Development of a web-based tool for automated processing and cataloging of a unique combinatorial drug screen.

Facing totally resistant bacteria, traditional drug discovery efforts have proven to be of limited use in replenishing our depleted arsenal of therapeutic antibiotics. Recently, the natural anti-bacterial properties of metal ions in synergy with metal-coordinating ligands have shown potential for generating new molecule candidates with potential therapeutic downstream applications. We recently developed a novel combinatorial screening approach to identify compounds with copper-dependent anti-bacterial properties. Through a parallel screening technique, the assay distinguishes between copper-dependent and independent activities against Mycobacterium tuberculosis with hits being defined as compounds with copper-dependent activities. These activities must then be linked to a compound master list to process and analyze the data and to identify the hit molecules, a labor intensive and mistake-prone analysis. Here, we describe a software program built to automate this analysis in order to streamline our workflow significantly. We conducted a small, 1440 compound screen against M. tuberculosis and used it as an example framework to build and optimize the software. Though specifically adapted to our own needs, it can be readily expanded for any small- to medium-throughput screening effort, parallel or conventional. Further, by virtue of the underlying Linux server, it can be easily adapted for chemoinformatic analysis of screens through packages such as OpenBabel. Overall, this setup represents an easy-to-use solution for streamlining processing and analysis of biological screening data, as well as offering a scaffold for ready functionality expansion.

A hybrid method for prediction and repositioning of drug Anatomical Therapeutic Chemical classes.

In the Anatomical Therapeutic Chemical (ATC) classification system, therapeutic drugs are divided into 14 main classes according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. This system, recommended by the World Health Organization (WHO), provides a global standard for classifying medical substances and serves as a tool for international drug utilization research to improve quality of drug use. In view of this, it is necessary to develop effective computational prediction methods to identify the ATC-class of a given drug, which thereby could facilitate further analysis of this system. In this study, we initiated an attempt to develop a prediction method and to gain insights from it by utilizing ontology information of drug compounds. Since only about one-fourth of drugs in the ATC classification system have ontology information, a hybrid prediction method combining the ontology information, chemical interaction information and chemical structure information of drug compounds was proposed for the prediction of drug ATC-classes. As a result, by using the Jackknife test, the 1st prediction accuracies for identifying the 14 main ATC-classes in the training dataset, the internal validation dataset and the external validation dataset were 75.90%, 75.70% and 66.36%, respectively. Analysis of some samples with false-positive predictions in the internal and external validation datasets indicated that some of them may even have a relationship with the false-positive predicted ATC-class, suggesting novel uses of these drugs. It was conceivable that the proposed method could be used as an efficient tool to identify ATC-classes of novel drugs or to discover novel uses of known drugs.

(Re-)reading medical trade catalogs: the uses of professional advertising in British medical practice, 1870-1914.

This article explores how medical practitioners read, used, and experienced medical trade catalogs in late-nineteenth- and early-twentieth-century Britain. Reader responses to the catalog, a book-like publication promoting medical tools, appliances, and pharmaceuticals, have been chronically understudied, as have professional reading practices within medicine more generally. Yet, evidence suggests that clinicians frequently used the catalog and did so in three main ways: to order medical products, to acquire new information about these products, and to display their own product endorsements and product designs. The seemingly widespread nature of these practices demonstrates an individual and collective professional desire to improve medical practice and highlights the importance of studying professional reading practices in the cultural history of medicine.

[Gender- and age-related differences in dosage and serum concentration of psychotropic drugs]. / Kjønns- og aldersforskjeller ved bruk av psykofarmaka.

BACKGROUND: The dose recommendations in the Norwegian Pharmaceutical Product Compendium (Felleskatalogen) are not gender-specific, despite evidence of gender-dependent differences in the metabolism of a number of drugs. The purpose of this study was to investigate the extent to which age and gender influence the prescription and serum concentration of psychotropic drugs. MATERIAL AND METHOD: The prescribed doses and serum concentrations of antidepressant, antipsychotic and antiepileptic drugs were studied in relation to age and gender in 1533 patients. RESULTS: Elderly women (≥ 65 years) were given somewhat lower doses of antidepressant drugs, but they had significantly higher serum concentrations than younger patients of either gender. Antidepressant drugs were prescribed in fairly high doses in the study population; the median number of defined daily doses was 1.5. INTERPRETATION: The study suggests that when prescribing drugs, Norwegian physicians do not take sufficient account of the effect of age and gender on the pharmacokinetics of antidepressant drugs.

[Execute Yinpian drug catalogue, traditional Chinese medicine Yinpian prescription dispensing rule, completely solve the problem of the dispensing specified varieties].

For solve confusion of the dispensing specified varieties of traditional Chinese medicine Yinpian, the state administration of traditional Chinese medicine had decreed in 2009 the on the Traditional Chinese Medicine Yinpian prescription name and the dispensing specified varieties notification, Require various regions medical institutions to solve the problem. But the notification permit that each medical institutions formulate the traditional Chinese medicine Yinpian prescription name and standards of the dispensing Specified varieties, be sure to cause each medical institutions on parallel tracks in the dispensing Specified varieties. Beijing the Beijing traditional Chinese medicine Yinpian prescription dispensing rule. It nor did completely solve the problem of the dispensing specified varieties, there is a difference between doctor and harmacist. So formulate statute universal and scientific, Completely solve the problem of the dispensing specified varieties, It is Long-cherished wish of government and traditional Chinese medicine sector for many years The article on appearance of the dispensing specified varieties problem, and think about actual statute of the dispensing specified varieties, and discuss Solving system, consider formulate and execute Yinpian drug catalogue and Chinese medicine Yinpian prescription dispensing rule by country and local two level, It provides legal protection to thoroughly resolve the dispensing Specified varieties Both can resolve that prescription of traditional Chinese medicine Yinpian unified provisioning in entire country, And conducive to defend local medical genre medication features, and defend precious local features processing varieties and conducive to exploit new drug, and conducive to inherit and evolve traditional Chinese medicine scientifically, It is simple and feasible final way to Chinese medicine Yinpian dispensing specified varieties.

Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment.

AIMS: To catalogue the perpetrators of CYP-mediated pharmacokinetic drug-drug interactions (PK-DDIs) using clinically relevant criteria, and to compare this with an analogous catalogue. METHODS: Candidate inhibitors and inducers of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A ('perpetrators') were evaluated using published clinical pharmacokinetic interaction studies. Studies were selected on the basis of ≥six human subjects, use of a validated in vivo probe substrate for the CYP enzyme, and clinically relevant dosing. Inhibitors were described according to the FDA classifications of strong, moderate or weak, whereas inducers were classified as major (≥twofold decrease in AUC) or weak (

[The National List of recommendations-- what is it based on?]. / National Rekommandationsliste--hvad hviler den på?

The National List of recommendations is a scientific survey of the most used drugs. It separates the drugs into three groups: 1) recommended drugs, 2) drugs only to be used in special circumstances, and 3) drugs which should not be used in normal circumstances because of too limited efficacy or serious adverse reactions. The list is made by specialists chosen by the scientific bodies. The Institute of Rational Pharmacotherapy acts as secretariat. The primary selection criterion is the relationship between effect and adverse reactions, while price issues are not considered. Special consideration has been given to how the effect is expressed, composite measurements of effect and to extrapolation. The list, which is updated annually, is available at the IRF's homepage. The list of recommendations is primarily an instrument for general practitioners and drug committees; in future it should be integrated into the regional drug lists.

[How do general practitioners keep up-to-date on pharmacotherapy?]. / Hvordan holder allmennleger seg oppdatert om legemidler?

BACKGROUND: Traditional methods for dissemination of knowledge, such as lecture-based courses and distribution of guidelines, have shown only modest effect on improving the quality of GPs' prescription practice. We aimed at assessing GPs' own views on various sources of knowledge within pharmacotherapy, and their attitudes to a potentially effective educational method: audit and feedback. MATERIAL AND METHODS: A questionnaire regarding the use of and views on various sources of knowledge concerning pharmacotherapy was sent to GPs in continuing medical education (CME) groups participating in an intervention study on quality improvement of prescription practice. RESULTS: 302 of 479 GPs (63 %) responded. The Norwegian Pharmaceutical Catalogue was the most widely used source of information on drugs. Industry- based sources were generally regarded as less useful and without great influence on prescription practice, but were nevertheless often mentioned as a source of information in specific prescribing situations. The GPs rated CME groups as useful and influential, and 94 % viewed the exposure of own prescription data in the CME group as unproblematic. INTERPRETATION: Audit and feedback in CME groups seems to be a suitable educational method in pharmacotherapy. Industry- based information sources are rated as being of low value, but seem to have influence on prescription practice.

Image-guided enzyme/prodrug cancer therapy.

PURPOSE: The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo. This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. With this capability, prodrug administration can be timed so that the enzyme concentration is high in the tumor and low in systemic circulation and normal tissue, thereby minimizing systemic toxicity without compromising therapeutic efficiency. EXPERIMENTAL DESIGN: The delivery of a multimodal imaging reporter functionalized prodrug enzyme, cytosine deaminase, was detected by MR and optical imaging in MDA-MB-231 breast cancer xenografts. Stability of the enzyme in the tumor was verified by (19)F MR spectroscopy, which detected conversion of 5-fluorocytosine to 5-flurouracil. The optimal time window for prodrug injection determined by imaging was validated by immunohistochemical, biodistribution, and high-performance liquid chromatographic studies. The therapeutic effect and systemic toxicity of this treatment strategy were investigated by histologic studies and tumor/body weight growth curves. RESULTS: The delivery of the functionalized enzyme in tumors was successfully imaged in vivo. The optimal time window for prodrug administration was determined to be 24 h, at which time the enzyme continued to show high enzymatic stability in tumors but was biodegraded in the liver. Significant tumor growth delay with tolerable systemic toxicity was observed when the prodrug was injected 24 h after the enzyme. CONCLUSION: These preclinical studies show the feasibility of using a MR-detectable prodrug enzyme to time prodrug administration in enzyme/prodrug cancer therapy.