not quite that tale: it's the account of how Mr. Kessler, …
Read more on New York Times (blog)


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