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PROVIDER: S-EPMC3695056 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
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Infectious disorders drug targets 20121116
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Project description:Post-marketing drug withdrawals can be associated with various events, ranging from safety issues such as reported deaths or severe side-effects, to a multitude of non-safety problems including lack of efficacy, manufacturing, regulatory or business issues. During the last century, the majority of drugs voluntarily withdrawn from the market or prohibited by regulatory agencies was reported to be related to adverse drug reactions. Understanding the underlying mechanisms of toxicity is of utmost importance for current and future drug discovery. Here, we present WITHDRAWN, a resource for withdrawn and discontinued drugs publicly accessible at http://cheminfo.charite.de/withdrawn. Today, the database comprises 578 withdrawn or discontinued drugs, their structures, important physico-chemical properties, protein targets and relevant signaling pathways. A special focus of the database lies on the drugs withdrawn due to adverse reactions and toxic effects. For approximately one half of the drugs in the database, safety issues were identified as the main reason for withdrawal. Withdrawal reasons were extracted from the literature and manually classified into toxicity types representing adverse effects on different organs. A special feature of the database is the presence of multiple search options which will allow systematic analyses of withdrawn drugs and their mechanisms of toxicity.
| S-EPMC4702851 | biostudies-literature
Project description: Not available
| S-EPMC6485337 | biostudies-literature
Project description:BackgroundSocial withdrawal is a core neuropsychiatric phenomenon in developmental psychopathology. Its presence predicts psychopathology across many domains, including depression, psychosis, autism, anxiety, and suicide. Withdrawn behavior is highly heritable, persistent, and characteristically worsens without intervention. To date, few studies have successfully identified genetic associations with withdrawn behavior, despite the abundance of evidence of its heritability. This may be due to reliance of categorical over dimensional measures of the behaviorally inhibited phenotype. The aim of this study is to identify associations between known psychiatric candidate genes and a dimensionally derived measure of withdrawn behavior.MethodsGenetic information was collected on 20 single-nucleotide polymorphisms (SNPs) from a custom-designed SNP chip and TAQMAN arrays of 4 variable number of tandem repeat (VNTR) genes for 551 individuals from 187 families. Linear mixed modeling was employed to examine the relationship between genotypes of interest and Child Behavior Checklist (CBCL) Withdrawn Behavior Subscale Score (WBS) while controlling for gender and age through multiple linear regressions.ResultsWithdrawn behavior was highly associated with polymorphism rs6314 of the serotonin receptor 2A (HTR2A) [p = .009, estimate = 0.310 (bootstrap 95% CI 0.155-0.448), bootstrap p = .001] and rs1800544 of the alpha 2-adrenergic (ADRA2A) [p = .001, estimate = -0.310 (bootstrap 95% CI -0.479 to -0.126), bootstrap p = .001] genes after correction for gender and age. The association between withdrawn behavior and ADRA2A was stronger for younger children.ConclusionsHTR2A and ADRA2A genes are associated with withdrawn behavior. This reinforces the role of catecholaminergic genes in the heritability of withdrawn behavior.
| S-EPMC3800258 | biostudies-literature
Project description:Selective withdrawal from a thermal stratified reservoir has been widely utilized in managing reservoir water withdrawal. Besides theoretical analysis and numerical simulation, model test was also necessary in studying the temperature of withdrawn water. However, information on the similarity theory of the withdrawn water temperature model remains lacking. Considering flow features of selective withdrawal, the similarity theory of the withdrawn water temperature model was analyzed theoretically based on the modification of governing equations, the Boussinesq approximation, and some simplifications. The similarity conditions between the model and the prototype were suggested. The conversion of withdrawn water temperature between the model and the prototype was proposed. Meanwhile, the fundamental theory of temperature distribution conversion was firstly proposed, which could significantly improve the experiment efficiency when the basic temperature of the model was different from the prototype. Based on the similarity theory, an experiment was performed on the withdrawn water temperature which was verified by numerical method.
| S-EPMC4433711 | biostudies-other
Project description:A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.
| S-EPMC3244390 | biostudies-literature
Project description:Chronic cocaine treatment is associated with changes in dendritic spines in the nucleus accumbens, but it is unknown whether this neuroplasticity alters the effect of a subsequent cocaine injection on spine morphology and protein content. Three weeks after daily cocaine or saline administration, neurons in the accumbens were filled with the lipophilic dye, DiI. Although daily cocaine pretreatment did not alter spine density compared with daily saline, there was a shift from smaller to larger diameter spines. During the first 2 h after an acute cocaine challenge, a bidirectional change in spine head diameter and increase in spine density was measured in daily cocaine-pretreated animals. In contrast, no change in spine diameter or density was elicited by a cocaine challenge in daily saline animals during the first 2 h after injection. However, spine density was elevated at 6 h after a cocaine challenge in daily saline-pretreated animals. The time-dependent profile of proteins in the postsynaptic density subfraction elicited by a cocaine challenge in daily cocaine-pretreated subjects indicated that the changes in spine diameter and density were associated with a deteriorating actin cytoskeleton and a reduction in glutamate signaling-related proteins. Correspondingly, the amplitude of field potentials in accumbens evoked by stimulating prefrontal cortex was reduced for up to 6 h after acute cocaine in daily cocaine-withdrawn animals. These data indicate that daily cocaine pretreatment dysregulates dendritic spine plasticity elicited by a subsequent cocaine injection.
| S-EPMC2698814 | biostudies-other
Project description:BackgroundThe success rate of correct endotracheal tube (ETT) placement for junior medical staff is less than 50% and accidental oesophageal intubation is common. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes including hypoxaemia, death, pneumothorax and right upper lobe collapse.ETT position can be confirmed using chest radiography, but this is often delayed; hence, a number of rapid point-of-care methods to confirm correct tube placement have been developed. Current neonatal resuscitation guidelines advise that correct ETT placement should be confirmed by the observation of clinical signs and the detection of exhaled carbon dioxide (CO2). Even though these devices are frequently used in the delivery room to assess tube placement, they can display false-negative results. Recently, newer techniques to assess correct tube placement have emerged (e.g. respiratory function monitor), which have been claimed to be superior in the assessment of tube placement.ObjectivesTo assess various techniques for the identification of correct ETT placement after oral or nasal intubation in newborn infants in either the delivery room or neonatal intensive care unit compared with chest radiography.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library 2012, Issue 4), MEDLINE (January 1996 to June 2014), EMBASE (January 1980 to Juen 2014) and CINAHL (January 1982 to June 2014). We searched clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research from 2004 to 2014. We did not apply any language restrictions.Selection criteriaWe planned to include randomised and quasi-randomised controlled trials and cluster trials that compared chest radiography with clinical signs, respiratory function monitors, exhaled CO2 detectors or ultrasound for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit.Data collection and analysisTwo review authors independently evaluated the search results against the selection criteria. We did not perform data extraction and 'Risk of bias' assessments because we identified no studies that met our inclusion criteria.Main resultsWe did not identify any studies meeting the criteria for inclusion in this review.Authors' conclusionsThere is insufficient evidence to determine the most effective technique for the assessment of correct ETT placement either in the delivery room or the neonatal intensive care unit. Randomised clinical trials comparing either of these techniques with chest radiography are warranted.
| S-EPMC6513417 | biostudies-literature
Project description:BackgroundIt has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of people with autism.ObjectivesTo determine the efficacy of gluten and/or casein free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism.Search methodsThe following electronic databases were searched: CENTRAL(The Cochrane Library Issue 2, 2007), MEDLINE (1966 to April 2007), PsycINFO (1971 to April 2007), EMBASE (1974 to April 2007), CINAHL (1982 to April 2007), ERIC (1965 to 2007), LILACS (1982 to April 2007), and the National Research register 2007 (Issue1). Review bibliographies were also examined to identify potential trials.Selection criteriaAll randomised controlled trials (RCT) involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with an autistic spectrum disorder.Data collection and analysisAbstracts of studies identified in searches of electronic databases were assessed to determine inclusion by two independent authors The included trials did not share common outcome measures and therefore no meta-analysis was possible. Data are presented in narrative form.Main resultsTwo small RCTs were identified (n = 35). No meta-analysis was possible. There were only three significant treatment effects in favour of the diet intervention: overall autistic traits, mean difference (MD) = -5.60 (95% CI -9.02 to -2.18), z = 3.21, p=0.001 (Knivsberg 2002) ; social isolation, MD = -3.20 (95% CI -5.20 to 1.20), z = 3.14, p = 0.002) and overall ability to communicate and interact, MD = 1.70 (95% CI 0.50 to 2.90), z = 2.77, p = 0.006) (Knivsberg 2003). In addition three outcomes showed no significant difference between the treatment and control group and we were unable to calculate mean differences for ten outcomes because the data were skewed. No outcomes were reported for disbenefits including harms.Authors' conclusionsResearch has shown of high rates of use of complementary and alternative therapies (CAM) for children with autism including gluten and/or casein exclusion diets. Current evidence for efficacy of these diets is poor. Large scale, good quality randomised controlled trials are needed.
| S-EPMC6445047 | biostudies-literature
Project description:BACKGROUND:Essential medicines lists and related policies are intended to meet the priority health needs of populations and their implementation is associated with more appropriate use of medicines. The World Health Organization (WHO) recommends that countries carefully select the medicines to be included in their national essential medicines lists. Lists that are used to prioritize access to important treatments should not include medicines that have been withdrawn elsewhere because of an unfavourable benefit-to-harm balance; however, countries still list and use medicines that have been withdrawn worldwide. The objective of this study was to determine whether the national essential medicines lists of 137 countries include medicines that have been withdrawn in other countries. METHODS AND FINDINGS:We performed an audit of national essential medicines lists for medicines that had been withdrawn. Medicines withdrawn from worldwide markets between 1953 and 2014 were identified using a systematic review of published literature and regulatory documents. The reviewers used sources including the WHO's database of drugs, PubMed, and the websites of regulatory agencies to obtain information regarding adverse effects associated with the medicines, the year of first withdrawal, markets of withdrawal, and the level of evidence supporting each withdrawal. We recorded the number of countries with a withdrawn medicine included in their national medicines list, the number of withdrawn medicines included in each nation's list, and the number of national essential medicines including each withdrawn medicine. 97 medicines were withdrawn in at least one country but still included in one more national essential medicines list. Of 137 countries with a national essential medicines list, 136 lists included at least one withdrawn medicine, with 54% of the lists containing 5 or fewer withdrawn medicines, and 27% including 10 or more withdrawn medicines. 11 medicines were withdrawn worldwide but still included on at least one national essential medicines list. Countries with longer essential medicines lists had more withdrawn medicines included in their lists. CONCLUSIONS:This study found that withdrawn medicines are included in all but one national essential medicines list, representing a need for more stringent processes for selecting and removing medicines on these lists. Countries may wish to apply special scrutiny to medicines withdrawn in other nations when selecting medicines to include on their lists.
| S-EPMC6887519 | biostudies-literature
Project description: Not available
| S-EPMC6457693 | biostudies-literature