Rapid Opiate Detoxification Treatment

Total Detox Friend

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Drug Courts

Drug courts evolved out of earlier unsuccessful, often fragmented, efforts to link drug offenders with treatment services. There are over 1000 drug courts in the planning and implementation phases in the United States and beyond (National Drug Court Institute, 2001). They are 'dedicated courtrooms that provide judicially-monitored treatment, drug testing and other services to drug-involved offenders' (Belenko, 1998, p. 4). These courts seek to craft custom-designed sentences for drug offenders that incorporate both supervision and treatment components. Drug courts take a therapeutic, non-adversarial approach that promotes public safety while promoting the treatment of drug dependency. They rely on community-based treatment options and supervision and require cooperation between various elements of the justice system and the community at large. In a study of one drug court, all drug felony defendants were randomly assigned to one of three dockets (lists or calendars of cases to be...

Segmental Duplications And Evolution

Finally, a recent survey of segmental duplications in the human genome found that approx 6 of transcribed exons are located in recently duplicated sequence (2). Genes associated with immunity and defense, membrane surface interactions, drug detoxification, and growth and development were preferentially enriched, suggesting that gene duplication plays a major role in the evolution of these functions. Thus, in contrast to the popular conception in which single nucleotide polymorphisms and small mutations are the major method of evolutionary change, larger genomic rearrangements may instead represent the driving force behind much of recent primate evolution, facilitated by the presence of abundant highly homologous duplicated sequences throughout the genome (68).

Morphological Changes Accompanying Aging In S Ratti

The parasitic and free-living females morphs of S. ratti are genetically identical. Therefore differences between these morphs must be due to differences in gene expression. This being so, these differences in intestinal pathology might reflect differences in regulated biochemical processes which determine longevity and aging. One intriguing and attractive possibility is that in parasitic females there is an increase in biochemical processes promoting detoxification. Recent microarray studies of long-lived insulin IGF-1 signalling mutants of C. elegans have implicated a broad range of detoxification processes in longevity assurance (Murphy et al., 2003 McElwee et al., 2004 Gems and McElwee, 2005). These include phase 1 and phase 2 drug detoxification, as well as anti-oxidant enzyme and chaperonin activities. Most of these processes require energy input, and excretion of solubi-lized toxic metabolites by the drug detoxification system occurs via the smooth endoplasmic reticulum....

Functional Expression Of G Proteincoupled Receptors In Yeast

The main utility of the yeast two-hybrid technology has been in gene discovery. In the arena of drug screening, this usually means target discovery. But in a broader definition of therapeutics, including gene therapy or transgenic crop generation, protein interaction screens are a direct way of discovering the therapeutic gene.

Potential Model Systems for Premature Aging Syndromes in Zebrafish

Functional aberrations of ATM protein cause a genetic disease A-T. We have recently demonstrated that zebrafish ATM (zATM) is functionally conserved at least in part because zebrafish embryos with disrupted ATM showed radiation hypersensitivity as observed in A-T patients and ATM-knockout mice (Imamura and Kishi, 2005). Since multiple aging senescence-associated markers are readily monitored, it is worthwhile trying to identify premature senescence phenotypes in ATM-deficient zebrafish embryos as a representative model. Moreover, once a stable model system of zebrafish for human progeroid syndromes including A-T is established, it will become a powerful tool for characterizing molecular functions in the signal transduction pathway and using chemical genetic approaches for drug screening.

Application Of Recombinant Technology To Cellbased

The accelerated pace of drug screening has led to an increased need for rapid generation of stable cell lines expressing suitable concentrations of the cloned, recombinant targets for the screening efforts. Classical methods for generating stable cell lines have generally relied on the integration of the recombinant gene into random locations within the genome of the host cell. The integrating gene is subjected to unpredictable rearrangements 1,2 , and expression is strongly influenced by flanking chromosomal sequences and variations in gene copy number 3 . Following selection, only 5-30 of the resulting clonally derived cell lines functionally express the recombinant protein of interest 4,5 . Methods that use lox-cre, locus control regions, or IRES (internal ribosome entry sites) to circumvent these problems have been described, but these solutions still require

Physical Examination

Labs CBC with differential, LFTs, amylase, lipase, hepatitis serologies (hepatitis B surface antibody, hepatitis B surface antigen, hepatitis A IgM, hepatitis C antibody), antimitochondrial antibody (primary biliary cirrhosis), ANA, ceruloplasmin, urine copper (Wilson's disease), alpha-1-antitrypsin deficiency, drug screen, serum iron, TIBC, ferritin (hemochromatosis), liver biopsy.

Engineering of Fusion Proteins

In this chapter, the various expression systems generally applied for overexpression of recombinant proteins are described. Most of these systems have also been used for GPCR expression and their special properties and achievements are presented below. Recombinantly expressed GPCRs provide the material for assays to monitor direct ligand binding activity as well as functional coupling to G proteins both types of assays are used widely for drug screening programs.

Data Analysis of Multidimensional Cellular Datasets

Datasets have come to the fore including techniques of hierarchical clustering analysis (HCA), multidimensional scaling (MDS), self-organizing maps (SOMs), and methods based on neural networks. Each of these methods has been adapted to parallel cell-based screening to extract knowledge, largely applied to if not inspired by the NCI's drug screening program of more than 60 different human tumors (Brown et al., 2000 Kohonen, 1999 Meyer and Cook, 2000 Rabow et al., 2002 Sneath and Sokal, 1962). In general, methods such as principal component analysis (PCA), MDS, and HCA cluster compounds from large multidimensional cellular datasets to assign putative functional relationships between compounds. PCA takes linear combinations of a data matrix such that the first principal component (PC) explains as much of the overall variation as possible, the second PC explains the next most variation subject to being orthogonal to the first, and so on (Shi et al., 2000). One of the powerful features of...

Proactive Judging And Specialized Courts

Problem-solving judges, and the paradigm of therapeutic courts, recently emerged as a result of the war on drugs and its effects on the courts (Lipscher, 1999). Drug courts, designed to deal with the overflow of drug cases in the late 1980s, attracted judges who sought 'a treatment-based alternative that also mandated judicially supervised sanctions' (Gebelein, 2000, p. 2). Policy-makers saw an innovative opportunity and established federal funding for drug courts in the 1994 Crime Act (Gebelein, 2000). The key elements include integration of treatment with court processing use of a non-adversarial approach early identification and placement access to a continuum of services frequent drug and alcohol testing a coordinated team approach ongoing judicial interaction and monitoring continuing interdisciplinary education and partnerships with community agencies. Proactive judges are an integral part of drug courts (Gebelein, 2000), and the relationship between drug-addicted defendants and...

Elements Common To Proactive Judges And Specialized Courts

Fourth, they have altered the dynamics of the courtroom and the adversarial system (Berman and Feinblatt, 2000). For example, in many drug courts, judges, attorneys, and treatment providers work as a team to devise systems of sanctions and rewards for offenders in drug treatment. By using the court's authority to coordinate the work of other agencies, judges assume untraditional roles as case managers. They

The Role Of The Judge In Specialized Courts

Judges in drug courts are successful because they are in a position of authority and they care. People see the judge as an empathic person who cares, and they want to please the judge. Offenders need praise. One guy said, 'I got my nudge from the judge.' When you see what addicts go through to change, you begin to see your own problems. One person who worked in the courtroom said that she had a hard enough time staying on a diet, and was impressed with how drug addicts are able to break the habit. It may be that judges are just human and are responding in a human way. (P. Hora, personal communication, March 21, 2001) In addition to therapeutic benefits to offenders, judges themselves benefit therapeutically from participation in therapeutic courts such as drug courts. In their study, Chase and Hora (2000) observe that drug treatment court judicial officers are significantly more likely than family law court judicial officers to have stopped drinking or using other substances. Drug...

Therapeutic Jurisprudence

Proactive judges can, at the organizational level, create special programs or specialized courts. A drug court program in Washington, DC, provides court-based interventions using psychological principles. 'Because the sanctioning rules were simple and clearly explained in advance, defendants viewed the penalties they received as fair' (Harrell et al., 2000, p. 6). Judicial access to sophisticated computers with up-to-date information allows them immediate access to drug test results, and the application of graduated sanctions is swift and certain. Evaluation of this program, and its use of graduated sanctions for drug defendants, demonstrated reduced drug use during the period of supervision (Harrell et al., 2000).

The First Automated Systems

The architecture developed by Zymark for automating sample preparation seemed to be ideal for the automation of processes in drug discovery research. Initially the developments derived from sample preparation automation were directly transferred to automate drug screening applications. In a way, the early integrated robotic systems were engineering challenges implemented by visionary technology adopters. Early automation projects were often awkward attempts that utilized the capabilities of the robotic arm to emulate the actions of human beings. For example, robots were used to pipette liquids as a human does with singlechannel or multichannel pipette hands, to blot plates, or to tweeze filter paper

Highthroughput Screening

Years, pharmaceutical researchers have responded to this pressure by utilizing automation and increased productivity to quicken the pace of drug discovery. Researchers are now expected to find new drug candidates at a faster rate, usually with little increase in personnel budgets to accomplish this task 6 . Robotic drug screening systems have provided the additional capacity to meet this need and fill the pipeline of drug candidates.

Software Operating System

Because there are multiple tasks to be performed simultaneously, most robotic systems for drug screening operate with software that operates in a multitasking environment. The controller issues device commands, receives data, and controls the system simultaneously. With today's increasingly complex systems, multitasking capability is a requirement. Due to their cost, availability, reliability, and user familiarity, standard personal computers are frequently used as system controllers. For a variety of reasons, at the time of this writing, most software for drug screening robotic systems operates in a Windows NT environment. The Windows graphical user interface (GUI) has become widely accepted in drug screening laboratories, making it easy to train new users and assuring familiarity between different systems and different vendors.

Elements of Typical Assays

A basic robotic system for drug screening will usually have the following components robot, servo track, digital gripper, plate storage unit,bar code reader, plate turning station, plate shaker, and liquid dispenser. Depending on the assays to be performed, additional devices will be required. Cell-based assays will require a 37 C temperature controlled CO2 incubator with humidity, and, if cells are being plated by the robotic system, a gentle dispenser, usually with a stirred reservoir to keep the cells in suspension, will be required. If ELISA or similar assays will be performed, a microplate washer will be used to wash unbound reagents from the plate wells and prepare the plate for the next step in the assay. Plate readers are used to quantify the amount of reaction that has taken place, and assays use a variety of modes, including colorimetric, absorbance, fluorescence, luminescence, etc.

Sourcing Robotic Systems

Because robotic laboratory systems can be customized for the user, there are a number of considerations in selecting a vendor for a robotic system for drug screening and suggestions to new users to improve the implementation process. Users have made a number of recommendations to improve the success of robotic systems 15 . When evaluating vendors, it is recommended to visit the vendor's references, see the system, and ask specific questions regarding the vendor's performance. It is also recommended to see a demonstration of the proposed system before purchasing and look for specific proof of the quality of their systems, software, training, and support.

Cost Justification

The cost justification for automation systems is usually a calculation of the monetary payback over time. The total expenditure for the robotic system is balanced against the cost savings that can be quantified, which usually includes labor, materials, etc. To calculate the cost of the present method of performing the task, the actual time for all of the manual steps is measured and a cost is calculated based upon the cost of the person or persons who are involved with the task. In the case of drug screening systems, this might include many people, including supervisors and managers, and usually includes the total costs of each person, including benefits, which is sometimes referred to as a person's ''loaded overhead cost.''

Novel Gpcr Features And Impact On Drug Discovery Approaches

Recent advances in GPCR research have provided additional opportunities for drug discovery beyond the single conventional binding site approach used to date for all currently marketed drugs that target liganded GPCRs. The discoveries of many yet-to-be defined orphan GPCRs, the finding that GPCRs can form homo- and or hetero-oligomeric complexes with other GPCRs and the ever-growing number of accessory proteins found to interact with and influence the GPCR signaling complex mean that the number of potential sites at which to target drug action continue to grow and perhaps provide new ways to increase the specificity of action. Advances in drug screening technologies that now allow for screening of orphan GPCRs in the

Blurring the Lines Between Primary Secondary and Tertiary Screening

Drug screening has traditionally been divided into three phases primary, secondary, and tertiary. As a result of the dramatic increase in targets and compounds to be screened, traditional screening is currently undergoing a re-evaluation. In addition to the move to miniaturization and increases in throughput, increased efficiency is also called for. One way to increase efficiency is to obtain more information at an earlier stage of drug screening.

Scope Of Book

Since most GPCRs are not overexpressed intrinsically in vivo and in situ, the facilitation of high-level recombinant heterologous expression systems has been one of the major bottlenecks in investigating the structural biologies of membrane proteins. Obviously, recombinant GPCR expression also serves an important function in the drug screening process. All applied and potentially interesting expression systems are described in Chapter 8. In silico methods including application of bioinformatics and molecular modeling for GPCRs as tools to support structural biology approaches are covered in Chapter 10. Chapter 11 provides further insight into structural biology identification and deals with the structures and dynamics of GPCRs using rhodopsin as a model protein. Chapter 12 deals with the problems and recent development in crystallization of GPCRs, and Chapter 13 demonstrates how novel solid-state NMR methods can be applied to GPCRs. Chapter 14 is an overview of several recently...


Drug screening for identifying novel chemical structures for different targets is moving to HTS and UHTS. The assays have to be simple, homogeneous, robust, reproducible, and fully automatable to adapt to HTS. The design of a cell based or an in vitro biochemical assay that is radioisotope based or nonradioisotope based takes into consideration the type of target, available reagents, assay readout, and availability of automation equipment. With the advent of homogeneous fluorescence based assays and other novel signal detection technologies and miniaturization strategies (384-, 1536-, 3456-, and 9600-well plates) it is possible to meet the 100,000 assays per day capacity. The microchip technology coupled with microfluidic technology or capillary electrophoresis is being developed to meet the needs of UHTS.


Drug discovery in the pharmaceutical and biotechnology companies has seen spectacular changes in the last decade mainly due to technological advances in biology, biochemical assays, genomics, proteomics, combinatorial chemistry, miniaturization, automation, computerization, and information technologies. With this technological revolution, drug screening capacities have increased immensely, allowing the pharmaceutical companies to process an increased number of drug targets rapidly by miniaturization and automation using robots for screening the large compound decks and combinatorial compound libraries. To bring a drug to market quickly by reducing the time taken from the target identification to the drug development, pharmaceutical companies have been implementing an assembly-line approach by automation of drug screening.


Several fluorescence, chemiluminescence, luminescence, and radioactive based assays that are one-step assays that do not require wash and multiple incubations or filtrations and washes are detailed in this chapter. There is not a single format that can completely replace all the assays for various targets in drug screening. Radioactive assays are generally very sensitive assays, but handling problems

Clinical Trials

NMDA Receptor Antagonists in the Treatment of Drug Withdrawal 4.1.1. Opiate Detoxification Laboratory animal studies consistently show that NMDAR antagonists in, particular channel blockers attenuate the severity of opioid withdrawal in dependent animals (1,3). The results of human laboratory studies are less decisive. Several preliminary trials have evaluated the utility of clinically available agents for opioid detoxification. The first published clinical study was conducted in Turkey by Koyuncuoglu and Say dam (32). Forty-eight patients seeking opioid detoxification were randomly assigned to dextromethorphan (360 mg d) or chlorpromazine (96 mg d), which was used as an active control. Both group received diazepam as an adjunct treatment. There was a major group difference in treatment retention. At the end of the 8-d trial, 68 of patients treated with DXM were still in treatment, whereas none treated with chlorpromazine completed the study. In fact, in the chlorpromazine group,...

Robot Controllers

The early robotic systems for drug screening applications were controlled by the robot controller, usually with the help of another controller for the ''on-off'' devices in the robotic system, such as a PLC (programmable logic controller). Quickly, however, robotic systems became more complex, and it became important to exchange data, such as the weight of a sample, the bar code identification, the volume of liquid to dispense, the reading from an analytical instrument such as a plate reader, etc. Laboratory robotic systems soon needed sophisticated data handling capabilities as well as data links via RS232 or network connections. Now, data handling and database interactions are a crucial part of any sophisticated drug screening robotic system, and a PC or PC-like platform is commonly used for the data handling tasks in the robotic system.

Liquid Transfer

Liquid transfer is a key element of any drug screening method, and virtually every robotic system will have some provisions for the transfer of reagents and other liquids. There are three main types of liquid transfer modes reagent dispensing from bulk reservoirs, single or multichannel transfer between micro Pipetting to 96 or 384 wells simultaneously is very useful in drug screening. As stated in other sections, the microplate with 96, 384, and most recently 1536 wells has become the standard testing format. These formats are all multiples of 96 (384 4 X 96, 1536 16 X 96). Not only it is much faster to transfer liquid to 96 wells simultaneously compared with 1, 4, or 8 wells at a time as with a liquid handler, but for assays where a reaction is started or stopped with the addition of a reagent, it is possible to start and stop reactions at the same time. The 96- or 384-well pipettor will be capable of pipetting from one plate to another, or from a reservoir to a plate. Some models...

Quality Evaluation

Among other possible advantages of assay miniaturization, one less well addressed issue is the gain of assay quality in drug screening from a statistical point of view. Assay miniaturization makes it possible for each data point to be measured multiple times without consumption of significantly more key reagents.

Practical Examples

What does the communitarian emphasis on our social duties mean in practice. In their normative agenda in health care policies, for instance, some of the communitarian ethicists, mainly in the United States, argue, on somewhat utilitarian grounds here, that because a great number of patients needlessly suffer or die because of a lack of donated organs, societies ought to adopt a policy that hold organ donation as a social duty or as an 'act of obligation to community' routinely expected of each of us.16 Communitarians also propose that people should be compelled to tell their partners if they are for instance HIV positive. It is also suggested that AIDS testing be obligatory for all pregnant women and infants. Some communitarians even go so far as opposing unhealthy personal behaviour because it increases the cost that the whole community must bear (a question arises if we have a duty be healthy, but we fail in this, do we then have a duty to die ). Communitarians also want to protect...


Tion, automation and multiple detection modes, this process can be moved forward in the drug screening process. New readout technologies will enable several parameters to be measured simultaneously, meaning that assays, rather than compounds, will be pooled in a single sample. Just as conventional strategies lead to the pooling of compounds to increase throughput, new detection technologies enable far more information to be obtained in a single measurement, leading to an increase in information and a shortening of screening time. This will make lead evaluation feasible in early stages of the drug discovery process.

C 122 Study Design

Considering the reported pharmacokinetic data (8) of lansoprazole, considering a 0.05, and the bioequivalence range (0.8-1.2), a total number of 26 volunteers is expected to be sufficient to obtain a statistical power greater than 80 . Based on this estimation, 26 healthy male volunteers completed this pharmacokinetic study at Flemington Pharmaceutical Corporation, New Jersey, U.S.A. Their mean age was 25.1 + 7.2 years with a range of 18 to 45 years and mean body weight was 76.7 +10.9 kg with a range of 56.6 to 97.4 kg. Every subject completed an acceptable medical history, medication history, physical examination, an electrocardiogram, screens for HIV 1 and 2 antibodies and hepatitis B surface antigen, and a urine drug screen prior to study initiation. Selected routine clinical laboratory measurements were performed during screening. Upon completion of study, the physical examination and clinical laboratory measurements were repeated. The subjects were instructed to abstain from...