The Inventory of Drug Use Consequences (InDUC): Test-retest stability and sensitivity to detect change.

The Inventory of Drug Use Consequences (InDUC) is a self-administered measure of consequences of drug use. Psychometric characteristics have been published for its alcohol-focused parent instrument (Drinker Inventory of Consequences; W. Miller, J. Tonigan, & R. Longabough, 1995). Two studies provided information about the test-retest reliability (lifetime) of InDUC scales (Study 1, N?=?34) and the replicability of findings to the 5 InDUC scales (recent; Study 2, N?=?208). Four scales had good to excellent test-retest reliability. Findings also indicate that reductions in drug use and problems after treatment are large and that the magnitude of change differs between drug use and consequences. Consequences of drug use should be measured directly rather than be inferred from measures of use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug target validation and identification of secondary drug target effects using DNA microarrays

We describe here a method for drug target validation and identification of secondary drug target effects based on genome-wide gene expression patterns. The method is demonstrated by several experiments, including treatment of yeast mutant strains defective in calcineurin, immunophilins or other genes with the immunosuppressants cyclosporin A or FK506. Presence or absence of the characteristic drug 'signature' pattern of altered gene expression in drug-treated cells with a mutation in the gene encoding a putative target established whether that target was required to generate the drug signature. Drug dependent effects were seen in 'targetless' cells, showing that FK506 affects additional pathways independent of calcineurin and the immunophilins. The described method permits the direct confirmation of drug targets and recognition of drug-dependent changes in gene expression that are modulated through pathways distinct from the drug's intended target. Such a method may prove useful in improving the efficiency of drug development programs.     

Cerebellar hypometabolism in focal epilepsy is related to age of onset and drug intoxication

BACKGROUND: The pathogenesis of transplantation-associated accelerated atherosclerosis is poorly understood, but it is likely to be an alloimmune response involving infiltration of the vessel wall by T lymphocytes and monocytes leading to smooth muscle cell proliferation and extracellular matrix deposition. RANTES is a chemokine that selectively chemoattracts T lymphocytes, NK cells, monocytes, and eosinophils. The expression of RANTES in accelerated atherosclerosis was investigated by in situ hybridization and immunohistochemistry. METHODS: Coronary arteries from six patients undergoing accelerated atherosclerosis were obtained at the time of retransplantation. Normal coronary arteries from two patients with idiopathic dilated cardiomyopathy were used as controls. Messenger RNA for RANTES was localized with digoxigenin-labeled complementary DNA probes. RANTES protein was detected by use of a monoclonal antibody and a three-step horseradish peroxidase method. RESULTS: RANTES mRNA and protein were detected in the lymphocytes, macrophages, myofibroblasts, and endothelial cells of arteries undergoing accelerated atherosclerosis but not in normal coronary arteries. CONCLUSIONS: In view of its in vitro biologic activity and in vivo expression pattern, RANTES may be a pivotal mediator of the cellular infiltrate seen in graft atherosclerosis. This information may help in the design of novel diagnostic and therapeutic approaches to this increasingly important disease process.     

Drug addiction as a physical disease: the role of physical dependence and other chronic drug-induced neurophysiological changes in compulsive drug self-administration

The effects of breast-feeding and supplementation practices on recent diarrhoea occurrence and stunted growth are modelled using logistic regression techniques. Data from the Demographic and Health Survey of Bolivia, 1989, show that, among children aged 3-36 months at the date of interview, the benefits of breast-feeding to child health were most pronounced among children living in rural poverty. Reduced breast-feeding among these children increased the likelihood of diarrhoea and stunted growth. In addition, the introduction of solid foods to currently lactating infants negatively influenced child health.     

Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities

Many of the symptoms of nicotine withdrawal are similar to those of other drug withdrawal syndromes: anxiety, awakening during sleep, depression, difficulty concentrating, impatience, irritability/anger and restlessness. Slowing of the heart rate and weight gain are distinguishing features of tobacco withdrawal. Although nicotine withdrawal may not produce medical consequences, it lasts for several weeks and can be severe in some smokers. Like most other drug withdrawals, nicotine withdrawal is time-limited, occurs in non-humans, is influenced by instructions/expectancy and abates with replacement therapy and gradual reduction. Unlike some other drug withdrawal syndromes, protracted, neonatal or precipitated withdrawal does not occur. Whether nicotine withdrawal is associated with tolerance, acute physical dependence, greater duration and intensity of use, rapid reinstatement, symptom stages, cross-dependence with other nicotine ligands, reduction by non-pharmacological interventions and genetic influences is unclear. Whether nicotine withdrawal plays a major role in relapse to smoking has not been established but this is also true for other drug withdrawal syndromes.     

Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles

Low density lipoprotein (LDL) has been found suitable as a targeting carrier for cytotoxic drugs. However, higher drug loading into LDL particles without disrupting their native integrity remains a major obstacle. The purpose of this study is to investigate the different physicochemical factors that may affect drug loading and to characterize LDL-drug conjugates. Doxorubicin (Dox) and 3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine (dpIUdR) were used as reference cytotoxic drugs. Drugs were loaded into LDL particles using the dry film method with or without surfactants, liposomal and the direct addition method. The effects of incubation temperature, time and stoichiometry of LDL-drug conjugates on drug loading were investigated. The LDL-drug conjugates were evaluated for their stability and characterized by differential scanning calorimetry (DSC), denatured gel (SDS-PAGE), and electron microscopy (EM). We have suitably incorporated 45+/-10 Dox and 150+/-25 dpIUdR molecules/LDL particle. A seven-fold increase in Dox incorporation was achieved with the liposomal preparation compared to the dry film method. A 4- to 6-h incubation at 37 degreesC was suitable to restore the native structure of LDL particles. No apo B fragmentation of LDL particles was noted on denatured gel. DSC studies showed no change in the Tm of the LDL and the LDL-drug conjugates. An increase in particle size of LDL-dpIUdR, not LDL-Dox was observed in EM compared to the native LDL which may be related to higher incorporation of dpIUdR. The results indicate that physicochemical factors significantly affect drug loading efficiency and may need to be considered to optimize drug incorporation into LDL particles.     

Change deafness: The inability to detect changes between two voices.

A shadowing task was used to demonstrate an auditory analogue of change blindness (the failure to detect a change in a visual scene), namely change deafness. Participants repeated words varying in lexical difficulty. Halfway through the word list, either the same or a different talker presented the words to participants. At least 40% of the participants failed to detect the change in talker. More interesting is that differences in shadowing times were found as a function of change detection. Alternative possibilities to the change detection phenomenon were ruled out. The results of these experiments suggest that the allocation of attention may influence the detection of changes as well as the processing of spoken words in complex ways. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Managing drug reactions to sulfonamides and other drugs in HIV infection: desensitization rather than rechallenge?

Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge.     

Utilizing the ultraviolet (UV detect) camera to enhance the appearance of photodamage and other skin conditions

Six isolates of Bacillus pumilus were tested for their ability to inhibit aflatoxin production of Aspergillus parasiticus NRRL 2999 in yeast extract sucrose (YES) broth. Aflatoxin production was inhibited in both simultaneous and deferred antagonism assays, suggesting that the inhibitory activity was due to extracellular metabolites(s) produced in cell-free supernatant fluids of cultured broth. The inhibition was not due to organic acids or hydrogen peroxide produced by B. pumilus since the inhibitory activity was not lost after pH adjustment or treatment of supernatant fluids with catalase. A range of media tested for the production of inhibitory metabolite(s) in supernatant fluids showed that all media supported bacterial growth and production of the metabolite(s). The metabolite(s) were produced over a wide range of temperature (25 to 37 degrees C) and pH (4 to 9) of growth of B. pumilus. They were stable over a wide range of pH (4 to 10) and were not inactivated after autoclaving at 121 degrees C for 30 minutes.     

The neurologic examination in adult psychiatry: from soft signs to hard science

Of the proliferating approaches to neuropsychiatric assessment, a relatively neglected technique is the venerable, accessible, noninvasive, and inexpensive neurologic examination. This article organizes and synthesizes the literature on neurological findings in adult psychiatric patients. Problems in conducting and interpreting research in this area are examined, clinically pertinent empirical findings are surveyed, and directions for future investigation are outlined. Most of the "soft signs" can be reliably evaluated, and many have been validated against other techniques. Several psychiatric diagnoses are associated with impaired neurologic performance. Prognosis and treatment selection may also be informed by neurologic findings. The neurologic exam should be regarded as a collection of neurobiologic probes rather than as a single irreducible variable. Future work must better establish interrater and test-retest reliability of individual elements of the neurologic exam in psychiatric populations and focus on developing the clinical utility of individual and combined elements of the neurologic exam.     

Applying laboratory research: Drug anticipation and the treatment of drug addiction.

Basic research concerning drug tolerance and withdrawal may inform clinical practice, and vice versa. Three areas that integrate the work of the laboratory and the clinic are discussed: (a) drug overdose, (b) cue exposure treatment of addiction, and (c) pharmacological treatment of withdrawal symptoms. The areas are related in that they indicate the contribution of drug-paired cues to the effects of addictive drugs and the role of Pavlovian conditioning of drug effects in drug tolerance and withdrawal symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new screening method to detect water-soluble antioxidants: acetaminophen (Tylenol) and other phenols react as antioxidants and destroy peroxynitrite-based luminol-dependent chemiluminescence

This study is based on a simple chemical interaction of peroxynitrite (O = N-O-O-) and luminol, which produces blue light upon oxidation. Since peroxynitrite has a half-life of about 1 s, a drug known as linsidomine (SIN-1) is used as a peroxynitrite generator. Peroxynitrite can oxidize lipids, proteins and nucleic acids. Upon the stimulation of inflammation and/or infection, macrophages and neutrophils can be induced to produce large amounts of peroxynitrite, which can oxidize phenols and sulphhydryl-containing compounds. Therefore, phenols and sulphhydryls eliminate peroxynitrite. This is an example of the Yin-Yang hypothesis e.g. oxidation-reduction. Acetaminophen (Tylenol) can inhibit fever and some types of pain without being a particularly effective anti-inflammatory. Since it is a phenol, it could act as a nitration target for peroxynitrite. Then peroxynitrite, the possible cause of pain and elevated temperature, might be destroyed in the reaction. Acetaminophen is a phenolic compound which produces a clear inhibitory dose-response curve with peroxynitrite in its range of clinical effectiveness. Whether acetaminophen actually works as we suggest is to be proven. Three different types of reaction could decrease the amount of peroxynitrite: (a) interference with base-catalysed opening of the SIN-1 molecule; (b) destruction of one or both substances needed to form it--superoxide and/or nitric oxide; when the SIN-1 degrades to superoxide and nitric oxide, the former may be destroyed by superoxide dismutase (SOD); (c) peroxynitrite may react directly with phenols (mono-, di-, tri- and tetraphenols), possibly by nitration. Nordihydroguaiaretic acid and 2-hydroxyestradiol (catechol estrogen) are potent inhibitors of luminol light emission. Epineprine, isoproterenol, pyrogallol, catechol and ascorbic acid (a classic antioxidant) are all inhibitors of luminol chemiluminescence. Isoproterenol, norepinephrine/and epinephrine first inhibit light but overall stimulate the light production. Initially, SIN-1 degrades to produce peroxynitrite, which reacts with luminol to produce blue light. If any of three catecholamines are present with the reaction that produces light, there is an initial inhibition of light production, and then a marked stimulation. A possible reason for this is that these catechols are oxidized and the metabolized phenol stimulates the production of light from luminol. Also, during oxidation of catecholamines superoxide is sometimes formed, which could stimulate production of peroxynitrite. This simple screening system is introduced to find useful antioxidants against peroxynitrite.     

Drug testing, drug treatment, and marijuana use: A fairness perspective.

The authors conducted a random statewide telephone survey of 1,484 individuals to study the relationship between marijuana use (in terms of participants' history of marijuana use) and reactions to drug testing and to study 2 hypothetical drug-treatment policies. Job safety sensitivity was related to perceived fairness of drug testing for the participant's job, and more recent marijuana use was associated with more negative reactions. Safety sensitivity was related to perceived fairness of drug treatment. Organizations with voluntary treatment were more attractive than ones with monitored treatment. Marijuana use interacted with drug treatment policy type in predicting reactions to drug treatment. Results suggest that organizations should consider job and employee characteristics when developing a drug treatment policy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Validity of self-reports of alcohol and other drug use: A multitrait-multimethod assessment.

Used 4 methods (self-reported rating, self-reported intake, peer-reported rating, and peer-reported intake) and multiple analytical criteria to assess the construct validity of reports of 3 types of substance use (alcohol, marihuana, and cigarettes) in a study of 194 college students who were members of friendship pairs. Ss answered questions about their own use and their friend's use of substances, classified their own and their friend's use of each substance according to 6 categories, and completed scales measuring the negative consequences of marihuana and alcohol. The resulting multitrait-multimethod matrix was analyzed in the traditional fashion as well as with confirmatory factor analysis. Convergent and discriminant validity for the 3 substance use traits were quite adequate, although the validity of the peer-reported intake measure of alcohol use may be considered inadequate according to some criteria. Results demonstrate the usefulness of multimethod assessment and confirmatory factor analysis for research on construct validity and for derivation of more accurate measures of drug use. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monitoring and Evaluation Scheme using the Multiple-Criteria-Decision-Making Technique: Application to Irrigation Projects

The application of monitoring and evaluation (M&E) systems to assess agricultural projects has received some attention in recent years. These systems provide valuable information for managers and decision makers by analyzing the implementation process, the progress of trends, and the long-term and short-term effectiveness of these projects. An algorithm is developed to monitor and evaluate drip and pressure irrigation projects in Iran. Different indicators are identified and the framework of an integrated evaluation system is demonstrated using an analytical hierarchy process for multiple-criteria-decision making. There is much subjective information that is quantified and normalized in order to remove any bias in evaluators’ assessment of qualitative measures or sensitivity to linguistic expressions. The application of this system to rank projects in different regions (zones) in Iran is also presented in this paper. The results have shown the significant value of such systems in providing information and input for different decision-making levels.     

Collaborative work to determine the optimal administration period and parameters to detect drug effects on male rat fertility--study on estradiol benzoate effects

In order to examine the optimal administration period and parameters for male fertility assessment, male rats were subcutaneously administered 0.2, 2 or 20 micrograms/kg of estradiol benzoate (E2B), a known testicular toxicant, for 4 weeks or 9 weeks before mating. After 4 weeks administration, suppression of body weight gain and food consumption, decreases in prostate and seminal vesicle weights, atrophy of Leydig cells, and mature spermatid retention at stages IX, X and XI were observed in the 2 and 20 micrograms/kg groups. In the 20, micrograms/kg group, decreases in epididymides weight and copulation index were also found but the number of sperm and sperm motility were not affected. In the 0.2 micrograms/kg group, no changes were noted in any parameters. After 9 weeks administration, decreases in testis weight and the number and motility of sperm were observed in the 20, micrograms/kg group, in addition to the changes found after 4 weeks administration. These results suggest that detailed histopathological evaluation and determination of accessory sex organ weights are sensitive for evaluating the effects of E2B on male fertility. Results with the 4-weeks treatment were comparable to those with the 9-weeks treatment in terms of these parameters.     

Evaluation of diagnostic procedures to detect Mycoplasma synoviae in commercial multiplier-breeder farms and commercial hatcheries in Florida

Sera from 5325 chickens representing 71 commercial poultry flocks were tested for Mycoplasma synoviae (MS) using standard National Poultry Improvement Program (NPIP) testing guidelines. Based on the NPIP guidelines, only sera (N = 195) from flocks that test positive by specific plate agglutination (SPA) were submitted for additional confirmatory tests. Flocks from three multihouse farms were identified as seropositive for MS and confirmed by culture and polymerase chain reaction (PCR). Serum samples (N = 195) from these seropositive flocks were compared by SPA, enzyme-linked immunoassay (ELISA), and hemagglutination-inhibition (HI). Of the 195 sera tested for MS from these flocks, 145 (74%) sera were positive by SPA. Of the 145 SPA-positive sera, the HI test was positive for 127 samples (90.2%), whereas the ELISA was positive for 141 samples (98.6%). This difference between the two tests was significant (P = 0.0006). Significant differences (P = 0.0002) in titer were obtained from paired serum samples that were submitted to three different laboratories for HI analysis. Both the SPA and HI tests failed to detect early infection in newly introduced flocks following depopulation of MS-positive facilities. Both ELISA and PCR detected new infections on these farms. In the MS outbreak described in this study, SPA was not adequate as the sole screening test and HI was not adequate for confirmation of flock infection status. Continued reliance on the same or a similar type of testing could result in missed infections. Confirmation of infection by PCR was preferable to HI and also may be used in place of culture. The findings of this study suggest that ELISA should be considered as a serologic screen in lieu of SPA, screening with SPA may miss MS-infected flocks, and PCR should be considered as a confirmatory test.     

Evaluation of a video-supplement to informed consent: injection drug users and preventive HIV vaccine efficacy trials

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.