The safety of tocolytics used for the inhibition of preterm labour.

PubMed

Lamont, Callum D; Jørgensen, Jan Stener; Lamont, Ronald F

2016-09-01

Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

[Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

PubMed

Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

2015-03-29

Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator Role of ART-Related Knowledge.

PubMed

Zhou, Guangyu; Li, Xiaoming; Qiao, Shan; Shen, Zhiyong; Zhou, Yuejiao

2018-03-01

Despite the medical advancements in HIV treatment, realities of side effects are faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART). Mixed findings have been reported on the association between side effects and ART adherence. However, few studies have explored the combined side effects and behavior-related information on medication adherence. The aim of the current study is to examine moderator role of ART-related knowledge between side effects and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from October 2012 to August 2013 in China. Of the total sample, 2095 patients had received ART and provided ART adherence. Side effects, ART-related knowledge, and ART adherence, as well as potential covariates were assessed. The results revealed that there was a negative relationship of side effects and ART adherence existed among low and medium levels of ART-related knowledge, but not among high level of knowledge. Future interventions to promote HIV medication adherence should focus on providing behavior-related information education among PLWH.

The dark side of browning.

PubMed

Tamucci, Kirstin A; Namwanje, Maria; Fan, Lihong; Qiang, Li

2018-02-01

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review.

PubMed

Smith, Stephen J; Smith, Brian D; Mohney, Brian G

2014-03-01

To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma. PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans. Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments. Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Side-effects and technical problems in cytapheresis with cell separators. Results of a retrospective multicenter study.

PubMed

Kretschmer, V

1987-09-01

On the basis of a survey, the acute side-effects and technical problems in a total of 77,525 cytaphereses (IFC 36,530, CFC 40,995) in donors at 39 hemapheresis centers were retrospectively analysed statistically. In general, relevant donor side-effects (0.78%-1.05%) were more rare than the primary donor-independent disturbances (1.65%-2.63%). The donor side-effects predominated merely with the use of the cell separators Haemonetics M30/Belco (1.06% vs. 0.57%). These were mainly circulatory reactions (0.83%), which were generally much more frequent with IFC (0.54%) than with CFC (IBM/Cobe 0.11%, CS-3000 0.19%). Potentially fatal complications were not reported. The frequency of side-effects, disturbances and discontinuations correlated inversely with the separation rate of the individual centers per method. Centers in which two or three methods were applied simultaneously reported a higher frequency of side-effects and disturbances. Hemolysis was only observed with IFC (0.09%), but not with the use of the Haemonetics V50. The greater susceptibility to disturbances of technical/methodological/operational origin essentially results from the more elaborate, but not yet perfected technology, including computer control and monitoring, as well as defects in the production of the much more complicated disposable sets. Thus the highest rate of discontinuations was calculated for the system which is so far the most sophisticated technically (CS-3000, 1.85%). Although the primary donor-independent problems sometimes correlate directly with the manifestation of donor side-effects, the greater technological sophistication of automatically controlled and monitored systems cannot be dispensed with, since only in this way can potentially fatal risks for the donors be largely ruled out.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Standardized New Medication Education Program on Postdischarge Patients' Knowledge and Satisfaction.

PubMed

Jones, Tammie R; Coke, Lola

2016-10-01

This study, implemented on 2 medical-surgical units, evaluated the impact of a standardized, evidence-based new medication education program. Outcomes evaluated included patient postdischarge knowledge of new medication purpose and side effects, patient satisfaction with new medication, and Medicare reimbursement earn-back potential. As a result, knowledge scores for new medication purpose and side effects were high post intervention. Patient satisfaction with new medication education increased. Value-based purchasing reimbursement earn-back potential improved.

Calcium channel blockers: spectrum of side effects and drug interactions.

PubMed

Hedner, T

1986-01-01

Calcium antagonists are a chemically heterogenous group of agents with potent cardiovascular effects which are beneficial in the treatment of angina pectoris, arterial hypertension and cardiac arrhythmias. The main side effects for the group are dose-dependent and the result of the main action or actions of the calcium antagonists, i.e. vasodilatation, negative inotropic effects and antiarrhythmic effects. Pronounced hypotension is reported for the main calcium antagonist drugs; verapamil, diltiazem and nifedipine. While conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, tachycardia, headache and flush are more frequent after nifedipine. Constipation is relatively frequent after verapamil while nifedipine is reported to induce diarrhea in som patients. Idiosyncratic side effects are rare but have been reported from the skin, mouth, musculoskeletal system, the liver and the central nervous system. These side effects include urticarial rashes, gingival hyperplasia, arthralgia, hepathotoxicity and transistory mental confusion or akathisia. Verapamil, diltiazem and possibly also nifedipine have been reported to increase serum digoxin concentrations but the clinical relevance of these drug interactions are not clear. Furthermore, verapamil and diltiazem may potentiate the effects of beta-adrenergic blocking drugs and verapamil may also potentiate the effects of neuromuscular blocking drugs. It is concluded that side effects after calcium antagonist drugs are mostly trivial and transient although they may sometimes be relatively common. Clinically relevant drug interactions are few. Judged from the point of efficacy and safety, calcium antagonists will have a major place in the future pharmacotherapy of several cardiovascular disorders.

The Unintended Consequences of School Inspection: The Prevalence of Inspection Side-Effects in Austria, The Czech Republic, England, Ireland, The Netherlands, Sweden, and Switzerland

ERIC Educational Resources Information Center

Jones, Karen L.; Tymms, Peter; Kemethofer, David; O'Hara, Joe; McNamara, Gerry; Huber, Stephan; Myrberg, Eva; Skedsmo, Guri; Greger, David

2017-01-01

It has been widely documented that accountability systems, including school inspections, bring with them unintended side effects. These unintended effects are often negative and have the potential to undo the intended positive effects. However the empirical evidence is limited. Through a European comparative study we have had the rare opportunity…

Pattern of Self Prescribed Analgesic Use in a Rural Area of Delhi: Exploring the Potential Role of Internet.

PubMed

Kochhar, Anjali; Gupta, Tanya

2017-07-01

Analgesics are the most common self prescribed drugs. Although considered to be relatively safe, side effects are often seen when these drugs are used for prolonged period, in high doses or used where contraindicated. Majority of the consumers are not aware of the side effects. These days ample amount of information is available on web, it is important to explore its role in educating the population regarding the safe use of self prescribed analgesics. To explore pattern of analgesic use, to identify population at risk of developing side effects related to analgesic use, awareness of side effects and potential role of internet to bring awareness about safe use of self prescribed analgesic drugs in a rural area of Delhi. A cross-sectional survey based study was done on 500 adults in the age group of 18-65 years of Madanpur Khadar area of South Delhi, India. Data collection was done by conducting visits to pharmacy shops from the people who were buying drugs without prescription and taking face to face interviews using a semi-structured questionnaire. Statistical analysis was performed using descriptive tests with Microsoft office excel 2007. Results of our study showed that among all the self prescribed analgesics paracetamol (57%) was used most frequently followed by aspirin and other NSAIDs. It was found that 9.6% of the consumers were having associated co-morbid illness, 11.4% were simultaneously taking other drugs and 15.2% were alcoholics. Majority (65.4%) of the buyers were not aware about any kind of side effects of the analgesics. Internet friendly consumers were found to be 44%. Ability to use internet and education level were found to be directly related (r=0.802). The pattern of analgesic consumption in the rural population of Delhi shows that a large number of consumers may be at risk of developing side effects of self prescribed analgesics. The awareness about the side effects is limited. A significant number of consumers are internet friendly. Hence, we recommend use of website/mobile apps as potential source of information in educating the population regarding the use of self prescribed analgesics.

The timeliness of patients reporting the side effects of chemotherapy.

PubMed

Olver, Ian; Carey, Mariko; Boyes, Allison; Hall, Alix; Noble, Natasha; Bryant, Jamie; Walsh, Justin; Sanson-Fisher, Rob

2018-05-03

To explore the actions cancer patients reported they would take in response to a range of common side effects of chemotherapy and whether these were considered appropriate based on current guidelines and evidence; and to explore the sociodemographic and cancer-related variables associated with patients selecting the appropriate action (immediate medical attention or reporting) for two potentially life-threatening side effects: fever, and unusual bleeding and bruising. Four hundred thirty-six medical oncology and haematology patients receiving chemotherapy completed two surveys to provide demographic, disease and treatment characteristics, and details on how they would respond if they experienced a range of specified side effects of chemotherapy (for example, nausea and vomiting, fatigue, and skin rash or nail changes). The proportion of patients reporting the appropriate action for each side effect was calculated. Multiple logistic regressions examined the patient demographic and cancer characteristics associated with selecting the appropriate action (seeking immediate medical attention) for two potentially life-threatening side effects of chemotherapy: high fever of 38 °C or more, and unusual bleeding or bruising. Two thirds of patients indicated that they would seek immediate medical attention for high fever (67%), but only 41% would seek immediate attention for bleeding or bruising. Cancer type and time since diagnosis were significantly associated with patients indicating that they would seek immediate medical attention for high fever; while time since diagnosis was the only variable significantly associated with patients reporting that they would seek immediate medical attention for unusual bleeding or bruising. For chronic side effects, like skin rash or nail changes, and tingling or numbness, which usually do not require urgent reporting, only between 12 and 16% would report them immediately. A significant proportion of patients reported that they would "do nothing" about fatigue or tiredness (24%). By comparison, less than 10% patients reported that they would do nothing for the other side effects investigated. Tools need to be created so that patients better understand the side effects after being treated with chemotherapy and what action they should take.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects.

PubMed

Pijls, Philippe A R R; Gilissen, Lennard P L

2016-11-01

The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Contraceptive effect and potential side-effects of deslorelin acetate implants in rats (Rattus norvegicus): Preliminary observations

PubMed Central

Grosset, Claire; Peters, Stijn; Peron, Franck; Figuéra, Joëlle; Navarro, Christelle

2012-01-01

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study. PMID:23277700

Monitoring Metabolic Side Effects of Atypical Antipsychotics in People with an Intellectual Disability

ERIC Educational Resources Information Center

Teeluckdharry, Sadira; Sharma, Sujit; O'Rourke, Elizabeth; Tharian, Priyanka; Gondalekar, Anjali; Nainar, Feroz; Roy, Meera

2013-01-01

This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of…

Polyuria with sevoflurane administration: a case report.

PubMed

Schirle, Lori

2011-02-01

Polyuria has been reported as a side effect of sevoflurane administration, but because of its relative rarity, many practitioners are not aware of this potential phenomenon. Polyuria in its extreme form can cause undesirable hemodynamic changes. A case study, in an 18-year-old man, is presented highlighting polyuria as a probable side effect of sevoflurane administration.

Potential errors in optical density measurements due to scanning side in EBT and EBT2 Gafchromic film dosimetry.

PubMed

Desroches, Joannie; Bouchard, Hugo; Lacroix, Frédéric

2010-04-01

The purpose of this study is to determine the effect on the measured optical density of scanning on either side of a Gafchromic EBT and EBT2 film using an Epson (Epson Canada Ltd., Toronto, Ontario) 10000XL flat bed scanner. Calibration curves were constructed using EBT2 film scanned in landscape orientation in both reflection and transmission mode on an Epson 10000XL scanner. Calibration curves were also constructed using EBT film. Potential errors due to an optical density difference from scanning the film on either side ("face up" or "face down") were simulated. Scanning the film face up or face down on the scanner bed while keeping the film angular orientation constant affects the measured optical density when scanning in reflection mode. In contrast, no statistically significant effect was seen when scanning in transmission mode. This effect can significantly affect relative and absolute dose measurements. As an application example, the authors demonstrate potential errors of 17.8% by inverting the film scanning side on the gamma index for 3%-3 mm criteria on a head and neck intensity modulated radiotherapy plan, and errors in absolute dose measurements ranging from 10% to 35% between 2 and 5 Gy. Process consistency is the key to obtaining accurate and precise results in Gafchromic film dosimetry. When scanning in reflection mode, care must be taken to place the film consistently on the same side on the scanner bed.

Low Voltage Activated Calcium Channels - Their Role in HER2 Driven Breast Cancer and Potential as a New Therapeutic Target

DTIC Science & Technology

2016-10-01

combined with chemotherapy , but chemotherapy causes undesirable side effects due to off-target effects on normal tissue, which diminishes quality of life...highest response rates when combined with chemotherapy , but chemotherapy causes undesirable side effects due to off-target effects on normal...patients. Therefore, the overall goal of this proposal is to develop a tumor-specific, safe and effective therapy for breast cancer. We concentrate on

Cardiac side effects of bruton tyrosine kinase (BTK) inhibitors.

PubMed

Tang, Chloe Pek Sang; McMullen, Julie; Tam, Constantine

2017-09-13

The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects. This review describes the current knowledge regarding BTKi and potential pathophysiologic mechanisms of AF and discusses the management of BTKi-associated AF. Finally, a review of the second generation BTKi is provided and gaps in knowledge in this evolving field are highlighted.

A side-effect free method for identifying cancer drug targets.

PubMed

Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

2018-04-27

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

PubMed

Taylor, Beth A; Thompson, Paul D

2015-06-01

This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

Inferring protein domains associated with drug side effects based on drug-target interaction network

PubMed Central

2013-01-01

Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

PubMed Central

Arriola Apelo, Sebastian I.

2016-01-01

Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. PMID:27208895

Alleviation of harmful effect in stillage reflux in food waste ethanol fermentation based on metabolic and side-product accumulation regulation.

PubMed

Ma, Hongzhi; Yang, Jian; Jia, Yan; Wang, Qunhui; Ma, Xiaoyu; Sonomoto, Kenji

2016-10-01

Stillage reflux fermentation in food waste ethanol fermentation could reduce sewage discharge but exert a harmful effect because of side-product accumulation. In this study, regulation methods based on metabolic regulation and side-product alleviation were conducted. Result demonstrated that controlling the proper oxidation-reduction potential value (-150mV to -250mV) could reduce the harmful effect, improve ethanol yield by 21%, and reduce fermentation time by 20%. The methods of adding calcium carbonate to adjust the accumulated lactic acid showed that ethanol yield increased by 17.3%, and fermentation time decreased by 20%. The accumulated glyceal also shows that these two methods can reduce the harmful effect. Fermentation time lasted for seven times without effect, and metabolic regulation had a better effect than side-product regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Side Effects of Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures

ERIC Educational Resources Information Center

Utari, Agustini; Chonchaiya, Weerasak; Rivera, Susan M.; Schneider, Andrea; Hagerman, Randi J.; Faradz, Sultana M. H.; Ethell, Iryna M.; Nguyen, Danh V.

2010-01-01

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received…

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Exploring Motivations, Awareness of Side Effects, and Attitudes among Potential Egg Donors

PubMed Central

Gezinski, Lindsay B.; Karandikar, Sharvari; Carter, James; White, Melinda

2016-01-01

This research study surveyed prospective egg donors at orientation to (a) understand women’s motivations to donate eggs, (b) assess awareness and knowledge of egg donation prior to entry into the egg donation program, and (c) explore attitudes toward egg donation. Ninety-two women completed the questionnaire at one fertility clinic located in the Midwest between August 2011 and August 2012. Descriptive and inferential statistics as well as textual analysis were used to analyze the data. Three themes emerged regarding participant motivations: (1) altruistic, (2) financial, and (3) desire to pass on genetic material. The majority of participants were unconcerned with potential physical and psychological side effects; however, differences emerged based on motherhood status and educational level. Although potential donors felt recipients should receive some information about the donor, they tended to value privacy regarding information giving to resultant offspring. This research study has implications for social work practice, policy, and future research. It is crucial that women receive adequate procedural and side effect information prior to engaging in egg donation. PMID:27263197

Clinical Significance of Repetitive Compound Muscle Action Potentials in Patients with Myasthenia Gravis: A Predictor for Cholinergic Side Effects of Acetylcholinesterase Inhibitors

PubMed Central

Lee, Hyo Eun; Kim, Yool-hee; Kim, Seung Min

2016-01-01

Background and Purpose Acetylcholinesterase inhibitors (AChEIs) are widely used to treat myasthenia gravis (MG). Although AChEIs are usually tolerated well, some MG patients suffer from side effects. Furthermore, a small proportion of MG patients show cholinergic hypersensitivity and cannot tolerate AChEIs. Because repetitive compound muscle action potentials (R-CMAPs) are an electrophysiologic feature of cholinergic neuromuscular hyperactivity, we investigated the clinical characteristics of MG patients with R-CMAPs to identify their clinical usefulness in therapeutic decision-making. Methods We retrospectively reviewed the clinical records and electrodiagnostic findings of MG patients who underwent electrodiagnostic studies and diagnostic neostigmine testing (NT). Results Among 71 MG patients, 9 could not tolerate oral pyridostigmine bromide (PB) and 17 experienced side effects of PB. R-CMAPs developed in 24 patients after NT. The highest daily dose of PB was lower in the patients with R-CMAPs (240 mg/day vs. 480 mg/day, p<0.001). The frequencies of PB intolerance and side effects were higher in the patients with R-CMAPs than in those without R-CMAPs [37.5% vs. 0% (p<0.001) and 45.8% vs. 12.8% (p=0.002), respectively]. The MG Foundation of America postintervention status did not differ significantly between MG patients with and without R-CMAPs, and the response to immunotherapy was also good in both groups. Conclusions Side effects of and intolerance to AChEIs are more common in MG patients with R-CMAPs than in those without R-CMAPs. AChEIs should be used carefully in MG patients with R-CMAPs. The presence of R-CMAPs after NT may be a good indicator of the risks of PB side effects and intolerance. PMID:27819419

Effects of granulocyte-colony-stimulating factor on potential normal granulocyte donors.

PubMed

McCullough, J; Clay, M; Herr, G; Smith, J; Stroncek, D

1999-10-01

The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.

Does contraceptive treatment in wildlife result in side effects? A review of quantitative and anecdotal evidence.

PubMed

Gray, Meeghan E; Cameron, Elissa Z

2010-01-01

The efficacy of contraceptive treatments has been extensively tested, and several formulations are effective at reducing fertility in a range of species. However, these formulations should minimally impact the behavior of individuals and populations before a contraceptive is used for population manipulation, but these effects have received less attention. Potential side effects have been identified theoretically and we reviewed published studies that have investigated side effects on behavior and physiology of individuals or population-level effects, which provided mixed results. Physiological side effects were most prevalent. Most studies reported a lack of secondary effects, but were usually based on qualitative data or anecdotes. A meta-analysis on quantitative studies of side effects showed that secondary effects consistently occur across all categories and all contraceptive types. This contrasts with the qualitative studies, suggesting that anecdotal reports are insufficient to investigate secondary impacts of contraceptive treatment. We conclude that more research is needed to address fundamental questions about secondary effects of contraceptive treatment and experiments are fundamental to conclusions. In addition, researchers are missing a vital opportunity to use contraceptives as an experimental tool to test the influence of reproduction, sex and fertility on the behavior of wildlife species.

Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception.

PubMed

Var, Chivorn; Keller, Sheryl; Tung, Rathavy; Freeland, Dylan; Bazzano, Alessandra N

2014-08-26

Hormonal contraceptives may produce side effects that deter women from their use as a method of family planning. In nutritionally vulnerable populations these effects may be more pronounced due to micronutrient deficiencies and health status. Previous studies have been unable to resolve whether micronutrient supplementation may reduce such side effects. In a longitudinal study, 1011 women obtaining oral contraception through the public health system in rural Cambodia were allocated to either intervention or control groups, receiving either daily Vitamin B6 supplement or care as usual (without placebo). The intervention participants (n = 577) reported fewer side effects in three categories: nausea/no appetite, headache, and depression compared with control group participants (n = 434). Women taking Vitamin B6 supplement were less likely to report side effects in a nutritionally vulnerable population. Underlying nutrition status should be considered by clinicians and reproductive health policy makers in the context of providing contraceptive services. Further investigation into micronutrient supplementation, particularly with B6, in reproductive-aged women using hormonal contraception should be conducted in other settings to determine the potential for widespread adoption.

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

PubMed

Hendriksen, Ruben G F; Lionarons, Judith M; Hendriksen, Jos G M; Vles, Johan S H; McAdam, Laura C; Biggar, W Douglas

There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample.

PubMed

Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita

2016-07-01

Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

PubMed

Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

2015-01-01

Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

PubMed

Rohleder, Cathrin; Müller, Juliane K; Lange, Bettina; Leweke, F M

2016-01-01

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) as a Target for Concurrent Management of Diabetes and Obesity-Related Cancer.

PubMed

Wang, Qingqing; Imam, Mustapha Umar; Yida, Zhang; Wang, Fudi

2017-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of ligand-inducible transcription factors that regulate adipogenesis, lipid metabolism, cell proliferation, inflammation and insulin sensitization. Abnormalities in PPARγ signaling have been associated with obesity, diabetes and cancer. The use of agonists to manage these diseases has been limited by their side effects. Accordingly, dual or pan agonists targeting the PPARα or PPARα and PPARδ, respectively, in addition to the PPARγ have been developed to overcome these side effects. This review details the shared PPARγ-dependent mechanisms between obesity-related cancers and diabetes and their potential therapeutic values. We performed a systematic literature search through pubmed, Scopus and google scholar for articles on PPARγ-dependent signaling in diabetes or cancer. There is growing co-occurrence of obesity-related cancers and diabetes, necessitating the use of effective therapies with the least amount of side effects for concurrent management of these diseases, by targeting potentially shared PPARγ-dependent mechanisms including abnormalities of the wnt/β-catenin, lysosomal acid lipase, inflammatory and cell cycle pathways, and the plasminogen activator system. Taking advantage of the multiple docking sites of the PPARγ and the pleiotropic nature of its signaling, structure-activity relationship and molecular docking studies have provided insights into designer PPARγ agonists or dual PPARα/γ agonists that modulate PPARγ signaling and negate side effects of full PPARγ agonists. Effective therapies, possibly devoid of side effects, for concurrent management of obesity-related cancers and diabetes can be developed through diligent structure-activity and molecular docking studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A numerical study of some potential sources of error in side-by-side seismometer evaluations

USGS Publications Warehouse

Holcomb, L. Gary

1990-01-01

This report presents the results of a series of computer simulations of potential errors in test data, which might be obtained when conducting side-by-side comparisons of seismometers. These results can be used as guides in estimating potential sources and magnitudes of errors one might expect when analyzing real test data. First, the derivation of a direct method for calculating the noise levels of two sensors in a side-by-side evaluation is repeated and extended slightly herein. This bulk of this derivation was presented previously (see Holcomb 1989); it is repeated here for easy reference.This method is applied to the analysis of a simulated test of two sensors in a side-by-side test in which the outputs of both sensors consist of white noise spectra with known signal-tonoise ratios (SNR's). This report extends this analysis to high SNR's to determine the limitations of the direct method for calculating the noise levels at signal-to-noise levels which are much higher than presented previously (see Holcomb 1989). Next, the method is used to analyze a simulated test of two sensors in a side-by-side test in which the outputs of both sensors consist of bandshaped noise spectra with known signal-tonoise ratios. This is a much more realistic representation of real world data because the earth's background spectrum is certainly not flat.Finally, the results of the analysis of simulated white and bandshaped side-by-side test data are used to assist in interpreting the analysis of the effects of simulated azimuthal misalignment in side-by-side sensor evaluations. A thorough understanding of azimuthal misalignment errors is important because of the physical impossibility of perfectly aligning two sensors in a real world situation. The analysis herein indicates that alignment errors place lower limits on the levels of system noise which can be resolved in a side-by-side measurement It also indicates that alignment errors are the source of the fact that real data noise spectra tend to follow the earth's background spectra in shape.

POTENTIAL OF HERBAL MEDICINES IN MODERN MEDICAL THERAPY

PubMed Central

Said, Hakim Mohammed

1984-01-01

The author discusses in this paper the potentialities of Herbal medicine in modern therapy. Also he throws some light on the importance of natural drugs which bring about cure without generation side-effects. PMID:22557447

Life-threatening complications of ibogaine: three case reports.

PubMed

Paling, F P; Andrews, L M; Valk, G D; Blom, H J

2012-11-01

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity.

PubMed

Oliveira, V M; Khalil, N M; Carraro, E

2018-02-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Value of local electrogram characteristics predicting successful catheter ablation of left-versus right-sided accessory atrioventricular pathways by radiofrequency current.

PubMed

Lin, J L; Schie, J T; Tseng, C D; Chen, W J; Cheng, T F; Tsou, S S; Chen, J J; Tseng, Y Z; Lien, W P

1995-01-01

Despite similar guidance by local electrogram criteria, catheter ablation of right-sided accessory atrioventricular (AV) pathways by radiofrequency current has been less effective than that of left-sided ones. In order to elucidate the possible diversities in local electrosignal criteria, we systematically analyzed the morphological and timing characteristics of 215 bipolar local electrograms from catheter ablation sites of 65 left-sided accessory AV pathways and of 356 from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson-White syndrome or AV reentrant tachycardia incorporating concealed accessory AV pathways. After stepwise multivariate analysis, we selected the presence of a possible accessory pathway potential, local ventricular activation preceding QRS complex for 20 ms or more during ventricular insertion mapping, and the local retrograde ventriculoatrial (VA) continuity, local retrograde VA interval < or = 50 ms, electrogram stability (left-sided targets only), retrograde accessory pathway potential (right-sided targets only) during atrial insertion mapping, as independent local electrogram predictors for successful ablation of left- and right-sided accessory AV pathways. Combination of all local electrogram predictors could have moderate chance of success (80 and 51%) for the ventricular and atrial insertion ablation of left-sided accessory AV pathways, but only low probability of success (40% in ventricular insertion ablation) or very low sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In conclusion, with the present approach, successful catheter ablation of right-sided accessory AV pathways, compared to left-sided ones, still necessitate a breakthrough in the precision mapping and the efficiency of energy delivery.

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island.

PubMed

Arriola Apelo, Sebastian I; Lamming, Dudley W

2016-07-01

Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biomass Scenario Model | Energy Analysis | NREL

Science.gov Websites

focuses on policy issues, their feasibility, and potential side effects. It integrates resource to those technologies. It emphasizes the effects of those influences in the context of land

Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case-control study.

PubMed

Chao, Samuel; Ying, Jay; Liew, Gailina; Marshall, Wayne; Liew, Choong-Chin; Burakoff, Robert

2013-07-23

Colonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided "blind spot". We previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient's risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population. The panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95). This seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations.

PubMed

Perez-Lopez, Áron R; Szalay, Kristóf Z; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-11

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine

PubMed Central

Hack, C. C.; Voiß, P.; Lange, S.; Paul, A. E.; Conrad, S.; Dobos, G. J.; Beckmann, M. W.; Kümmel, S.

2015-01-01

With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patientsʼ wellbeing and quality of life, reducing stress, and improving patientsʼ mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle. PMID:26257404

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

NASA Astrophysics Data System (ADS)

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

PubMed Central

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-01-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates. PMID:25960144

Worldsid Assessment of Far Side Impact Countermeasures

PubMed Central

Pintar, Frank A.; Yoganandan, Narayan; Stemper, Brian D.; Bostrom, Ola; Rouhana, Stephen W.; Smith, Stuart; Sparke, Laurie; Fildes, Brian N.; Digges, Kennerly H.

2006-01-01

Far side impact trauma has been demonstrated as a significant portion of the total trauma in side impacts. The objective of the study was to assess the potential usefulness of countermeasures and assess the trade-offs associated with generic countermeasure design. Because the WorldSID dummy has demonstrated promise as a potential far side impact dummy, it was chosen to assess countermeasures in this mode. A unique far side impact buck was designed for a sled test system that included, as a standard configuration, a center console and outboard three-point belt system. This configuration assumed a left side driver with a right side impact. The buck allowed for additional options of generic restraints including shoulder or thorax plates or an inboard shoulder belt. The entire buck could be mounted on the sled in either a 90-degree (3-o’clock PDOF) or a 60-degree (2-o’clock PDOF) orientation. A total of 19 WorldSID tests were completed. The inboard shoulder belt configuration produced high shear forces in the lower neck (2430 N) when the belt position was placed over the mid portion of the neck. Shear forces were reduced and of opposite sign when the inboard belt position was horizontal and over the shoulder; forces were similar to the standard outboard belt configuration (830 – 1100 N). A shoulder or thorax restraint was effective in limiting the head excursion, but each caused significant displacement at the corresponding region on the dummy. A shoulder restraint resulted in shoulder displacements of 30 – 43 mm. A thorax restraint caused thorax deflections of 39 – 64 mm. Inboard restraints for far side impacts can be effective in reducing head excursion but the specific design and placement of these restraints determine their overall injury mitigating characteristics. PMID:16968638

Herbal products and serious side effects: a case of ginseng-induced manic episode.

PubMed

Vázquez, I; Agüera-Ortiz, L F

2002-01-01

Ginseng root extract is a widely used herbal product not devoid of side effects. This report describes the development of manic symptoms after ginseng consumption in a patient with affective disorder. Other potentially harmful side effects of ginseng are also reviewed. A single case report. A 56-year-old woman with previous affective disorder presented a manic episode during ginseng intake. Symptoms disappeared rapidly with low doses of neuroleptics and benzodiazepines after ginseng suppression. Ginseng may produce manic symptoms. A special risk situation seems to be affective patients under antidepressant medication. The case emphasizes the lack of harmlessness of herbal products. Patients should be routinely asked about the use of herbal products and diet supplements.

Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

PubMed

Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

2011-11-01

Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

Medicolegal Implications of Common Rhinologic Medications.

PubMed

Poetker, David M; Smith, Timothy L

2015-10-01

As otolaryngologists, we prescribe many medications to our patients. The objective of this article is to review the potential side effects and medicolegal risks of the common medications used to treat chronic rhinosinusitis. The authors evaluate some of the common side effects as well as the published literature on the lawsuits associated with those medications. Finally, the authors review the informed consent discussion and opportunities to improve patient care and decrease the risk of litigation. Published by Elsevier Inc.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria].

PubMed

Kolarz, Gernot; Mayrhofer, Franz; Neumann, Kurt; Singer, Franz

2003-01-31

Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PubMed

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

Two-sided friction stir riveting by extrusion: A process for joining dissimilar materials

DOE PAGES

Evans, William T.; Cox, Chase D.; Strauss, Alvin M.; ...

2016-06-25

Two-sided friction stir riveting (FSR) by extrusion is an innovative process developed to rapidly, efficiently, and securely join dissimilar materials. This process extends a previously developed one sided friction stir extrusion process to create a strong and robust joint by producing a continuous, rivet-like structure through a preformed hole in one of the materials with a simultaneous, two-sided friction stir spot weld. The two-sided FSR by extrusion process securely joins the dissimilar materials together and effectively locks them in place without the use of any separate materials or fasteners. Lastly, in this paper we demonstrate the process by joining aluminummore » to steel and illustrate its potential application to automotive and aerospace manufacturing processes.« less

Magnetic Heat Pump Containing Flow Diverters

NASA Technical Reports Server (NTRS)

Howard, Frank S.

1995-01-01

Proposed magnetic heat pump contains flow diverters for suppression of undesired flows. If left unchecked, undesired flows mix substantial amounts of partially heated and partially cooled portions of working fluid, effectively causing leakage of heat from heated side to cooled side. By reducing leakage of heat, flow diverters increase energy efficiency of magnetic heat pump, potentially offering efficiency greater than compressor-driven refrigerator.

The Zero-vision: potential side effects of communicating health perfection and zero risk.

PubMed

Fugelli, Per

2006-03-01

Public health education may have harmful side effects: generate fear, give rise to healthism and contribute to a medical sorting society. To prevent these adverse reactions a new deal for public health communication is presented. It is commended to move public health from omnipotence to moderation, from life style to living conditions, from risk to the bright sides of health, from statistical clone to the holy individual. Furthermore public health communication ought to include uncertainty as authoritarian truth mongering erodes trust. The public health educator must convey compassion and dedication. Rational techno-info is not sufficient. The last golden rule for a new public health is to respect the people. The people are not an inferior mass subjected to basic instincts and irrational fears. Common sense and lay experiences may contribute to the wise management of risk. Therefore public health should develop a people-centered method, recognizing people's own values, perceptions and potentials for preventing disease and promoting health.

Promoting innovation in small markets: Evidence from the market for rare and intractable diseases.

PubMed

Iizuka, Toshiaki; Uchida, Gyo

2017-07-01

In many medical care markets with limited profit potential, firms often have little incentive to innovate. These include the market for rare diseases, "neglected" tropical diseases, and personalized medicine. Governments and not-for-profit organizations promote innovation in such markets but empirical evidence on the policy effect is limited. We study this issue by analyzing the impact of a demand-side policy in Japan, which reduces the cost sharing of patients with some rare and intractable diseases and attempts to establish and promote the treatment of those diseases. Using clinical trials data taken from public registries, we identify the effect of the policy using a difference-in-difference approach. We find that the demand-side policy increased firms' incentive to innovate: firm-sponsored clinical trials increased 181% (0.16 per disease per year) when covered by the policy. This result indicates that the demand-side policy can be an important part of innovation policies in markets with limited profit potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles

PubMed Central

Marshall, Pamela A; Jurutka, Peter W; Wagner, Carl E; van der Vaart, Arjan; Kaneko, Ichiro; Chavez, Pedro I; Ma, Ning; Bhogal, Jaskaran S; Shahani, Pritika; Swierski, Johnathon C; MacNeill, Mairi

2015-01-01

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1). PMID:26038698

Informing the introduction of contraceptive implants in the Pacific: a mixed methods study of contraceptive beliefs and behaviours in Tonga.

PubMed

Winn-Dix, Edward A; Nathan, Sally A; Rawstorne, Patrick

2016-04-01

To explore the knowledge and attitudes underlying contraceptive use and non-use among Tongan adults and investigate the potential acceptability of contraceptive implants. A mixed methods study was conducted that used two focus groups and a short self-completed survey (n=109). Participants were recruited from a Tongan non-governmental sexual and reproductive health clinic. Contraceptive method discontinuation was high among the study group, with reasons for discontinuation often relating to misconceptions circulating in the community about the side effects of contraceptives. A high proportion (38%) reported using 'natural' contraceptive methods. A total of 47% of survey participants reported having heard of implants and 37% indicated they would be willing to try them. Current Tongan contraceptive uptake and continuation is hampered by misconceptions about side effects of methods and their risks, particularly among long-acting and reversible methods. Contraceptive implants may be acceptable to Tongans given their arm placement, reversibility and long-lasting effect. Efforts to improve contraceptive continuation in Tonga should focus on improving counselling on potential side effects for all methods. The introduction of contraceptive implants as an additional long-acting reversible method should be considered. © 2015 Public Health Association of Australia.

Exploratory Investigation of Aerodynamic Characteristics of Helicopter Tail Boom Cross-Section Models with Passive Venting

NASA Technical Reports Server (NTRS)

Banks, Daniel W.; Kelley, Henry L.

2000-01-01

Two large-scale, two-dimensional helicopter tail boom models were used to determine the effects of passive venting on boom down loads and side forces in hovering crosswind conditions. The models were oval shaped and trapezoidal shaped. Completely porous and solid configurations, partial venting in various symmetric and asymmetric configurations, and strakes were tested. Calculations were made to evaluate the trends of venting and strakes on power required when applied to a UH-60 class helicopter. Compared with the UH-60 baseline, passive venting reduced side force but increased down load at flow conditions representing right sideward flight. Selective asymmetric venting resulted in side force benefits close to the fully porous case. Calculated trends on the effects of venting on power required indicated that the high asymmetric oval configuration was the most effective venting configuration for side force reduction, and the high asymmetric with a single strake was the most effective for overall power reduction. Also, curves of side force versus flow angle were noticeable smoother for the vented configurations compared with the solid baseline configuration; this indicated a potential for smoother flight in low-speed crosswind conditions.

Sodium channel slow inactivation as a therapeutic target for myotonia congenita

PubMed Central

Novak, Kevin R; Norman, Jennifer; Mitchell, Jacob R; Pinter, Martin J; Rich, Mark M

2014-01-01

Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita. PMID:25515836

Anticholinergic medications: use among older adults with memory problems.

PubMed

Kemper, Rachel F; Steiner, Victoria; Hicks, Barbara; Pierce, Linda; Iwuagwu, Cletus

2007-01-01

The purpose of this study was to determine the frequency with which over-the-counter and prescription medications with potential anticholinergic side effects were used by a sample of 193 older adults with memory problems. Medications with anticholinergic side effects are contraindicated in this population because they can worsen memory impairment and increase confusion. A retrospective chart review of clients seen between October 1999 and April 2004 was completed, with a secondary analysis of the medications older adults (older than 50 years) were taking at their initial clinic visit. Findings revealed that 10.3% of these older adults were consuming one or more medications with anticholinergic side effects. These findings demonstrate an ongoing opportunity for nurses to educate health care providers, as well as consumers, regarding the dangers of these medications.

[Ketamine as anesthetic agent in electroconvulsion therapy].

PubMed

Janke, C; Bumb, J M; Aksay, S S; Thiel, M; Kranaster, L; Sartorius, A

2015-05-01

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

Orientation-dependent potential of mean force for protein folding

NASA Astrophysics Data System (ADS)

Mukherjee, Arnab; Bhimalapuram, Prabhakar; Bagchi, Biman

2005-07-01

We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states.

Transient three-dimensional startup side load analysis of a regeneratively cooled nozzle

NASA Astrophysics Data System (ADS)

Wang, Ten-See

2009-07-01

The objective of this effort is to develop a computational methodology to capture the side load physics and to anchor the computed aerodynamic side loads with the available data by simulating the startup transient of a regeneratively cooled, high-aspect-ratio nozzle, hot-fired at sea level. The computational methodology is based on an unstructured-grid, pressure-based, reacting flow computational fluid dynamics and heat transfer formulation, and a transient inlet history based on an engine system simulation. Emphases were put on the effects of regenerative cooling on shock formation inside the nozzle, and ramp rate on side load reduction. The results show that three types of asymmetric shock physics incur strong side loads: the generation of combustion wave, shock transitions, and shock pulsations across the nozzle lip, albeit the combustion wave can be avoided with sparklers during hot-firing. Results from both regenerative cooled and adiabatic wall boundary conditions capture the early shock transitions with corresponding side loads matching the measured secondary side load. It is theorized that the first transition from free-shock separation to restricted-shock separation is caused by the Coanda effect. After which the regeneratively cooled wall enhances the Coanda effect such that the supersonic jet stays attached, while the hot adiabatic wall fights off the Coanda effect, and the supersonic jet becomes detached most of the time. As a result, the computed peak side load and dominant frequency due to shock pulsation across the nozzle lip associated with the regeneratively cooled wall boundary condition match those of the test, while those associated with the adiabatic wall boundary condition are much too low. Moreover, shorter ramp time results show that higher ramp rate has the potential in reducing the nozzle side loads.

Intravitreal injection therapy in the treatment of noninfectious uveitis.

PubMed

Modorati, Giulio; Miserocchi, Elisabetta

2012-01-01

Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects. Copyright © 2012 S. Karger AG, Basel.

Advances in Pharmacotherapeutics of Space Motion Sickness

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2006-01-01

Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.

Longitudinal perceptions of the side effects of chemotherapy in patients with gynecological cancer.

PubMed

Hsu, Hui-Chun; Tsai, Su-Yu; Wu, Shang-Liang; Jeang, Shiow-Roug; Ho, Mei-Yao; Liou, Wen-Shiung; Chiang, An-Jen; Chang, Tsung-Hsien

2017-11-01

This study aimed to assess the incidence and difference of side effects among six courses of chemotherapy (C/T) in gynecological cancer patients. The study period was from Sep. 2010 to Dec. 2011 at the Kaohsiung Veterans General Hospital in Taiwan. The treating protocols, courses, and drugs of C/T in patient were considered according to the different malignant cancers and clinical conditions. The patient data of age, marriage status, education, religion, and experiences of C/T were collected. The patients' or their families' reported side effects of C/T were recorded daily from the beginning of C/T to the 10th day after C/T in each cycle and every course of C/T. Total 89 patients enrolled into the study received total 450 courses of C/T. The mean age was 54.52 ± 11.02. Ovarian cancer was the most common malignant disease (64.0%). The most often combination of drugs used was Taxol and carboplatin (40.9%). Patients complained peripheral numbness of limbs, with the highest incidence of 58.6%. The side effects with incidence about 50% were decreased fatigue (55.0%) and hair loss (49.9%). Other side effects with different levels of incidence were also noticed, such as lack of appetite, changes in taste, and muscle ache. The incidences of peripheral limb numbness and hair loss were increased with following courses of C/T. The high incidence of fatigue did not show variation between different courses of C/T. This study revealed the incidence of side effects and occurrence timing during C/T in patients with gynecological cancer. These data provide substantial information to patients and their families to understand the potential side effects of C/T courses, which might increase their compliance in receiving adjuvant C/T. Relieving the side effects in C/T would be important to improve their quality of daily life and treatment willingness.

Comprehension of the description of side effects in drug information leaflets: a survey of doctors, pharmacists and lawyers.

PubMed

Ziegler, Andreas; Hadlak, Anka; Mehlbeer, Steffi; König, Inke R

2013-10-01

The German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) states that it uses standardized terms to describe the probabilities of side effects in drug information leaflets. It is unclear, however, whether these terms are actually understood correctly by doctors, pharmacists, and lawyers. A total of 1000 doctors, pharmacists, and lawyers were questioned by mail, and 60.4% of the questionnaires were filled out and returned. In the absence of any particular, potentially suggestive context, the respondents were asked to give a numerical interpretation of each of 20 verbal expressions of probability. Side effects were the subject of a hypothetical physician-patient case scenario. The respondents were also asked to give percentages that they felt corresponded to the terms "common," "uncommon," and "rare." The values obtained were compared with the intended values of the BfArM. The results obtained from the three professional groups resembled each other but stood in marked contrast to the BfArM definitions. With respect to side effects, the pharmacists matched the BfArM definitions most closely (5.8% "common," 1.9% "uncommon" and "rare"), followed by the physicians (3.5%, 0.3%, 0.9%) and the lawyers (0.7%, 0%, 0.7%). When the context of the side effects was not mentioned, the degree of agreement was much lower. Statements about the frequency of side effects are found in all drug information leaflets. Only a small minority of the respondents correctly stated the meaning of terms that are used to describe the frequency of occurrence of side effects, even though they routinely have to convey probabilities of side effects in the course of their professional duties. It can be concluded that the BfArM definitions of these terms do not, in general, correspond to their meanings in ordinary language.

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

PubMed Central

Iffland, Kerstin; Grotenhermen, Franjo

2017-01-01

Abstract Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking. PMID:28861514

A Review on the Traditional Chinese Medicinal Herbs and Formulae with Hypolipidemic Effect

PubMed Central

Sham, Tung-Ting; Chan, Chi-On; Wang, You-Hua; Yang, Jian-Mei; Mok, Daniel Kam-Wah; Chan, Shun-Wan

2014-01-01

Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the dominant factors of many chronic diseases such as diabetes, obesity, and cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side effects, the popularity of using traditional Chinese medicine (TCM) to handle hyperlipidemia is increasing and its role in health care has been recognized by the public at large. Despite the importance of TCM herbs and formulations, there is no comprehensive review summarizing their scientific findings on handling hyperlipidemia. This review summarizes the recent experimental and clinical results of nine representative single Chinese herbs and seven classic TCM formulae that could improve lipid profiles so as to help understand and compare their underlying mechanisms. Most of single herbs and formulae demonstrated the improvement of hyperlipidemic conditions with multiple and diverse mechanisms of actions similar to conventional Western drugs in spite of their mild side effects. Due to increasing popularity of TCM, more extensive, well-designed preclinical and clinical trials on the potential synergistic and adverse side effects of herb-drug interactions as well as their mechanisms are warranted. Hyperlipidemic patients should be warned about the potential risks of herb-drug interactions, particularly those taking anticoagulants and antiplatelet drugs. PMID:25110708

Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

PubMed

Kawaguchi, Jun; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

2015-02-01

The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB). Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB. On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB. Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

Critical side channel effects in random bit generation with multiple semiconductor lasers in a polarization-based quantum key distribution system.

PubMed

Ko, Heasin; Choi, Byung-Seok; Choe, Joong-Seon; Kim, Kap-Joong; Kim, Jong-Hoi; Youn, Chun Ju

2017-08-21

Most polarization-based BB84 quantum key distribution (QKD) systems utilize multiple lasers to generate one of four polarization quantum states randomly. However, random bit generation with multiple lasers can potentially open critical side channels that significantly endangers the security of QKD systems. In this paper, we show unnoticed side channels of temporal disparity and intensity fluctuation, which possibly exist in the operation of multiple semiconductor laser diodes. Experimental results show that the side channels can enormously degrade security performance of QKD systems. An important system issue for the improvement of quantum bit error rate (QBER) related with laser driving condition is further addressed with experimental results.

Association between side air bags and risk of injury in motor vehicle collisions with near-side impact.

PubMed

McGwin, Gerald; Metzger, Jesse; Porterfield, John R; Moran, Stephan G; Rue, Loring W

2003-09-01

Side air bags (SABs) have been introduced in an attempt to reduce the risk of injury in near-side-impact motor vehicle collisions (MVCs). The impact of SABs on MVC-related mortality and morbidity has yet to be evaluated with a large population-based study. The objective of this study was to assess the effectiveness of SABs in reducing the risk of injury or death in near-side-impact MVCs. A retrospective study investigated outboard front seat occupants involved in police-reported, near-side-impact MVCs using data from the General Estimates System (1997-2000). The risk of MVC-related nonfatal and fatal injury for occupants of vehicles with and without SABs was compared. Front seat occupants of vehicles with SABs had a risk of injury similar to that of occupants of vehicles without SABs (risk ratio [RR], 0.96; 95% CI confidence interval [CI], 0.79-1.15). Adjustment for the potentially confounding effects of age, gender, seat belt use, seating position, damage severity and location, and vehicle body type did not meaningfully affect the association (RR, 0.90; 95% CICI, 0.76-1.08). There is no association between the availability of SABs and overall injury risk in near-side-impact MVCs. Future research is necessary to determine the effectiveness of SABs in preventing the injuries for which they were specifically designed.

Deconstructing Decisions to Initiate, Maintain, or Discontinue Adjuvant Endocrine Therapy in Breast Cancer Survivors: A Mixed-Methods Study

PubMed Central

Bluethmann, Shirley M.; Murphy, Caitlin C.; Tiro, Jasmin A.; Mollica, Michelle A.; Vernon, Sally W.; Bartholomew, Leona Kay

2017-01-01

Purpose/Objectives Adjuvant endocrine therapy (AET) has been shown to improve survival in hormone receptor–positive breast cancer survivors, but as many as half do not complete recommended treatment. Management of medication-related side effects and engagement with providers are two potentially modifiable factors, but their associations with adherence are not well understood. The aims were to build on survey results to qualitatively explore survivors’ experiences with prescribed AET to (a) describe appraisal and management of AET side effects and (b) deconstruct decisions to initiate, discontinue, or maintain AET. Research Approach The authors used a mixed-methods explanatory sequence research design with a qualitative emphasis. Setting Survivors were recruited from a clinical cancer registry maintained at the University of Texas Southwestern Medical Center, which includes the Harold C. Simmons Comprehensive Cancer Center (National Cancer Institute–designated), in Dallas. Participants 452 survivors completed a survey, and 30 took part in telephone interviews. Methodologic Approach Qualitative methods were used in which the authors recorded and transcribed interviews for analysis and used open coding to reduce data into themes. Findings Among adherent survivors, the themes of tolerance of side effects and perseverance were strong. Nonadherent survivors expressed more difficulty managing side effects and perceived fewer benefits when side effects were bothersome. The most common side effects mentioned by all survivors were menopausal symptoms and joint pain; less common side effects were cognitive decline and cardiac distress. Some sought advice from their oncology team. Nonadherent survivors appeared initially motivated to maintain AET but identified a tolerance limit for side effects after which a provider’s recommendation was less influential in their decision to maintain or discontinue AET. Interpretation This study elucidated adherence as a complex continuum of behaviors, appraisals, and decision points. These insights may be particularly useful in counseling survivors taking AET and promoting timely delivery of clinical interventions to enhance adherence. Implications for Nursing Nurses should be involved in the planning and implementation of clinical interventions to manage side effects and other barriers to AET adherence. PMID:28635973

Validation of a side-scan sonar method for quantifying walleye spawning habitat availability in the littoral zone of northern Wisconsin Lakes

USGS Publications Warehouse

Richter, Jacob T.; Sloss, Brian L.; Isermann, Daniel A.

2016-01-01

Previous research has generally ignored the potential effects of spawning habitat availability and quality on recruitment of Walleye Sander vitreus, largely because information on spawning habitat is lacking for many lakes. Furthermore, traditional transect-based methods used to describe habitat are time and labor intensive. Our objectives were to determine if side-scan sonar could be used to accurately classify Walleye spawning habitat in the nearshore littoral zone and provide lakewide estimates of spawning habitat availability similar to estimates obtained from a transect–quadrat-based method. Based on assessments completed on 16 northern Wisconsin lakes, interpretation of side-scan sonar images resulted in correct identification of substrate size-class for 93% (177 of 191) of selected locations and all incorrect classifications were within ± 1 class of the correct substrate size-class. Gravel, cobble, and rubble substrates were incorrectly identified from side-scan images in only two instances (1% misclassification), suggesting that side-scan sonar can be used to accurately identify preferred Walleye spawning substrates. Additionally, we detected no significant differences in estimates of lakewide littoral zone substrate compositions estimated using side-scan sonar and a traditional transect–quadrat-based method. Our results indicate that side-scan sonar offers a practical, accurate, and efficient technique for assessing substrate composition and quantifying potential Walleye spawning habitat in the nearshore littoral zone of north temperate lakes.

Focused Study on the Quiet Side Effect in Dwellings Highly Exposed to Road Traffic Noise

PubMed Central

Renterghem, Timothy Van; Botteldooren, Dick

2012-01-01

This study provides additional evidence for the positive effect of the presence of a quiet façade at a dwelling and aims at unraveling potential mechanisms. Locations with dominant road traffic noise and high Lden-levels at the most exposed façade were selected. Dwellings both with and without a quiet façade were deliberately sought out. Face-to-face questionnaires (N = 100) were taken to study the influence of the presence of a quiet side in relation to noise annoyance and sleep disturbance. As a direct effect, the absence of a quiet façade in the dwelling (approached as a front-back façade noise level difference smaller than 10 dBA) leads to an important increase of at least moderately annoyed people (odds-ratio adjusted for noise sensitivity equals 3.3). In an indirect way, a bedroom located at the quiet side leads to an even stronger reduction of the self-reported noise annoyance (odds-ratio equal to 10.6 when adjusted for noise sensitivity and front façade Lden). The quiet side effect seems to be especially applicable for noise sensitive persons. A bedroom located at the quiet side also reduces noise-induced sleep disturbances. On a loud side, bedroom windows are more often closed, however, conflicting with the preference of dwellers. PMID:23330222

Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model

PubMed Central

Adamson Barnes, Nicholas S.; Mitchell, Vanessa A.; Kazantzis, Nicholas P.

2015-01-01

Background and Purpose While cannabinoids have been proposed as a potential treatment for neuropathic pain, they have limitations. Cannabinoid receptor agonists have good efficacy in animal models of neuropathic pain; they have a poor therapeutic window. Conversely, selective fatty acid amide hydrolase (FAAH) inhibitors that enhance the endocannabinoid system have a better therapeutic window, but lesser efficacy. We examined whether JZL195, a dual inhibitor of FAAH and monacylglycerol lipase (MAGL), could overcome these limitations. Experimental Approach C57BL/6 mice underwent the chronic constriction injury (CCI) model of neuropathic pain. Mechanical and cold allodynia, plus cannabinoid side effects, were assessed in response to systemic drug application. Key Results JZL195 and the cannabinoid receptor agonist WIN55212 produced dose‐dependent reductions in CCI‐induced mechanical and cold allodynia, plus side effects including motor incoordination, catalepsy and sedation. JZL195 reduced allodynia with an ED50 at least four times less than that at which it produced side effects. By contrast, WIN55212 reduced allodynia and produce side effects with similar ED50s. The maximal anti‐allodynic effect of JZL195 was greater than that produced by selective FAAH, or MAGL inhibitors. The JZL195‐induced anti‐allodynia was maintained during repeated treatment. Conclusions and Implications These findings suggest that JZL195 has greater anti‐allodynic efficacy than selective FAAH, or MAGL inhibitors, plus a greater therapeutic window than a cannabinoid receptor agonist. Thus, dual FAAH/MAGL inhibition may have greater potential in alleviating neuropathic pain, compared with selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists. PMID:26398331

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

Study of Proximity Effect at D-Wave Superconductors in Quasiclassical Methods

NASA Astrophysics Data System (ADS)

Tanuma, Y.; Tanaka, Y.; Kashiwaya, S.

2005-08-01

Tunneling spectra via Andreev bound states between a normal metal (N) / dx2-y2-wave superconductor (S) (in the presence of a subdominant s-wave pair potential) junction are investigated. In the present work, in order to study the role of proximity effect, we employ quasiclassical Green's function methods. This merit is that we can determine the spatial variation of the pair potentials self-consistently, where the leaking of pair potentials into the N side is involved. In the N/S junction with orientational angle θ = π/4, we can regard as the isolated d-wave superconductor, where attractive interaction in the N side is negligible. On the other hand, in the case of a high transparent contact to the d-wave superconductor (θ = 0), the pair potential penetrates into the inside of the N due to the proximity effect, where the is-wave is not indued at all. Then, the tunneling spectra has a very sharp zero-energy peak (ZEP). This ZEP originates from the fact that quasiparticles feel different sign of the pair potentials between normal metals and d-wave superconductors through Andreev reflections. We show that the spatial dependence of pair potentials is significantly sensitive to the transparency of the junction.

Nanomedicinal products: a survey on specific toxicity and side effects

PubMed Central

Giannakou, Christina; De Jong, Wim H; Kooi, Myrna W; Park, Margriet VDZ; Vandebriel, Rob J; Bosselaers, Irene EM; Scholl, Joep HG; Geertsma, Robert E

2017-01-01

Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention. PMID:28883724

Preferences for a potential longer-acting injectable contraceptive: perspectives from women, providers, and policy makers in Kenya and Rwanda.

PubMed

Tolley, Elizabeth E; McKenna, Kevin; Mackenzie, Caroline; Ngabo, Fidele; Munyambanza, Emmanuel; Arcara, Jennet; Rademacher, Kate H; Lendvay, Anja

2014-05-01

Between 1995 and 2005, injectable use doubled worldwide. However, discontinuation rates remain high, partly because of side effects but also because of missed appointments for reinjection. A longer-acting injectable (LAI) may improve compliance by reducing the required number of reinjection visits, thereby reducing unintentional discontinuation. This study examined acceptability of LAI characteristics comprising the target product profile (TPP). In 2012, we conducted qualitative case studies in Kenya and Rwanda, consisting of 19 focus group discussions (FGDs) with 177 current, previous, or never users of injectables and 46 in-depth interviews (IDIs) with providers, program implementers, and policy makers. FGDs and IDIs assessed current injectable experiences; attitudes toward potential LAI products; and perceptions of TPP attributes, including ranking preferences for the most and least important characteristics. In addition, we obtained completed electronic surveys from 28 international family planning opinion leaders about the perceived need for an LAI, important product characteristics, and challenges to LAI development or introduction. Many FGD participants and interviewees spontaneously expressed strong interest in an LAI, but there was some variation in TPP preferences. The majority of participants ranked effectiveness as the most important TPP attribute. Providers were generally more concerned about side effects than potential users; some potential users suggested that side effects were related less to the product than to their own body chemistry and that side effects were acceptable as long as they did not last a long time or disrupt daily activities. Women and providers, especially in Kenya, preferred a method with a predictable return to fertility. Some participants associated amenorrhea with delayed or reduced fertility. Most women and providers preferred delivery of the LAI in a single, prepackaged, disposable injection system to facilitate injections by providers and to reduce the risk of pain or discomfort for women. While providers and policy makers ranked cost as one of the most important issues, it was among the least important issues for most potential users. Many Kenyan, but few Rwandan, participants appeared willing to pay for an LAI, with some presuming cost savings from reduced menstruation and fewer clinic visits. Some TPP preferences for an LAI have implications for product development decisions about formulation, delivery mechanism, or presentation, while others point to the need for tailored communication and counseling approaches to ensure acceptability and adherence within clinical trials and beyond.

Measuring Hydrogen Concentrations in Metals

NASA Technical Reports Server (NTRS)

Danford, M. D.

1985-01-01

Commercial corrosion-measurement system adapted to electrochemical determination of hydrogen concentrations in metals. New technique based on diffusion of hydrogen through foil specimen of metal. In sample holder, hydrogen produced on one side of foil, either by corrosion reaction or by cathodic current. Hydrogen diffused through foil removed on other side by constant anode potential, which leads to oxidation of hydrogen to water. Anode current is measure of concentration of hydrogen diffusing through foil. System used to study hydrogen uptake, hydrogen elimination by baking, effect of heat treatment, and effect of electroplating on high-strength steels.

A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew

2010-01-01

Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

[Towards an improvement of the quality of life after radiotherapy in children].

PubMed

Demoor-Goldschmidt, Charlotte; Bernier, Valérie

2015-01-01

Pediatric radiotherapy did not differ technically from adult radiotherapy but its characteristics, its difficulties and challenges are specific. Thanks in part to this treatment, overall survival of French children with cancer is around 80%. It is therefore important to integrate in the elaboration of the treatment planning potential side long-term effects. Indeed, whatever the technique is, even the most sophisticated, it is usually inevitable that healthy nearby organs receive a dose of radiation. Dose limits on organs at risk come from adult data and are adapted for children. After the treatment, it is important to graduate the potential risks of side effects to propose a personalized monitoring protocol avoiding excessive medicalization. This article presents the medical thinking concerning radiotherapy in different anatomical areas (brain, head and neck, chest, abdomen) including concepts of dose level corresponding to side effects usually described. In parallel, we present follow-up recommendations with the aim to preserve an optimal quality of life for the adults cured of a childhood cancer, currently called survivors. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

PubMed

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

Roles of urea and TMAO on the interaction between extended non-polar peptides

NASA Astrophysics Data System (ADS)

Su, Zhaoqian; Dias, Cristiano

Urea and trimethylamine n-oxide (TMAO) are small molecules known to destabilize and stabilize, respectively, the structure of proteins when added to aqueous solution. To unravel the molecular mechanisms of these cosolvents on protein structure we perform explicit all-atom molecular dynamics simulations of extended poly-alanine and polyleucine dimers. We use an umbrella sampling protocol to compute the potential of mean force (PMF) of dimers at different concentrations of urea and TMAO. We find that the large non-polar side chain of leucine is affected by urea whereas backbone atoms and alanine's side chain are not. Urea is found to occupy positions between leucine's side chains that are not accessible to water. This accounts for extra Lennard-Jones bonds between urea and side chains that favors the unfolded state. These bonds compete with urea-solvent interactions that favor the folded state. The sum of these two energetic terms provide the enthalpic driving force for unfolding. We show here that this enthalpy correlate with the potential of mean force of poly-leucine dimers. Moreover, the framework developed here is general and may be used to provide insights into effects of other small molecules on protein interactions. The effect of the TMAO will be in the presentation. Department of Physics, University Heights, Newark, New Jersey, 07102-1982.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

PubMed

Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

2015-08-01

In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Applications of XRF, NAA and low-kV radiographic techniques in the study of body composition and diseased tissue

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Ng, K. H.; Green, S.; Mountford, P. J.; Shukri, A.; Evans, J.

1996-05-01

Members of this group have responded to a number of challenging health issues by attempting to devise sensitive XRF, NAA and low-kV radiographic measurement systems foboth in vivo and in vitro applications. These studies are generally either of toxicological importance, examine potential for diagnosing the presence of disease, or offer effective means for monitoring potentially harmful side-effects of therapy. Particular examples include the in vivo XRF investigation of human skeletal uptake of Pb in working and living environments, in vivo XRF monitoring of elevated levels of Fe in skin (indicating the presence of an undesirable side-effect of the treatment of thalassaemia), in vivo NAA monitoring of elevated levels of Al in bone (indicating an undesirable side-effect of the treatment of chronic renal failure) and in vitro characterization, by means of low-kV imaging, of a range of calcification parameters in healthy and diseased breast tissue. The latter investigation has been conducted in association with an in vitro NAA study of concentrations of trace elements in the same types of tissue. Figures of merit for the various measurement systems have been obtained in terms of minimum detectable levels and concentrations (MDL's and MDC's) and where applicable, image related parameters.

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

PubMed

Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

2018-05-16

Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

‘You never told me I would turn into a gambler’: a first person account of dopamine agonist – induced gambling addiction in a patient with restless legs syndrome

PubMed Central

Jones, Henrietta Bowden; George, Sanju

2011-01-01

Dopaminergic agents are commonly used and effective treatments for restless legs syndrome (RLS), a disabling sensorimotor disorder. Less known are some of the potentially disabling side effects of these treatments, particularly iatrogenic gambling addiction, as is described here. Here the authors present a 62-year-old man, with a 20–year history of RLS, who developed gambling addiction while on dopaminergic treatment. He was not forewarned of this side effect, nor was he ever screened for gambling behaviours prior to or during treatment. Eight months after discontinuation of dopaminergic treatment and after 10 sessions of cognitive–behavioural therapy for gambling addiction, his gambling behaviours have partially resolved. To our knowledge, this is the first ever first person account of this condition. To prevent the devastating consequences of gambling addiction or to minimise its impact by early intervention, the authors call for clinicians involved in treatment of RLS to follow these simple measures: screen patients for gambling behaviours prior to the onset and during dopaminergic treatment; forewarn patients of this potential side effect; and if patients screen positive, refer them to specialist gambling treatment services, in addition to making necessary changes to their medication regime. PMID:22678941

Potential of Eucalyptus Oil as Repellent against House Rat, Rattus rattus

PubMed Central

Thind, Ramandeep Kaur; Mahal, Amrit Kaur

2014-01-01

Rodent repellents are chemicals which by taste or odour or possibly by both will prevent animal from feeding or gnawing. Such substances may be used in protecting an area from rodent infestation or in protecting packaged food, packing materials, electric cables, and other important vulnerable materials. Mature and healthy house rat, Rattus rattus of both sexes, was exposed to 5, 10, and 20% eucalyptus oil applied as spray in laboratory pens in bichoice tests. Each concentration was applied through three different modes of application, that is, daily, once, and alternatively in a week. Repellent effect of the oil was assessed based on food consumption from treated and untreated sides for four days. In overall, food consumption was significantly (P < 0.0001) low from treatment side compared to the untreated side indicating significant repellent effect of the oil at all the three concentrations tested. Repellent effect of the oil was, however, not found to differ significantly between the two sexes. Percent repellency in both male and female rats was apparently more with daily application of 5 and 10% eucalyptus oil. Present studies reveal the potential of eucalyptus oil in repelling away R. rattus; however, further studies may be conducted to enhance the persistence of repellent effect for longer period of time. PMID:24523633

[Theoretical and practical considerations in rational polytherapy for epilepsy].

PubMed

Rajna, Péter

2011-11-30

Author analyses the consideration of rational polytherapy for epilepsy. Among the theoretical aspects he points the different effect of seizure inhibitory drugs on the epilepsy models but didn't find data enough for the basis of any successful combination. Combinations of compounds having different way of action are more promising. Rational polytherapy can serve also the epileptic patients' tailored therapy in the daily routine. There have already been some proved synergisms concerning drug interactions. Based on detailed analysis of side effects a possibility occurs for neutralization of side effects when anticonvulsants with side effects of opposite nature are combined. Considering both the side effect profiles and the different (somatic and psychic) habits of the patients we can create a special list of favourable combinations. Co-morbid states and their treatments play a significant role in the application of rational polytherapy. Combination of anticonvulsants of lower potential but without drug-interactions can be the choice in these cases. The non-epileptic indications of the anticonvulsants can also be utilized in polymorbid patients. Based on the theoretical and practical considerations the author defines the ten-step-cognitive-preparation-process in planning the optimal (poly)therapy. On speculative basis he suggests eight beneficial versions of seizure inhibitory rational polytherapy.

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

PubMed

Gao, Mengxuan; Sato, Motoshige; Ikegaya, Yuji

2018-01-01

　During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

PubMed

Gao, Mengxuan; Igata, Hideyoshi; Takeuchi, Aoi; Sato, Kaoru; Ikegaya, Yuji

2017-02-01

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Kratom: a dangerous player in the opioid crisis.

PubMed

Tayabali, Khadija; Bolzon, Colin; Foster, Paul; Patel, Janki; Kalim, Mohammad Omar

2018-01-01

Kratom use as a herbal supplement is on the rise in the United States, with reported medical outcomes and lethal effects suggesting a public health threat. Even though the Drug Enforcement Administration has included kratom on its drugs of concern list and the FDA has published a press release to identify it as an opioid with a potential for abuse, its therapeutic and side effects are still not well defined in the literature. Here, we present a case of a 32-year-old man with a history of kratom use who became acutely ill with a brief prodromal illness, followed by jaundice and elevated liver enzymes showing a cholestatic picture, and his successful treatment. In this case, we emphasize the need for awareness of kratom exposure as a key contributor in the expansion of the opioid crisis, with therapeutic benefits earned at the expense of potentially lethal side effects.

Targeting interleukin-6 for noninfectious uveitis

PubMed Central

Lin, Phoebe

2015-01-01

Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in the pathogenesis of many immune-mediated disorders including several types of non-infectious uveitis. These uveitic conditions include Vogt-Koyanagi-Harada syndrome, uveitis associated with Behçet disease, and sarcoidosis. This review summarizes the role of IL-6 in immunity, highlighting its effect on Th17, Th1, and plasmablast differentiation. It reviews the downstream mediators activated in the process of IL-6 binding to its receptor complex. This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. The target, dosage, potential side effects, and potential uses of these biologics are summarized in this article based on the existing literature. In summary, anti-IL-6 therapy for non-infectious uveitis shows promise in terms of efficacy and side effect profile. PMID:26392750

The Potential Benefit of Radiotherapy with Protons in Head and Neck Cancer with Respect to Normal Tissue Sparing: A Systematic Review of Literature

PubMed Central

Bijl, Hendrik P.; Schilstra, Cornelis; Pijls-Johannesma, Madelon; Langendijk, Johannes A.

2011-01-01

Purpose. Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies. Materials and Methods. A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques. Results. Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction. Conclusion. The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials. PMID:21349950

Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery.

PubMed

Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu

2017-03-14

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p < 0.05), respectively. COS reduces the side effects caused by antibiotics ( p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.

Comparison of curative effect of 131I and antithyroid drugs in Graves' disease: a meta analysis.

PubMed

Yuan, Ju; Lu, Xiuqing; Yue, Yan

2017-03-01

Radioactive 131I is currently reported to be a potential effective intervention for Graves' Disease treatment in China. Whether 131I treatment was associated with effective outcome or reduced risk of side effects, reccurence rate remained unknown. Eligible studies were selected from Chinese VIP, Wangfang, CNKI databases using the keywords "Iodine" and "Graves Disease". Finally, 13 clinical trials met the inclusion criterion and were included this meta-analysis. Our meta-analysis included 1355 patients diagnosed of Graves' Disease with regular anti-thyroid drugs oral administration and 1320 patients with 131I therapy. The results showed that there was significant symptom improvement with radioactive iodine intervention (Odd Ratio (OR)=4.50, 95% CI [3.55, 5.71], P<0.01). 3 studies mentioned side effects, 6 mentioned reccurence rate and another 6 mentioned hypothyroidism. The ORs and 95%CIs for these subgroups were 0.12 [0.06, 0.21], 0.08 [0.05, 0.13] and 2.27 [1.77, 2.92] respectively. It means a significant reduction of side effects and reccurence rate but increased hypothyroidism after 131I intervention in Graves' Disease. Treatment with 131I was associated with better clinical outcome; it reduced side effects and reccurence rate but increased hypothyroidism in Graves' Disease.

Penis Pump

MedlinePlus

... health conditions and any medications you take, including herbal supplements. This will help prevent potential problems. Side effects ... testicles or prostate What medications you take , including herbal supplements What erectile dysfunction treatments you've tried and ...

Thermochemical Assessment of Oxygen Gettering by SiC or ZrC in PuO2-x TRISO Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Besmann, Theodore M

2010-01-01

Particulate nuclear fuel in a modular helium reactor is being considered for the consumption of excess plutonium and related transuranics. In particular, efforts to largely consume transuranics in a single-pass will require the fuel to undergo very high burnup. This deep burn concept will thus make the proposed plutonia TRISO fuel particularly likely to suffer kernel migration where carbon in the buffer layer and inner pyrolytic carbon layer is transported from the high temperature side of the particle to the low temperature side. This phenomenon is oberved to cause particle failure and therefore must be mitigated. The addition of SiCmore » or ZrC in the oxide kernel or in a layer in communication with the kernel will lower the oxygen potential and therefore prevent kernel migration, and this has been demonstrated with SiC. In this work a thermochemical analysis was performed to predict oxygen potential behavior in the plutonia TRISO fuel to burnups of 50% FIMA with and without the presence of oxygen gettering SiC and ZrC. Kernel migration is believed to be controlled by CO gas transporting carbon from the hot side to the cool side, and CO pressure is governed by the oxygen potential in the presence of carbon. The gettering phases significantly reduce the oxygen potential and thus CO pressure in an otherwise PuO2-x kernel, and prevent kernel migration by limiting CO gas diffusion through the buffer layer. The reduction in CO pressure can also reduce the peak pressure within the particles by ~50%, thus reducing the likelihood of pressure-induced particle failure. A model for kernel migration was used to semi-quantitatively assess the effect of controlling oxygen potential with SiC or ZrC and did demonstrated the dramatic effect of the addition of these phases on carbon transport.« less

Opioid Receptors: Toward Separation of Analgesic from Undesirable Effects

PubMed Central

Law, P.Y.; Reggio, Patricia H.; Loh, H.H.

2013-01-01

The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157

Structural safety assessment for FLNG-LNGC system during offloading operation scenario

NASA Astrophysics Data System (ADS)

Hu, Zhi-qiang; Zhang, Dong-wei; Zhao, Dong-ya; Chen, Gang

2017-04-01

The crashworthiness of the cargo containment systems (CCSs) of a floating liquid natural gas (FLNG) and the side structures in side-by-side offloading operations scenario are studied in this paper. An FLNG vessel is exposed to potential threats from collisions with a liquid natural gas carrier (LNGC) during the offloading operations, which has been confirmed by a model test of FLNG-LNGC side-by-side offloading operations. A nonlinear finite element code LS-DYNA is used to simulate the collision scenarios during the offloading operations. Finite element models of an FLNG vessel and an LNGC are established for the purpose of this study, including a detailed LNG cargo containment system in the FLNG side model. Based on the parameters obtained from the model test and potential dangerous accidents, typical collision scenarios are defined to conduct a comprehensive study. To evaluate the safety of the FLNG vessel, a limit state is proposed based on the structural responses of the LNG CCS. The different characteristics of the structural responses for the primary structural components, energy dissipation and collision forces are obtained for various scenarios. Deformation of the inner hull is found to have a great effect on the responses of the LNG CCS, with approximately 160 mm deformation corresponding to the limit state. Densely arranged web frames can absorb over 35% of the collision energy and be proved to greatly enhance the crashworthiness of the FLNG side structures.

The effect of curve sawing two-sided cants from small diameter hardwood sawlogs on lumber and pallet part yields

Treesearch

Peter Hamner; Marshall S. White; Philip A. Araman

2006-01-01

Curve sawing is a primary log breakdown process that incorporates gang-saw technology to allow two-sided cants from logs with sweep to be cut parallel to the log surface or log axis. Since curve-sawn logs with sweep are cut along the grain, the potential for producing high quality straight-grain lumber and cants increases, and strength, stiffness, and dimensional...

Energy efficiency, human behavior, and economic growth: Challenges to cutting energy demand to sustainable levels

NASA Astrophysics Data System (ADS)

Santarius, Tilman

2015-03-01

Increasing energy efficiency in households, transportation, industries, and services is an important strategy to reduce energy service demand to levels that allow the steep reduction of greenhouse gases, and a full fledged switch of energy systems to a renewable basis. Yet, technological efficiency improvements may generate so-called rebound effects, which may `eat up' parts of the technical savings potential. This article provides a comprehensive review of existing research on these effects, raises critiques, and points out open questions. It introduces micro-economic rebound effect and suggests extending consumer-side analysis to incorporate potential `psychological rebound effects.' It then discusses meso-economic rebound effects, i.e. producer-side and market-level rebounds, which so far have achieved little attention in the literature. Finally, the article critically reviews evidence for macro-economic rebound effects as energy efficiency-induced economic growth impacts. For all three categories, the article summarizes assessments of their potential quantitative scope, while pointing out remaining methodological weaknesses and open questions. As a rough "rule of thumb", in the long term and on gross average, only half the technical savings potential of across-the-board efficiency improvements may actually be achieved in the real world. Policies that aim at cutting energy service demand to sustainable levels are well advised to take due note of detrimental behavioral and economic growth impacts, and should foster policies and measures that can contain them.

Development of robust building energy demand-side control strategy under uncertainty

NASA Astrophysics Data System (ADS)

Kim, Sean Hay

The potential of carbon emission regulations applied to an individual building will encourage building owners to purchase utility-provided green power or to employ onsite renewable energy generation. As both cases are based on intermittent renewable energy sources, demand side control is a fundamental precondition for maximizing the effectiveness of using renewable energy sources. Such control leads to a reduction in peak demand and/or in energy demand variability, therefore, such reduction in the demand profile eventually enhances the efficiency of an erratic supply of renewable energy. The combined operation of active thermal energy storage and passive building thermal mass has shown substantial improvement in demand-side control performance when compared to current state-of-the-art demand-side control measures. Specifically, "model-based" optimal control for this operation has the potential to significantly increase performance and bring economic advantages. However, due to the uncertainty in certain operating conditions in the field its control effectiveness could be diminished and/or seriously damaged, which results in poor performance. This dissertation pursues improvements of current demand-side controls under uncertainty by proposing a robust supervisory demand-side control strategy that is designed to be immune from uncertainty and perform consistently under uncertain conditions. Uniqueness and superiority of the proposed robust demand-side controls are found as below: a. It is developed based on fundamental studies about uncertainty and a systematic approach to uncertainty analysis. b. It reduces variability of performance under varied conditions, and thus avoids the worst case scenario. c. It is reactive in cases of critical "discrepancies" observed caused by the unpredictable uncertainty that typically scenario uncertainty imposes, and thus it increases control efficiency. This is obtainable by means of i) multi-source composition of weather forecasts including both historical archive and online sources and ii) adaptive Multiple model-based controls (MMC) to mitigate detrimental impacts of varying scenario uncertainties. The proposed robust demand-side control strategy verifies its outstanding demand-side control performance in varied and non-indigenous conditions compared to the existing control strategies including deterministic optimal controls. This result reemphasizes importance of the demand-side control for a building in the global carbon economy. It also demonstrates a capability of risk management of the proposed robust demand-side controls in highly uncertain situations, which eventually attains the maximum benefit in both theoretical and practical perspectives.

Sexual Dysfunction in a Patient Taking Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C: A Case Report.

PubMed

Lenz, Destin U; Crutcher, Effie L; Greene, Elisa M

2017-01-01

Sexual dysfunction is a bothersome side effect of several medications, though it has not yet been reported with the use of ledipasvir/sofosbuvir for the treatment of hepatitis C. However, sexual dysfunction is a potentially unrecognized side effect of ledipasvir/sofosbuvir that could result in nonadherence and treatment failure. We report a case of a 42-year-old man with a sudden onset of sexual dysfunction with the initiation of ledipasvir/sofosbuvir for the treatment of hepatitis C. The patient had no prior history or risk factors for the development of sexual dysfunction. His symptoms resolved upon discontinuation of ledipasvir/sofosbuvir after a successful 12-week course. Clinicians should be aware that sexual dysfunction is a possible side effect of ledipasvir/sofosbuvir and educate patients appropriately. Adherence should be emphasized as the risks of untreated hepatitis C virus far outweigh transient sexual dysfunction.

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

[Pharmacogenetics in primary health care: implementation and future expectations].

PubMed

Houwink, Elisa J F; Rigter, Tessel; Swen, Jesse J; Cornel, Martina C; Kienhuis, Anne; Rodenburg, Wendy; Weda, Marjolein

2015-01-01

Personalised medicine is a targeted approach to the prevention, diagnosis and treatment of disorders on the basis of the specific genetic profile of the patient. Pharmacogenetics research shows that differences in the genetic profile of patients explain the interindividual differences in efficacy and side effects of medicines. Although there are high expectations of personalised medicine and pharmacogenetics in healthcare, both are only used to a limited extent to date. Pharmacogenetics seems particularly important in diseases with a poor prognosis and treatments with potentially serious side effects. Pharmacogenetics testing is reimbursed in the case of serious side effects or unexpected ineffectiveness. 95% of patients in the Netherlands have at least one abnormality in the panel of genes for which guidance is available. The KNMP (Royal Dutch Pharmacists' Association) provides dosing advice based on genotype for 80 medicines, 27 of which are regularly prescribed in primary health care.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

Nonlinear side effects of fs pulses inside corneal tissue during photodisruption

NASA Astrophysics Data System (ADS)

Heisterkamp, A.; Ripken, T.; Mamom, T.; Drommer, W.; Welling, H.; Ertmer, W.; Lubatschowski, H.

In order to evaluate the potential for refractive surgery, fs laser pulses of 150-fs pulse duration were used to process corneal tissue of dead and living animal eyes. By focusing the laser radiation down to spot sizes of several microns, very precise cuts could be achieved inside the treated cornea, accompanied with minimum collateral damage to the tissue by thermal or mechanical effects. During histo-pathological analysis by light and transmission electron microscopy considerable side effects of fs photodisruption were found. Due to the high intensities at the focal region several nonlinear effects occurred. Self-focusing, photodissociation, UV-light production were observed, leading to streak formation inside the cornea.

Methylphenidate Abuse and Psychiatric Side Effects

PubMed Central

Morton, W. Alexander; Stockton, Gwendolyn G.

2000-01-01

Methylphenidate is a central nervous system stimulant drug that has become the primary drug of choice in treating attention-deficit/hyperactivity disorder in children. Side effects are usually mild and are generally well tolerated by patients. Along with increases in prescribing frequency, the potential for abuse has increased. Intranasal abuse produces effects rapidly that are similar to the effects of cocaine in both onset and type. The clinical picture of stimulant abuse produces a wide array of psychiatric symptoms. There is little in the literature to differentiate methylphenidate from other stimulants when they are abused. The need for education of all involved with the use of methylphenidate is discussed to help prevent an increasing pattern of methylphenidate abuse. PMID:15014637

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

PubMed

Besi, E; Boniface, D R; Cregg, R; Zakrzewska, J M

2015-01-01

Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

A double-sided microscope to realize whole-ganglion imaging of membrane potential in the medicinal leech

PubMed Central

Wagenaar, Daniel A

2017-01-01

Studies of neuronal network emergence during sensory processing and motor control are greatly facilitated by technologies that allow us to simultaneously record the membrane potential dynamics of a large population of neurons in single cell resolution. To achieve whole-brain recording with the ability to detect both small synaptic potentials and action potentials, we developed a voltage-sensitive dye (VSD) imaging technique based on a double-sided microscope that can image two sides of a nervous system simultaneously. We applied this system to the segmental ganglia of the medicinal leech. Double-sided VSD imaging enabled simultaneous recording of membrane potential events from almost all of the identifiable neurons. Using data obtained from double-sided VSD imaging, we analyzed neuronal dynamics in both sensory processing and generation of behavior and constructed functional maps for identification of neurons contributing to these processes. PMID:28944754

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

PubMed

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

42 CFR 484.55 - Condition of participation: Comprehensive assessment of patients.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Standard: Drug regimen review. The comprehensive assessment must include a review of all medications the patient is currently using in order to identify any potential adverse effects and drug reactions, including ineffective drug therapy, significant side effects, significant drug interactions, duplicate drug...

Analysis of zolpidem in postmortem fluids and tissues using ultra-performance liquid chromatography-mass spectrometry.

DOT National Transportation Integrated Search

2014-02-01

Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its : use is common and wide-spread. While quite effective in producing sedation, zolpidem has potentially : hazardous side effects when put in the ...

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

PubMed

Sanacora, G; Smith, M A; Pathak, S; Su, H-L; Boeijinga, P H; McCarthy, D J; Quirk, M C

2014-09-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

PubMed

Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

2017-08-03

To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, p<0.001, after adjustment for potential confounders), with parkinsonism and akathisia showing the greatest difference between the groups. Neuroleptic malignant syndrome, although occurring infrequently, was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

PubMed

Bujalska-Zadrożny, Magdalena; Tatarkiewicz, Jan; Kulik, Kamila; Filip, Małgorzata; Naruszewicz, Marek

2017-03-01

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg 2+ ), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of platelet-rich plasma on the outcome of short-term narrowband-ultraviolet B phototherapy in the treatment of vitiligo: a pilot study.

PubMed

Ibrahim, Zeinab A; El-Ashmawy, Amal A; El-Tatawy, Rania A; Sallam, Fersan A

2016-06-01

Narrowband - ultraviolet B (NB-UVB) is an emerging, effective, and safe therapy for vitiligo, but the treatment course often requires a long duration of time which may carry a potential risk for various side effects and patients' noncompliance. To explore the effect of platelet-rich plasma (PRP) injection on the outcome of short-term NB-UVB therapy for the patients with stable vitiligo. The study included 60 stable vitiligo patients with overall symmetrical lesions. For each patient, the left side of the body was treated with NB-UVB alone (control side) while the right side was treated with NB-UVB therapy in addition to intradermal injection of PRP, every 2 weeks for 4 months. There was statistically highly significant improvement in the repigmentation in the combination group(PRP plus NB-UVB) compared with NB-UVB group. Intradermal PRP injection in combination with NB-UVB could be considered as a simple, safe, tolerable, and cheap technique for treatment of vitiligo. It shortens the duration of NB-UVB therapy and is expected to increase patient compliance. Longer follow-up is needed. © 2015 Wiley Periodicals, Inc.

Radial Keratotomy Surgery: What Health Educators Should Know.

ERIC Educational Resources Information Center

Donaldson, Kenley; Page, Randy M.

1988-01-01

A discussion is presented on the safety and potential side effects of radial keratotomy, a surgical procedure that results in a flattening of the cornea and a reduction of refractive myopia (nearsightedness). (JD)

Potential Side Effect of Inadvertent Intravascular Administration of Liposomal Bupivacaine

DTIC Science & Technology

2017-06-01

treat and is potentially fatal. LAST can impair function of the central nervous system and cause cardiovascular collapse, with potentially...in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. ILE is gaining...to the sites of toxic action in the central nervous system and the heart. However, liposomal formulations of local anesthetics (EXPAREL in

Technology versus humanism: how patients perceive the use of electronic health records in physicians' offices--a qualitative study.

PubMed

Mwachofi, Ari K; Khaliq, Amir A; Carrillo, Estevan R; Winfree, William

2016-01-01

Electronic Health Records (EHRs) have the potential to improve the quality of care. In view of the accelerated adoption of EHRs, there is a need to understand conditions necessary for their effective use. Patients are the focus of healthcare and their perceptions and expectations need to be included in developing and implementing EHRs. The purpose of this study was to gather exploratory qualitative information from patients about their experiences and perceptions regarding the effects of EHRs on healthcare quality in physicians' offices. We conducted five focus groups with patients representing a random mix of diverse socio-demographic backgrounds in Oklahoma. Related to EHRs, patients reported improvements on the technical side of care but no change on the human side. They expressed concerns about the potential for breach of confidentiality and security of medical records. They were also concerned about the possibility of governmental agencies or insurance companies having unauthorized access to patient records. Patients differentiated between the human and technical sides of care and reported no change or improvement in the doctor-patient interaction. Patients have an important perspective on the use of EHRs and their perceptions and experiences should be considered in the development, adoption and implementation of EHRs. Otherwise, the use of EHRs may not be fully effective. There is also a need to educate patients about the potential benefits and risks of EHRs and the steps being taken to mitigate such risks.

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Potentially risky postural behaviors during worksite keyboard use

PubMed Central

Baker, Nancy A.; Redfern, Mark

2016-01-01

Objective This study describes the frequency and distribution of potentially risky postural behaviors of keyboard users. Method Forty-three subjects’ keyboard postural behaviors were rated with the Keyboard – Personal Computer Style instrument (K-PeCS) while they worked at their own workstations. The frequency and distribution of keyboard postural behaviors, and the associations and differences between the right and left sides were assessed. Results Generally, each static body posture had a single criterion that occurred most frequently, (e.g. elbow flexion posture 80 – 120 degrees), while dynamic postures of the wrists and hands were distributed throughout their criteria. Right and left side postural behaviors were significantly associated for shoulder flexion, elbow flexion, hand displacement, wrist extension, forearm rotation, isolated 5th digit, MCP hyperextension, and wrist support use, and significantly different for hand displacement, isolated thumb, number of digits used, and MCP hyperextension. Conclusion Potentially problematic keyboard postural behaviors are common among keyboard users. Our results suggest that occupational therapists must systematically assess body, arm, wrist, and hand postures on both the right and left sides to be able to develop the most effective intervention strategies. PMID:19708467

Bone age in children with obstetrical brachial plexus palsy: effect of peripheral nerve injury on skeletal maturation.

PubMed

Oktay, Fügen; Cömert, Didem; Gökkaya, Nilüfer Kutay Ordu; Ozbudak, Sibel Demir; Uysal, Hilmi

2014-02-01

The purpose of this retrospective study was to analyze the effect of peripheral nerve injury on the skeletal maturation process. The bone ages of the affected and unaffected hand-wrists of 42 children with obstetrical brachial palsy were determined according to the Greulich and Pyle atlas. In 23 patients, the bone ages of the both sides were identical (bone-age-symmetrical group), in 19 patients the bone age of the affected side was delayed (bone-age-delayed group). The mean bone age of the affected side was delayed 0.48 ± 0.25 years that of the unaffected side (P = .000), and the delay of bone age was inversely correlated with chronological age (R (2) = .45, P < .02) in the bone-age-delayed group. Skeletal retardation can be recognized after appearance of ossification centers by plain radiography, dating from the third month of life, in early infancy. Thus, bone age determination method might be helpful for predicting potential future limb shortness.

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial.

PubMed

Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj; Hageman, Ida; Olsen, Niels Vidiendal; Kessing, Lars Vedel; Jørgensen, Martin Balslev; Miskowiak, Kamilla Woznica

2018-04-19

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity. The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library. If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT. ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

Terbinafine: novel formulations that potentiate antifungal activities.

PubMed

Ma, Y; Chen, X; Guan, S

2015-03-01

Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

Central nervous system stimulants and sport practice

PubMed Central

Avois, L; Robinson, N; Saudan, C; Baume, N; Mangin, P; Saugy, M

2006-01-01

Background and objectives Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. Results CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti‐doping laboratories statistics and the media, and their potentially serious adverse effects. Conclusions Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced. PMID:16799095

Enzymatic Hydrolysis of Peanut Flour Produces Bioactive Peptides with Reduced Allergenicity

USDA-ARS?s Scientific Manuscript database

Peanut allergy is one of the most severe food allergies due to its life-threatening nature and persistency. Current immunotherapy methods, though effective, are often accompanied by allergic side-effects. Enzymatic hydrolysis of peanut flour has the potential to produce bioactive peptides with impro...

Side-to-side cavocavostomy with an endovascular stapler: Rescue technique for severe hepatic vein and/or inferior vena cava outflow obstruction after liver transplantation using the piggyback technique.

PubMed

Quintini, Cristiano; Miller, Charles M; Hashimoto, Koji; Philip, Ding; Uso, Teresa Diago; Aucejo, Federico; Kelly, Dympna; Winans, Charles; Eghtesad, Bijan; Vogt, David; Fung, John

2009-01-01

Venous outflow obstruction is a rare but potentially lethal complication after orthotopic liver transplantation (OLT) with the "piggyback" technique. Therapeutic options include angioplasty with or without stent placement, surgical reconstruction of the venous anastomosis, and retransplantation. Surgical options are technically very challenging and the outcomes discouraging. We describe here two cases of venous outflow obstruction in recipients of piggyback liver grafts, one involving both the vena cava and hepatic veins and the other affecting only hepatic vein outflow. Both patients were treated successfully with side-to-side cavo-cavostomy using an endovascular (endo-GIA) stapler. This novel technique is fast and effective in resolving the outflow obstruction. Copyright 2008 AASLD.

Subsonic aerodynamic characteristics of interacting lifting surfaces with separated flow around sharp edges predicted by a vortex-lattice method

NASA Technical Reports Server (NTRS)

Lamar, J. E.; Gloss, B. B.

1975-01-01

Because the potential flow suction along the leading and side edges of a planform can be used to determine both leading- and side-edge vortex lift, the present investigation was undertaken to apply the vortex-lattice method to computing side-edge suction force for isolated or interacting planforms. Although there is a small effect of bound vortex sweep on the computation of the side-edge suction force, the results obtained for a number of different isolated planforms produced acceptable agreement with results obtained from a method employing continuous induced-velocity distributions. By using the method outlined, better agreement between theory and experiment was noted for a wing in the presence of a canard than was previously obtained.

Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

PubMed

Tian, Xiao-bin; Sun, Li; Yang, Shu-hua; Zhang, Yu-kun; Hu, Ru-yin; Fu, De-hao

2008-04-20

Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capability than that of nanobone putty only.

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

PubMed Central

Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K

2015-01-01

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

Triglycerides: Why Do They Matter?

MedlinePlus

... peanut and canola oils. Substitute fish high in omega-3 fatty acids — such as mackerel and salmon — for ... potential side effect. Fish oils. Also known as omega-3 fatty acids, fish oil supplements can help lower ...

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains.

PubMed

Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A

2017-01-19

The physics-based potentials of side-chain-side-chain interactions corresponding to pairs composed of charged and polar, polar and polar, charged and hydrophobic, and hydrophobic and hydrophobic side chains have been determined. A total of 144 four-dimensional potentials of mean force (PMFs) of all possible pairs of molecules modeling these pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expressions were then fitted to the PMFs. Depending on the type of interacting sites, the analytical approximation to the PMF is a sum of terms corresponding to van der Waals interactions and cavity-creation involving the nonpolar sections of the side chains and van der Waals, cavity-creation, and electrostatic (charge-dipole or dipole-dipole) interaction energies and polarization energies involving the charged or polar sections of the side chains. The model used in this work reproduces all features of the interacting pairs. The UNited RESidue force field with the new side-chain-side-chain interaction potentials was preliminarily tested with the N-terminal part of the B-domain of staphylococcal protein A (PDBL 1BDD ; a three-α-helix bundle) and UPF0291 protein YnzC from Bacillus subtilis (PDB: 2HEP ; an α-helical hairpin).

Occurrence of serious injury in real-world side impacts of vehicles with good side-impact protection ratings.

PubMed

Brumbelow, Matthew L; Mueller, Becky C; Arbelaez, Raul A

2015-01-01

The Insurance Institute for Highway Safety (IIHS) introduced its side impact consumer information test program in 2003. Since that time, side airbags and structural improvements have been implemented across the fleet and the proportion of good ratings has increased to 93% of 2012-2014 model year vehicles. Research has shown that drivers of good-rated vehicles are 70% less likely to die in a left-side crash than drivers of poor-rated vehicles. Despite these improvements, side impact fatalities accounted for about one quarter of passenger vehicle occupant fatalities in 2012. This study is a detailed analysis of real-world cases with serious injury resulting from side crashes of vehicles with good ratings in the IIHS side impact test. NASS-CDS and Crash Injury Research and Engineering Network (CIREN) were queried for occupants of good-rated vehicles who sustained an Abbreviated Injury Scale (AIS) ≥ 3 injury in a side-impact crash. The resulting 110 cases were categorized by impact configuration and other factors that contributed to injury. Patterns of impact configuration, restraint performance, and occupant injury were identified and discussed in the context of potential upgrades to the current IIHS side impact test. Three quarters of the injured occupants were involved in near-side impacts. For these occupants, the most common factors contributing to injury were crash severities greater than the IIHS test, inadequate side-airbag performance, and lack of side-airbag coverage for the injured body region. In the cases where an airbag was present but did not prevent the injury, occupants were often exposed to loading centered farther forward on the vehicle than in the IIHS test. Around 40% of the far-side occupants were injured from contact with the struck-side interior structure, and almost all of these cases were more severe than the IIHS test. The remaining far-side occupants were mostly elderly and sustained injury from the center console, instrument panel, or seat belt. In addition, many far-side occupants were likely out of position due to events preceding the side impact and/or being unbelted. Individual changes to the IIHS side impact test have the potential to reduce the number of serious injuries in real-world crashes. These include impacting the vehicle farther forward (relevant to 28% of all cases studied), greater test severity (17%), the inclusion of far-side occupants (9%), and more restrictive injury criteria (9%). Combinations of these changes could be more effective.

Risk factors for non-adherence to antidepressant treatment in patients with mood disorders.

PubMed

De las Cuevas, Carlos; Peñate, Wenceslao; Sanz, Emilio J

2014-01-01

Adherence to antidepressant therapy by patients with depressive disorders is essential not only to achieve a positive patient outcome but also to prevent a relapse. The aim of this study was to identify potential modelling factors influencing adherence to antidepressant treatment by patients with mood disorders in the community mental health care setting A total of 160 consecutive psychiatric outpatients attending two Community Mental Health Centres on Tenerife Island between September 2011 and May 2012 were asked to participate in the study; of these, 145 accepted. The Morisky self-report scale was used to assess adherence. The potential predictors examined included socio-demographic, clinical and therapeutic variables. The Clinical Global Impression-Severity and -Improvement scales and the Beck Depression Inventory were used for clinical assessment. Drug treatment side-effects were assessed using the "Self-report Antidepressant Side-Effect Checklist." All participants were also asked to complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale". Discriminant analyses were performed to predict non-adherence. There was no clear correlation between adherence and the socio-demographic variables examined, but adherence was related to a positive attitude of the patients towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern subscales. Non-adherence was also related to an increasing severity of depression and to the presence and severity of side-effects. Among our study cohort, the profiles of adherent patients to antidepressant treatment were more closely associated with each patient's attitudes and beliefs than to objective socio-demographic variables. The severity of depression played a relevant role in adherence, but whether this role is direct or an interaction with several concurrent factors is not yet clear. Side-effects were also closely related to adherence, as conditioned by frequent polypharmacy.

Energy drink and energy shot use in the military.

PubMed

Stephens, Mark B; Attipoe, Selasi; Jones, Donnamaria; Ledford, Christy J W; Deuster, Patricia A

2014-10-01

Use of energy drinks and energy shots among military personnel is controversial. High amounts of caffeine (the primary active ingredient in these products) may impact performance of military duties. The impact of caffeine overconsumption and potential subsequent side effects that might be experienced by service members with unique roles and responsibilities is a concern. Reported here are the prevalence of use, reasons for use, and side effects associated with consumption of energy drinks and energy shots among several populations of active duty personnel in the US military. A snowball survey was sent to over 10,000 active duty personnel. A total of 586 (∼6% response rate) individuals completed a 30-item electronic survey. Over half of respondents (53%) reported consuming an energy drink at least once in the past 30 days. One in five (19%) reported energy shot consumption in the prior 30 days. One in five (19%) also reported consuming an energy drink in combination with an alcoholic beverage. Age and gender were significantly associated with energy drink consumption. Young male respondents (18-29 years) reported the highest use of both energy drinks and energy shots. Among those reporting energy drink and energy shot use, the most common reasons for consumption were to improve mental alertness (61%) and to improve mental (29%) and physical (20%) endurance. Nearly two-thirds (65%) of users self-reported at least one side effect. The most commonly reported side effects included increased pulse rate/palpitations, restlessness, and difficulty sleeping. Use of energy products among military personnel is common and has the potential to impact warrior health and military readiness. © 2014 International Life Sciences Institute.

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

PubMed

Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

2016-10-21

Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

Lindane in forestry: a continuing controversy

Treesearch

Thomas W. Koerber

1976-01-01

Use of the chlorinated hydrocarbon insecticide lindane to control bark beetles is controversial. Differences of opinion persist, even among knowledgeable entomologists, on whether use is justified in view of potentially harmful side effects. Effectiveness of lindane treatments, as employed in preventing tree mortality from bark beetles, is also in question. In seven...

The role of nitrates, beta blockers, and calcium antagonists in stable angina pectoris.

PubMed

Chan, P K; Heo, J Y; Garibian, G; Askenase, A; Segal, B L; Iskandrian, A S

1988-09-01

Numerous controlled studies have shown that nitrates, beta blockers, and calcium antagonists are effective in the treatment of stable angina pectoris. The pharmacokinetics, pharmacodynamics, and hemodynamic effects of these agents are different, and thus combination therapy offers additive improvement and also counterbalancing of the undesirable side effects of each drug. The choice of therapy depends on the severity of symptoms, associated diseases, compliance, side effects, and status of left ventricular function. The main mechanism of improvement is a decrease in myocardial oxygen consumption, though an increase in coronary blood flow is another potential reason for the use of calcium blockers. This review considers the properties of these drugs, their mechanism of action, and the results of randomized studies.

Modulation of p-Cyanophenylalanine Fluorescence by Amino Acid Side-chains and Rational Design of Fluorescence Probes of α-Helix Formation

PubMed Central

Taskent-Sezgin, Humeyra; Marek, Peter; Thomas, Rosanne; Goldberg, Daniel; Chung, Juah; Carrico, Isaac; Raleigh, Daniel P.

2011-01-01

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure which can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions and amyloid formation, however the factors that control its fluorescence are not fully understood. Hydrogen bonding to the cyano group is known to play a major role in modulating the fluorescence quantum yield, but the role of potential side-chain quenchers has not yet been elucidated. A systematic study on the effects of different side-chains on p-cyanophenylalanine fluorescence is reported. Tyr is found to have the largest effect followed by deprotonated His, Met, Cys, protonated His, Asn, Arg, and protonated Lys. Deprotonated amino groups are much more effective fluorescence quenchers than protonated amino groups. Free neutral imidazole and hydroxide ion are also effective quenchers of p-cyanophenylalanine fluorescence with Stern-Volmer constants of 39.8 M−1 and 22.1 M−1, respectively. The quenching of p-cyanophenylalanine fluorescence by specific side-chains is exploited to develop specific, high sensitivity, fluorescence probes of helix formation. The approach is demonstrated with Ala based peptides that contain a p-cyanophenylalanine-His or a p-cyanophenylalanine-Tyr pair located at positions i and i+4. The p-cyanophenylalanine-His pair is most useful when the His side-chain is deprotonated and is, thus, complimentary to Trp-His pair which is most sensitive when the His side-chain is protonated. PMID:20565125

Fractional CO2 laser is as effective as Q-switched ruby laser for the initial treatment of a traumatic tattoo.

PubMed

Seitz, Anna-Theresa; Grunewald, Sonja; Wagner, Justinus A; Simon, Jan C; Paasch, Uwe

2014-12-01

Q-switched laser treatments are considered the standard method for removing both regular and traumatic tattoos. Recently, the removal of tattoo ink using ablative fractional lasers has been reported. Ablative fractional CO2 laser and q-switched ruby laser treatments were used in a split-face mode to compare the safety and efficacy of the two types of laser in removing a traumatic tattoo caused by the explosion of a firework. A male patient suffering from a traumatic tattoo due to explosive deposits in his entire face was subjected to therapy. A series of eleven treatments were performed. The right side of the face was always treated using an ablative fractional CO2 laser, whereas the left side was treated only using a q-switched ruby laser. After a series of eleven treatments, the patient demonstrated a significant lightening on both sides of his traumatic tattoo, with no clinical difference. After the first six treatments, the patient displayed greater lightening on the right side of his face, whereas after another five treatments, the left side of the patient's face appeared lighter. No side effects were reported. In the initial stage of removing the traumatic tattoo, the ablative fractional laser treatment appeared to be as effective as the standard ruby laser therapy. However, from the 6th treatment onward, the ruby laser therapy was more effective. Although ablative fractional CO2 lasers have the potential to remove traumatic tattoos, they remain a second-line treatment option.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

PubMed Central

Allam, Ahmed N; Hamdallah, Sherif I; Abdallah, Ossama Y

2017-01-01

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase (P≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals’ formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher Cmax of 0.74±0.15 µg/mL at a delayed Tmax of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration. PMID:28740381

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation.

PubMed

Allam, Ahmed N; Hamdallah, Sherif I; Abdallah, Ossama Y

2017-01-01

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase ( P ≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals' formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher C max of 0.74±0.15 µg/mL at a delayed T max of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration.

[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

PubMed

Haefliger, T; Bonsack, C

2006-01-01

Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case-reports describe the occurrence of retrograde ejaculation associated with risperidone but the exact prevalence is unknown. Retrograde ejaculation is thought to be related to the strong adrenolytic activity of risperidone. Alberto refused his medication because the ejaculatory dysfunction was unbearable for him. A switch to haloperidol depot was eventually well tolerated, without any sexual complaints. His case emphasizes the importance of sexual function for self-esteem and how this may amplify the intolerance to side-effects. David is on depot-risperidone in a setting of a legally forced treatment. Though he - reluctantly - accepts his medication, this side effect exacerbates his pre-existing delusions, strongly focused on sexual themes. His case illustrates how intolerance to sexual side-effects may be amplified by nature of delusions. Mireille is a 58 year old psychotic female patient, whose 2 mg risperidone treatment produced a unilateral galactorrhea. This sign became problematic because potentially visible at a time when Mireille started an activity in a sheltered occupation in town. Lowering dosage of antipsychotic allowed disappearance of the problem. Subjective responses to galactorrhea have been reported to be highly individual. Apart being a potentially visible side-effect, it may be misinterpreted as evidence of pregnancy or of a tumoral process. The cases of Ermina and Denise illustrate two contrasted situations in terms of subjective tolerability of reproductive function side-effects. Both were pre-menopausal patients with hyperprolactinemia secondary to risperidone treatment, resulting in amenorrhea. This was unbearable for Ermina. A switch to olanzapine allowed, one month later, the menses to resume. For Denise, on the other hand, the amenorrhea was a positive event, freeing her of unpleasant menses. Amenorrhea occurs in about 30% of pre-menopausal women treated with risperidone. It is a consequence of hyperprolactinemia, which, although often silent, is not devoid of potential negative consequences (ie increased risk of osteoporosis or neoplasia, worsening of psychopathology) (34). When hyperprolactinemia is symptomatic, lowering of the dose of the antipsychotic, or switching to a prolactin-sparing agent (olanzapine, quetiapine, aripiprazole and clozapine) is recommended. Before this, women with amenorrhea secondary to antipsychotic-induced hyperprolactinemia should be advised that menses may resume. Especially after long-standing amenorrhea they may assume being menopaused, hence may believe birth control measures are no longer required. The prevalence of antipsychotic-induced sexual and reproductive function side-effects is high. Clinicians should be aware of them, because they are often badly tolerated, are associated with a low satisfaction and may therefore result in low adherence with treatment. This implies for the clinician to overtly discuss with the patient of his sexuality and the potential negative impact of antipsychotic treatment on it. The recognition of these problems allows the searching together for a solution. The described cases indicate that solving the problem is often possible, provided that individual preferences and subjective impact are taken in account. Antipsychotic treatment is often prescribed for very long periods. A better knowledge of - and attention to - the associated side effects, particularly on the sexual and reproductive functions, is necessary in order to reduce some potentially negative long-term effects and to improve the adherence to treatment of our patients.

Effect of dopant density on contact potential difference across n-type GaAs homojunctions using Kelvin Probe Force Microscopy

NASA Astrophysics Data System (ADS)

Boumenou, C. Kameni; Urgessa, Z. N.; Djiokap, S. R. Tankio; Botha, J. R.; Nel, J.

2018-04-01

In this study, cross-sectional surface potential imaging of n+/semi-insulating GaAs junctions is investigated by using amplitude mode kelvin probe force microscopy. The measurements have shown two different potential profiles, related to the difference in surface potential between the semi-insulating (SI) substrate and the epilayers. It is shown that the contact potential difference (CPD) between the tip and the sample is higher on the semi-insulating substrate side than on the n-type epilayer side. This change in CPD across the interface has been explained by means of energy band diagrams indicating the relative Fermi level positions. In addition, it has also been found that the CPD values across the interface are much smaller than the calculated values (on average about 25% of the theoretical values) and increase with the electron density. Therefore, the results presented in study are only in qualitative agreement with the theory.

The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice.

PubMed

Wilkerson, Jenny L; Ghosh, Sudeshna; Mustafa, Mohammed; Abdullah, Rehab A; Niphakis, Micah J; Cabrera, Roberto; Maldonado, Rafael L; Cravatt, Benjamin F; Lichtman, Aron H

2017-03-01

Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB) 1 and CB 2 receptors; however, only CB 2 receptors were necessary for the anti-edematous effects in the carrageenan assay. Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects. Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin. In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Endocannabinoid Hydrolysis Inhibitor SA-57: Intrinsic Antinociceptive Effects, Augmented Morphine-induced Antinociception, and Attenuated Heroin Seeking Behavior in Mice

PubMed Central

Wilkerson, Jenny L.; Ghosh, Sudeshna; Mustafa, Mohammed; Abdullah, Rehab A.; Niphakis, Micah J.; Cabrera, Roberto; Maldonado, Rafael L.; Cravatt, Benjamin F.; Lichtman, Aron H.

2017-01-01

Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB)1 and CB2 receptors; however, only CB2 receptors were necessary for the anti-edematous effects in the carrageenan assay. Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects. Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin. In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse. PMID:27890602

High test-retest-reliability of pain-related evoked potentials (PREP) in healthy subjects.

PubMed

Özgül, Özüm Simal; Maier, Christoph; Enax-Krumova, Elena K; Vollert, Jan; Fischer, Marc; Tegenthoff, Martin; Höffken, Oliver

2017-04-24

Pain-related evoked potentials (PREP) is an established electrophysiological method to evaluate the signal transmission of electrically stimulated A-delta fibres. Although prerequisite for its clinical use, test-retest-reliability and side-to-side differences of bilateral stimulation in healthy subjects have not been examined yet. We performed PREP twice within 3-14days in 33 healthy subjects bilaterally by stimulating the dorsal hand. Detection (DT) and pain thresholds (PT) after electrical stimulation, the corresponding pain ratings, latencies of P0, N1, P1 and N2 components and the corresponding amplitudes were assessed. Impact of electrically induced pain intensity, age, sex, and arm length on PREP was analysed. MANOVA, t-Test, interclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland-Altmann-Analysis as well as ANCOVA were used for statistical analysis. Measurement from both sides on both days resulted in mean N1-latencies from 142.39±18.12ms to 144.03±16.62ms and in mean N1P1-amplitudes from 39.04±12.26μV to 40.53±12.9μV. Analysis of a side-to-side effect showed for the N1-latency a F-value of 0.038 and for the N1P1-amplitude of 0.004 (p>0.8). We found intraclass correlation coefficients (ICC) from 0.88 to 0.93 and a standard error of measurement (SEM)<10% of mean values for all measurements concerning the N1-Latency and N1P1-amplitude. Intraclass correlation coefficients, standard error of measurement and Bland-Altman-Analyses revealed excellent test-retest-reliability for N1-latency and N1P1-amplitude without systematic error and there was no side-to-side effect on PREP. N1-latency (r=0.35, p<0.05) and N1P1-amplitude (r=-0.45, p<0.05) correlated with age and additionally N1-latency correlated with arm length (r=0.45, p<0.001). In contrast, pain intensity during the stimulation had no effect on both N1-latency and N1P1-amplitude. In summary, PREP showed high test-retest-reliability and negligible side-to-side differences concerning the commonly used parameters N1-latency and N1P1-amplitude. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

PubMed

Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases. Copyright © 2015. Published by Elsevier Ireland Ltd.

Energy efficiency, human behavior, and economic growth: Challenges to cutting energy demand to sustainable levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santarius, Tilman, E-mail: tilman@santarius.de

Increasing energy efficiency in households, transportation, industries, and services is an important strategy to reduce energy service demand to levels that allow the steep reduction of greenhouse gases, and a full fledged switch of energy systems to a renewable basis. Yet, technological efficiency improvements may generate so-called rebound effects, which may ‘eat up’ parts of the technical savings potential. This article provides a comprehensive review of existing research on these effects, raises critiques, and points out open questions. It introduces micro-economic rebound effect and suggests extending consumer-side analysis to incorporate potential ‘psychological rebound effects.’ It then discusses meso-economic rebound effects,more » i.e. producer-side and market-level rebounds, which so far have achieved little attention in the literature. Finally, the article critically reviews evidence for macro-economic rebound effects as energy efficiency-induced economic growth impacts. For all three categories, the article summarizes assessments of their potential quantitative scope, while pointing out remaining methodological weaknesses and open questions. As a rough “rule of thumb”, in the long term and on gross average, only half the technical savings potential of across-the-board efficiency improvements may actually be achieved in the real world. Policies that aim at cutting energy service demand to sustainable levels are well advised to take due note of detrimental behavioral and economic growth impacts, and should foster policies and measures that can contain them.« less

Double-sided anodic titania nanotube arrays: a lopsided growth process.

PubMed

Sun, Lidong; Zhang, Sam; Sun, Xiao Wei; Wang, Xiaoyan; Cai, Yanli

2010-12-07

In the past decade, the pore diameter of anodic titania nanotubes was reported to be influenced by a number of factors in organic electrolyte, for example, applied potential, working distance, water content, and temperature. All these were closely related to potential drop in the organic electrolyte. In this work, the essential role of electric field originating from the potential drop was directly revealed for the first time using a simple two-electrode anodizing method. Anodic titania nanotube arrays were grown simultaneously at both sides of a titanium foil, with tube length being longer at the front side than that at the back side. This lopsided growth was attributed to the higher ionic flux induced by electric field at the front side. Accordingly, the nanotube length was further tailored to be comparable at both sides by modulating the electric field. These results are promising to be used in parallel configuration dye-sensitized solar cells, water splitting, and gas sensors, as a result of high surface area produced by the double-sided architecture.

Assessing the potential and side effects of ocean albedo modification in the Arctic

NASA Astrophysics Data System (ADS)

Mengis, N.; Oschlies, A.; Keller, D. P.; Martin, T.

2015-12-01

The ice albedo feedbacks in the Arctic are a key factor of the positive feedback mechanisms, which amplify climate change in the high northern latitudes. This study assesses the potential and side effects of an idealised Arctic ocean albedo modification (AOAM) experiment under varying emissions scenarios. A first finding is the fact that the decreasing trend in the Arctic summer sea ice extent could only be offset rather than reversed by the implementation of AOAM under increasing atmospheric CO2 emissions. What becomes evident in this study is that the Earth system regulates its internal heat budgets. Therefore a local cooling at the high northern latitudes causes compensatory heat fluxes in the atmosphere and the ocean. Meaning that firstly, the effectiveness of local scale climate intervention will, in the long term, be lowered by these compensatory fluxes and secondly that there are consequences, such as the subsurface warming signal found in this study, which are unexpected and unintended.

Are Diuretics Underutilized in Dialysis Patients?

PubMed

Trinh, Emilie; Bargman, Joanne M

2016-09-01

While oral diuretics are commonly used in patients with chronic kidney disease for the management of volume and blood pressure, they are often discontinued upon initiation of dialysis. We suggest that diuretics are considerably underutilized in peritoneal dialysis and haemodialysis patients despite numerous potential benefits and few side effects. Moreover, when diuretics are used, optimal doses are not always prescribed. In peritoneal dialysis, the use of diuretics can improve volume status and minimize the need for higher glucose-containing solutions. In patients on haemodialysis, diuretics can help lessen interdialytic weight gain, resulting in decreased ultrafiltration rates and fewer episodes of intradialytic hypotension. This paper will review the mechanism of action of diuretics in patients with renal insufficiency, quantify the risk of side effects and elaborate on the potential advantages of diuretic use in peritoneal dialysis and hemodialysis patients with residual kidney function. © 2016 Wiley Periodicals, Inc.

Phytochemical and pharmacological properties of essential oils from Cedrus species.

PubMed

Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

2018-06-01

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

Sweet proteins – Potential replacement for artificial low calorie sweeteners

PubMed Central

Kant, Ravi

2005-01-01

Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with development of bladder cancer. Naturally occurring sweet and taste modifying proteins are being seen as potential replacements for the currently available artificial low calorie sweeteners. Interaction aspects of sweet proteins and the human sweet taste receptor are being investigated. PMID:15703077

Intractable epilepsy: management and therapeutic alternatives.

PubMed

Schuele, Stephan U; Lüders, Hans O

2008-06-01

More than half of patients with newly diagnosed epilepsy achieve complete seizure control without major side-effects. Patients who continue to have seizures after initial medical therapy should have an early and detailed assessment to confirm the diagnosis, to determine the underlying cause and epilepsy syndrome, and to choose an adequate treatment strategy. The risks and potential benefits of surgical procedures or experimental therapy have to be weighed against the chance of improvement and the potential side-effects of additional medical therapy. Surgery for temporal lobe epilepsy, the most common cause of focal epilepsy, can control seizures and improve quality of life in appropriately selected patients. However, around 20-30% of patients do not respond to medical or surgical treatment. The management of chronic intractable epilepsy requires comprehensive care to address the adverse events of medical treatment, quality of life issues, and comorbid disorders. Much research focuses on the experimental treatment options that offer hope of seizure reduction or cure.

Disentangling gaze shifts from preparatory ERP effects during spatial attention

PubMed Central

Kennett, Steffan; van Velzen, José; Eimer, Martin; Driver, Jon

2007-01-01

After a cue directing attention to one side, anterior event-related potentials (ERPs) show contralateral negativity (Anterior Directing Attention Negativity, ADAN). It is unclear whether ADAN effects are contaminated by contralateral negativity arising from residual gaze shifts. Conversely, it is possible that ADAN-related potentials contaminate the horizontal electrooculogram (HEOG), via volume conduction. To evaluate these possibilities, we used high-resolution infrared eye tracking, while recording EEG and HEOG in a cued spatial-attention task. We found that, after conventional ERP and HEOG pre-processing exclusions, small but systematic residual gaze shifts in the cued direction can remain, as revealed by the infrared measure. Nevertheless, by using this measure for more stringent exclusion of small gaze shifts, we confirmed that reliable ADAN components remain for preparatory spatial attention in the absence of any systematic gaze shifts toward the cued side. PMID:17241141

How much land-based greenhouse gas mitigation can be achieved without compromising food security and environmental goals?

PubMed

Smith, Pete; Haberl, Helmut; Popp, Alexander; Erb, Karl-Heinz; Lauk, Christian; Harper, Richard; Tubiello, Francesco N; de Siqueira Pinto, Alexandre; Jafari, Mostafa; Sohi, Saran; Masera, Omar; Böttcher, Hannes; Berndes, Göran; Bustamante, Mercedes; Ahammad, Helal; Clark, Harry; Dong, Hongmin; Elsiddig, Elnour A; Mbow, Cheikh; Ravindranath, Nijavalli H; Rice, Charles W; Robledo Abad, Carmenza; Romanovskaya, Anna; Sperling, Frank; Herrero, Mario; House, Joanna I; Rose, Steven

2013-08-01

Feeding 9-10 billion people by 2050 and preventing dangerous climate change are two of the greatest challenges facing humanity. Both challenges must be met while reducing the impact of land management on ecosystem services that deliver vital goods and services, and support human health and well-being. Few studies to date have considered the interactions between these challenges. In this study we briefly outline the challenges, review the supply- and demand-side climate mitigation potential available in the Agriculture, Forestry and Other Land Use AFOLU sector and options for delivering food security. We briefly outline some of the synergies and trade-offs afforded by mitigation practices, before presenting an assessment of the mitigation potential possible in the AFOLU sector under possible future scenarios in which demand-side measures codeliver to aid food security. We conclude that while supply-side mitigation measures, such as changes in land management, might either enhance or negatively impact food security, demand-side mitigation measures, such as reduced waste or demand for livestock products, should benefit both food security and greenhouse gas (GHG) mitigation. Demand-side measures offer a greater potential (1.5-15.6 Gt CO2 -eq. yr(-1) ) in meeting both challenges than do supply-side measures (1.5-4.3 Gt CO2 -eq. yr(-1) at carbon prices between 20 and 100 US$ tCO2 -eq. yr(-1) ), but given the enormity of challenges, all options need to be considered. Supply-side measures should be implemented immediately, focussing on those that allow the production of more agricultural product per unit of input. For demand-side measures, given the difficulties in their implementation and lag in their effectiveness, policy should be introduced quickly, and should aim to codeliver to other policy agenda, such as improving environmental quality or improving dietary health. These problems facing humanity in the 21st Century are extremely challenging, and policy that addresses multiple objectives is required now more than ever. © 2013 John Wiley & Sons Ltd.

The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy.

PubMed

Wallace, V C J; Segerdahl, A R; Lambert, D M; Vandevoorde, S; Blackbeard, J; Pheby, T; Hasnie, F; Rice, A S C

2007-08-01

Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB(1)) receptor-mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L-29), which via inhibition of fatty acid amide hydrolase (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side effects. The in vivo analysis of the effect of L-29 on measures of pain behaviour in three rat models of neuropathic pain. Systemically administered L-29 (10 mg kg(-1)) reduced hypersensitivity to mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral (ddC)-associated hypersensitivity and a model of varicella zoster virus (VZV)-associated hypersensitivity. The effects of L-29 were comparable to those of gabapentin (50 mg kg(-1)). The CB(1) receptor antagonist SR141716a (1 mg kg(-1)) and the CB(2) receptor antagonist SR144528 (1 mg kg(-1)) reduced the effect of L-29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The peroxisome proliferator-activated receptor-alpha antagonist, MK-886 (1 mg kg(-1)), partially attenuated the effect of L-29 on hypersensitivity in the PSNI model. L-29 (10 mg kg(-1)) significantly attenuated thigmotactic behaviour in the open field arena without effect on locomotor activity. L-29 produces analgesia in a range of neuropathic pain models. This presents L-29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation.

Frontal Plane Knee Moments in Golf: Effect of Target Side Foot Position at Address

PubMed Central

Lynn, Scott K.; Noffal, Guillermo J.

2010-01-01

Golf has the potential to keep people active well into their later years. Injuries to the target side knee have been reported in golfers, yet no mechanisms for these injuries have been proposed. The loads on the knee during the golf swing may be insufficient to cause acute injury, yet they may be a factor in the progression of overuse/degenerative conditions; therefore, research developing swing modifications that may alter loading of the knee is warranted. It has been suggested that the proper golf set-up position has the target-side foot externally rotated but no reasoning for this modification has been provided. Frontal plane knee moments have been implicated in many knee pathologies. Therefore, this study used a 3-dimensional link segment model to quantify the frontal plane knee moments during the golf swing in a straight (STR) and externally rotated (EXT) target-side foot position. Subjects were 7 collegiate golfers and knee moments were compared between conditions using repeated measures T-tests. The golf swing knee moment magnitudes were also descriptively compared to those reported for two athletic maneuvers (drop jump landing, side-step cutting) and activities of daily living (gait, stair ascent). The EXT condition decreased the peak knee adduction moment as compared to the STR condition; however, foot position had no effect on the peak knee abduction moment. Also, the magnitude of the knee adduction moments during the two activities of daily living were 9-33% smaller than those experienced during the two different golfing conditions. The drop jump landing and golf swing knee moments were of similar magnitude (STR= - 5%, EXT= + 8%); however, the moments associated with side- step cutting were 50-71% larger than those on the target side knee during the golf swing. The loading of the target side knee during the golf swing may be a factor in the development and progression of knee pathologies and further research should examine ways of attenuating these loads through exercise and swing modifications. Key points An externally rotated front foot position at address would be recommended for those with medial knee pathology in the target side limb. There is a large valgus moment on the target side knee during the golf swing that is not decreased with external rotation of the foot at address. The potential of the knee moments on the target side limb to lead to knee pathologies in golfers needs to be further investigated. PMID:24149696

Liver immunology and herbal treatment

PubMed Central

Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

2017-01-01

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

Dietary nutraceuticals as backbone for bone health.

PubMed

Pandey, Manoj K; Gupta, Subash C; Karelia, Deepkamal; Gilhooley, Patrick J; Shakibaei, Mehdi; Aggarwal, Bharat B

2018-03-27

Bone loss or osteoporosis, is a slow-progressing disease that results from dysregulation of pro-inflammatory cytokines. The FDA has approved number of drugs for bone loss prevention, nonetheless all are expensive and have multiple side effects. The nutraceuticals identified from dietary agents such as butein, cardamonin, coronarin D curcumin, diosgenin, embelin, gambogic acid, genistein, plumbagin, quercetin, reseveratrol, zerumbone and more, can modulate cell signaling pathways and reverse/slow down osteoporosis. Most of these nutraceuticals are inexpensive; show no side effect while still possessing anti-inflammatory properties. This review provides various mechanisms of osteoporosis and how nutraceuticals can potentially prevent the bone loss. Published by Elsevier Inc.

Electric field effects on ion currents in satellite wakes

NASA Technical Reports Server (NTRS)

Parks, D. E.; Katz, I.

1985-01-01

Small currents associated with satellite spin, dielectric conduction, or trace concentrations of H+, can have a substantial effect on the potential of a satellite and the particle currents reaching its surface. The importance of such small currents at altitudes below about 300 km stems from the extremely small 0+ currents impinging on the wake-side of the spacecraft. The particle current on the downstream side of the AE-C satellite is considered. Theoretical estimates based on a newly described constant of the motion of a particle indicate that accounting for small concentrations of H+ remove a major discrepancy between calculated and measured currents.

Designing greener plasticizers: Effects of alkyl chain length and branching on the biodegradation of maleate based plasticizers.

PubMed

Erythropel, Hanno C; Brown, Tobin; Maric, Milan; Nicell, Jim A; Cooper, David G; Leask, Richard L

2015-09-01

The ubiquitous presence of the plasticizer di (2-ethylhexyl) phthalate (DEHP) in the environment is of concern due to negative biological effects associated with it and its metabolites. In particular, the metabolite mono (2-ethylhexyl) phthalate (MEHP) is a potential endocrine disruptor. Earlier work had identified the diester di (2-ethylhexyl) maleate (DEHM) as a potential greener candidate plasticizer to replace DEHP, yet its biodegradation rate was reported to be slow. In this study, we modified the side chains of maleate diesters to be linear (i.e., unbranched) alkyl chains that varied in length from ethyl to n-octyl. The plasticization efficiency of these compounds blended into PVC at 29 wt.% increased with the overall length of the molecule, but all compounds performed as well as or better than comparable samples with DEHP. Tests conducted with the equally long DEHM and dihexyl maleate (DHM) showed that branching has no effect on glass transition temperature (Tg) reduction efficiency. Biodegradation experiments with the common soil bacterium Rhodococcus rhodocrous in the presence of the plasticizer showed acceptable hydrolysis rates of maleates with unbranched side chains, while the branched DEHM showed almost no degradation. The addition of hexadecane as auxiliary carbon source improved hydrolysis rates. Temporary buildup of the respective monoester of the compounds were observed, but only in the case of the longest molecule, dioctyl maleate (DOM), did this buildup lead to growth inhibition of the bacteria. Maleates with linear side chains, if designed and tested properly, show promise as potential candidate plasticizers as replacements for DEHP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

PubMed

Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

2018-03-12

The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Side-chain-side-chain interactions and stability of the helical state

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.

Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.

PubMed

Reutfors, Johan; Clapham, Eric; Bahmanyar, Shahram; Brandt, Lena; Jönsson, Erik G; Ekbom, Anders; Bodén, Robert; Ösby, Urban

2016-07-01

This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Risks and Benefits of Cannabis in the Dermatology Clinic.

PubMed

Dhadwal, Gurbir; Kirchhof, Mark G

Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for medicinal and recreational purposes for millennia. There has been a recent trend to legalize the use of cannabis, as illustrated by the recent legalization votes in numerous states in the United States and legislation in Canada to allow recreational cannabis use. With this increasing consumption of cannabis, dermatologists will see increased pressure to prescribe cannabis and will see the side effects of cannabis use with greater frequency. There are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain. In addition, very preliminary studies have suggested cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound healing, and skin cancer. Further well-controlled studies are required to explore these potential uses. Conversely, the side effects of cannabis use are relatively well documented, and dermatologists should be aware of these presentations. Side effects of cannabis use include cannabis allergy manifesting as urticaria and pruritus, cannabis arteritis presenting with necrosis and ulcers, and oral cancers from cannabis smoke. In this review, we summarize some of the studies and reports regarding the medicinal uses of cannabis in the dermatology clinic and some of the side effects that might present more often to dermatologists as the use of cannabis increases.

Structure-based discovery of opioid analgesics with reduced side effects.

PubMed

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K; McCorvy, John D; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F; Giguère, Patrick M; Löber, Stefan; Da Duan; Scherrer, Grégory; Kobilka, Brian K; Gmeiner, Peter; Roth, Bryan L; Shoichet, Brian K

2016-09-08

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent G i activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.

Use of Hematopoietic Growth Factor in the Management of Hematological Side Effects Associated to Antiviral Treatment for Hcv Hepatitis

PubMed Central

Mancino, Paola; Falasca, Katia; Ucciferri, Claudio; Pizzigallo, Eligio; Vecchiet, Jacopo

2010-01-01

Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection. PMID:21415945

Patients' perspectives about why they have their contraceptive Implanon NXT device removed early.

PubMed

Flore, Meike; Chen, Xiaoshuang Lilly; Bonney, Andrew; Mullan, Judy; Dijkmans-Hadley, Bridget; Hodgkins, Adam; Evans, Gina; Frew, Haley; Lloyd, Gail

2016-10-01

Women with long-acting, reversible contraceptive devices inserted may choose to remove them prior to their planned expiry dates. The objective of this study was to explore Australian women's experiences with the etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it removed early. Semi-structured interviews were conducted with 18 women between June 2013 and January 2014. Transcriptions of the audio-taped interviews were analysed using a constant comparative analysis framework. Two core themes of participants' responses that were identified in this study were influences on choice of contraception, which included convenience and information sources; and influences on removal of contraception, which included side effects and their negative impacts on relationships and financial costs. This study highlights that women's experiences with side effects contribute to the early removal of long-acting contraceptive devices such as Implanon NXT. This study emphasises the importance of general practitioners (GPs) in providing comprehensive information about the benefits and potential side effects associated with using these implants.

Structure–based discovery of opioid analgesics with reduced side effects

PubMed Central

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K.; McCorvy, John D.; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C.; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F.; Giguère, Patrick M.; Löber, Stefan; Duan, Da; Scherrer, Grégory; Kobilka, Brian K.; Gmeiner, Peter; Roth, Bryan L.; Shoichet, Brian K.

2016-01-01

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids—which include fatal respiratory depression—are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21—a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids. PMID:27533032

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

PubMed

Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

2017-07-14

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

PubMed Central

Ho, Vincent; Stewart, Maxwell; Boyd, Peter

2008-01-01

Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity. PMID:18452597

Telluric currents: A meeting of theory and observation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boteler, D.H.; Seager, W.H.

Pipe-to-soil (P/S) potential variations resulting from telluric currents have been observed on pipelines in many locations. However, it has never teen clear which parts of a pipeline will experience the worst effects. Two studies were conducted to answer this question. Distributed-source transmission line (DSTL) theory was applied to the problem of modeling geomagnetic induction in pipelines. This theory predicted that the largest P/S potential variations would occur at the ends of the pipeline. The theory also predicted that large P/S potential variations, of opposite sign, should occur on either side of an insulating flange. Independently, an observation program was conductedmore » to determine the change in telluric current P/S potential variations and to design counteractive measures along a pipeline in northern Canada. Observations showed that the amplitude of P/S potential fluctuations had maxima at the northern and southern ends of the pipeline. A further set of recordings around an insulating flange showed large P/S potential variations, of opposite sign, on either side of the flange. Agreement between the observations and theoretical predictions was remarkable. While the observations confirmed the theory, the theory explains how P/S potential variations are produced by telluric currents and provides the basis for design of cathodic protection systems for pipelines that can counteract any adverse telluric effects.« less

Mining adverse drug reactions from online healthcare forums using hidden Markov model.

PubMed

Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

2014-10-23

Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also identified. The results from the HMM based Text Miner are encouraging to pursue further enhancements to this approach. The mined novel side-effects can act as early indicators for health authorities to help focus their efforts in post-marketing drug surveillance.

Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

PubMed

Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

2015-02-01

Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of driver's age and side of impact on crash severity along urban freeways: a mixed logit approach.

PubMed

Haleem, Kirolos; Gan, Albert

2013-09-01

This study identifies geometric, traffic, environmental, vehicle-related, and driver-related predictors of crash injury severity on urban freeways. The study takes advantage of the mixed logit model's ability to account for unobserved effects that are difficult to quantify and may affect the model estimation, such as the driver's reaction at the time of crash. Crashes of 5 years occurring on 89 urban freeway segments throughout the state of Florida in the United States were used. Examples of severity predictors explored include traffic volume, distance of the crash to the nearest ramp, and detailed driver's age, vehicle types, and sides of impact. To show how the parameter estimates could vary, a binary logit model was compared with the mixed logit model. It was found that the at-fault driver's age, traffic volume, distance of the crash to the nearest ramp, vehicle type, side of impact, and percentage of trucks significantly influence severity on urban freeways. Additionally, young at-fault drivers were associated with a significant severity risk increase relative to other age groups. It was also observed that some variables in the binary logit model yielded illogic estimates due to ignoring the random variation of the estimation. Since the at-fault driver's age and side of impact were significant random parameters in the mixed logit model, an in-depth investigation was performed. It was noticed that back, left, and right impacts had the highest risk among middle-aged drivers, followed by young drivers, very young drivers, and finally, old and very old drivers. To reduce side impacts due to lane changing, two primary strategies can be recommended. The first strategy is to conduct campaigns to convey the hazardous effect of changing lanes at higher speeds. The second is to devise in-vehicle side crash avoidance systems to alert drivers of a potential crash risk. The study provided a promising approach to screening the predictors before fitting the mixed logit model using the random forest technique. Furthermore, potential countermeasures were proposed to reduce the severity of impacts. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Quercetin and rutin as potential agents antifungal against Cryptococcus spp.

PubMed

Oliveira, V M; Carraro, E; Auler, M E; Khalil, N M

2016-01-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.

Industrial demand side management: A status report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopkins, M.F.; Conger, R.L.; Foley, T.J.

This report provides an overview of and rationale for industrial demand side management (DSM) programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential energy savings in kilowatt hours. The report presents types and examples of programs and explores elements of successful programs. Two in-depth case studies (from Boise Cascade and Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. A comprehensive bibliography is included, technical assistance programsmore » are listed and described, and a methodology for evaluating potential or actual savings from projects is delineated.« less

Wave radiation and diffraction by a two-dimensional floating body with an opening near a side wall

NASA Astrophysics Data System (ADS)

Zhang, Hong-sheng; Zhou, Hua-wei

2013-08-01

The radiation and diffraction problem of a two-dimensional rectangular body with an opening floating on a semi-infinite fluid domain of finite water depth is analysed based on the linearized velocity potential theory through an analytical solution procedure. The expressions for potentials are obtained by the method of variation separation, in which the unknown coefficients are determined by the boundary condition and matching requirement on the interface. The effects of the position of the hole and the gap between the body and side wall on hydrodynamic characteristics are investigated. Some resonance is observed like piston motion in a moon pool and sloshing in a closed tank because of the existence of restricted fluid domains.

Treatment of pseudofolliculitis barbae in very dark skin with a long pulse Nd:YAG laser.

PubMed Central

Ross, E. Victor; Cooke, Linda M.; Overstreet, Kristen A.; Buttolph, Greg D.; Blair, Mark A.

2002-01-01

BACKGROUND: Pseudofolliculitis barbae affects some individuals with coarse curly hair. Currently available treatment modalities are often ineffective. In some studies, lasers have been shown to be potentially helpful in mitigating disease severity by reducing the number and/or thickness of hair shafts. METHODS: This was a side-by-side interventional study conducted at a military tertiary medical facility. The study group included 26 patients (skin types IV, V, and VI) referred from primary care physicians with a diagnosis of pseudofolliculitis barbae refractory to medical therapy. A neodymium YAG laser was used to treat one half of the neck. One month later, shaving bumps were counted and compared to their preoperative levels on both sides. RESULTS: Mean postoperative papule counts were 11.6 +/- 6 (SD) and 30.1 +/- 19 (SD) on the treated side and untreated sides, respectively. CONCLUSION: Neodymium YAG laser treatment represents a safe and effective option for reducing papule formation in patients with pseudofolliculitis barbae. Images Figure 1 PMID:12408693

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

PubMed Central

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-01-01

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects.

PubMed

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-12-02

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

Clinical and Histologic Effects of Fractional Microneedling Radiofrequency Treatment on Rosacea.

PubMed

Park, Seon Yong; Kwon, Hyuck Hoon; Yoon, Ji Young; Min, Seonguk; Suh, Dae Hun

2016-12-01

Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods.

Full-Potential Modeling of Blade-Vortex Interactions. Degree awarded by George Washington Univ., Feb. 1987

NASA Technical Reports Server (NTRS)

Jones, Henry E.

1997-01-01

A study of the full-potential modeling of a blade-vortex interaction was made. A primary goal of this study was to investigate the effectiveness of the various methods of modeling the vortex. The model problem restricts the interaction to that of an infinite wing with an infinite line vortex moving parallel to its leading edge. This problem provides a convenient testing ground for the various methods of modeling the vortex while retaining the essential physics of the full three-dimensional interaction. A full-potential algorithm specifically tailored to solve the blade-vortex interaction (BVI) was developed to solve this problem. The basic algorithm was modified to include the effect of a vortex passing near the airfoil. Four different methods of modeling the vortex were used: (1) the angle-of-attack method, (2) the lifting-surface method, (3) the branch-cut method, and (4) the split-potential method. A side-by-side comparison of the four models was conducted. These comparisons included comparing generated velocity fields, a subcritical interaction, and a critical interaction. The subcritical and critical interactions are compared with experimentally generated results. The split-potential model was used to make a survey of some of the more critical parameters which affect the BVI.

Using semipermeable membrane devices (SPMDs) to estimate bioconcentration potential of petroleum additives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crecelius, E.A.; Rausina, G.A.; Biggs, W.R.

1995-12-31

Lubricant additives can be released into the environment during transport, usage, or improper disposal. Therefore, it is necessary to evaluate these substances for their potential to cause adverse environmental effects. Because lubricant additives tend to be large molecular size hydrophobic substances with very limited water solubility, they could possibly bioconcentrate if released into the environment. A test was developed using SPMD technology to assess the bioconcentration potential of lubricant additives. SPMDs are low-density polyethylene tubing with an effective pore size of 600 daltons, similar to that of cellular membranes. SPMDs filled with triolein, the predominant lipid in fish, function asmore » model fish or mollusks, with selective membranes and lipid reservoirs to concentrate organic compounds from water. Using the SPMD test system, bioconcentration factors were determined for a poly alpha olefin (PAO) base stock and lubricant additive compounds that represent three additive use categories. The SPMD test system was validated using a radiocarbon-labeled calcium detergent lubricant additive in side-by-side exposures to SPMDs and aquatic organisms. Radiocarbon-labeled pyrene was used as a reference compound in the tests.« less

Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report.

PubMed

Lambert Kuhn, E; Levêque, D; Lioure, B; Gourieux, B; Bilbault, P

2016-02-01

Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly. © 2016 John Wiley & Sons Ltd.

Problem Definition Studies on Potential Environmental Pollutants. VII. Physical, Chemical, Toxicological, and Biological Properties of DDT and Its Derivatives

DTIC Science & Technology

1979-06-01

WORDS (C-enlnuo on reverse side If n*co*or and Identlif by block numbe) Amphibians Birds DDT Man Analytical Methods Carcinogenesis Fish Metabolism ...18 Bioaccumulation and the Food Chain .. .. .. .. .. . .19 Effects on Terrestrial Animals. .. ........ .. .... 21 Effects on...Aquatic Organisms .. . . .. .. .. .. .. . .25 Effects on Microorganisms .. ........... .. .... 41 VI. STANDARDS AND CRITERIA FOR DDT

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

PubMed

Heller, Monika K; Chapman, Sarah C E; Horne, Rob

2017-04-01

Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall  = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity  = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution  = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

Consumer perspectives on a pericoital contraceptive pill in India and Uganda.

PubMed

Cover, Jane K; Drake, Jennifer Kidwell; Kyamwanga, Imelda T; Turyakira, Eleanor; Dargan, Tanya; Kumakech, Edward; Harner-Jay, Claudia

2013-12-01

Studies suggest that women in some countries have adopted emergency contraceptive pills as a routine method of family planning. This practice indicates there may be latent demand for a pericoital contraceptive pill taken only when a woman has sexual intercourse, and labeled and marketed for use as a regular contraceptive method. To understand the appeal and potential market for a pericoital contraceptive pill, 39 focus groups and 23 in-depth interviews were conducted with women and men in Lucknow, Uttar Pradesh, India, and Kampala, Uganda. A total of 281 individuals participated in this qualitative study. In general, women embraced the idea of a female-controlled method that would be easier than taking a daily oral contraceptive pill and that could be taken either before or after sexual intercourse; in Uganda, especially, women approved of the fact that the method could be taken without a partner's knowledge. Although we do not yet know the extent of side effects for this method, women expressed some concerns about the level and nature of potential side effects. The results suggest that a pericoital contraceptive pill would be well-received by consumers in both country settings. If its efficacy and side effects are acceptable, a pericoital contraceptive pill could fill a gap for female-controlled, discreet, coitus-related contraception, particularly among women who do not have sex very frequently.

Tolerance and safety of superficial chemical peeling with salicylic acid in various facial dermatoses.

PubMed

Bari, Arfan Ul; Iqbal, Zafar; Rahman, Simeen Ber

2005-01-01

Chemical peeling is a skin-wounding procedure that may have some potentially undesirable side-effects. The present study is directed towards safety concerns associated with superficial chemical peeling with salicylic acid in various facial dermatoses. The study was a non-comparative and a prospective one. Two hundred and sixty-eight patients of either sex, aged between 10 to 60 years, undergoing superficial chemical peeling for various facial dermatoses (melasma, acne vulgaris, freckles, post-inflammatory scars/pigmentation, actinic keratoses, plane facial warts, etc.) were included in the study. Eight weekly peeling sessions were carried out in each patient. Tolerance to the procedure and any undesirable effects noted during these sessions were recorded. Almost all the patients tolerated the procedure well. Mild discomfort, burning, irritation and erythema were quite common but the incidence of major side-effects was very low and these too, were easily manageable. There was no significant difference in the incidence of side-effects between facial dermatoses (melasma, acne and other pigmentary disorders). Chemical peeling with salicylic acid is a well tolerated and safe treatment modality in many superficial facial dermatoses.

Theoretical study on the potential energy surfaces of CaNC and CaCN

NASA Astrophysics Data System (ADS)

Ishii, Keisaku; Taketsugu, Tetsuya; Hirano, Tsuneo

2003-06-01

The potential energy surfaces of CaNC ( overlineX2Σ+) and CaCN ( overlineX2Σ+) have been investigated by the highly correlated ab initio molecular orbital methods. The bending potential for CaNC is shallow, and shows quite anharmonic and anomalous character, which can explain why the centrifugal distortion constants up to the tenth order were required for the analysis of its rotational spectrum. The reaction path for the isomerization reaction of CaNC and CaCN was also determined: The activation barrier is 2111 cm -1 from the CaNC side, and 602 cm -1 from the CaCN side. Core-core and core-valence correlation contributions of Ca M-shell electrons make the Ca-N (for CaNC) and Ca-C (for CaCN) bond lengths shorter by 0.05 and 0.04 Å, respectively, which indicates the significance of these core-correlation effects.

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

PubMed Central

Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

2016-01-01

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V. PMID:27966605

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility

NASA Astrophysics Data System (ADS)

Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

2016-12-01

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility.

PubMed

Wedege, Kristina; Dražević, Emil; Konya, Denes; Bentien, Anders

2016-12-14

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

Framing and personalizing informed consent to prevent negative expectations: An experimental pilot study.

PubMed

Heisig, Sarah R; Shedden-Mora, Meike C; Hidalgo, Pablo; Nestoriuc, Yvonne

2015-10-01

Informing patients about medical treatments and their possible side effects is ethically and legally obligatory but may trigger negative expectations and nocebo-related side effects. This pilot study aims to investigate the effect of different informed consent procedures on treatment expectations for adjuvant breast cancer treatments (Study 1: endocrine therapy; Study 2: chemotherapy). Using an experimental 2-factorial design, healthy women were informed about endocrine therapy (n = 60) or chemotherapy (n = 64) within a hypothetical scenario. Information was framed with or without treatment benefit information and delivered in a personalized or standardized interaction. Primary outcomes were necessity-concern beliefs about the treatment and side-effect expectations, secondary outcomes were decisional conflicts. In Study 1, side-effect expectations (η²p= .08) and decisional conflicts (η²p = .07) were lower when framed treatment information was given. Providing personalized information resulted in more functional necessity-concern beliefs (η²p = .06) and lower decisional conflicts (η²p = .07). Personalizing and framing of information resulted in more functional necessity-concern beliefs (η²p = .10) and lower decisional conflicts. In Study 2, necessity-concern beliefs were more functional with framing (η²p = .06). Participants in the personalized groups reported lower decisional conflicts (η²p = .06). No differences in side-effect expectations were revealed. This is the first study to provide evidence for optimized treatment expectations through altered informed consent strategies. The results emphasize that framing and personalizing informed consent can positively influence treatment expectations and reduce decisional conflicts. However, generalizations are impaired by the study's pilot character. The potential to prevent nocebo responses in clinical practice should be analyzed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Research in biomechanics of occupant protection.

PubMed

King, A I; Yang, K H

1995-04-01

This paper discusses the biomechanical bases for occupant protection against frontal and side impact. Newton's Laws of Motion are used to illustrate the effect of a crash on restrained and unrestrained occupants, and the concept of ride down is discussed. Occupant protection through the use of energy absorbing materials is described, and the mechanism of injury of some of the more common injuries is explained. The role of the three-point belt and the airbag in frontal protection is discussed along with the potential injuries that can result from the use of these restraint systems. Side impact protection is more difficult to attain but some protection can be derived from the use of padding or a side impact airbag. It is concluded that the front seat occupants are adequately protected against frontal impact if belts are worn in an airbag equipped vehicle. Side impact protection may not be uniform in all vehicles.

Investigation of the novel attributes in double recessed gate SiC MESFETs at drain side

NASA Astrophysics Data System (ADS)

Orouji, Ali A.; Razavi, S. M.; Ebrahim Hosseini, Seyed; Amini Moghadam, Hamid

2011-11-01

In this paper, the potential impact of drain side-double recessed gate (DS-DRG) on silicon carbide (SiC)-based metal semiconductor field effect transistors (MESFETs) is studied. We investigate the device performance focusing on breakdown voltage, threshold voltage, drain current and dc output conductance with two-dimensional and two-carrier device simulation. Our simulation results demonstrate that the channel thickness under the gate in the drain side is an important factor in the breakdown voltage. Also, the positive shift in the threshold voltage for the DS-DRG structure is larger in comparison with that for the source side-double recessed gate (SS-DRG) SiC MESFET. The saturated drain current for the DS-DRG structure is larger compared to that for the SS-DRG structure. The maximum dc output conductance in the DS-DRG structure is smaller than that in the SS-DRG structure.

Accurate Estimation of Target amounts Using Expanded BASS Model for Demand-Side Management

NASA Astrophysics Data System (ADS)

Kim, Hyun-Woong; Park, Jong-Jin; Kim, Jin-O.

2008-10-01

The electricity demand in Korea has rapidly increased along with a steady economic growth since 1970s. Therefore Korea has positively propelled not only SSM (Supply-Side Management) but also DSM (Demand-Side Management) activities to reduce investment cost of generating units and to save supply costs of electricity through the enhancement of whole national energy utilization efficiency. However study for rebate, which have influence on success or failure on DSM program, is not sufficient. This paper executed to modeling mathematically expanded Bass model considering rebates, which have influence on penetration amounts for DSM program. To reflect rebate effect more preciously, the pricing function using in expanded Bass model directly reflects response of potential participants for rebate level.

Optimal Drug Policy in Low-Income Neighborhoods

PubMed Central

Chang, Sheng-Wen; Coulson, N. Edward; Wang, Ping

2015-01-01

The control of drug activity currently favors supply-side policies: drug suppliers in the U.S. face a higher arrest rate and longer sentences than demanders. We construct a simple model of drug activity with search and entry frictions in labor and drug markets. Our calibration analysis suggests a strong “dealer replacement effect.” As a result, given a variety of community objectives, it is beneficial to lower supplier arrests and raise the demand arrest rate from current values. A 10% shift from supply-side to demand-side arrests can reduce the population of potential drug dealers by 22–25,000 and raise aggregate local income by $380–400 million, at 2002 prices. (JEL Classification: D60, J60, K42, H70) PMID:27616878

Computational Study of Porous Treatment for Altering Flap Side-Edge Flowfield

NASA Technical Reports Server (NTRS)

Choudhari, Meelan; Khorrami, Mehdi R.

2003-01-01

Reynolds-averaged Navier-Stokes calculations are used to investigate porous side-edge treatment as a passive means for flap noise reduction. Steady-state simulations are used to infer effects of the treatment on acoustically relevant features of the mean flow near the flap side edge. Application of the porous treatment over a miniscule fraction of the wetted flap area (scaling with the flap thickness) results in significantly weaker side-edge vortex structures via modification of the vortex initiation and roll-up processes. At high flap deflections, the region of axial flow reversal associated with the breakdown of the side-edge vortex is also eliminated, indicating an absence of vortex bursting in the presence of the treatment. Potential ramifications of the mean-flow modifications for flap-noise reduction are examined in the light of lessons learned from recent studies on flap noise. Computations confirm that any noise reduction benefit via the porous treatment would be achieved without compromising the aerodynamic effectiveness of the flap. Results of the parameter study contribute additional insight into the measured data from the 7x10 wind tunnel at NASA Ames and provide preliminary guidance for specifying optimal treatment characteristics in terms of treatment location, spatial extent, and flow resistance of the porous skin.

Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.

PubMed

Broersen, Leonie H A; Jha, Meghna; Biermasz, Nienke R; Pereira, Alberto M; Dekkers, Olaf M

2018-05-31

To systematically review the effectiveness of medical treatment for Cushing's syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies. Eight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing's syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals. We included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing's disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing's disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data. This meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing's disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.

Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners.

PubMed

Roman, Cortnee; Menning, Kara

2017-10-01

This review discusses the role of the nurse practitioner (NP) in evaluating the clinical effects, potential side effects, and monitoring requirements for treatment options in multiple sclerosis (MS) and provides guidance on how to help patients understand these issues. A literature search was conducted on PubMed to identify publications on monitoring and disease management of MS patients. Additional resources included drug information web sites and package inserts. NPs play an active role in the management of MS patients via effective monitoring and communication throughout the patient's treatment regimen and disease course. In the shared decision-making model of MS treatment, NPs ensure that patients understand the implications of their disease-modifying therapies (DMTs). As patients move through treatments during the course of their disease, the importance of this role increases, and it is critical that NPs follow the guidelines in each medication's product label and take into account any potential lingering effects of prior medications. It is critical for NPs to promote patient adherence, to ensure that patients understand treatment side effects and monitoring requirements, and to take sequencing and reversibility implications of DMTs into account when making clinical decisions. ©2017 American Association of Nurse Practitioners.

A Study to Determine if Pharmaceutical Cost is Related to Diagnostic Complexity for the Treatment of Essential Hypertension Patients at Womack Army Community Hospital

DTIC Science & Technology

1987-05-01

angiotensin without actually measuring sodium electrolyte levels), and pancreatic disease (to remove potential confounding effects of diabetes ...side effects such as muscle weakness, polyuria and an increased propensity toward cardiac arrhythmias. When uric acid (UA) levels increase to 6.0 mg per

Toxicities of topical ophthalmic anesthetics.

PubMed

McGee, Hall T; Fraunfelder, F W

2007-11-01

Topical ocular anesthesia has been part of ophthalmology for more than a century. The most commonly used drugs today are proparacaine, tetracaine, benoxinate (oxybuprocaine) cocaine and lidocaine. Although generally well tolerated, all these can be toxic, particularly when abused. The most common toxicities are to the ocular surface, but abuse can cause deep corneal infiltrates, ulceration and even perforation. Fortunately, systemic side effects are rare. Cocaine is unique for its higher incidence of systemic side effects and high abuse potential, both of which impede its clinical use. When used appropriately, all these drugs are remarkably safe. They are generally not prescribed for home use, as prolonged abuse of these drugs can be expected to result in serious complications.

Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons

PubMed Central

Ohta, Toshio; Ikemi, Yuki; Murakami, Matsuka; Imagawa, Toshiaki; Otsuguro, Ken-ichi; Ito, Shigeo

2006-01-01

5-Hydroxytryptamine (5-HT) is one of the major chemical mediators released in injured and inflamed tissue and is capable of inducing hyperalgesia in vivo. However, the cellular mechanisms of 5-HT-induced hyperalgesia remain unclear. Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive receptors. In the present study, we determined whether 5-HT changes TRPV1 functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal rats, using Ca2+ imaging and whole-cell patch-clamp techniques. In more than 70% of DRG neurons, 5-HT potentiated the increases of [Ca2+]i induced by capsaicin, protons and noxious heat. Capsaicin-induced current and depolarizing responses, and proton-induced currents were also augmented by 5-HT. RT-PCR analysis revealed the expression of 5-HT2A and 5-HT7 receptors in rat DRG neurons. Agonists for 5-HT2A and 5-HT7 receptors mimicked the potentiating effect of 5-HT, and their antagonists decreased it. In DRG ipsilateral to the complete Freund's adjuvant-injected inflammation side, expression levels of 5-HT2A and 5-HT7 mRNAs increased, and the potentiating effect of 5-HT was more prominent than in the contralateral control side. These results suggest that the PKC- and PKA-mediated signalling pathways are involved in the potentiating effect of 5-HT on TRPV1 functions through the activation of 5-HT2A and 5-HT7 receptors, respectively. Under inflammatory conditions, the increases of the biosynthesis of these 5-HT receptors may lead to further potentiation of TRPV1 functions, resulting in the generation of inflammatory hyperalgesia in vivo. PMID:16901936

A K(+)/H (+) P-ATPase transport in the accessory cell membrane of the blowfly taste chemosensilla sustains the transepithelial potential.

PubMed

Sollai, Giorgia; Solari, Paolo; Masala, Carla; Liscia, Anna; Crnjar, Roberto

2008-11-01

An electrogenic K(+) transport in the tormogen cell of insect chemosensilla is involved in the generation and maintenance of the transepithelial potential (TEP). To gain more information about the K(+) transport system underlying the TEP generation and the location of its components in the plasma membrane of the tormogen cell, we studied the effects of inhibitors of K(+)/H(+) P-ATPase (bafilomycin A1, omeprazole and Na-orthovanadate), of K(+)/Cl(-) co-transport (bumetanide), of Cl(-) channels (NPPB) and of a K(+) channel blocker (BaCl(2)). The relationship between TEP amplitude and spike firing activity was also studied. Experiments were performed on the labellar chemosensilla of the blowfly Protophormia terraenovae using a modified tip-recording technique. Results show that: (a) K(+)/H(+) P-ATPase inhibitors significantly decrease the TEP, when properly applied to the labellum for 20 min, so as to reach the basolateral side of the plasma membrane, while no effect was detected when applied to the apical side, (b) bumetanide, NPPB and BaCl(2) decrease the TEP value only when administered to the apical side, (c) spike activity is positively correlated with the TEP. A model is proposed of the active and passive K(+) transports sustaining the TEP associated with the blowfly chemosensilla.

Junk-Time Junkies: An Emerging Addiction among Students.

ERIC Educational Resources Information Center

Soper, W. Barlow; Miller, Mark J.

1983-01-01

Discusses video games as an emerging addiction among students. Describes the appeal of the games, their impact on students, and measures passed in some cities to curb adolescent involvement. Counselors must be prepared to anticipate and ameliorate potentially negative side effects. (JAC)

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

Drug side effect extraction from clinical narratives of psychiatry and psychology patients

PubMed Central

Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

2011-01-01

Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Practical Insight to Monitor Home NIV in COPD Patients.

PubMed

Arnal, Jean-Michel; Texereau, Joëlle; Garnero, Aude

2017-08-01

Home noninvasive ventilation (NIV) is used in COPD patients with concomitant chronic hypercapnic respiratory failure in order to correct nocturnal hypoventilation and improve sleep quality, quality of life, and survival. Monitoring of home NIV is needed to assess the effectiveness of ventilation and adherence to therapy, resolve potential adverse effects, reinforce patient knowledge, provide maintenance of the equipment, and readjust the ventilator settings according to the changing condition of the patient. Clinical monitoring is very informative. Anamnesis focuses on the improvement of nocturnal hypoventilation symptoms, sleep quality, and side effects of NIV. Side effects are major cause of intolerance. Screening side effects leads to modification of interface, gas humidification, or ventilator settings. Home care providers maintain ventilator and interface and educate patients for correct use. However, patient's education should be supervised by specialized clinicians. Blood gas measurement shows a significant decrease in PaCO 2 when NIV is efficient. Analysis of ventilator data is very useful to assess daily use, unintentional leaks, upper airway obstruction, and patient ventilator synchrony. Nocturnal oximetry and capnography are additional monitoring tools to assess the impact of NIV on gas exchanges. In the near future, telemonitoring will reinforce and change the organization of home NIV for COPD patients.

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.

PubMed

Kuo, Hsiou-Ting; Liu, Shing-Lung; Chiu, Wen-Chieh; Fang, Chun-Jen; Chang, Hsien-Chen; Wang, Wei-Ren; Yang, Po-An; Li, Jhe-Hao; Huang, Shing-Jong; Huang, Shou-Ling; Cheng, Richard P

2015-05-01

β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.

How gender and boat-side affect shape characteristics of force-angle profiles in single sculling: Insights from functional data analysis.

PubMed

Warmenhoven, John; Cobley, Stephen; Draper, Conny; Harrison, Andrew; Bargary, Norma; Smith, Richard

2018-05-01

To examine whether gender or side of the boat influenced shape characteristics of the force-angle profile in on-water single sculling. Cross-sectional study design. Bivariate functional principal components analysis (bfPCA) was applied to force-angle data to identify the main modes of variance in curves of forty highly skilled male and female rowers (national and international level), rowing at 32 strokes per minute in a single scull boat. Separate discriminant function analyses for each side of the boat showed strong classification of rowers for gender. Force application close to (or closely around) the perpendicular oar position was demonstrated to be different between genders. A mixed ANOVA exploring gender, boat side and their interaction revealed that bow and stroke side forces were also statistically different from each other independently of gender. A main effect, independent of side of the boat, was also present for gender and no interaction was found between gender and boat side. Bow side forces seemingly acted as a driver of power and peak force production, while stroke side forces may have acted as a mediator of propulsive forces with an additional potential role in steering due to known asymmetrical offsets in boat rigging. Results demonstrate that propulsive force differences according to gender and boat-side are evident and must be acknowledged and accounted for before force-angle graphs are explored relative to performance measures. Copyright © 2017. Published by Elsevier Ltd.

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Modeling occupants in far-side impacts.

PubMed

Douglas, Clay; Fildes, Brian; Gibson, Tom

2011-10-01

Far-side impacts are not part of any regulated NCAP, FMVSS, or similar test regime despite accounting for 43 percent of the seriously injured persons and 30 percent of the harm in U.S. side impact crashes. Furthermore, injuries to the head and thorax account for over half of the serious injuries sustained by occupants in far-side crashes. Despite this, there is no regulated or well-accepted anthropomorphic test device (ATD) or computer model available to investigate far-side impacts. As such, this presents an opportunity to assess a computer model that can be used to measure the effect of varying restraint parameters on occupant biomechanics in far-side impacts. This study sets out to demonstrate the modified TASS human facet model's (MOTHMO) capabilities in modeling whole-body response in far-side impacts. MOTHMO's dynamic response was compared to that of postmortem human subjects (PMHS), WorldSID, and Thor-NT in a series of far-side sled tests. The advantages, disadvantages, and differences of using MOTHMO compared to ATDs were highlighted and described in terms of model design and instrumentation. Potential applications and improvements for MOTHMO were also recommended. The results showed that MOTHMO is capable of replicating the seat belt-to-shoulder complex interaction, pelvis impacts, head displacement, neck and shoulder belt loading from inboard mounted belts, and impacts from multiple directions. Overall, the model performed better than Thor-NT and at least as well as WorldSID when compared to PMHS results. Though WorldSID and Thor-NT ATDs were capable of reproducing many of these impact loads, measuring the seat belt-to-shoulder complex interaction and thoracic deflection at multiple sites and directions was less accurately handled. This study demonstrated that MOTHMO is capable of modeling whole-body response in far-side impacts. Furthermore, MOTHMO can be used as a virtual design tool to explore the effect of varying restraint parameters on occupant kinematics in far-side crash configurations.

Current and Potential Tree Locations in Tree Line Ecotone of Changbai Mountains, Northeast China: The Controlling Effects of Topography

PubMed Central

Zong, Shengwei; Wu, Zhengfang; Xu, Jiawei; Li, Ming; Gao, Xiaofeng; He, Hongshi; Du, Haibo; Wang, Lei

2014-01-01

Tree line ecotone in the Changbai Mountains has undergone large changes in the past decades. Tree locations show variations on the four sides of the mountains, especially on the northern and western sides, which has not been fully explained. Previous studies attributed such variations to the variations in temperature. However, in this study, we hypothesized that topographic controls were responsible for causing the variations in the tree locations in tree line ecotone of the Changbai Mountains. To test the hypothesis, we used IKONOS images and WorldView-1 image to identify the tree locations and developed a logistic regression model using topographical variables to identify the dominant controls of the tree locations. The results showed that aspect, wetness, and slope were dominant controls for tree locations on western side of the mountains, whereas altitude, SPI, and aspect were the dominant factors on northern side. The upmost altitude a tree can currently reach was 2140 m asl on the northern side and 2060 m asl on western side. The model predicted results showed that habitats above the current tree line on the both sides were available for trees. Tree recruitments under the current tree line may take advantage of the available habitats at higher elevations based on the current tree location. Our research confirmed the controlling effects of topography on the tree locations in the tree line ecotone of Changbai Mountains and suggested that it was essential to assess the tree response to topography in the research of tree line ecotone. PMID:25170918

Current and potential tree locations in tree line ecotone of Changbai Mountains, Northeast China: the controlling effects of topography.

PubMed

Zong, Shengwei; Wu, Zhengfang; Xu, Jiawei; Li, Ming; Gao, Xiaofeng; He, Hongshi; Du, Haibo; Wang, Lei

2014-01-01

Tree line ecotone in the Changbai Mountains has undergone large changes in the past decades. Tree locations show variations on the four sides of the mountains, especially on the northern and western sides, which has not been fully explained. Previous studies attributed such variations to the variations in temperature. However, in this study, we hypothesized that topographic controls were responsible for causing the variations in the tree locations in tree line ecotone of the Changbai Mountains. To test the hypothesis, we used IKONOS images and WorldView-1 image to identify the tree locations and developed a logistic regression model using topographical variables to identify the dominant controls of the tree locations. The results showed that aspect, wetness, and slope were dominant controls for tree locations on western side of the mountains, whereas altitude, SPI, and aspect were the dominant factors on northern side. The upmost altitude a tree can currently reach was 2140 m asl on the northern side and 2060 m asl on western side. The model predicted results showed that habitats above the current tree line on the both sides were available for trees. Tree recruitments under the current tree line may take advantage of the available habitats at higher elevations based on the current tree location. Our research confirmed the controlling effects of topography on the tree locations in the tree line ecotone of Changbai Mountains and suggested that it was essential to assess the tree response to topography in the research of tree line ecotone.

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

Bioterrorism and the nervous system.

PubMed

Han, M H; Zunt, J R

2003-11-01

Recent events of war, terrorist attacks, and mail-borne anthrax exposure have produced increasing awareness of potential bioterrorism attacks in the United States and other parts of the world. Physicians and healthcare personnel play a key role in identifying potential bioterrorist attacks. Early recognition and preparedness for bioterrorism-associated illnesses is especially important for neurologists because most bioterrorism agents can directly or indirectly affect the nervous system. This article reviews the neurologic manifestations, diagnosis, and treatments of syndromes caused by potential bioterrorism agents, as well as the potential side effects of vaccines against some of these agents.

Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

PubMed Central

Abbasi, Sana; Paul, Arghya; Shao, Wei; Prakash, Satya

2012-01-01

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs. PMID:22187654

Photosensitivity: a current biological overview.

PubMed

Elkeeb, Dena; Elkeeb, Laila; Maibach, Howard

2012-12-01

The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects. To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U.S Food and Drug Administration and the European Union regulatory agencies). We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.

Ruxolitinib-conjugated gold nanoparticles for topical administration: An alternative for treating alopecia?

PubMed

Boca, Sanda; Berce, Cristian; Jurj, Ancuta; Petrushev, Bobe; Pop, Laura; Gafencu, Grigore-Aristide; Selicean, Sonia; Moisoiu, Vlad; Temian, Daiana; Micu, Wilhelm-Thomas; Astilean, Simion; Braicu, Cornelia; Tomuleasa, Ciprian; Berindan-Neagoe, Ioana

2017-11-01

Alopecia is a dermatological condition for which Janus kinase (JAK) inhibitors have recently emerged as potential therapy options, but with limited practical use because of the systemic side effects. The topical use of Ruxolitinib in alopecia universalis has been demonstrated, but little is known about the pharmacodynamics and pharmacokinetics of this way of administration. Nanomedicine provides improved therapeutics. In the current paper we present preliminary data regarding the potential use of Ruxolitinib-conjugated gold nanoparticles (GNPs) in dermatological conditions, as GNPs have been proven to have a reduced absorption rate into the systemic blood flow for cutaneous administration. Internalization of the newly formed bioconjugate was assessed by electron microscopy and the functional effects of the drug were investigated by cell counting, flow cytometry and western blotting. Our data show that gold nanoparticles conjugated with Ruxolitinib inhibit the proliferation of fibroblasts by inhibiting JAK2 protein. Ruxolitinib carried by gold nanoparticles alters the proliferation of human fibroblasts, which is of great clinical importance as it can be readily administered on the skin with minimal risk of systemic side effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

PubMed Central

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. PMID:29491719

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

PubMed

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca; Setia, Sajita

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.

How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review.

PubMed

Breccia, Massimo; Molica, Matteo; Alimena, Giuliana

2014-12-01

Tyrosine kinase inhibitors (TKIs) advent has deeply changed the outcome of chronic myeloid leukemia (CML) patients, with improved rates of response and overall survival. However, for this success some patients paid the price of a number of peculiar side effects, the so-called off-target side effects, specific for each one TKI. These effects are due to non-selective inhibition of other tyrosine kinase receptors, such as PDGFR, c-KIT, Src, VEGF. Consequences of this inhibition, some metabolic changes during the treatment with TKIs are reported. Aim of present review is to report metabolic changes and potential mechanisms involved in the pathogenesis related to imatinib, second (nilotinib and dasatinib) and third generation (bosutinib and ponatinib) TKIs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis

PubMed Central

Rummel-Kluge, Christine; Komossa, Katja; Schwarz, Sandra; Hunger, Heike; Schmid, Franziska; Lobos, Claudia Asenjo; Kissling, Werner; Davis, John M; Leucht, Stefan

2010-01-01

Objective The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine. Method We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis. Results We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine. Conclusions Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient. PMID:20692814

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

Chemosensitization as a Means to Augment Commercial Antifungal Agents

PubMed Central

Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

2012-01-01

Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance. PMID:22393330

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

PubMed

Mandhane, Sanjay N; Shah, Jigar H; Bahekar, Prashant C; Mehetre, Sameer V; Pawar, Chandrashekhar A; Bagad, Ashish S; Chidrewar, Gajanan U; Rao, Chitturi Trinadha; Rajamannar, Thennati

2010-01-01

The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Using marine reserves to manage impact of bottom trawl fisheries requires consideration of benthic food-web interactions.

PubMed

van Denderen, P Daniël; Rijnsdorp, Adriaan D; van Kooten, Tobias

2016-10-01

Marine protected areas (MPAs) are widely used to protect exploited fish species as well as to conserve marine habitats and their biodiversity. They have also become a popular management tool for bottom trawl fisheries, a common fishing technique on continental shelves worldwide. The effects of bottom trawling go far beyond the impact on target species, as trawls also affect other components of the benthic ecosystem and the seabed itself. This means that for bottom trawl fisheries, MPAs can potentially be used not only to conserve target species but also to reduce impact of these side effects of the fishery. However, predicting the protective effects of MPAs is complicated because the side effects of trawling potentially alter the food-web interactions between target and non-target species. These changes in predatory and competitive interactions among fish and benthic invertebrates may have important ramifications for MPAs as tools to manage or mitigate the effects of bottom trawling. Yet, in current theory regarding the functioning of MPAs in relation to bottom trawl fisheries, such predatory and competitive interactions between species are generally not taken into account. In this study, we discuss how food-web interactions that are potentially affected by bottom trawling may alter the effectiveness of MPAs to protect (1) biodiversity and marine habitats, (2) fish populations, (3) fisheries yield, and (4) trophic structure of the community. We make the case that in order to be applicable for bottom trawl fisheries, guidelines for the implementation of MPAs must consider their potential food-web effects, at the risk of failing management. © 2016 by the Ecological Society of America.

76 FR 46337 - Self-Regulatory Organizations; NASDAQ OMX BX; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... limit on the same side of the market.\\13\\ This has, in light of the huge run-up in SPY option trading... will be beneficial to large market makers (which generally have the greatest potential and actual...

Antidiabetic potential of some less commonly used plants in traditional medicinal systems of India and Nigeria

PubMed Central

Mohammed, Abubakar; Kumar, Dileep; Rizvi, Syed Ibrahim

2015-01-01

The incidence of diabetes mellitus continue to rise annually all over the world with India and Nigeria having recorded cases of 65.1 and 3.9 million respectively in 2013 and expected to increase by a large amount in 2035. Hyperglycemia is a pre-condition for the development of diabetic complications and is accompanied by an increase in the production of free radicals. The present available treatment option for diabetes like sulfonylurea, metformin and alpha-glucosidase are restricted by their limited actions, secondary failure rates, and side-effects; and unaffordable to the majority of the population. Hence, the need to screen for more medicinal plants with antidiabetic ability due to the fact that plants are; biodegradable, safe and cheap with fewer side-effects. In this review article, we have presented the current status of diabetes in India and Nigeria and the role of some less commonly used medicinal plants from both countries that have antidiabetic potential. PMID:26401390

Could cannabidiol be used as an alternative to antipsychotics?

PubMed

Fakhoury, Marc

2016-09-01

Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Global facilitation of attended features is obligatory and restricts divided attention.

PubMed

Andersen, Søren K; Hillyard, Steven A; Müller, Matthias M

2013-11-13

In many common situations such as driving an automobile it is advantageous to attend concurrently to events at different locations (e.g., the car in front, the pedestrian to the side). While spatial attention can be divided effectively between separate locations, studies investigating attention to nonspatial features have often reported a "global effect", whereby items having the attended feature may be preferentially processed throughout the entire visual field. These findings suggest that spatial and feature-based attention may at times act in direct opposition: spatially divided foci of attention cannot be truly independent if feature attention is spatially global and thereby affects all foci equally. In two experiments, human observers attended concurrently to one of two overlapping fields of dots of different colors presented in both the left and right visual fields. When the same color or two different colors were attended on the two sides, deviant targets were detected accurately, and visual-cortical potentials elicited by attended dots were enhanced. However, when the attended color on one side matched the ignored color on the opposite side, attentional modulation of cortical potentials was abolished. This loss of feature selectivity could be attributed to enhanced processing of unattended items that shared the color of the attended items in the opposite field. Thus, while it is possible to attend to two different colors at the same time, this ability is fundamentally constrained by spatially global feature enhancement in early visual-cortical areas, which is obligatory and persists even when it explicitly conflicts with task demands.

Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.

PubMed

Gur, Serap; Kadowitz, Philip J; Hellstrom, Wayne Jg

2013-01-01

Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown. The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available. Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.

The mental cost of cognitive enhancement.

PubMed

Iuculano, Teresa; Cohen Kadosh, Roi

2013-03-06

Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

Screening and characterization of selected drugs having antibacterial potential.

PubMed

Javed, Hina; Tabassum, Sobia; Erum, Shazia; Murtaza, Iram; Muhammad, Aish; Amin, Farhana; Nisar, Muhammad Farrukh

2018-05-01

Due to ever increasing antibiotic resistance offered by pathogenic bacterial strains and side effects of synthetic antibiotics, thereof, there is a need to explore the effective phytochemicals from natural resources. In order to help overcoming the problem of effective natural drug and the side effects posed by the use of the synthetic drugs, five different plants namely Thymus vulgaris, Lavandula angustifolia, Rosmarinus officinalis, Cymbopogon citratus and Achillea millefolium were selected to study their antibacterial potential. Antibacterial activity and minimum inhibitory concentration (MIC) checked against the selected bacterial strains. As compared to other test plants, ethanolic extract of Rosmarinus officinalis leaves showed the most promising inhibitory effect i.e: inhibition zone (18.17± 0.44mm) against Klebsiella pneumoniae and the lowest inhibition (15.5±0.29mm) against Pseudomonas aeruginosa and Escherichia coli (p<0.05). The MIC values were recorded in the range of 1 to 20mg/ml. Screening of the selected extracts for the test plants additionally indicate some unique variations. Results were further confirmed through TLC for alkaloids and terpenoids (15% sulphuric acid and Dragedroff's reagent) in ethanolic extract. Characterization of Rosmarinus officinalis of ethanolic extract was carried out using column chromatography. The appearance of orange crystals may indicate the presence of alkaloidal bioactive compounds which need to be further investigated. The tested plants may have a potential for fighting against some infectious diseases caused by selected human pathogenic bacterial strains. This knowledge may incite a gateway to effective drug search and so on.

Side Effect Perceptions and Their Impact on Treatment Decisions in Women.

PubMed

Waters, Erika A; Pachur, Thorsten; Colditz, Graham A

2017-04-01

Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.

2016-01-01

Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

PubMed

Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S

2016-10-25

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

PubMed

Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

2017-06-01

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Unilateral ultra-brief pulse electroconvulsive therapy for depression in Parkinson's disease.

PubMed

Williams, N R; Bentzley, B S; Sahlem, G L; Pannu, J; Korte, J E; Revuelta, G; Short, E B; George, M S

2017-04-01

Electroconvulsive therapy (ECT) has demonstrated efficacy in treating core symptoms of Parkinson's disease (PD); however, widespread use of ECT in PD has been limited due to concern over cognitive burden. We investigated the use of a newer ECT technology known to have fewer cognitive side effects (right unilateral [RUL] ultra-brief pulse [UBP]) for the treatment of medically refractory psychiatric dysfunction in PD. This open-label pilot study included 6 patients who were assessed in the motoric, cognitive, and neuropsychiatric domains prior to and after RUL UBP ECT. Primary endpoints were changes in total score on the HAM-D-17 and GDS-30 rating scales. Patients were found to improve in motoric and psychiatric domains following RUL UBP ECT without cognitive side effects, both immediately following ECT and at 1-month follow-up. This study demonstrates that RUL UBP ECT is safe, feasible, and potentially efficacious in treating multiple domains of PD, including motor and mood, without clear cognitive side effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modafinil as a potential motion sickness countermeasure.

PubMed

Hoyt, Robert E; Lawson, Benton D; McGee, Heather A; Strompolis, Melissa L; McClellan, Molly A

2009-08-01

Motion sickness adversely affects military air and sea operations. Medications help prevent motion sickness but are frequently associated with side effects. Better medications or combinations of medications are needed. Dextroamphetamine has documented anti-motion sickness effects but also has a potential for abuse. Modafinil is a relatively new central nervous system stimulant that has none of the drawbacks of dextroamphetamine, but has not been evaluated for the treatment of motion sickness. This double-blind, placebo-controlled study evaluated the anti-motion sickness efficacy of modafinil, alone or in combination with oral scopolamine. Moderate nausea was induced via a Coriolis cross-coupling stimulus. There were 60 participants who were assigned randomly to 1 of 3 conditions: 1) 2 placebo pills (DP); 2) modafinil plus placebo (MP); or 3) modafinil plus oral scopolamine (MS). The primary measure of drug efficacy was the number of head tilts tolerated upon reaching moderate nausea for 1 min without abatement. The combination of modafinil and scopolamine (MS) allowed subjects to tolerate significantly more head tilts than placebo, but modafinil alone (MP) failed to differ significantly from placebo (DP). No significant cognitive performance decrements were observed among the three experimental conditions. Modafinil was not found to be more effective than placebo. Further testing is recommended to determine whether the potentially promising combination of modafinil and scopolamine provides better efficacy or fewer side effects than scopolamine administered alone.

Hypoglycaemia: an overview.

PubMed

Graveling, Alex J; Frier, Brian M

2009-08-01

Hypoglycaemia is a frequent side-effect of treatment with insulin and sulfonylureas for people with diabetes, threatening potentially serious morbidity and preventing optimal glycaemic control. Fear of hypoglycaemia and development of syndromes such as impaired awareness and counterregulatory deficiency provide additional hazards for intensification of treatment. Rapid lowering of HbA1c may be potentially dangerous in type 2 diabetes because of the adverse cardiovascular effects induced by hypoglycaemia. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and recreational pursuits. Measures to reduce the risk of hypoglycaemia are labour-intensive and require substantial resources.

Towards demand-side solutions for mitigating climate change

NASA Astrophysics Data System (ADS)

Creutzig, Felix; Roy, Joyashree; Lamb, William F.; Azevedo, Inês M. L.; Bruine de Bruin, Wändi; Dalkmann, Holger; Edelenbosch, Oreane Y.; Geels, Frank W.; Grubler, Arnulf; Hepburn, Cameron; Hertwich, Edgar G.; Khosla, Radhika; Mattauch, Linus; Minx, Jan C.; Ramakrishnan, Anjali; Rao, Narasimha D.; Steinberger, Julia K.; Tavoni, Massimo; Ürge-Vorsatz, Diana; Weber, Elke U.

2018-04-01

Research on climate change mitigation tends to focus on supply-side technology solutions. A better understanding of demand-side solutions is missing. We propose a transdisciplinary approach to identify demand-side climate solutions, investigate their mitigation potential, detail policy measures and assess their implications for well-being.

Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.

PubMed

Bertrand, Helene; Kyriazis, Marylene; Reeves, K Dean; Lyftogt, John; Rabago, David

2015-11-01

Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Randomized, placebo-controlled, double-blind clinical trial. Outpatient pain clinic. Twenty-five adults with pain-free lips. Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001). Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis.

PubMed

Reich, Michael; Mackensen, Friederike

2015-11-01

The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular toxoplasmosis. Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be justified in patients with a high risk of recurrence because of antibiotic's potential side-effects. Therefore, predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic prophylaxis is most appropriate are reviewed. Finally, a patient-individualized treatment recommendation is summarized. In the current literature, two prospective, randomized case-control studies exist, which show the protective effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the immune status of the host and the patient's age. Therefore, an antibiotic prophylaxis should be considered for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly patients and patients with a compromised immune system. This should be discussed with each patient individually, especially if the lesion is close to the macula.

Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.

PubMed

Müller, Thomas

2013-08-01

Recent experimental and clinical research has shown that A2A adenosine receptor antagonism can bring about an improvement in the motor behavior of patients with Parkinson's disease. Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity. In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline. Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential. A2A adenosine receptor antagonists are efficacious in combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects. Future research on A2A adenosine receptor antagonism should consider compounds like istradefylline as l-dopa and/or dopamine agonist-sparing treatment alternatives, since their clinical handling, safety and side-effect profile are superior to l-dopa and/or dopamine agonists. The current focus to demonstrate a specific dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in clinical trials is risky, since the presentation of dyskinesia varies on a day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. The demonstration of an antidyskinetic effect may convince authorities, but this is far less relevant in clinical practice as patients generally better tolerate dyskinesia than other phenomena and dopaminergic side effects.

The impact of polypharmacy on the health of Canadian seniors.

PubMed

Reason, Ben; Terner, Michael; Moses McKeag, Ali; Tipper, Brenda; Webster, Greg

2012-08-01

Prescription medication use increases with age. Seniors face an increased risk of adverse drug reactions from medications, partly because the kidneys and liver can lose functional ability with increasing age, resulting in the need for changes in dosage. To use population survey data to understand the extent and impact of multiple medication use and adverse drug events among Canadian seniors. This study consists of analysis of data from the Canadian Survey of Experiences with Primary Health Care, which was conducted through telephone by Statistics Canada in 2008. These analyses focussed on the 3132 respondents who were ≥ 65 years of age. Twenty-seven per cent of seniors reported taking five or more medications on a regular basis. Within the past year, 12% of seniors taking five or more medications experienced a side effect that required medical attention compared with 5% of seniors taking only one or two medications. Even when controlling for age and number of chronic conditions, the number of prescription medications was associated with the rate of emergency department use. Less than half of all seniors reported having received medication reviews and having the possible side effects of their prescription medications explained to them by their physician. Many Canadian seniors have an elevated risk of adverse events due to taking a high number of prescription medications and not having the potential side effects and drug interactions explained to them. There are interventions that can potentially reduce polypharmacy and adverse events, including routine medication reviews.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Systematic Review and Meta-Analysis of Brief Versus Ultrabrief Right Unilateral Electroconvulsive Therapy for Depression.

PubMed

Tor, Phern-Chern; Bautovich, Alison; Wang, Min-Jung; Martin, Donel; Harvey, Samuel B; Loo, Colleen

2015-09-01

Electroconvulsive therapy (ECT) is an effective depression treatment, but it has potential cognitive side effects. Ultrabrief pulse (UBP) right unilateral (RUL) ECT is an increasingly used treatment option that can potentially combine efficacy with lesser cognitive side effects. However, current trials are underpowered or have conflicting results. A systematic review and meta-analysis was conducted to evaluate the relative efficacy and cognitive effects of brief pulse (BP) and UBP RUL ECT. MEDLINE, EMBASE, PsycINFO, CENTRAL, DARE, and the International Clinical Trials Registry Platform were searched with the search terms ECT, electroconvulsive therapy, electroconvulsive shock, electroconvulsive shock therapy, electrical stimulation, electroconvulsive combined with brief, ultra*, pulse, and trial in English, all fields including title, abstract, subject heading, and full text up to June 20, 2013, for studies comparing BP and UBP RUL ECT in depressed patients that reported formalized mood ratings for depression. Six studies met the inclusion criteria, comprising a total of 689 patients. Efficacy, cognitive, response, and remission outcomes were extracted from each publication or obtained directly from authors. BP RUL ECT was significantly more efficacious in treating depression than UBP RUL ECT (standardized mean difference = 0.25; 95% CI, 0.08–0.41; P = .004) but showed significantly more cognitive side effects in all cognitive domains examined (global cognition, anterograde learning and recall, retrograde memory) (P < .01). The mean number of treatment sessions given was 8.7 for BP ECT and 9.6 for UBP ECT (P < .001). UBP had a lower remission rate (OR = 0.71; 95% CI, 0.51–0.99; P = .045), with a number needed to treat of 12.1. BP compared with UBP RUL ECT was slightly more efficacious in treating depression and required fewer treatment sessions, but led to greater cognitive side effects. The decision of whether to use BP or UBP RUL ECT should be made on an individual patient basis and should be based on a careful weighing of the relative priorities of efficacy versus minimization of cognitive impairment.

Homeostasis in leaf water potentials on leeward and windward sides of desert shrub crowns: water loss control vs. high hydraulic efficiency.

PubMed

Iogna, Patricia A; Bucci, Sandra J; Scholz, Fabián G; Goldstein, Guillermo

2013-11-01

Phenotypic plasticity in morphophysiological leaf traits in response to wind was studied in two dominant shrub species of the Patagonian steppe, used as model systems for understanding effects of high wind speed on leaf water relations and hydraulic properties of small woody plants. Morpho-anatomical traits, hydraulic conductance and conductivity and water relations in leaves of wind-exposed and protected crown sides were examined during the summer with nearly continuous high winds. Although exposed sides of the crowns were subjected to higher wind speeds and air saturation deficits than the protected sides, leaves throughout the crown had similar minimum leaf water potential (ΨL). The two species were able to maintain homeostasis in minimum ΨL using different physiological mechanisms. Berberis microphylla avoided a decrease in the minimum ΨL in the exposed side of the crown by reducing water loss by stomatal control, loss of cell turgor and low epidermal conductance. Colliguaja integerrima increased leaf water transport efficiency to maintain transpiration rates without increasing the driving force for water loss in the wind-exposed crown side. Leaf physiological changes within the crown help to prevent the decrease of minimum ΨL and thus contribute to the maintenance of homeostasis, assuring the hydraulic integrity of the plant under unfavorable conditions. The responses of leaf traits that contribute to mechanical resistance (leaf mass per area and thickness) differed from those of large physiological traits by exhibiting low phenotypic plasticity. The results of this study help us to understand the unique properties of shrubs which have different hydraulic architecture compared to trees.

RU-486: Abortion Controversy in U.S. Clouds Future of Promising Drug.

ERIC Educational Resources Information Center

Baum, Rudy M.

1991-01-01

Reviewed is the debate over research and approval of the use of this drug in the United States. Potential benefits and side effects of the drug are discussed. The points of view of several government officials, scientists, and social activists are presented. (CW)

The Sidebar Computer Program, a seismic-shaking intensity meter: users' manual and software description

USGS Publications Warehouse

Evans, John R.

2003-01-01

The SideBar computer program provides a visual display of seismic shaking intensity as recorded at one specific seismograph. This software allows a user to tap into the seismic data recorded on that specific seismograph and to display the overall level of shaking at the single location where that seismograph resides (usually the same place the user is). From this shaking level, SideBar also estimates the potential for damage nearby. SideBar cannot tell you the “Richter magnitude” of the earthquake (see box), only how hard the ground shook locally and this estimate of how much damage is likely in the neighborhood. This combination of local effects is called the “seismic intensity”. SideBar runs on a standard desktop or laptop PC, and is intended for the media, schools, emergency responders, and any other group hosting a seismograph and who want to know immediately after an earthquake the levels of shaking measured by that instrument. These local values can be used to inform the public and help initiate appropriate local emergency response activities in the minutes between the earthquake and availability of the broader coverage provided by the USGS over the Web, notably by ShakeMap. For example, for instruments installed in schools, the level of shaking and likely damage at the school could immediately be Web broadcast and parents could quickly determine the likely safety of their children—their biggest postearthquake concern. Also, in the event of a Web outage, SideBar may be a continuing primary source of local emergency response information for some additional minutes. Specifically, SideBar interprets the peak level of acceleration (that is, the force of shaking, as a percentage of the force of gravity) as well as the peak velocity, or highest speed, at which the ground moves. Using these two basic measurements, SideBar computes what is called Instrumental Intensity—a close approximation of the Modified Mercalli Intensity scale, or “MMI” (using the Wald et al., 1999a, relationships between acceleration, velocity, and shaking intensity). Intensity is a measure of local shaking strength and the potential for damage—of how bad the earthquake effects were locally. The intensity level is what SideBar displays most prominently on the PC monitor. Intensity is shown as a large, colored bar that gets taller and changes color up a rainbow from blues toward reds as the shaking level increases. As opposed to earthquake magnitudes, which are reported as decimal values (like “7.6”), intensity is traditionally given as a Roman numeral, with “I” to “X+” assigned to levels of potential damage and perceived shaking strength. For good measure, SideBar shows the actual values of the force of shaking (peak ground acceleration as a percentage of gravity) and the speed of ground motion (peak ground velocity in inches per second, by default, or in centimeters per second, if you wish), both these values as decimal numbers. SideBar also remembers the most recent earthquakes (for up to one week), and can store as many of these previous earthquakes as the user allows (and as the user’s PC has room for)—typically thousands. SideBar also remembers forever the three largest earthquakes it has seen and all earthquakes over intensity IV so that one never loses particularly important events.

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report [ISRCTN98074661

PubMed Central

Hutchins, Andrea M; McIver, Imogene E; Johnston, Carol S

2005-01-01

Background Isoflavones are gaining popularity as alternatives to hormone replacement therapy. However, few guidelines exist to inform the public as to an appropriate dose. This case involves a postmenopausal woman who experienced a hypertensive crisis while consuming a high-dose isoflavone supplement as part of a research protocol. Case Presentation The participant was part of a placebo-controlled crossover trial to investigate the potential synergism of the antioxidant activity of soy isoflavones and vitamin C. Upon entry into the study, this healthy, well-nourished, normotensive postmenopausal woman (51 years old), consumed the first of four randomly assigned treatments (500 mg vitamin C plus 5 mg/kg body weight soy isoflavones). During this treatment, the participant's systolic blood pressure spiked to a recorded 226/117 mmHg, necessitating medical intervention and discontinuation of study participation. Two plausible mechanisms for this hypertensive crisis are discussed. Conclusion Due to the availability and increasing popularity of soy supplements, practitioners should be aware of the potential side effects associated with their use. Practitioners counseling clients who are consuming soy isoflavone supplements should advise them that elevated blood pressure may be a potential side-effect to consider and monitor. PMID:15975148

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

PubMed

Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo

2017-09-01

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

PubMed

Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

2017-09-01

People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

PubMed

Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

2017-02-01

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.

PubMed

McDonald, William M

2016-12-01

There is increasing evidence for the efficacy of neuromodulation in the treatment of resistant mood disorders and emerging data supporting the use of neuromodulation in cognitive disorders. A significant minority of depressed elders do not respond to pharmacotherapy and/or psychotherapy. This has led clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in the treatment of medication-resistant or life-threatening geriatric depression. Multiple studies have supported the safety and efficacy of ECT in the elderly, yet ECT is associated with side effects including cardiovascular and cognitive side effects. Neuromodulation therapies have the potential for providing effective treatment for treatment-resistant older adults with reduced side effects and this review will outline the risks and benefits of neuromodulation treatment in geriatric psychiatry. There is also emerging evidence of the efficacy of neuromodulation devices in the treatment of cognitive disorders. Pharmacotherapy has been largely ineffective in changing the course of neurodegenerative diseases causing dementia and other treatments are clearly needed. This review will outline the available evidence for neuromodulation in the treatment of mood and cognitive disorders in the elderly. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Comparing the effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in the treatment of depression: a systematic review and meta-analysis.

PubMed

Micallef-Trigona, Beppe

2014-01-01

Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the "gold standard" treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.

Implicit memory for novel figure-ground displays includes a history of cross-border competition.

PubMed

Peterson, Mary A; Lampignano, Daniel W

2003-08-01

When configural cues specify that a figure lies on opposite sides of a repeated border in prime andprobe shapes, probe latencies are longer than when prime and probe borders are unrelated. Do such results reflect negative priming for the shape of the prime ground or cross-border competition from figure memory? The present study tested these alternatives by adding partial closure as a competing cue and reducing the similarity between the prime ground and the shape of the probe. Results supported the cross-border competition interpretation. Additional findings were that partial closure is a configural cue and that response effects can emerge from the potential shape on the ground side of a border. One prior experience was sufficient for these effects.

Adenosine-Associated Delivery Systems

PubMed Central

Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

2016-01-01

Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

Painful nipple hyperkeratosis secondary to vemurafenib.

PubMed

Carr, Emily S; Brown, Shannon C; Fiala, Katherine H

2017-05-01

Vemurafenib is a selected BRAF kinase inhibitor approved for treating metastatic or unresectable melanoma, which has numerous cutaneous side effects unfortunately, including three previously reported cases of asymptomatic areola and/or nipple hyperkeratosis. We present the first case of painful bilateral nipple hyperkeratosis secondary to vemurafenib in an 84-year-old woman. She was successfully treated with tretinoin 0.05% cream that allowed her to comfortably continue treatment. With increased awareness of this condition, we found a second case of asymptomatic nipple hyperkeratosis secondary to vemurafenib in our clinic. As this medication gains acceptance for treatment of metastatic melanoma, it is imperative that dermatologists are aware of this potentially uncomfortable side effect that can result in decreased compliance and impaired quality of life. © 2017 Wiley Periodicals, Inc.

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen

2008-01-01

Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712

Continuous prostaglandin-F 2 infusion for middle-trimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1973-05-26

Induction of midtrimester abortion with a continuous intravenous infusion of prostaglandin (PG) was described by Karim and Filshie and Roth-Brandel et al. in 1970, but the effective dose of PGF2alpha was associated with side effects severely limiting clinical usefulness. Karim and Sharma induced abortion by intravaginal PG, but again this route also seemed complicated by severe side effects. Independent reports followed of successful induction of midtrimester abortion by intraamniotic PGF2alpha and PGE2 with few side effects. Although we also successfully induced abortion in 20 patients with a single intraamniotic instillation of 40 mg PGF2alpha, there is a potential hazard in this method; i.e., PG may leak from the amniotic cavity around the catheter and pass in large quantity into the systemic circulation, resulting in undesirable, severe side effects. A more reasonable and effective method would be to inject the PGF2alpha directly at the target organ, the myometrium, by extraovular administration. Side effects could thus be minimized and effective doses of PG reduced. Such intrauterine extraovular administration of PG has been reported. The incidence of side effects was greatly reduced, although the instillation of PG was required every 1-3 hours and there were some incomplete abortions. The investigation of extraovular PGF2alpha administration for induction of abortion in gestations between 12 and 16 weeks has been especially interesting. The procedure outlined by Wiqvist and Bygdeman and Embrey and Hillier was the 1 that the authors followed initially. 250 mcg PGF2alpha was instilled initially and was followed by 750 mcg in 5 minutes and 1 mg in 30 minutes. 1 mg was then instilled at 6 hour intervals. However, the failure rate with this dosage schedule was quite high. There was a good initial uterine response, but during the administrationsat 12, 18, and 24 hours, the response diminished considerably . The frequency of administration was then increased to every 2-3 hours and the amount instilled was increased to 2-3 mg. Although somewhat more successful than the original dose schedule, this method was also unsatisfactory. It appeared from our results that the closer the injections, the higher the success rate. Thus, a brief case report is presented using continuous extraovular administration of PGF2alpha with a Harvard pump, and the results indicate it is quite satisfactory. The patients complained of very little pain and side effects have been slight. The mean abortion time for 15 patients was 14 hours. The mean time for multiparas, 11.7 hours, was faster than the 15.8 hours for primiparas.

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors.

PubMed

Osio, A; Mateus, C; Soria, J-C; Massard, C; Malka, D; Boige, V; Besse, B; Robert, C

2009-09-01

Acute and subacute cutaneous side-effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. Much less is known about the chronic cutaneous effects of these drugs and about their potential psychosocial impact on patients. We performed a retrospective study of patients treated with EGFRIs for more than 6 months. All patients had a detailed dermatological examination. The primary cancer, associated chemotherapies, skin treatment, evolution of skin symptoms and their impact on quality of life (QoL) as evaluated by the Dermatology Life Quality Index (DLQI) were noted. Seven men and nine women were identified. The mean length of EGFRI treatment was 10 months (range 6-27). At the time of examination, all patients (100%) had cutaneous side-effects. Grade I or II folliculitis was found in 37.5% of the patients. Additional skin manifestations were xerosis (100%), mucositis (69%), hair abnormalities (87.5%), eyelash trichomegaly (62.5%), facial hypertrichosis (56%), painful paronychia (56%) and onycholysis (44%). Dose reduction or EGFRI discontinuation for skin toxicity were needed in six patients (37.5%). DLQI evaluation showed a moderate to strong impact on QoL in four patients (25%). Cutaneous side-effects are found in 100% of patients treated with EGFRIs for more than 6 months and have a significant effect on patients' QoL. The clinical spectrum of skin manifestation varies over time. As the use of EGFRIs rapidly increases, it is critical for us to improve our knowledge in the understanding and managment of these skin manifestations.

Epilepsy and recommendations for breastfeeding.

PubMed

Veiby, Gyri; Bjørk, Marte; Engelsen, Bernt A; Gilhus, Nils Erik

2015-05-01

The objective of this paper is to provide a synopsis of benefits and potential harmful effects of exposure to antiepileptic drugs (AEDs) via breastmilk, and present recommendations for breastfeeding in women with epilepsy. The article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, the LactMed database, and the authors' clinical experience. Breastfeeding is associated with benefits for the infant, including nutrition, protection against infectious and immunological disease, and promotion of development and psychological attachment. Exposure to AEDs via breastmilk could potentially produce side effects or negatively affect development. Most studies on AED transfer through breastmilk report infant serum levels well below the limit of an expected pharmacological effect. Some drugs have the potential to reach significant serum levels in breastfed infants, such as barbiturates, benzodiazepines, lamotrigine, and ethosuximide. Thus, breastfed infants should be monitored for side effects. Still, adverse symptoms are rarely reported in breastfed infants of mothers taking AEDs, and prospective studies have failed to demonstrate any negative developmental effects in children that have been exposed to AEDs via breastmilk. The nursing infant's degree of drug exposure can be minimized by breastfeeding when drug concentrations in the milk are low, reducing maternal AED dosage to prepregnancy levels, and administering mixed nutrition. Most AEDs are considered safe or moderately safe during breastfeeding. Mothers with epilepsy should be encouraged to breastfeed, provided careful monitoring of the infant. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

Pituitary-directed medical therapy in Cushing's disease.

PubMed

Petersenn, Stephan; Fleseriu, Maria

2015-04-01

Transsphenoidal surgery remains the first line therapy in Cushing's disease, but a large number of patients will not be cured or disease will recur over time. Repeat pituitary surgery, bilateral adrenalectomy, and radiation have limitations with respect to efficacy and/or side effects. Therefore, there is a clear need for an effective medical treatment. The studies reviewed here suggest a role for pituitary-directed therapies, applying multireceptor ligand somatostatin analogs like pasireotide or second-generation dopamine agonists. Retinoic acid has been also studied in a small prospective study. These compounds target ACTH-secretion at the pituitary level and possibly inhibit corticotrope proliferation. Specific side effects of these compounds need to be considered, especially when used as long-term therapy. These novel approaches could provide options for treatment of patients in whom surgery has failed or is not possible, and while awaiting effects of radiation therapy. Preoperative use to decrease cortisol excess, potentially reducing perioperative complications, needs to be further studied.

Apparatus for sensing patterns of electrical field variations across a surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, William L.; Devine, Roderick A. B.

An array of nonvolatile field effect transistors used to sense electric potential variations. The transistors owe their nonvolatility to the movement of protons within the oxide layer that occurs only in response to an externally applied electric potential between the gate on one side of the oxide and the source/drain on the other side. The position of the protons within the oxide layer either creates or destroys a conducting channel in the adjacent source/channel/drain layer below it, the current in the channel being measured as the state of the nonvolatile memory. The protons can also be moved by potentials createdmore » by other instrumentalities, such as charges on fingerprints or styluses above the gates, pressure on a piezoelectric layer above the gates, light shining upon a photoconductive layer above the gates. The invention allows sensing of fingerprints, handwriting, and optical images, which are converted into digitized images thereof in a nonvolatile format.« less

Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant Use in Young Adults.

PubMed

Smith, Tess E; Martel, Michelle M; DeSantis, Alan D

2017-03-21

Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.

Seizures as a Potential Complication of Treatment With Simeprevir and Sofosbuvir.

PubMed

Syal, Gaurav; Heldenbrand, Seth D; Duarte-Rojo, Andres

2016-01-01

Newer direct-acting antiviral agents have revolutionized the medical management of chronic hepatitis C. In addition to being extremely efficacious, they report very mild adverse drug reactions from experience in clinical trials. However, because they are relatively new on the horizon, postmarketing surveillance studies refining the safety profile are not yet available. We present a case of seizures as a potential side effect of antiviral therapy with sofosbuvir and simeprevir.

A Teacher's Guide to Using Extinction in School Settings

ERIC Educational Resources Information Center

Burt, Jonathan L.; Pennington, Robert C.

2017-01-01

The use of extinction procedures or the discontinuation of reinforcement following a behavior targeted for reduction is often used to enhance the efficacy of behavioral interventions. Unfortunately, the application of extinction procedures is associated with several side effects that can produce potentially harmful and counterproductive outcomes.…

21 CFR 312.53 - Selecting investigators and monitors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... only investigators qualified by training and experience as appropriate experts to investigate the drug... review and approval of the study(ies); (vi) A commitment by the investigator that he or she: (a) Will... potential risks and side effects of the drug; and (g) Will ensure that all associates, colleagues, and...

The Purposeful Use of Technology.

ERIC Educational Resources Information Center

Asfeldt, Morten; Hvenegaard, Glen

2003-01-01

Equipment use in outdoor education is secondary to having clear goals and sound pedagogy. Examples from the authors' 21-day canoe expeditions to the Canadian tundra illustrate how the reflection component of an outdoor program can mitigate the potential negative side effects of emerging technology. Involving the group in decisions concerning…

An orthologous transcriptional signature differentiates responses towards closely related chemicals in Arabidopsis thaliana and brassica napus

EPA Science Inventory

Herbicides are structurally diverse chemicals that inhibit plant-specific targets, however their off-target and potentially differentiating side-effects are less well defined. In this study, genome-wide expression profiling based on Affymetrix AtH1 arrays was used to identify dis...

Adolescents' Misperceptions of the Dangerousness of Acetaminophen in Overdose.

ERIC Educational Resources Information Center

Harris, Hope Elaine; Myers, Wade C.

1997-01-01

Assesses the generality and strength of nonclinical youths' (N=569) perceptions of the harmfulness and lethality of acetaminophen in overdose. Findings indicate that adolescents have ready access to acetaminophen and use it in suicide attempts but underestimate its potential for toxicity, lacking knowledge regarding side effects of overdose. (RJM)

An Update on Psychopharmacologic Medication: What Teachers, Clinicians, and Parents Need To Know.

ERIC Educational Resources Information Center

Sweeney, Dwight P.; Forness, Steven R.; Kavale, Kenneth A.; Levitt, Jennifer G.

1997-01-01

Discusses the potential uses and abuses of psychopharmacologic therapy with children or adolescents who display learning, emotional, or behavioral disorders. Explores the indications and contraindications of such therapy and enumerates the known side effects of the most frequently prescribed medications, including psychostimulants,…

Computer-assisted design in perceptual-motor skills research

NASA Technical Reports Server (NTRS)

Rogers, C. A., Jr.

1974-01-01

A categorization was made of independent variables previously found to be potent in simple perceptual-motor tasks. A computer was then used to generate hypothetical factorial designs. These were evaluated in terms of literature trends and pragmatic criteria. Potential side-effects of machine-assisted research strategy were discussed.

Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine chemotherapeutic agent.

PubMed

Podsiadlo, Paul; Sinani, Vladimir A; Bahng, Joong Hwan; Kam, Nadine Wong Shi; Lee, Jungwoo; Kotov, Nicholas A

2008-01-15

6-mercaptopurine and its riboside derivatives are some of the most widely utilized anti-leukemic and anti-inflammatory drugs. Their short biological half-life and severe side effects limit their use. A new delivery method for these drugs based on 4-5 nm gold nanoparticles can potentially resolve these issues. We have found substantial enhancement of the antiproliferative effect against K-562 leukemia cells of Au nanoparticles bearing 6-mercaptopurine-9-beta-d-ribofuranoside compared to the same drug in typically administered free form. The improvement was attributed to enhanced intracellular transport followed by the subsequent release in lysosomes. Enhanced activity and nanoparticle carriers will make possible the reduction of the overall concentration of the drug, renal clearance, and, thus, side effects. The nanoparticles with mercaptopurine also showed excellent stability over 1 year without loss of inhibitory activity.

Perceptual load in central and peripheral regions and its effects on driving performance: advertizing billboards.

PubMed

Marciano, Hadas; Yeshurun, Yaffa

2012-01-01

A broadened version of the perceptual load model was utilized to explore systematically the influence of four variables on driver's behavior: a. levels of load on the road; b. levels of load at the sides of the road; c. event's initial location (on the road vs. at the sides of the road); and d. the presence and size of advertizing billboards. 18 participants participated in two experimental sessions in a driving simulator. One of the sessions contained advertizing billboards and the other session did not. The results indicated that billboards can have a considerable effect on various aspects of driving like the time required responding to a potentially dangerous event or simply the number of accidents occurring during driving, but importantly the effect of billboards on driving was modulated by the levels of perceptual load.

New statistical potential for quality assessment of protein models and a survey of energy functions

PubMed Central

2010-01-01

Background Scoring functions, such as molecular mechanic forcefields and statistical potentials are fundamentally important tools in protein structure modeling and quality assessment. Results The performances of a number of publicly available scoring functions are compared with a statistical rigor, with an emphasis on knowledge-based potentials. We explored the effect on accuracy of alternative choices for representing interaction center types and other features of scoring functions, such as using information on solvent accessibility, on torsion angles, accounting for secondary structure preferences and side chain orientation. Partially based on the observations made, we present a novel residue based statistical potential, which employs a shuffled reference state definition and takes into account the mutual orientation of residue side chains. Atom- and residue-level statistical potentials and Linux executables to calculate the energy of a given protein proposed in this work can be downloaded from http://www.fiserlab.org/potentials. Conclusions Among the most influential terms we observed a critical role of a proper reference state definition and the benefits of including information about the microenvironment of interaction centers. Molecular mechanical potentials were also tested and found to be over-sensitive to small local imperfections in a structure, requiring unfeasible long energy relaxation before energy scores started to correlate with model quality. PMID:20226048

Distribution of leaf characteristics in relation to orientation within the canopy of woody species

NASA Astrophysics Data System (ADS)

Escudero, Alfonso; Fernández, José; Cordero, Angel; Mediavilla, Sonia

2013-04-01

Over the last few decades considerable effort has been devoted to research of leaf adaptations to environmental conditions. Many studies have reported strong differences in leaf mass per unit area (LMA) within a single tree depending on the photosynthetic photon flux density (PPFD) incident on different locations in the crown. There are fewer studies, however, of the effects of differences in the timing of light incidence during the day on different crown orientations. Leaves from isolated trees of Quercus suber and Quercus ilex in a cold Mediterranean climate were sampled to analyze differences in LMA and other leaf traits among different crown orientations. Gas-exchange rates, leaf water potentials, leaf temperatures and PPFD incident on leaf surfaces in different crown orientations were also measured throughout one entire summer day for each species. Mean daily PPFD values were similar for the leaves from the eastern and western sides of the canopy. On the western side, PPFD reached maximum values during the afternoon. Maximum leaf temperatures were approximately 10-20% higher on the west side, whereas minimum leaf water potentials were between 10 and 24% higher on the east side. Maximum transpiration rates were approximately 22% greater on the west, because of the greater leaf-to-air vapor pressure deficits (LAVPD). Mean individual leaf area was around 10% larger on the east than on the west side of the trees. In contrast, there were no significant differences in LMA between east and west sides of the crown. Contrary to our expectations, more severe water stress on the west side did not result in increases in LMA, although it was associated with lower individual leaf area. We conclude that increases in LMA measured by other authors along gradients of water stress would be due to differences in light intensity between dry and humid sites.

Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

PubMed

Mohammadian, Zahra; Sahraei, Hedayat; Meftahi, Gholam Hossein; Ali-Beik, Hengameh

2017-03-01

The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 μL/site) or CeA (0.5 μL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward. © 2016 John Wiley & Sons Australia, Ltd.

Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells.

PubMed

Cuthbert, A W; George, A M; MacVinish, L

1985-09-01

Confluent monolayers of pig renal papillary collecting tubule (RPCT) cells were formed on Millipore filters coated with collagen. They were clamped in Ussing-type chambers and used to measure short-circuit current (SCC). The monolayers had low potentials (0.1 mV) with the basolateral side positive. Small inward currents flowed under short-circuit conditions. Increases in SCC were obtained following addition of a number of agents. Receptors associated with SCC changes were disposed as follows: for kinins (e.g., lysyl-bradykinin) they were present on both sides of the tissue, while those for arginine vasopressin and norepinephrine were present on the basolateral side only. Epithelia responded to PGE2 added to the apical or basolateral face of the tissue; application to one side prevented the response from the contralateral side. The tissues also responded to forskolin, an activator of adenylate cyclase, with a sustained inward current that was sensitive to furosemide. Similar sustained inward currents were recorded following exposure to 8-bromoadenosine-3',5'-cyclic monophosphate (BrcAMP). Responses to kinins were attenuated by inhibition of fatty acid cyclooxygenase with either indomethacin or piroxicam or by replacing chloride with impermeant ions. If the SCC was first increased with forskolin, BrcAMP, or norepinephrine, the kinin effects on SCC were either abolished or reversed. It is concluded that kinin can cause chloride secretion in RPCT monolayers, possibly via a prostaglandin or a prostaglandin-adenylate cyclase mechanism. Secondary effects of kinin, exposed by first raising tissue cAMP levels, are not precluded.

Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold.

PubMed

Lim, Seng Han; Chia, Samuel Ming Yuan; Kang, Lifeng; Yap, Kevin Yi-Lwern

2016-07-01

Carbamazepine is the first-line anti-epileptic drug for focal seizures and generalized tonic-clonic seizures. Although sustained-release formulations exist, an initial burst of drug release is still present and this results in side effects. Zero-order release formulations reduce fluctuations in serum drug concentrations, thereby reducing side effects. Three-dimensional printing can potentially fabricate zero-order release formulations with complex geometries. 3D printed scaffolds with varying hole positions (side and top/bottom), number of holes (4, 8, and 12), and hole diameters (1, 1.5, and 2 mm) were designed. Dissolution tests and high performance liquid chromatography analysis were conducted. Good correlations in the linear release profiles of all carbamazepine-containing scaffolds with side holes (R(2) of at least 0.91) were observed. Increasing the hole diameters (1, 1.5, and 2 mm) resulted in increased rate of drug release in the scaffolds with 4 holes (0.0048, 0.0065, and 0.0074 mg/min) and 12 holes (0.0021, 0.0050, and 0.0092 mg/min), and the initial amount of carbamazepine released in the scaffolds with 8 holes (0.4348, 0.7246, and 1.0246 mg) and 12 holes (0.1995, 0.8598, and 1.4366 mg). The ultimate goal of this research is to improve the compliance of patients through a dosage form that provides a zero-order drug release profile for anti-epileptic drugs, so as to achieve therapeutic doses and minimize side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Orofacial and respiratory tardive dyskinesia: potential side effects of 2-dimethylaminoethanol (deanol)?

PubMed

Haug, B A; Holzgraefe, M

1991-01-01

A case of essential tremor since early adultness is presented, which has been treated successfully with the acetylcholine precursor 2-dimethylaminoethanol (deanol) for 10 years. Development of a marked dyskinesia syndrome affecting predominantly orofacial and respiratory musculature has been noticed with this medication. Partial remission after discontinuation and a favorable response to anticholinergics are suggestive of an adverse drug effect.

Prescribing methadone for pain management in end-of-life care.

PubMed

Manfredonia, John F

2005-03-01

Methadone hydrochloride is an effective, inexpensive, and relatively safe opioid to use in the treatment of patients with chronic pain. It is especially effective in management of pain during the final stages of life, as it is the only long-acting analgesic available in liquid form. However, because methadone has a long half-life, individual wide variations, and potential for accumulation and overdosage, physicians must judiciously and conscientiously prescribe it. Also, they should closely monitor patients during the titration phase and educate them with regard to basic pharmacologic properties and potential side effects. A plan to start at low doses and proceed slowly is applicable to methadone.

Light and laser treatment modalities for disseminated superficial actinic porokeratosis: a systematic review.

PubMed

Aird, Gregory A; Sitenga, Jenna L; Nguyen, Austin Huy; Vaudreuil, Adam; Huerter, Christopher J

2017-05-01

Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser and light modalities in the treatment of DSAP. A systematic review of light and laser treatment modalities was conducted to include 26 cases of patients with DSAP. Systematic review resulted in 14 articles to be included. Photodynamic therapy (PDT) overall was the least successful treatment modality, with clinical improvement seen in a minority of patients (MAL-PDT: N = 9 patients, 33.3% showed improvement; ALA-PDT: N = 3 patients, 0% improvement; hypericin-PDT: N = 2 patients, 0% improvement) after numerous post-procedural side effects of hyperpigmentation, inflammation, erythema, and discomfort. Overall, in the available reports, PDT demonstrates poor outcomes with greater incidence of side effects. The response rates of DSAP lesions treated with lasers were as follows: (Q-switched ruby lasers: N = 2, 100%; CO 2 laser: N = 1, 100%; PDT and CO 2 combination therapy: N = 2, 0-50%; erbium and neodymium YAG lasers: N = 2, 100%; fractional 1927-nm thulium fiber lasers: N = 2, 100%; Grenz rays: N = 1, 100%; and fractional photothermolysis: N = 2, 100%). The side effects of laser therapy were minimal and included mild erythema, slight hyperpigmentation, and moderate edema. Laser therapy is a promising treatment option for DSAP with an excellent side effect profile. However, higher power studies are required to determine optimal guidelines for laser treatment of DSAP.

National Rehabilitation Hospital Assistive Technology Research Center

DTIC Science & Technology

1997-11-01

Individuals to be included are those who had a recent stroke, are judged not to be at high risk for having potential medical side - effects of taking the...detecting and characterizing concussion; investigation of the cognitive effects of ginkgo on stroke patients; application and evaluation of virtual reality... effectiveness of the video game based therapy. Proposed Work and Outcomes for Year 4: For year 4, the research team proposes to complete a pilot test of a

Guidance for effective discipline. American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health.

PubMed

1998-04-01

When advising families about discipline strategies, pediatricians should use a comprehensive approach that includes consideration of the parent-child relationship, reinforcement of desired behaviors, and consequences for negative behaviors. Corporal punishment is of limited effectiveness and has potentially deleterious side effects. The American Academy of Pediatrics recommends that parents be encouraged and assisted in the development of methods other than spanking for managing undesired behavior.

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

PubMed

Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

2016-06-01

Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potentials and Risks of Collaboration: Two Sides of the Same Coin or the Same Side of the Coin? A Response to Vassiliki Papatsiba

ERIC Educational Resources Information Center

Barnett, Ronald

2013-01-01

In collaborative ventures in higher education are to be seen both potentials and risks. But how, then, is collaboration to be understood? Is it simply a matter of a point of view, with individuals focusing more on the potentials or more on the risks, depending on their dispositions? The risks and potentials of collaboration, it might be suggested,…

Conformational analysis investigation into the influence of nano-porosity of ultra-permeable ultra-selective polyimides on its diffusivity as potential membranes for use in the "green" separation of natural gases

NASA Astrophysics Data System (ADS)

Madkour, Tarek M.

2013-08-01

Nano-porous polymers of intrinsic microporosity, PIM, have exhibited excellent permeability and selectivity characteristics that could be utilized in an environmentally friendly gas separation process. A full understanding of the mechanism through which these membranes effectively and selectively allow for the permeation of specific gases will lead to further development of these membranes. Three factors obviously influenced the conformational behavior of these polymers, which are the presence of electronegative atoms, the presence of non-linearity in the polymeric backbones (backbone kinks) and the presence of bulky side groups on the polymeric chains. The dipole moment increased sharply with the presence of backbone kinks more than any other factor. Replacing the fluorine atoms with bulky alkyl groups didn't influence the dipole moment greatly indicating that the size of the side chains had much less dramatic influence on the dipole moment than having a bent backbone. Similarly, the presence of the backbone kinks in the polymeric chains influenced the polymeric chains to assume less extended configuration causing the torsional angles around the interconnecting bonds unable to cross the high potential energy barriers. The presence of the bulky side groups also caused the energy barriers of the cis-configurations to increase dramatically, which prevented the polymeric segments from experiencing full rotation about the connecting bonds. For these polymers, it was clear that the fully extended configurations are the preferred configurations in the absence of strong electronegative atoms, backbones kinks or bulky side groups. The addition of any of these factors to the polymeric structures resulted in the polymeric chains being forced to assume less extended configurations. Rather interestingly, the length or bulkiness of the side groups didn't affect the end-to-end distance distribution to a great deal since the presence of quite large bulky side chain such as the pentyl group has caused the polymeric chains to revert back to the fully extended configurations possibly due to the quite high potential energy barriers that the chains have to cross to reach the less extended configurational states.

Weighing the relative potential impacts of climate change and land-use change on an endangered bird.

PubMed

Bancroft, Betsy A; Lawler, Joshua J; Schumaker, Nathan H

2016-07-01

Climate change and land-use change are projected to be the two greatest drivers of biodiversity loss over the coming century. Land-use change has resulted in extensive habitat loss for many species. Likewise, climate change has affected many species resulting in range shifts, changes in phenology, and altered interactions. We used a spatially explicit, individual-based model to explore the effects of land-use change and climate change on a population of the endangered Red-cockaded Woodpecker (RCW; Picoides borealis). We modeled the effects of land-use change using multiple scenarios representing different spatial arrangements of new training areas for troops across Fort Benning. We used projected climate-driven changes in habitat and changes in reproductive output to explore the potential effects of climate change. We summarized potential changes in habitat based on the output of the dynamic vegetation model LPJ-GUESS, run for multiple climate change scenarios through the year 2100. We projected potential changes in reproduction based on an empirical relationship between spring precipitation and the mean number of successful fledglings produced per nest attempt. As modeled in our study, climate change had virtually no effect on the RCW population. Conversely, simulated effects of land-use change resulted in the loss of up to 28 breeding pairs by 2100. However, the simulated impacts of development depended on where the development occurred and could be completely avoided if the new training areas were placed in poor-quality habitat. Our results demonstrate the flexibility inherent in many systems that allows seemingly incompatible human land uses, such as development, and conservation actions to exist side by side.

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.

PubMed

Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven

2017-09-03

Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

PubMed Central

Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-01-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

PubMed

Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-10-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

Relationship between somatosensory event-related potential N140 aberrations and hemispatial agnosia in patients with stroke: a preliminary study.

PubMed

Ueno, Tomoyuki; Hada, Yasushi; Shimizu, Yukiyo; Yamada, Thoru

2018-06-01

The somatosensory event-related potential N140 is thought to be related to selective attention. This study aimed to compare the somatosensory event-related potential N140 in healthy subjects to that in patients with stroke to determine whether N140 and attentiveness are associated in patients with stroke with or without hemispatial agnosia. Normal somatosensory event-related potential N140 values were determined using data from ten healthy subjects. Fifteen patients with stroke were divided into two groups based on the presence of hemispatial neglect. Somatosensory event-related potential N140 components were compared between the two groups. Stimulation of the affected limb in the hemispatial agnosia group resulted in significantly longer N140 latency at the contralateral vs. the ipsilateral electrode. This was the inverse of the relationship observed in normal subjects, with stimulation of the intact side in patients with hemispatial agnosia, and with stimulation of both the intact and affected sides in patients without agnosia. In the hemispatial agnosia group, the peak latency of N140 following stimulation of the affected side was significantly longer than it was following stimulation of the intact side and when compared to that in patients without agnosia. In addition, abnormal N140 peak latencies were observed at the Cz and ipsilateral electrodes in patients with hemispatial agnosia following stimulation of the intact side. These findings suggest that somatosensory event-related potential N140 is independently generated in each hemisphere and may reflect cognitive attention.

A novel approach to surveying sturgeon using side-scan sonar and occupancy modeling

USGS Publications Warehouse

Flowers, H. Jared; Hightower, Joseph E.

2013-01-01

Technological advances represent opportunities to enhance and supplement traditional fisheries sampling approaches. One example with growing importance for fisheries research is hydroacoustic technologies such as side-scan sonar. Advantages of side-scan sonar over traditional techniques include the ability to sample large areas efficiently and the potential to survey fish without physical handling-important for species of conservation concern, such as endangered sturgeons. Our objectives were to design an efficient survey methodology for sampling Atlantic Sturgeon Acipenser oxyrinchus by using side-scan sonar and to developmethods for analyzing these data. In North Carolina and South Carolina, we surveyed six rivers thought to contain varying abundances of sturgeon by using a combination of side-scan sonar, telemetry, and video cameras (i.e., to sample jumping sturgeon). Lower reaches of each river near the saltwater-freshwater interface were surveyed on three occasions (generally successive days), and we used occupancy modeling to analyze these data.We were able to detect sturgeon in five of six rivers by using these methods. Side-scan sonar was effective in detecting sturgeon, with estimated gear-specific detection probabilities ranging from 0.2 to 0.5 and river-specific occupancy estimates (per 2-km river segment) ranging from 0.0 to 0.8. Future extensions of this occupancy modeling framework will involve the use of side-scan sonar data to assess sturgeon habitat and abundance in different river systems.

Use of an innovative T-tube maze assay and the proboscis extension response assay to assess sublethal effects of GM products and pesticides on learning capacity of the honey bee Apis mellifera L.

PubMed

Han, Peng; Niu, Chang-Ying; Lei, Chao-Liang; Cui, Jin-Jie; Desneux, Nicolas

2010-11-01

Transgenic Cry1Ac+CpTI cotton (CCRI41) is a promising cotton cultivar throughout China but side effects and especially sublethal effects of this transgenic cultivar on beneficial insects remain poorly studied. More specifically potential sublethal effects on behavioural traits of the honey bee Apis mellifera L. have not been formally assessed despite the importance of honey bees for pollination. The goal of our study was to assess potential effects of CCRI41 cotton pollen on visual and olfactory learning by honey bees. After a 7-day oral chronic exposure to honey mixed with either CCRI41 pollen, imidacloprid-treated conventional pollen (used as positive sublethal control) or conventional pollen (control), learning performance was evaluated by the classical proboscis extension reflex (PER) procedure as well as a T-tube maze test. The latter assay was designed as a new device to assess potential side effects of pesticides on visual associative learning of honey bees. These two procedures were complementary because the former focused on olfactory learning while the latter was involved in visual learning based on visual orientation ability. Oral exposure to CCRI41 pollen did not affect learning capacities of honey bees in both the T-tube maze and PER tests. However, exposure to imidacloprid resulted in reduced visual learning capacities in T-tube maze evaluation and decreased olfactory learning performances measured with PER. The implications of these results are discussed in terms of risks of transgenic CCRI41 cotton crops for honey bees.

Splenic trauma as an adverse effect of torso-protecting side airbags: biomechanical and case evidence.

PubMed

Hallman, Jason J; Brasel, Karen J; Yoganandan, Narayan; Pintar, Frank A

2009-10-01

Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis.

Splenic Trauma as an Adverse Effect of Torso-Protecting Side Airbags: Biomechanical and Case Evidence

PubMed Central

Hallman, Jason J.; Brasel, Karen J.; Yoganandan, Narayan; Pintar, Frank A.

2009-01-01

Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis. PMID:20184829

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

PubMed

Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

2013-12-01

Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Suggestibility as a predictor of response to antidepressants: A preliminary prospective trial.

PubMed

Nitzan, Uri; Chalamish, Yossi; Krieger, Israel; Erez, Hany Burstein; Braw, Yoram; Lichtenberg, Pesach

2015-10-01

The growing awareness that so many do not respond adequately to antidepressant (AD) pharmacotherapy has sparked research seeking to characterize those who do. While the pharmacological mechanisms of AD treatment have been extensively evaluated, much remains unknown about the placebo component of the response to medication. This study examined the association between suggestibility levels and response to ADs amongst depressed patients. Twenty unipolar depression outpatients, recruited before starting AD monotherapy, received clear, standardized instructions that the therapeutic effects of AD, though not side effects, would require 2-4 weeks. At baseline (T1), 1 week (T2), and 1 month (T3), participants were evaluated for depressive symptoms, using the Hamilton Rating Scale for Depression-17 items (HAM-D); for anxiety by the Hamilton Rating Scale for Anxiety (HAM-A); for side effects by the Antidepressant Side Effect Checklist (ASEC); and for suggestibility, using the Multidimensional Iowa Suggestibility Scale (MISS). High levels of baseline suggestibility were associated with less improvement in depression level and more side-effects during the first week. In accordance with our hypothesis the more suggestible patients improved more between T2 and T3. No significant correlations were found between baseline suggestibility levels and change in anxiety. Small sample size and a self-report questionnaire assessing suggestibility were limitations. This study offers a potentially new and clinically useful approach to understanding and predicting who will respond to AD treatment. Suggestibility seems to play a role, presumably by shaping expectation, in response to AD treatment. We hope that this avenue will be further explored. Copyright © 2015 Elsevier B.V. All rights reserved.

What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014.

PubMed

Visco, Anthony G; Fraser, Matthew O; Newgreen, Donald; Oelke, Matthias; Cardozo, Linda

2016-02-01

The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects. © 2016 Wiley Periodicals, Inc.

“So far it’s been choosing which side effects I want or I can deal with”: A grounded theory of HIV treatment side effects among people living with HIV

PubMed Central

Holmes, Dave

2016-01-01

Despite the availability of new antiretroviral drugs and the simplification of treatment options, side effects continue to affect people living with HIV. In this paper, we present the findings of a grounded theory study designed to gain a critical understanding of the experience of side effects. Three main categories emerged from the data: the side effects, the experience, and the connections. The first category suggests that we need to change how we think about side effects in order to take into account the context in which they are experienced as well as the types and nature of side effects. The second category puts forward the idea that the experience of side effects is composed of three interrelated processes: becoming with, living with, and dealing with. Finally, the third category points to new connections that are formed with people, things and systems in the presence of side effects. PMID:27867446

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Does transgenic Cry1Ac + CpTI cotton pollen affect hypopharyngeal gland development and midgut proteolytic enzyme activity in the honey bee Apis mellifera L. (Hymenoptera, Apidae)?

PubMed

Han, Peng; Niu, Chang-Ying; Biondi, Antonio; Desneux, Nicolas

2012-11-01

The transgenic Cry1Ac (Bt toxin) + CpTI (Cowpea Trypsin Inhibitor) cotton cultivar CCRI41 is increasingly used in China and potential side effects on the honey bee Apis mellifera L. have been documented recently. Two studies have assessed potential lethal and sublethal effects in young bees fed with CCRI41 cotton pollen but no effect was observed on learning capacities, although lower feeding activity in exposed honey bees was noted (antifeedant effect). The present study aimed at providing further insights into potential side effects of CCRI41 cotton on honey bees. Emerging honey bees were exposed to different pollen diets using no-choice feeding protocols (chronic exposure) in controlled laboratory conditions and we aimed at documenting potential mechanisms underneath the CCRI41 antifeedant effect previously reported. Activity of midgut proteolytic enzyme of young adult honey bees fed on CCRI41 cotton pollen were not significantly affected, i.e. previously observed antifeedant effect was not linked to disturbed activity of the proteolytic enzymes in bees' midgut. Hypopharyngeal gland development was assessed by quantifying total extractable proteins from the glands. Results suggested that CCRI41 cotton pollen carries no risk to hypopharyngeal gland development of young adult honey bees. In the two bioassays, honey bees exposed to 1 % soybean trypsin inhibitor were used as positive controls for both midgut proteolytic enzymes and hypopharyngeal gland proteins quantification, and bees exposed to 48 ppb (part per billion) (i.e. 48 ng g(-1)) imidacloprid were used as controls for exposure to a sublethal concentration of toxic product. The results show that the previously reported antifeedant effect of CCRI41 cotton pollen on honey bees is not linked to effects on their midgut proteolytic enzymes or on the development of their hypopharyngeal glands. The results of the study are discussed in the framework of risk assessment of transgenic crops on honey bees.

Side Effects

Cancer.gov

Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Anti-Diabetic Potential of Noni: The Yin and the Yang.

PubMed

Nerurkar, Pratibha V; Hwang, Phoebe W; Saksa, Erik

2015-09-25

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni's several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni's exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their "natural" origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation "from bench side to bedside". In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni's health benefits.

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

PubMed

Mohammad, Othman; Osser, David N

2014-01-01

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

Mesalamine-induced myopericarditis - A case report.

PubMed

Bernardo, Sónia; Fernandes, Samuel Raimundo; Araújo-Correia, Luís

2016-11-01

Myopericarditis has occasionally been reported as a side effect of mesalamine in patients with inflammatory bowel disease. We present a 20-year-old woman with ulcerative colitis admitted with chest pain. After thorough investigation she was diagnosed with myopericarditis potentially related to mesalamine. There was complete clinical and laboratorial recovery following drug withdrawal. Although uncommon, the possibility of myopericarditis should be considered in patients with inflammatory bowel disease presenting with cardiac complaints. Early recognition can avoid potential life-threatening complications.

The effect of real-time pricing on load shifting in a highly renewable power system dominated by generation from the renewable sources of wind and photovoltaics

NASA Astrophysics Data System (ADS)

Kies, Alexander; Brown, Tom; Schlachtberger, David; Schramm, Stefan

2017-04-01

The supply-demand imbalance is a major concern in the presence of large shares of highly variable renewable generation from sources like wind and photovoltaics (PV) in power systems. Other than the measures on the generation side, such as flexible backup generation or energy storage, sector coupling or demand side management are the most likely option to counter imbalances, therefore to ease the integration of renewable generation. Demand side management usually refers to load shifting, which comprises the reaction of electricity consumers to price fluctuations. In this work, we derive a novel methodology to model the interplay of load shifting and provided incentives via real-time pricing in highly renewable power systems. We use weather data to simulate generation from the renewable sources of wind and photovoltaics, as well as historical load data, split into different consumption categories, such as, heating, cooling, domestic, etc., to model a simplified power system. Together with renewable power forecast data, a simple market model and approaches to incorporate sector coupling [1] and load shifting [2,3], we model the interplay of incentives and load shifting for different scenarios (e.g., in dependency of the risk-aversion of consumers or the forecast horizon) and demonstrate the practical benefits of load shifting. First, we introduce the novel methodology and compare it with existing approaches. Secondly, we show results of numerical simulations on the effects of load shifting: It supports the integration of PV power by providing a storage, which characteristics can be described as "daily" and provides a significant amount of balancing potential. Lastly, we propose an experimental setup to obtain empirical data on end-consumer load-shifting behaviour in response to price incentives. References [1] Brown, T., Schlachtberger, D., Kies. A., Greiner, M., Sector coupling in a highly renewable European energy system, Proc. of the 15th International Workshop on Large-Scale Integration of Wind Power into Power Systems as well as on Transmission Networks for Offshore Wind Power Plants, Vienna, Austria, 15.-17. November 2016 [2] Kleinhans, D.: Towards a systematic characterization of the potential of demand side management, arXiv preprint arXiv:1401.4121, 2014 [3] Kies, A., Schyska, B. U., von Bremen, L., The Demand Side Management Potential to Balance a Highly Renewable European Power System. Energies, 9(11), 955, 2016

Transcutaneous Electrical Nerve Stimulation Effects on Neglect: A Visual-Evoked Potential Study

PubMed Central

Pitzalis, Sabrina; Spinelli, Donatella; Vallar, Giuseppe; Di Russo, Francesco

2013-01-01

We studied the effects of transcutaneous electrical nerve stimulation (TENS) in six right-brain-damaged patients with left unilateral spatial neglect (USN), using both standard clinical tests (reading, line, and letter cancelation, and line bisection), and electrophysiological measures (steady-state visual-evoked potentials, SSVEP). TENS was applied on left neck muscles for 15′, and measures were recorded before, immediately after, and 60′ after stimulation. Behavioral results showed that the stimulation temporarily improved the deficit in all patients. In cancelation tasks, omissions and performance asymmetries between the two hand-sides were reduced, as well as the rightward deviation in line bisection. Before TENS, SSVEP average latency to stimuli displayed in the left visual half-field [LVF (160 ms)] was remarkably longer than to stimuli shown in the right visual half-field [RVF (120 ms)]. Immediately after TENS, latency to LVF stimuli was 130 ms; 1 h after stimulation the effect of TENS faded, with latency returning to baseline. TENS similarly affected also the latency SSVEP of 12 healthy participants, and their line bisection performance, with effects smaller in size. The present study, first, replicates evidence concerning the positive behavioral effects of TENS on the manifestations of left USN in right-brain-damaged patients; second, it shows putatively related electrophysiological effects on the SSVEP latency. These behavioral and novel electrophysiological results are discussed in terms of specific directional effects of left somatosensory stimulation on egocentric coordinates, which in USN patients are displaced toward the side of the cerebral lesion. Showing that visual-evoked potentials latency is modulated by proprioceptive stimulation, we provide electrophysiological evidence to the effect that TENS may improve some manifestations of USN, with implications for its rehabilitation. PMID:23966919

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

... Drugs Clinical Trials Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact ... and Immunizations What is a Drug Interaction? Side Effects of HIV Medicines HIV Medicines and Side Effects ...

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

PubMed

Eschenhagen, Thomas; Force, Thomas; Ewer, Michael S; de Keulenaer, Gilles W; Suter, Thomas M; Anker, Stefan D; Avkiran, Metin; de Azambuja, Evandro; Balligand, Jean-Luc; Brutsaert, Dirk L; Condorelli, Gianluigi; Hansen, Arne; Heymans, Stephane; Hill, Joseph A; Hirsch, Emilio; Hilfiker-Kleiner, Denise; Janssens, Stefan; de Jong, Steven; Neubauer, Gitte; Pieske, Burkert; Ponikowski, Piotr; Pirmohamed, Munir; Rauchhaus, Mathias; Sawyer, Douglas; Sugden, Peter H; Wojta, Johann; Zannad, Faiez; Shah, Ajay M

2011-01-01

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

Positive allosteric modulators of the μ-opioid receptor: a novel approach for future pain medications

PubMed Central

Burford, N T; Traynor, J R; Alt, A

2015-01-01

Morphine and other agonists of the μ-opioid receptor are used clinically for acute and chronic pain relief and are considered to be the gold standard for pain medication. However, these opioids also have significant side effects, which are also mediated via activation of the μ-opioid receptor. Since the latter half of the twentieth century, researchers have sought to tease apart the mechanisms underlying analgesia, tolerance and dependence, with the hope of designing drugs with fewer side effects. These efforts have revolved around the design of orthosteric agonists with differing pharmacokinetic properties and/or selectivity profiles for the different opioid receptor types. Recently, μ-opioid receptor-positive allosteric modulators (μ-PAMs) were identified, which bind to a (allosteric) site on the μ-opioid receptor separate from the orthosteric site that binds an endogenous agonist. These allosteric modulators have little or no detectable functional activity when bound to the receptor in the absence of orthosteric agonist, but can potentiate the activity of bound orthosteric agonist, seen as an increase in apparent potency and/or efficacy of the orthosteric agonist. In this review, we describe the potential advantages that a μ-PAM approach might bring to the design of novel therapeutics for pain that may lack the side effects currently associated with opioid therapy. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24460691

Methylphenidate-induced acute orofacial and extremity dyskinesia.

PubMed

Yilmaz, Ayse Esra; Donmez, Ahsen; Orun, Emel; Tas, Tugba; Isik, Bunyamin; Sonmez, Fatma Mujgan

2013-06-01

Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors' knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug-receptor interactions via different mechanisms.

SideRack: A Cost-Effective Addition to Commercial Zebrafish Housing Systems

PubMed Central

Burg, Leonard; Gill, Ryan; Balciuniene, Jorune

2014-01-01

Abstract Commercially available aquatic housing systems provide excellent and relatively trouble-free hardware for rearing and housing juvenile as well as adult zebrafish. However, the cost of such systems is quite high and potentially prohibitive for smaller educational and research institutions. The need for tank space prompted us to experiment with various additions to our existing Aquaneering system. We also noted that high water exchange rates typical in commercial systems are suboptimal for quick growth of juvenile fish. We devised a housing system we call “SideRack,” which contains 20 large tanks with air supply and slow water circulation. It enables cost-effective expansion of existing fish facility, with a key additional benefit of increased growth and maturation rates of juvenile fish. PMID:24611601

A case of generalized bromhidrosis following whole-body depilatory laser.

PubMed

Helou, Josiane; Haber, Roger; Kechichian, Elio; Tomb, Roland

2015-01-01

Laser treatment is a widespread method for hair removal. Despite its very common use, side effects remain relatively rare and transient. Axillary hyperhidrosis and bromhidrosis have already been reported in the literature after depilatory lasers. We report here a novel side effect of total body bromhidrosis following hair removal laser. A 27-year-old man, phototype 3 underwent four sessions of total body depilatory laser, combining pulsed alexandrite and pulsed diode lasers. A few days afterwards, a generalized foul odor was noted and was resistant to regular deodorants and Aluminum chloride based antiperspirants. Possible mechanisms include the activation of dormant bacteria in the skin flora, sweat gland dysfunction, altered skin flora, sweat gland hormone receptor disturbances, and genetic factors. Total body bromhidrosis and hyperhidrosis are potential complications of total body laser hair removal.

IPS Empress crown system: three-year clinical trial results.

PubMed

Sorensen, J A; Choi, C; Fanuscu, M I; Mito, W T

1998-02-01

The IPS Empress system is a highly esthetic hot pressed glass ceramic material for fabrication of single crowns. Adhesive cementation of the system not only contributes to the esthetics but is necessary for increased strength of the crown. The purpose of this prospective clinical trials was to evaluate the longevity of 75 adhesively cemented Empress full crowns. An additional aim was to assess the adhesive cementation methodology and potential side effects. At the three-year point, one molar crown fractured for a 1.3 percent failure rate. The resin cementation technique that was employed exhibited a low incidence of microleakage with few clinical side effects. There was a 5.6 percent incidence of post-cementation sensitivity, with all symptoms subsiding by eight weeks. None of the crowns in the study required endodontic therapy.

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

PubMed Central

BANERJI, JULIAN

2015-01-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

PubMed

Banerji, Julian

2015-09-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

Immigration and earnings inequality in America's new small-town destinations.

PubMed

Hyde, Allen; Pais, Jeremy; Wallace, Michael

2015-01-01

Research on the relationship between immigrant population concentration and earnings inequality is divided between two perspectives. Supply-side arguments maintain that areas attracting large numbers of immigrants experience minimal wage growth at the bottom of the earnings distribution, which increases local levels of earnings inequality. Demand-side arguments contend that industrial restructuring reduces the pay of manual labor regardless of, and even prior to, the arrival of foreign-born workers. Adjudicating between these two perspectives is hindered by issues of potential endogeneity, which confound attempts to independently assess the effects of immigration on inequality or vice versa using OLS regression. We consider a third perspective called the reciprocal effects hypothesis which contends that immigrant concentration and earnings inequality emerge together through a mutually reinforcing feedback process. We explore this question in America's "new small-town destinations" using data from U.S. micropolitan statistical areas. We use three-stage least squares estimation to address the endogeneity problem and to test these three hypotheses. While we find support for both the supply- and demand-side perspectives, the results are best explained by the reciprocal effects hypothesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Suspected side effects of doxycycline use in dogs - a retrospective study of 386 cases.

PubMed

Schulz, B S; Hupfauer, S; Ammer, H; Sauter-Louis, C; Hartmann, K

2011-08-27

This study investigated doxycycline-related side effects in a large population of dogs. Data from 386 dogs that had received doxycycline for the treatment of various infectious diseases were analysed retrospectively. Potential side effects that developed during treatment were documented, and correlations with signalment, dose, duration of treatment, frequency of application, doxycycline preparation and use of additional drugs were investigated. Vomiting was reported in 18.3 per cent of dogs, 7.0 per cent developed diarrhoea and 2.5 per cent developed anorexia. While being treated with doxycycline, 39.4 per cent of dogs showed an increase in alanine aminotransferase (ALT) activity and 36.4 per cent showed an increase in alkaline phosphatase (ALP) activity. There was a dose-related risk of an increase in ALP activity (P=0.011, odds ratio [OR]=1.27, 95 per cent confidence interval [CI] 1.06 to 1.53), and older dogs treated with doxycycline were more likely to develop an increase in ALT activity (P=0.038, OR=1.23, 95 per cent CI 1.01 to 1.50) and vomiting (P=0.017, OR=1.11, 95 per cent CI 1.02 to 1.21).

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

The first report of gynandromorphy in termites (Isoptera; Kalotermitidae; Neotermes koshunensis).

PubMed

Miyaguni, Yasushi; Nozaki, Tomonari; Yashiro, Toshihisa

2017-08-01

This is the first report of gynandromorphy in Isoptera. An Asian dry-wood termite, Neotermes koshunensis (Shiraki) [Kalotermitidae], possessing both male and female phenotypic characteristics, was found on Okinawa Island, Japan. This deformed individual showed morphological and anatomical hermaphroditism in the abdomen. The right side of the seventh sternite was the female form and contained an ovary, while the left side was the male form and contained a testis. Genotypic analysis revealed that this individual was a genotypic bilateral chimera. These results suggested that the termite was a bilateral gynandromorph with a male left side and a female right side. As reported previously in other insects, double fertilization (by two sperms, one with an X and one with a Y chromosome) of a binucleate egg is the most likely mechanism that generated this genotypic bilateral chimera. N. koshunensis has the ability to reproduce through parthenogenesis, in which the secondary polar body is likely to be used for nuclear phase recovery. If the second polar body in this mechanism has high fertility and healthy embryogenic potential, like an egg nucleus, some of gynandromorphs might be produced by a side effect of parthenogenetic ability.

The first report of gynandromorphy in termites (Isoptera; Kalotermitidae; Neotermes koshunensis)

NASA Astrophysics Data System (ADS)

Miyaguni, Yasushi; Nozaki, Tomonari; Yashiro, Toshihisa

2017-08-01

This is the first report of gynandromorphy in Isoptera. An Asian dry-wood termite, Neotermes koshunensis (Shiraki) [Kalotermitidae], possessing both male and female phenotypic characteristics, was found on Okinawa Island, Japan. This deformed individual showed morphological and anatomical hermaphroditism in the abdomen. The right side of the seventh sternite was the female form and contained an ovary, while the left side was the male form and contained a testis. Genotypic analysis revealed that this individual was a genotypic bilateral chimera. These results suggested that the termite was a bilateral gynandromorph with a male left side and a female right side. As reported previously in other insects, double fertilization (by two sperms, one with an X and one with a Y chromosome) of a binucleate egg is the most likely mechanism that generated this genotypic bilateral chimera. N. koshunensis has the ability to reproduce through parthenogenesis, in which the secondary polar body is likely to be used for nuclear phase recovery. If the second polar body in this mechanism has high fertility and healthy embryogenic potential, like an egg nucleus, some of gynandromorphs might be produced by a side effect of parthenogenetic ability.

Neratinib Approved for HER2+ Breast Cancer.

PubMed

2017-09-01

The FDA approved the tyrosine kinase inhibitor neratinib for extended adjuvant treatment of early-stage HER2-positive breast cancer. The decision adds another treatment option to help prevent recurrence, but its relatively small potential benefit must be weighed against the risk of serious side effects. ©2017 American Association for Cancer Research.

Special Educators' Knowledge regarding Psychotropic Interventions for Students with Emotional and Behavioral Disorders

ERIC Educational Resources Information Center

Ryan, Joseph B.; Reid, Robert; Ellis, Cynthia

2008-01-01

The use of psychotropic interventions to manage the inappropriate behaviors displayed by students with emotional and behavior disorders has become more common over the past several decades. The efficacious use of these medications requires monitoring students for desired behavioral outcomes as well as potential side effects. Educators are in an…

76 FR 77895 - Schedules of Controlled Substances: Placement of Ezogabine Into Schedule V

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... ester, is a new chemical substance with central nervous system depressant properties and is classified... nervous system as an anticonvulsant and the potential side effects of the drug therein, warrant closer... the central nervous system is alone not enough to merit its inclusion into Schedule IV of the CSA, nor...

Student and Teacher Perception of Disciplinary Practices: Types, Reasons, Consequences and Alternatives

ERIC Educational Resources Information Center

Mumthas, N. S.; Munavvir, Jouhar; Abdul Gafoor, K.

2014-01-01

Inculcating self-discipline is important for systematic pursuit of learning, development of interest and potential in the child. Punishments involve employing a noxious or painful stimulus that generates a variety of problems and negative side effects to the child. Corporal punishments severely affect the human dignity of children. This study…

Psychotropic Drug Use among College Students: Patterns of Use, Misuse, and Medical Monitoring

ERIC Educational Resources Information Center

Oberleitner, Lindsay M. S.; Tzilos, Golfo K.; Zumberg, Kathryn M.; Grekin, Emily R.

2011-01-01

Objective: To assess whether college students who use psychotropic drugs are (1) aware of potential side effects, (2) appropriately monitored by prescribing physicians, and (3) taking medications as prescribed. Participants: Fifty-five college students, currently taking psychotropic medications, were recruited between Summer 2008 and Fall 2009.…

Learning Abroad or Just Going Abroad? International Education in Opposite Sides of the Border

ERIC Educational Resources Information Center

Ramírez, Gerardo Blanco

2013-01-01

International education, particularly through study abroad experiences, has the potential of preparing students for a globally interconnected world. While challenging, it is necessary to translate aspirations of global citizenship into educational programs and assessing their effectiveness. A necessary step in such process consists in taking a…

A program of data synthesis from the ALSEP/CPLEE ALSEP/SIDE, and Explorer 35 magnetometer to investigate lunar terminator and nightside particle fluxes and surface interactions

NASA Technical Reports Server (NTRS)

Reasoner, D. L.

1976-01-01

Lunar nightside electron fluxes were studied with the aid of the ALSEP/CPLEE and other instruments. The flux events were shown to be due to (a) electrons propagating upstream from the earth's bow shock, (b) electrons thermalized and scattered to the lunar surface by disturbances along the boundary of the lunar solarwind cavity, and (c) solar wind electrons scattered to the lunar surface by lunar limb shocks and/or compressional disturbances. These electrons were identified as a cause of the high night surface negative potentials observed in tha ALSEP/SIDE ion data. A study was also made of the shadowing of magnetotail plasma sheet electrons by interactions between the lunar body and the ambient magnetic field and by interactions between charged particles and lunar remnant magnetic fields. These shadowing effects were shown to modify lunar surface and near-lunar potential distributions.

Quantum solution for the one-dimensional Coulomb problem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nunez-Yepez, H. N.; Salas-Brito, A. L.; Solis, Didier A.

2011-06-15

The one-dimensional hydrogen atom has been a much studied system with a wide range of applications. Since the pioneering work of Loudon [R. Loudon, Am. J. Phys. 27, 649 (1959).], a number of different features related to the nature of the eigenfunctions have been found. However, many of the claims made throughout the years in this regard are not correct--such as the existence of only odd eigenstates or of an infinite binding-energy ground state. We explicitly show that the one-dimensional hydrogen atom does not admit a ground state of infinite binding energy and that the one-dimensional Coulomb potential is notmore » its own supersymmetric partner. Furthermore, we argue that at the root of many such false claims lies the omission of a superselection rule that effectively separates the right side from the left side of the singularity of the Coulomb potential.« less

Neutron-deuteron analyzing power data at En=22.5 MeV

NASA Astrophysics Data System (ADS)

Weisel, G. J.; Tornow, W.; Crowell, A. S.; Esterline, J. H.; Hale, G. M.; Howell, C. R.; O'Malley, P. D.; Tompkins, J. R.; Witała, H.

2014-05-01

We present measurements of n-d analyzing power, Ay(θ), at En=22.5 MeV. The experiment uses a shielded neutron source which produced polarized neutrons via the 2H(d⃗,n⃗)3He reaction. It also uses a deuterated liquid-scintillator center detector and six pairs of liquid-scintillator neutron side detectors. Elastic neutron scattering events are identified by using time-of-flight techniques and by setting a window in the center detector pulse-height spectrum. The beam polarization is monitored by using a high-pressure helium gas cell and an additional pair of liquid-scintillator side detectors. The n-d Ay(θ) data were corrected for finite-geometry and multiple-scattering effects using a Monte Carlo simulation of the experiment. The 22.5-MeV data demonstrate that the three-nucleon analyzing power puzzle also exists at this energy. They show a significant discrepancy with predictions of high-precision nucleon-nucleon potentials alone or combined with Tucscon-Melbourne or Urbana IX three-nucleon forces, as well as currently available effective-field theory based potentials of next-to-next-to-next-to-leading order.

Upper gastrointestinal bleeding in a patient with depression receiving selective serotonin reuptake inhibitor therapy.

PubMed

Kumar, Deepak; Saaraswat, Tanuj; Sengupta, S N; Mehrotra, Saurabh

2009-02-01

Serotonin plays an important role in the normal clotting phenomenon and is released by platelets. Platelets are dependent on a serotonin transporter for the uptake of serotonin, as they cannot synthesize it themselves. Selective serotonin reuptake inhibitors (SSRIs) block the uptake of serotonin into platelets and can cause problems with clotting leading to bleeding. This case report highlights the occurrence of upper gastrointestinal bleeding in the index case on initiating SSRI therapy for depression and the prompt resolution of the same on its discontinuation on two separate occasions. SSRIs may cause upper gastrointestinal (GI) bleeding. Physicians should be aware of the same and should try to rule out previous episodes of upper GI bleed or the presence of other risk factors which might predispose to it before prescribing SSRIs; they should also warn the patients about this potential side effect. Also, the presence of thalassemia trait in the index patient deserves special attention and needs to be explored to see if it might in any way contribute in potentiating this side effect of SSRIs.

Latest advances in novel cannabinoid CB2 ligands for drug abuse and their therapeutic potential

PubMed Central

Yang, Peng; Wang, Lirong; Xie, Xiang-Qun

2012-01-01

The field of cannabinoid (CB) drug research is experiencing a challenge as the CB1 antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB2 drugs without CB1 psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB1 receptor was discovered predominantly in the brain, whereas the CB2 is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB2 receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB2 neurons activity remains controversial, the CB2 receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB2 ligands from the literature as well as patents. PMID:22300098

Effectiveness of Citrus Fruits on Helicobacter pylori

PubMed Central

2017-01-01

It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies. PMID:28408943

Safety of stable isotope use.

PubMed

Koletzko, B; Sauerwald, T; Demmelmair, H

1997-08-01

The increased employment of stable isotope tracers for diagnostic and research purposes frequently raises questions on potential risks associated with their use, which is of particular importance in the paediatric age group. Biological effects and the potential of adverse events has been evaluated in a large number of animal and, in part, also human studies. Possible differences in physical, chemical and biochemical behaviour resulting in kinetic and thermodynamic isotope effects between stable isotopes of the same element are related to the relative differences in atomic weight. Deuterium (2H), which differs markedly in mass from the predominant hydrogen isotope 1H, may induce serious side-effects at high concentrations in body fluids. The threshold dose for the occurrence of side-effects lies well above the usual tracer dosages for clinical use. In contrast to deuterium, heavier stable isotopes such as 13C, 15N or 18O that differ relatively little in mass from the predominant isotopes such as 12C, does not show any adverse biological effects even at highest enrichments. The doses of stable isotope tracer substances that are used for clinical diagnostic and research purposes appear safe and without any adverse effects. Stable isotope tracers should only be used in children if the trace is safe at the doses applied, and tracer is chemically pure and stable. In the case of intravenous application, the tracer preparation must also be sterile and pyrogen free.

Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate.

PubMed

Gori, Tommaso; Daiber, Andreas

2009-01-01

Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate). Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced in Western countries. In light of their wide use, and of the (re)introduction of PETN in Western markets, the present review focuses on the novel effects of organic nitrates, describing their potential clinical implications and discussing differences among different compounds. We believe that these recent findings have important clinical implications. Since the side effects of organic nitrates such as nitroglycerin and isosorbides appear to be mediated by reactive oxygen species, care should be taken that drugs with antioxidant properties are co-administered. On the other hand, efforts should be made to clinically exploit the preconditioning effects of these drugs.

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Anti-diabetic and hypolipidemic effects of Sargassum yezoense in db/db mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Su-Nam, E-mail: snkim@kist.re.kr; Lee, Woojung; Bae, Gyu-Un

2012-08-10

Highlights: Black-Right-Pointing-Pointer Sargassum yezoense (SY) treatment improved glucose and lipid impairment in vivo. Black-Right-Pointing-Pointer This pharmacological action is associated with PPAR{alpha}/{gamma} dual activation. Black-Right-Pointing-Pointer It decreases the expression of G6Pase for gluconeogenesis in liver. Black-Right-Pointing-Pointer It increases the expression of UCP3 for lipid metabolism in adipose tissue. Black-Right-Pointing-Pointer There are no significant side effects such as body weight gain and hepatomegaly. -- Abstract: Peroxisome proliferator-activated receptors (PPARs) have been considered to be desirable targets for metabolic syndrome, even though their specific agonists have several side effects including body weight gain, edema and tissue failure. Previously, we have reported in vitromore » effects of Sargassum yezoense (SY) and its ingredients, sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA), on PPAR{alpha}/{gamma} dual transcriptional activation. In this study, we describe in vivo pharmacological property of SY on metabolic disorders. SY treatment significantly improved glucose and lipid impairment in db/db mice model. More importantly, there are no significant side effects such as body weight gain and hepatomegaly in SY-treated animals, indicating little side effects of SY in liver and lipid metabolism. In addition, SY led to a decrease in the expression of G6Pase for gluconeogenesis in liver responsible for lowering blood glucose level and an increase in the expression of UCP3 in adipose tissue for the reduction of total and LDL-cholesterol level. Altogether, our data suggest that SY would be a potential therapeutic agent against type 2 diabetes and related metabolic disorders by ameliorating the glucose and lipid metabolism.« less

Ziprasidone versus clozapine in the treatment of dually diagnosed (DD) patients with schizophrenia and cannabis use disorders: a randomized study.

PubMed

Schnell, Thomas; Koethe, Dagmar; Krasnianski, Anna; Gairing, Stefanie; Schnell, Knut; Daumann, Jörg; Gouzoulis-Mayfrank, Euphrosyne

2014-01-01

Clozapine is considered to be particularly effective in the treatment of dually diagnosed (DD) patients with psychosis and substance use disorders. However, its use is restricted by potentially severe side effects. The aim of the present pilot study was to compare the effects of clozapine with the newer second generation antipsychotic (SGA) ziprasidone in DD-patients. Thirty (n = 30) patients with schizophrenia and cannabis abuse/dependence were randomized to ziprasidone or clozapine and were followed up for up to 12 months. Cannabis use was reduced in both groups during follow-up. Clozapine treatment was associated with less positive symptoms of schizophrenia, more side effects and poorer compliance with treatment. Results from this small pilot RCT suggest beneficial effects of both clozapine and ziprasidone in the treatment of cannabis use disorders in psychotic patients. Larger-scale RCTs are needed in order to assess advantages and disadvantages of the different SGAs in dually diagnosed populations. © American Academy of Addiction Psychiatry.

Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study

PubMed Central

2012-01-01

Background Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. Results EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. Conclusions We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects. PMID:22452924

Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study.

PubMed

Szűcs, Dénes; Soltész, Fruzsina

2012-03-27

Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects.

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes.

PubMed

Ververis, Katherine; Rodd, Annabelle L; Tang, Michelle M; El-Osta, Assam; Karagiannis, Tom C

2011-12-01

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.

Three-terminal graphene single-electron transistor fabricated using feedback-controlled electroburning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puczkarski, Paweł; Gehring, Pascal, E-mail: pascal.gehring@materials.ox.ac.uk; Lau, Chit S.

2015-09-28

We report room-temperature Coulomb blockade in a single layer graphene three-terminal single-electron transistor fabricated using feedback-controlled electroburning. The small separation between the side gate electrode and the graphene quantum dot results in a gate coupling up to 3 times larger compared to the value found for the back gate electrode. This allows for an effective tuning between the conductive and Coulomb blocked state using a small side gate voltage of about 1 V. The technique can potentially be used in the future to fabricate all-graphene based room temperature single-electron transistors or three terminal single molecule transistors with enhanced gate coupling.

Apparatus for fabricating composite ceramic members

DOEpatents

Roy, P.; Simpson, J.L.; Aitken, E.A.

1975-10-28

Methods and apparatus for fabrication of composite ceramic members having particular application for measuring oxygen activities in liquid sodium are described. The method involves the simultaneous deposition of ThO$sub 2$: 15 percent Y$sub 2$O$sub 3$ on a sintered stabilized zirconia member by decomposition of gaseous ThCl$sub 4$ and YCl$sub 3$ and by reacting with oxygen gas. Means are provided for establishing an electrical potential gradient across the zirconia member whereby oxygen ions, from a source on one side of the member portion to be coated, are migrated to the opposite side where a reaction and said decomposition and deposition are effected.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

PubMed

Loo, Colleen; Sheehan, Patrick; Pigot, Melissa; Lyndon, William

2007-11-01

Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe.

PubMed

Desmedt, B; Courselle, P; De Beer, J O; Rogiers, V; Grosber, M; Deconinck, E; De Paepe, K

2016-06-01

Lightening skin tone is an ancient and well-documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side-effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side-effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health problems due to the presence of illegal products on the market is summarized. © 2016 European Academy of Dermatology and Venereology.

Nutraceuticals in Acute and Prophylactic Treatment of Migraine.

PubMed

Daniel, Oved; Mauskop, Alexander

2016-04-01

People who suffer from headaches often prefer nutraceutical treatment over traditional pharmacological approaches, due to fear of possible side effects, drug dependence, or addiction. Since treatment with nutraceuticals does not require a doctor's prescription, many patients rely on their own judgment as to when and which one to take, often without consultation or guidance from their physician. Some physicians could provide information about potential efficacy and side effects of various products, but many are not familiar with the nutraceuticals. Widespread skepticism persists among doctors about the effectiveness of these treatments. This is largely due to the lack of rigorous clinical studies. However, even when incontrovertible scientific evidence exists, many physicians remain distrustful of the evidence. The following review summarizes randomized controlled trials of some of the most commonly used non-pharmacological treatments, including magnesium, coenzyme Q10, riboflavin (vitamin B2), petasites, and feverfew (Table 1).

Risperidone induced angioedema with concurrent EPS symptoms: a case report and review of literature

PubMed Central

Samra, Gursharan Singh; Kant, Saumitra; Chow, Robert

2018-01-01

ABSTRACT Angioedema has recently been reported as a side effect associated with the antipsychotic risperidone. We report a case of dystonia with concurrent angioedema due to risperidone. A 40-year-old male with a history of schizophrenia was started on 3 mg of risperidone BID and developed perioral and periorbital edema along with increased muscle rigidity and hand tremor within 24 h of initial administration. His symptoms abated after cessation of risperidone and intravenous administration of corticosteroids and antihistamine. This case study adds to the current literature, which has already established angioedema as a dose-dependent side effect of risperidone. Moreover, this case study aims to increase awareness about the potential for the simultaneous occurrence of angioedema and extrapyramidal symptoms, and promotes vigilance among prescribers so that the life-threatening consequences of such effects can be avoided. PMID:29686794

Polyamines are Inhibitors of Gastric Acid Secretion

NASA Astrophysics Data System (ADS)

Ray, Tushar K.; Nandi, Jyotirmoy; Pidhorodeckyj, Nykolai; Meng-Ai, Zhou

1982-03-01

The naturally occurring organic polycations such as spermine and spermidine inhibit histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro; spermine is much more potent than spermidine. Unlike the H2 receptor antagonists, the polyamines are completely ineffective from the nutrient side and are effective only from the secretory side of the chambered mucosa. The polyamine effects could be reversed by increasing K+ concentration in the secretory solution. Studies with isolated gastric microsomal vesicles demonstrate that the polyamines do not inhibit the gastric H+,K+-ATPase but greatly decrease the ATPase-mediated uptake of H+ under appropriate conditions. For the latter effects the presence of polyamine within the vesicle interior was found to be essential. Our data strongly suggest an uncoupling of the gastric H+,K+-ATPase system by the polyamines. The therapeutic potential of these and similar compounds in the treatment of hyperacidity and peptic ulcer is discussed.

[Doping. High-tech cheating in sport].

PubMed

Striegel, H; Simon, P

2007-07-01

Today, doping is no longer limited to the classical drugs with well known effects and side effects. Older generation anabolic steroids are used mainly in fitness and recreational sports. In contrast, due to doping tests, substances used in competitive sports include peptide hormones, medications not yet approved, and even specially developed drugs, such as designer steroids. Of the peptide hormones, particularly growth hormones (human growth hormone), erythropoietin and generics, insulin, and presumably insulin-like growth factor 1 are used. Substance groups potentially relevant for doping are selective androgen receptor modulators and gene therapy drugs. For most of these, there is no knowledge about side effects in healthy individuals, and no adequate doping tests. Therefore, anti-doping measures cannot rely solely on the continual improvement of doping analyses, but should include increased measures for doping prevention. Not only sports organizations, but also governmental agencies should be involved in developing and implementing these measures.

Protection of children in forward-facing child restraint systems during oblique side impact sled tests: Intrusion and tether effects.

PubMed

Hauschild, Hans W; Humm, John R; Pintar, Frank A; Yoganandan, Narayan; Kaufman, Bruce; Kim, Jinyong; Maltese, Matthew R; Arbogast, Kristy B

2016-09-01

Testing was conducted to quantify the kinematics, potential for head impact, and influence on head injury metrics for a center-seated Q3s in a forward-facing child restraint system (FFCRS) in oblique impacts. The influences of a tether and intruded door on these measures were explored. Nine lateral oblique sled tests were conducted on a convertible forward-facing child restraint seat (FFCRS). The FFCRSs were secured to a bench seat from a popular production small SUV at the center seating position utilizing the lower anchor and tether for children (LATCH). The vehicle seat was fixed on the sled carriage at 60° and 80° from full frontal (30° and 10° forward rotation from pure lateral) providing an oblique lateral acceleration to the Q3s and FFCRS. A structure simulating an intruded door was mounted to the near (left) side of vehicle seat. The sled input acceleration was the proposed FMVSS 213 lateral pulse scaled to a 35 km/h delta-V. Tests were conducted with and without the tether attached to the FFCRS. Results indicate the influence of the tether on kinematics and injury measures in oblique side impact crashes for a center- or far-side-seated child occupant. All tests without a tether resulted in head contact with the simulated door, and 2 tests at the less oblique angle (80°) with a tether also resulted in head contact. No head-to-door contact was observed in 2 tests utilizing a tether. High-speed video analysis showed that the head moved beyond the CRS head side wings and made contact with the simulated intruded door. Head injury criterion (HIC) 15 median values were 589 without the tether vs. 332 with the tether attached. Tests utilizing a tether had less lateral head excursion than tests without a tether (median 400 vs. 442 mm). These tests demonstrate the important role of the tether in controlling head excursion for center- or far-side-seated child occupants in oblique side impact crashes and limiting the head injury potential with an intruded door. The tether may not influence the kinematics of a near-side-seated occupant as strongly where the vehicle door or side structure interacts with the CRS and influences its motion. The results indicate that there may be an opportunity to improve child head kinematics and head protection in oblique side impacts through different CRS attachment methods and/or alternative vehicle side structure protection or padding.

Motor Unit Activity during Fatiguing Isometric Muscle Contraction in Hemispheric Stroke Survivors

PubMed Central

McManus, Lara; Hu, Xiaogang; Rymer, William Z.; Suresh, Nina L.; Lowery, Madeleine M.

2017-01-01

Enhanced muscle weakness is commonly experienced following stroke and may be accompanied by increased susceptibility to fatigue. To examine the contributions of central and peripheral factors to isometric muscle fatigue in stroke survivors, this study investigates changes in motor unit (MU) mean firing rate, and action potential duration during, and directly following, a sustained submaximal fatiguing contraction at 30% maximum voluntary contraction (MVC). A series of short contractions of the first dorsal interosseous muscle were performed pre- and post-fatigue at 20% MVC, and again following a 10-min recovery period, by 12 chronic stroke survivors. Individual MU firing times were extracted using surface EMG decomposition and used to obtain the spike-triggered average MU action potential waveforms. During the sustained fatiguing contraction, the mean rate of change in firing rate across all detected MUs was greater on the affected side (-0.02 ± 0.03 Hz/s) than on the less-affected side (-0.004 ± 0.003 Hz/s, p = 0.045). The change in firing rate immediately post-fatigue was also greater on the affected side than less-affected side (-13.5 ± 20 and 0.1 ± 19%, p = 0.04). Mean MU firing rates increased following the recovery period on the less-affected side when compared to the affected side (19.3 ± 17 and 0.5 ± 20%, respectively, p = 0.03). MU action potential duration increased post-fatigue on both sides (10.3 ± 1.2 to 11.2 ± 1.3 ms on the affected side and 9.9 ± 1.7 to 11.2 ± 1.9 ms on the less-affected side, p = 0.001 and p = 0.02, respectively), and changes in action potential duration tended to be smaller in subjects with greater impairment (p = 0.04). This study presents evidence of both central and peripheral fatigue at the MU level during isometric fatiguing contraction for the first time in stroke survivors. Together, these preliminary observations indicate that the response to an isometric fatiguing contraction differs between the affected and less-affected side post-stroke, and may suggest that central mechanisms observed here as changes in firing rate are the dominant processes leading to task failure on the affected side. PMID:29225574

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Are Medications Involved in Vision and intracranial Pressure Changes Seen in Spaceflight?

NASA Technical Reports Server (NTRS)

Wotring, V. E.

2016-01-01

Some crewmembers have experienced changes in their vision after long-duration spaceflight on the ISS. These impairments include visual performance decrements, development of cotton-wool spots or choroidal folds, optic-disc edema, optic nerve sheath distention, and/or posterior globe flattening with varying degrees of severity and permanence. These changes are now used to define the visual impairment/intracranial pressure (VIIP) syndrome. The reasons for these potentially debilitating medical issues are currently unknown. The potential role of administered medications has not yet been examined, but it is known that many medications can have side effects that are similar to VIIP symptoms. Some medications raise blood pressure, which can affect intracranial pressure. Many medications that act in the central nervous system can affect intracranial pressures and/or vision. About 40% of the medications in the ISS kit are known to cause side effects involving changes in blood pressure, intracranial pressure and/or vision. For this reason, we proposed an investigation of the potential relationship between ISS medications and their risk of causing or exacerbating VIIP-like symptoms. The purpose of this study was to use medication usage records for affected and unaffected crew to determine if use of particular medications seemed to correlate with VIIP occurrence or severity.

Medications and Side Effects

MedlinePlus

... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Potential of a precrash lateral occupant movement in side collisions of (electric) minicars.

PubMed

Hierlinger, T; Lienkamp, M; Unger, J; Unselt, T

2015-01-01

In minicars, the survival space between the side structure and occupant is smaller than in conventional cars. This is an issue in side collisions. Therefore, in this article a solution is studied in which a lateral seat movement is imposed in the precrash phase. It generates a pre-acceleration and an initial velocity of the occupant, thus reducing the loads due to the side impact. The assessment of the potential is done by numerical simulations and a full-vehicle crash test. The optimal parameters of the restraint system including the precrash movement, time-to-fire of head and side airbag, etc., are found using metamodel-based optimization methods by minimizing occupant loads according to European New Car Assessment Programme (Euro NCAP). The metamodel-based optimization approach is able to tune the restraint system parameters. The numerical simulations show a significant averaged reduction of 22.3% in occupant loads. The results show that the lateral precrash occupant movement offers better occupant protection in side collisions.

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

... the clitoris. These play a major part in sexual arousal in women. Removing the vulva and the clitoris ... www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/sexuality-for-women-with-cancer.html. ...

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

The effect of mobile phone to audiologic system.

PubMed

Kerekhanjanarong, Virachai; Supiyaphun, Pakpoom; Naratricoon, Jantra; Laungpitackchumpon, Prinya

2005-09-01

Mobile phones have come into widespread use. There are a lot of possible adverse effect to health. Use of mobile phone generate potentially harmful radiofrequency electromagnetic field (EMF) particularly for the hearing aspect. 98 subjects underwent hearing evaluations at Department of Otolaryngology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University. 31 males and 67females, mean age was 30.48 +/- 9.51 years old, all subjects were investigated the hearing level by audiometry, tympanometry, otoacoustic emission (OAE) and auditory brain stem evoked response (ABR). The average of using time were 32.54 +/- 27.64 months, 57 subjects usually used the right side and 41 the left side. Average time of use per day was 26.31 +/- 30.91 minutes (range from 3 to 180 mins). When the authors compared the audiogram, both pure tone and speech audiometry, between the dominant and nondominant side, it indicated that there is no significant different. When the authors focused on the 8 subjects that used the mobile phone more than 60 mins per day. It indicated that the hearing threshold of the dominant ears was worse than the nondominant ears.

ROTAS: a rotamer-dependent, atomic statistical potential for assessment and prediction of protein structures.

PubMed

Park, Jungkap; Saitou, Kazuhiro

2014-09-18

Multibody potentials accounting for cooperative effects of molecular interactions have shown better accuracy than typical pairwise potentials. The main challenge in the development of such potentials is to find relevant structural features that characterize the tightly folded proteins. Also, the side-chains of residues adopt several specific, staggered conformations, known as rotamers within protein structures. Different molecular conformations result in different dipole moments and induce charge reorientations. However, until now modeling of the rotameric state of residues had not been incorporated into the development of multibody potentials for modeling non-bonded interactions in protein structures. In this study, we develop a new multibody statistical potential which can account for the influence of rotameric states on the specificity of atomic interactions. In this potential, named "rotamer-dependent atomic statistical potential" (ROTAS), the interaction between two atoms is specified by not only the distance and relative orientation but also by two state parameters concerning the rotameric state of the residues to which the interacting atoms belong. It was clearly found that the rotameric state is correlated to the specificity of atomic interactions. Such rotamer-dependencies are not limited to specific type or certain range of interactions. The performance of ROTAS was tested using 13 sets of decoys and was compared to those of existing atomic-level statistical potentials which incorporate orientation-dependent energy terms. The results show that ROTAS performs better than other competing potentials not only in native structure recognition, but also in best model selection and correlation coefficients between energy and model quality. A new multibody statistical potential, ROTAS accounting for the influence of rotameric states on the specificity of atomic interactions was developed and tested on decoy sets. The results show that ROTAS has improved ability to recognize native structure from decoy models compared to other potentials. The effectiveness of ROTAS may provide insightful information for the development of many applications which require accurate side-chain modeling such as protein design, mutation analysis, and docking simulation.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

PubMed

Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

2017-02-01

Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use.

PubMed

daCosta DiBonaventura, Marco; Gupta, Shaloo; Cho, Michelle; Mrus, Joseph

2012-01-01

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

Effect of hexamethonium on the vascular response to noradrenaline in man

PubMed Central

Hodge, R. L.; Whelan, R. F.

1962-01-01

Intra-arterial infusion of hexamethonium into the brachial artery had no potentiating effect on the constrictor response of the vessels of the forearm or hand to noradrenaline given by the same route. The response of the hand vessels to intravenous infusion of noradrenaline was enhanced after intra-arterial hexamethonium, but this was attributed to entry of the blocking agent into the general circulation resulting in blockade of baroreceptor reflexes since the potentiation was seen to an equal degree on both sides. It is concluded that if increased sensitivity to noradrenaline plays a part in the phenomenon of tolerance to hexamethonium this must be a slowly developing effect. PMID:13907950

[Micronutrients in oncology. Current data about vitamin D, selenium, L-carnitine and vitamin C].

PubMed

Gröber, Uwe; Mücke, Ralph; Holzhauer, Peter; Kisters, Klaus

2013-04-01

Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway.

PubMed

Sui, Yuxia; Yao, Hong; Li, Shaoguang; Jin, Long; Shi, Peiying; Li, Zhijun; Wang, Gang; Lin, Shilan; Wu, Youjia; Li, Yuxiang; Huang, Liying; Liu, Qicai; Lin, Xinhua

2017-03-01

Searching for potential anticancer agents from natural sources is an effective strategy for developing novel chemotherapeutic agents. In this study, data supporting the in vitro and in vivo anticancer effects of delicaflavone, a rarely occurring biflavonoid from Selaginella doederleinii, were reported. Delicaflavone exhibited favorable anticancer properties, as shown by the MTT assay and xenograft model of human non-small cell lung cancer in male BALB/c nude mice without observable adverse effect. By transmission electron microscopy with acridine orange and Cyto-ID®Autophagy detection dyes, Western blot analysis, and RT-PCR assay, we confirmed that delicaflavone induces autophagic cell death by increasing the ratio of LC3-II to LC3-I, which are autophagy-related proteins, and promoting the generation of acidic vesicular organelles and autolysosomes in the cytoplasm of human lung cancer A549 and PC-9 cells in a time- and dose-dependent manner. Delicaflavone downregulated the expression of phospho-Akt, phospho-mTOR, and phospho-p70S6K in a time- and dose-dependent manner, suggesting that it induced autophagy by inhibiting the Akt/mTOR/p70S6K pathway in A549 and PC-9 cells. Delicaflavone is a potential anticancer agent that can induce autophagic cell death in human non-small cell lung cancer via the Akt/mTOR/p70S6K signaling pathway. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer.

Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication.

PubMed

Chambon, Caroline; Jatzke, Claudia; Wegener, Nico; Gravius, Andreas; Danysz, Wojciech

2012-12-15

Benzylquinolone carboxylic acid (BQCA) is a recently described cholinergic muscarinic M(1) receptor positive allosteric modulator having potential as cognitive enhancer in dementia. The present study focused on the characterisation of BQCA's mode of action in relation to positive effects on memory and side-effects in an animal model. To get insight into this mode of action, in vitro receptor potency/left shift experiments in cells stably expressing the rat's M(1) receptor were performed. They revealed an inflection point value of BQCA corresponding to 306nM, and potentiation of the agonist response up to 47-fold in presence of 10μM of BQCA. In vivo, brain microdialysis showed a maximal brain level of 270nM, 40min after i.p. administration at 10mg/kg. Based on in vitro data obtained with this dose, it can be concluded that BQCA reaches brain levels which should potentiate the agonist response about 4-fold. Behavioural data confirmed that BQCA used at 10mg/kg attenuated scopolamine-induced memory deficit in a spontaneous alternation task. Moreover, BQCA showed no side effect at 10mg/kg and above in spontaneous locomotion and salivation tests. The profile of BQCA observed in the present study displays a clear advantage over the M(1)-M(3) agonist cevimeline. The present data show the therapeutic potential of the M(1) receptor positive allosteric modulator BQCA for the treatment of memory deficits observed in Alzheimer's disease. Copyright © 2012. Published by Elsevier B.V.

Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

PubMed

Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

2018-05-21

Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

PubMed

Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

Beliefs about medications predict adherence to antidepressants in older adults.

PubMed

Fawzi, Waleed; Abdel Mohsen, Mohamed Yousry; Hashem, Abdel Hamid; Moussa, Suaad; Coker, Elizabeth; Wilson, Kenneth C M

2012-01-01

Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients' adherence to antidepressants and their beliefs about and knowledge of the medication. Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs. 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as "my health depends on antidepressants" (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects. Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients' beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.

Religious Involvement, Social Support, and Health Among African-American Women on the East Side of Detroit

PubMed Central

Van Olphen, Juliana; Schulz, Amy; Israel, Barbara; Chatters, Linda; Klem, Laura; Parker, Edith; Williams, David

2003-01-01

BACKGROUND A significant body of research suggests that religious involvement is related to better mental and physical health. Religion or spirituality was identified as an important health protective factor by women participating in the East Side Village Health Worker Partnership (ESVHWP), a community-based participatory research initiative on Detroit's east side. However, relatively little research to date has examined the mechanisms through which religion may exert a positive effect on health. OBJECTIVE The research presented here examines the direct effects of different forms of religious involvement on health, and the mediating effects of social support received in the church as a potential mechanism that may account for observed relationships between church attendance and health. DESIGN This study involved a random sample household survey of 679 African-American women living on the east side of Detroit, conducted as part of the ESVHWP. MAIN RESULTS Results of multivariate analyses show that respondents who pray less often report a greater number of depressive symptoms, and that faith, as an important source of strength in one's daily life, is positively associated with chronic conditions such as asthma or arthritis. Tests of the mediating effect of social support in the church indicated that social support received from church members mediates the positive relationship between church attendance and specific indicators of health. CONCLUSIONS These findings are consistent with the hypothesis that one of the major ways religious involvement benefits health is through expanding an individual's social connections. The implications of these findings for research and practice are discussed. PMID:12848838

The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

PubMed Central

Fond, Guillaume; d’Albis, Marc-Antoine; Jamain, Stéphane; Tamouza, Ryad; Arango, Celso; Fleischhacker, W. Wolfgang; Glenthøj, Birte; Leweke, Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Sommer, Iris E.; Winter-van Rossum, Inge; Kapur, Shitij; Kahn, René S.; Rujescu, Dan; Leboyer, Marion

2015-01-01

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded—beside markers for metabolism of antipsychotics—no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results. PMID:25759473

A missing link between RON expression and oncological outcomes in resected left-sided pancreatic cancer.

PubMed

Han, Dai Hoon; Kang, Chang Moo; Lee, Sung Whan; Hwang, Ho Kyoung; Lee, Woo Jung

2017-10-01

Alteration and activation of recepteur d'origine nantais (RON) expression is known to be associated with cancer progression and decreased survival in various types of human cancer, including pancreatic cancer. Therefore, in the present study, RON expression levels were determined in resected left-sided pancreatic cancer to evaluate the potential oncological role of RON in the clinical setting of distal pancreatic cancer. From January 2005 to December 2011, a total of 57 patients underwent radical distal pancreatectomy for left-sided pancreatic cancer. Ductal adenocarcinoma was confirmed in all patients. Among these patients, 17 patients who received preoperative neoadjuvant treatment and 7 patients without available paraffin-embedded tissue blocks were excluded from the present study. RON expression in a the pancreatic cancer cell lines ASPC-1, BxPC-3, MiaPaCa-3 and Panc-1, as well as in resected left-sided pancreatic cancer specimens was determined by Western blot analysis. RON and vascular endothelial growth factor (VEGF) overexpression in resected left-sided pancreatic cancer was also evaluated by immunohistochemistry using pre-diluted anti-RON and anti-VEGF antibodies. An association was identified between the oncological outcome and RON overexpression. Increased levels of RON expression were observed in two pancreatic cancer cell lines, AsPC-1 and BxPC-3. RON overexpression was detected in specimens from 15/33 patients (45.5%) using immunohistochemistry. No significant association was identified between RON overexpression and VEGF overexpression (25.5 vs. 87.9%; P=0.667). No significant differences in disease-free survival or disease-specific survival associated with RON overexpression were identified. Although the results of previous studies have suggested that RON is a potential target for the treatment of pancreatic cancer, in the present study no association between RON overexpression and any adverse oncological effect was identified.

Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

PubMed

Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

2011-05-01

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

Modeling Indications of Technology in Planetary Transit Light Curves-Dark-side Illumination

NASA Astrophysics Data System (ADS)

Korpela, Eric J.; Sallmen, Shauna M.; Leystra Greene, Diana

2015-08-01

We analyze potential effects of an extraterrestrial civilization’s use of orbiting mirrors to illuminate the dark side of a synchronously rotating planet on planetary transit light curves. Previous efforts to detect civilizations based on side effects of planetary-scale engineering have focused on structures affecting the host star output (e.g., Dyson spheres). However, younger civilizations are likely to be less advanced in their engineering efforts, yet still capable of sending small spacecraft into orbit. Since M dwarfs are the most common type of star in the solar neighborhood, it seems plausible that many of the nearest habitable planets orbit dim, low-mass M stars, and will be in synchronous rotation. Logically, a civilization evolving on such a planet may be inspired to illuminate their planet’s dark side by placing a single large mirror at the L2 Lagrangian point, or launching a fleet of small thin mirrors into planetary orbit. We briefly examine the requirements and engineering challenges of such a collection of orbiting mirrors, then explore their impact on transit light curves. We incorporate stellar limb darkening and model a simplistic mirror fleet’s effects for transits of Earth-like (R = 0.5 to 2 {R}{Earth}) planets which would be synchronously rotating for orbits within the habitable zone of their host star. Although such an installation is undetectable in Kepler data, the James Webb Space Telescope will provide the sensitivity necessary to detect a fleet of mirrors orbiting Earth-like habitable planets around nearby stars.

Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior

NASA Technical Reports Server (NTRS)

Kuhn, H.; Galston, A. W.

1992-01-01

Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior.

PubMed

Kuhn, H; Galston, A W

1992-01-01

Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.

PubMed

Zhang, Chengmi; Wang, Zhenmeng; Zhang, Jinmin; Qiu, Haibo; Sun, Yuming; Yang, Liqun; Wu, Feixiang; Zheng, Jijian; Yu, Weifeng

2014-05-01

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Effective homogeneity of the exchange-correlation and non-interacting kinetic energy functionals under density scaling.

PubMed

Borgoo, Alex; Teale, Andrew M; Tozer, David J

2012-01-21

Correlated electron densities, experimental ionisation potentials, and experimental electron affinities are used to investigate the homogeneity of the exchange-correlation and non-interacting kinetic energy functionals of Kohn-Sham density functional theory under density scaling. Results are presented for atoms and small molecules, paying attention to the influence of the integer discontinuity and the choice of the electron affinity. For the exchange-correlation functional, effective homogeneities are highly system-dependent on either side of the integer discontinuity. By contrast, the average homogeneity-associated with the potential that averages over the discontinuity-is generally close to 4/3 when the discontinuity is computed using positive affinities for systems that do bind an excess electron and negative affinities for those that do not. The proximity to 4/3 becomes increasingly pronounced with increasing atomic number. Evaluating the discontinuity using a zero affinity in systems that do not bind an excess electron instead leads to effective homogeneities on the electron abundant side that are close to 4/3. For the non-interacting kinetic energy functional, the effective homogeneities are less system-dependent and the effect of the integer discontinuity is less pronounced. Average values are uniformly below 5/3. The study provides information that may aid the development of improved exchange-correlation and non-interacting kinetic energy functionals. © 2012 American Institute of Physics

[Treatment side effects and compliance in patients with depression].

PubMed

Petrova, N N; Kucher, E O

2012-01-01

The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

PubMed Central

Zecha, Judith A. E. M.; Raber-Durlacher, Judith E.; Nair, Raj G.; Epstein, Joel B.; Elad, Sharon; Hamblin, Michael R.; Barasch, Andrei; Migliorati, Cesar A.; Milstein, Dan M. J.; Genot, Marie-Thérèse; Lansaat, Liset; van der Brink, Ron; Arnabat-Dominguez, Josep; van der Molen, Lisette; Jacobi, Irene; van Diessen, Judi; de Lange, Jan; Smeele, Ludi E.; Schubert, Mark M.

2016-01-01

Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes. PMID:26984249

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols.

PubMed

Zecha, Judith A E M; Raber-Durlacher, Judith E; Nair, Raj G; Epstein, Joel B; Elad, Sharon; Hamblin, Michael R; Barasch, Andrei; Migliorati, Cesar A; Milstein, Dan M J; Genot, Marie-Thérèse; Lansaat, Liset; van der Brink, Ron; Arnabat-Dominguez, Josep; van der Molen, Lisette; Jacobi, Irene; van Diessen, Judi; de Lange, Jan; Smeele, Ludi E; Schubert, Mark M; Bensadoun, René-Jean

2016-06-01

There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780-830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2-3 J (J/cm(2)), and no more than 6 J/cm(2) on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

Effect of same-sided and cross-body load carriage on 3D back shape in young adults.

PubMed

O'Shea, C; Bettany-Saltikov, J A; Warren, J G

2006-01-01

Regular carriage of heavy loads such as backpacks, satchels and mailbags results in a variety of acute medical problems and increased potential for back injury. There is a paucity of information about the specific changes in back posture that occur in response to asymmetrical loading. The purpose of this study was to examine the changes in back shape that occurred in response to asymmetrical load carriage, either on one shoulder (same-side) or across the body (cross-body), in healthy young adults. A convenience sample of 21 physiotherapy students randomly performed three trials (unloaded, same-side loaded, cross-body loaded) in standing with a 15% body load. The Microscribe 3DX digitiser (Immersion Group Ltd) recorded the three dimensional coordinates of 15 Key anatomical landmarks on the back in the three conditions. A one-way ANOVA with repeated measures and post-hoc tests was implemented to highlight statistical differences in the data collected (p<0.05). Significant differences were found in the x, y and z coordinates of the anatomical landmarks in the upper back between unloaded and loaded conditions. Results demonstrated significantly less impact on spinal posture from cross-body loading as compared to same-sided loading. This study confirms that there are significant three-dimensional changes in back shape in response to asymmetrical loading. Further work is needed to evaluate the optimal carriage type and maximal body load that results in the least spinal impact and injury potential in young adults.

Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

PubMed

Becker, G M; Gandolfi, A J; Nagle, R B

1987-05-01

Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

Increasing the demand for childhood vaccination in developing countries: a systematic review

PubMed Central

2009-01-01

Background Attempts to maintain or increase vaccination coverage almost all focus on supply side interventions: improving availability and delivery of vaccines. The effectiveness and cost-effectiveness of efforts to increase demand is uncertain. Methods We performed a systematic review of studies that provided quantitative estimates of the impact of demand side interventions on uptake of routine childhood vaccination. We retrieved studies published up to Sept 2008. Results The initial search retrieved 468 potentially eligible studies, including four systematic reviews and eight original studies of the impact of interventions to increase demand for vaccination. We identified only two randomised controlled trials. Interventions with an impact on vaccination uptake included knowledge translation (KT) (mass media, village resource rooms and community discussions) and non-KT initiatives (incentives, economic empowerment, household visits by extension workers). Most claimed to increase vaccine coverage by 20 to 30%. Estimates of the cost per vaccinated child varied considerably with several in the range of $10-20 per vaccinated child. Conclusion Most studies reviewed here represented a low level of evidence. Mass media campaigns may be effective, but the impact depends on access to media and may be costly if run at a local level. The persistence of positive effects has not been investigated. The economics of demand side interventions have not been adequately assessed, but available data suggest that some may be very cost-effective. PMID:19828063

Quantum transport in graphene Hall bars: Effects of side gates

NASA Astrophysics Data System (ADS)

Petrović, M. D.; Peeters, F. M.

2017-05-01

Quantum electron transport in side-gated graphene Hall bars is investigated in the presence of quantizing external magnetic fields. The asymmetric potential of four side-gates distorts the otherwise flat bands of the relativistic Landau levels, and creates new propagating states in the Landau spectrum (i.e. snake states). The existence of these new states leads to an interesting modification of the bend and Hall resistances, with new quantizing plateaus appearing in close proximity of the Landau levels. The electron guiding in this system can be understood by studying the current density profiles of the incoming and outgoing modes. From the fact that guided electrons fully transmit without any backscattering (similarly to edge states), we are able to analytically predict the values of the quantized resistances, and they match the resistance data we obtain with our numerical (tight-binding) method. These insights in the electron guiding will be useful in predicting the resistances for other side-gate configurations, and possibly in other system geometries, as long as there is no backscattering of the guided states.

Effect of intravenous parecoxib on post-craniotomy pain.

PubMed

Williams, D L; Pemberton, E; Leslie, K

2011-09-01

Pain management in craniotomy patients is challenging, with mild-to-moderate pain intensity, moderate-to-high risk of postoperative nausea and vomiting (PONV), and potentially catastrophic consequences of analgesic-related side-effects. The aim of this study was to determine whether i.v. parecoxib administered at dural closure during craniotomy decreased total morphine consumption and morphine-related side-effects compared with placebo. One hundred adult patients presenting for supratentorial craniotomy under propofol/remifentanil anaesthesia were randomized to receive parecoxib, 40 mg i.v., or placebo in a double-blind manner. All patients received local anaesthetic scalp infiltration, regular i.v. paracetamol, nurse-administered morphine in the post-anaesthesia care unit (PACU) until verbal analogue pain scores were ≤4/10 and patient-controlled morphine thereafter. Morphine consumption, pain intensity, and analgesia-related side-effects were recorded during the first 24 h after operation. Ninety-six patients (49 control and 47 parecoxib) were included in the analyses. Fifty-nine (61%) patients received morphine in the PACU and only one patient (control) did not receive any morphine in the postoperative period. There were no significant differences between the two groups in morphine consumption [20 (range: 0-102) vs 16 (range: 1-92) mg; P=0.38], pain intensity [excellent/very good pain relief in 78% of parecoxib patients; 74% of control patients (P=0.72)] or analgesia-related side-effects (PONV in 51% of parecoxib patients; 56% of control patients; P=0.55) in the first 24 h after operation. No major morbidity was recorded. Our study demonstrated no clinical benefit to adding i.v. parecoxib to local anaesthetic scalp infiltration, i.v. paracetamol, and patient-controlled i.v. morphine after supratentorial craniotomy.

Use of an innovative T-tube maze assay and the proboscis extension response assay to assess sublethal effects of GM products and pesticides on learning capacity of the honey bee Apis mellifera L.

PubMed Central

Han, Peng; Lei, Chao-Liang; Cui, Jin-Jie; Desneux, Nicolas

2010-01-01

Transgenic Cry1Ac+CpTI cotton (CCRI41) is a promising cotton cultivar throughout China but side effects and especially sublethal effects of this transgenic cultivar on beneficial insects remain poorly studied. More specifically potential sublethal effects on behavioural traits of the honey bee Apis mellifera L. have not been formally assessed despite the importance of honey bees for pollination. The goal of our study was to assess potential effects of CCRI41 cotton pollen on visual and olfactory learning by honey bees. After a 7-day oral chronic exposure to honey mixed with either CCRI41 pollen, imidacloprid-treated conventional pollen (used as positive sublethal control) or conventional pollen (control), learning performance was evaluated by the classical proboscis extension reflex (PER) procedure as well as a T-tube maze test. The latter assay was designed as a new device to assess potential side effects of pesticides on visual associative learning of honey bees. These two procedures were complementary because the former focused on olfactory learning while the latter was involved in visual learning based on visual orientation ability. Oral exposure to CCRI41 pollen did not affect learning capacities of honey bees in both the T-tube maze and PER tests. However, exposure to imidacloprid resulted in reduced visual learning capacities in T-tube maze evaluation and decreased olfactory learning performances measured with PER. The implications of these results are discussed in terms of risks of transgenic CCRI41 cotton crops for honey bees. PMID:20872243

Comparative Effects of Antihistamines on Aircrew Performance of Simple and Complex Tasks Under Sustained Operations

DTIC Science & Technology

1991-12-01

personnel by identifying the potential symptoms and side effects of each antihistamine and a lactose intolerance reaction. These "symptoms" were then...bachelors degree. All subjects were screened for current prescription medication use, history of antihistamine use, and known lactose sensitivity. Study...assigned drug condition (Seldane, Benadryl, or lactose placebo; see Table 1). Drug group assignment was double-blind. Neither the investigators nor the

Secure, Policy-Based, Multi-Recipient Data Sharing

DTIC Science & Technology

2009-01-01

effects of a new drug to all patients at participating hospitals, who have a certain medical condition and have indicated a willingness to partici...pate in clinical trials at their discretion. The drug company considers the potential side effects of the new drug private data and thus would like to...health care example discussed above. Attribute-Based Encryption (ABE) [63, 37, 10, 23, 56, 24, 55, 36, 43, 49] is a new public-key encryption paradigm

Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.

PubMed

Tuplin, Erin W; Holahan, Matthew R

2017-11-14

The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole.s. We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects in animal models of schizophrenia symptoms. Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instances, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracellular signaling pathways. A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review examines these mechanisms of action to further clarify the pharmacological actions of aripiprazole. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

PubMed

Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli

2016-01-01

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Hepatitis C-related cryoglobulinemic neuropathy: potential role of oxcarbazepine for pain control.

PubMed

Moretti, Rita; Caruso, Paola; Dal Ben, Matteo; Gazzin, Silvia; Tiribelli, Claudio

2018-01-25

Peripheral neuropathy is one most common, limiting and invalidating neurological symptom in subjects with hepatitis C virus and mixed cryoglobulinemia. Notably, the medical therapy proposed to eradicate HCV, can frequently exacerbate the painful neuropathy. Therefore, neuropathy therapies are insufficient and inadequate, and comprise immunosuppressive drugs, such as steroid or cyclosporine, intravenous immunoglobulin or plasma exchange. These have shown variable success in case reports, with a presumably temporary effect, but with major side effects. We assessed the effects of oxcarbazepine treatment in 67 cases of cryoglobulinemia related neuropathy, who did not respond to either steroid or Gabapentin, or Pregabalin. Oxcarbazepine was chosen based on the promising preliminary results. Patients treated with Oxcarbazepine showed a rapid, discrete and persistent relief of polyneuropathic signs, without consistent side effects, and with a limited interaction with concomitant drugs. These data favor the use of oxcarbazepine as a useful tool in the management of neuropathic pain associated with Hepatitis-C cryoglobulin neuropathy.

[Iron deficiency anemia and pregnancy. Prevention and treatment].

PubMed

Beucher, G; Grossetti, E; Simonet, T; Leporrier, M; Dreyfus, M

2011-05-01

To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy. French and English publications were searched using PubMed and Cochrane library. Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion. Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Asymmetric Volcano Trend in Oxygen Reduction Activity of Pt and Non-Pt Catalysts: In Situ Identification of the Site-Blocking Effect.

PubMed

Li, Jingkun; Alsudairi, Amell; Ma, Zi-Feng; Mukerjee, Sanjeev; Jia, Qingying

2017-02-01

Proper understanding of the major limitations of current catalysts for oxygen reduction reaction (ORR) is essential for further advancement. Herein by studying representative Pt and non-Pt ORR catalysts with a wide range of redox potential (E redox ) via combined electrochemical, theoretical, and in situ spectroscopic methods, we demonstrate that the role of the site-blocking effect in limiting the ORR varies drastically depending on the E redox of active sites; and the intrinsic activity of active sites with low E redox have been markedly underestimated owing to the overlook of this effect. Accordingly, we establish a general asymmetric volcano trend in the ORR activity: the ORR of the catalysts on the overly high E redox side of the volcano is limited by the intrinsic activity; whereas the ORR of the catalysts on the low E redox side is limited by either the site-blocking effect and/or intrinsic activity depending on the E redox .

Cannabidiol monotherapy for treatment-resistant schizophrenia.

PubMed

Zuardi, Antonio Waldo; Hallak, Jaime E C; Dursun, Serdar Murat; Morais, Sílvio L; Sanches, Rafael Faria; Musty, Richard E; Crippa, José Alexandre S

2006-09-01

Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana's typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data (Zuardi et al., 2002). In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS). This was an in-patient study. All patients were given placebo for the initial 5 days, and from the 6th to 35th day (inclusive) they received CBD (initial oral dose of 40 mg reaching 1280 mg/day). On the 36th day, CBD treatment was discontinued and replaced by placebo for 5 days, which was subsequently switched to olanzapine for over 15 days. Efficacy, tolerability and side effects were assessed. One patient showed mild improvement, but two patients didn't show any improvement during CBD monotherapy. All patients tolerated CBD very well and no side effects were reported. These preliminary data suggest that CBD monotherapy may not be effective for TRS.

Role of natural herbs in the treatment of hypertension

PubMed Central

Tabassum, Nahida; Ahmad, Feroz

2011-01-01

Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness. Conventional antihypertensives are usually associated with many side effects. About 75 to 80% of the world population use herbal medicines, mainly in developing countries, for primary health care because of their better acceptability with human body and lesser side effects. In the last three decades, a lot of concerted efforts have been channeled into researching the local plants with hypotensive and antihypertensive therapeutic values. The hypotensive and antihypertensive effects of some of these medicinal plants have been validated and others disproved. However, ayurvedic knowledge needs to be coupled with modern medicine and more scientific research needs to be done to verify the effectiveness, and elucidate the safety profile of such herbal remedies for their antihypertensive potential. PMID:22096316

Antipsychotics and physical attractiveness.

PubMed

Seeman, Mary V

2011-10-01

Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

PubMed

Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2018-06-02

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Effects of fire and fuels management on water quality in eastern North America

Treesearch

R. K. Kolka

2012-01-01

Fuels management, especially prescribed fire, can have direct impacts on aquatic resources through deposition of ash to surface waters. On the terrestrial side, fuels management leads to changes in vegetative structure and potentially soil properties that affect ecosystem cycling of water and inorganic and organic constituents. Because surface water systems (streams,...

Clinical trial tests precision radiotherapy for recurrent prostate cancer | Center for Cancer Research

Cancer.gov

CCR investigators are leading a trial of stereotactic body radiation therapy (SBRT) to treat localized prostate cancer that has recurred after standard radiation therapy. The technique uses advanced molecular imaging to guide the delivery of high doses of radiation just to tumors that have recurred, potentially leading to fewer side effects. Read more…

Megestrol acetate in cachexia and anorexia

PubMed Central

Yeh, Shing-shing; Schuster, Michael W

2006-01-01

The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed. PMID:17722275

Perspective-Taking Judgments Among Young Adults, Middle-Aged, and Elderly People

ERIC Educational Resources Information Center

Ligneau-Herve, Catherine; Mullet, Etienne

2005-01-01

Perspective-taking judgments among young adults, middle-aged, and elderly people were examined. In 1 condition, participants were instructed to judge the likelihood of acceptance of a painkiller as a function of 3 cues: severity of the condition, potential side effects, and level of trust in the health care provider. In the other condition,…

SSRI adverse events: how to monitor and manage.

PubMed

Murphy, Tanya K; Segarra, Ana; Storch, Eric A; Goodman, Wayne K

2008-04-01

Antidepressants are efficacious for pediatric major depressive disorder, obsessive compulsive disorder (OCD), and non-OCD anxiety disorders. Antidepressants should be used in an evidence-based fashion, with frequent monitoring for side effects, especially when initiating treatment and adjusting dosage. With diligence to appropriate prescribing and monitoring, the benefits of therapy outweigh the potential of treatment related risk.

The role of exercise in migraine treatment.

PubMed

Koseoglu, E; Yetkin, M F; Ugur, F; Bilgen, M

2015-09-01

This review aims to provide a comprehensive overview of the literature on the use of exercise for migraine treatment with regard to its efficacy, mechanism of action and role in practice. Many randomized studies have reported the efficacy of prophylactic treatment of migrane with medications such as beta blockers or antiepileptic drugs. Studies on alternative approaches, like aerobic exercise and biofeedback, are however limited but also considered to be effective. Scientific databases were searched with keywords "exercise" and "migraine". The resulting publications were gathered, examined and discussed throughly. Past studies had limitations and were few in number, but more recent randomized controlled studies have concretely provided level of evidence about the effectiveness of exercise in prophylactic treatment of migraine. Core properties of exercise like intensity, duration, frequency, type and warming up period are required to be monitored while treating migraine to increase the beneficial effects and, also to prevent injuries and side effects which may include exertional headache. Isometric neck exercise is helpful when the migraine is accompanied by neck pain. Patient population with low beta endorphin level in blood, high physical fitness and high motivation receives significant benefits from the exercise treatment. The action of exercise on migraine is in general related to neurochemical factors, psychological states and increase in cardivascular and cerebrovascular fitness. Considering its effectiveness and minimal side effects, migraine patients should often be encouraged to practice physical exercise with intensity, frequency and duration that should be carefully instituted to achieve the most beneficial outcome while preventing potential injuries and side effects.

Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS): conjugation chemistry, characterization, in vitro and in vivo evaluation.

PubMed

Cao, Na; Feng, Si-Shen

2008-10-01

To develop a polymer-anticancer drug conjugate, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was employed as a carrier of doxorubicin (DOX) to enhance its therapeutic effects and reduce its side effects. Doxorubicin was chemically conjugated to TPGS. The molecular structure, drug loading efficiency, drug release kinetics and stability of the conjugate were characterized. The cellular uptake, intracellular distribution, and cytotoxicity were accessed by using MCF-7 breast cancer cells and C6 glioma cells as in vitro cell model. The conjugate showed higher cellular uptake efficiency and broader distribution within the cells. Judged by IC(50), the conjugate was found 31.8, 69.6, 84.1% more effective with MCF-7 cells and 43.9, 87.7, 42.2% more effective with C6 cells than the parent drug after 24, 48, 72 h culture, respectively. The in vivo pharmacokinetics and biodistribution were investigated after an i.v. administration at 5 mg DOX/kg body weight in rats. Promisingly, 4.5-fold increase in the half-life and 24-fold increase in the area-under-the-curve (AUC) of DOX were achieved for the TPGS-DOX conjugate compared with the free DOX. The drug level in heart, gastric and intestine was significantly reduced, which is an indication of reduced side effects. Our TPGS-DOX conjugate showed great potential to be a prodrug of higher therapeutic effects and fewer side effects than DOX itself.

Radiation Therapy Side Effects

Cancer.gov

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care

PubMed Central

Jamison, Robert N.; Dorado, Kathleen; Mei, Anna; Edwards, Robert R.; Martel, Marc O.

2017-01-01

Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care. PMID:29392205

Loop Diuretics in the Treatment of Hypertension.

PubMed

Malha, Line; Mann, Samuel J

2016-04-01

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

TAC management in North Sea flatfish fisheries

NASA Astrophysics Data System (ADS)

Daan, Niels

1997-11-01

The Common Fisheries Policy of the European Union adopted in 1983 is primarily focused on a science-based TAC management system with fixed national quota shares. The quality of the assessments of plaice and sole, the consistency of the scientific advice, the congruency of the management decisions, and the enforcement of the regulations are reviewed over a 15-year period. The conclusion is that there have been problems at each level, with the ultimate effect that the policy has not been able to restrict fishing mortality and that the level of overexploitation has only increased. It is argued that the present TAC system has created more problems than it has resolved. Attention is drawn to the autonomic economic developments within the fishery and to the potential for managing the fishery more effectively from the cost side rather than the profit side.

Effects of slow repetitive transcranial magnetic stimulation in patients with corticobasal syndrome.

PubMed

Civardi, Carlo; Pisano, Fabrizio; Delconte, Carmen; Collini, Alessandra; Monaco, Francesco

2015-06-01

Corticobasal syndrome is characterized by asymmetric cortical sensorimotor dysfunction and parkinsonism; an altered cortical excitability has been reported. We explored with transcranial magnetic stimulation the motor cortical excitability in corticobasal syndrome, and the effects of slow repetitive transcranial magnetic stimulation. With transcranial magnetic stimulation, we studied two corticobasal syndrome patients. We determined bilaterally from the first dorsal interosseous muscle: relaxed threshold, and contralateral and ipsilateral silent period. We also evaluated the contralateral silent period after active/sham slow repetitive transcranial magnetic stimulation on the most affected side. At T0 the silent period was bilaterally short. On the most affected side, active slow repetitive transcranial magnetic stimulation induced a short lasting prolongation of the contralateral silent period. In corticobasal syndrome, transcranial magnetic stimulation showed a reduction cortical inhibitory phenomenon potentially reversed transiently by slow repetitive transcranial magnetic stimulation.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Cooled radiofrequency ablation for bilateral greater occipital neuralgia.

PubMed

Vu, Tiffany; Chhatre, Akhil

2014-01-01

This report describes a case of bilateral greater occipital neuralgia treated with cooled radiofrequency ablation. The case is considered in relation to a review of greater occipital neuralgia, continuous thermal and pulsed radiofrequency ablation, and current medical literature on cooled radiofrequency ablation. In this case, a 35-year-old female with a 2.5-year history of chronic suboccipital bilateral headaches, described as constant, burning, and pulsating pain that started at the suboccipital region and radiated into her vertex. She was diagnosed with bilateral greater occipital neuralgia. She underwent cooled radiofrequency ablation of bilateral greater occipital nerves with minimal side effects and 75% pain reduction. Cooled radiofrequency ablation of the greater occipital nerve in challenging cases is an alternative to pulsed and continuous RFA to alleviate pain with less side effects and potential for long-term efficacy.

Cooled Radiofrequency Ablation for Bilateral Greater Occipital Neuralgia

PubMed Central

Chhatre, Akhil

2014-01-01

This report describes a case of bilateral greater occipital neuralgia treated with cooled radiofrequency ablation. The case is considered in relation to a review of greater occipital neuralgia, continuous thermal and pulsed radiofrequency ablation, and current medical literature on cooled radiofrequency ablation. In this case, a 35-year-old female with a 2.5-year history of chronic suboccipital bilateral headaches, described as constant, burning, and pulsating pain that started at the suboccipital region and radiated into her vertex. She was diagnosed with bilateral greater occipital neuralgia. She underwent cooled radiofrequency ablation of bilateral greater occipital nerves with minimal side effects and 75% pain reduction. Cooled radiofrequency ablation of the greater occipital nerve in challenging cases is an alternative to pulsed and continuous RFA to alleviate pain with less side effects and potential for long-term efficacy. PMID:24716017

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

[Milk Thistle (Silybum Marianum) as a Supportive Phytotherapeutic Agent in Oncology].

PubMed

Frassová, Z; Rudá-Kučerová, J

2017-01-01

Milk thistle (Silybum marianum) has been traditionally used in medicine, particularly in the treatment of liver diseases. Today, it is used for the same purpose in evidence-based medicine (EBM). Its main active ingredient is a complex of flavonolignans, known as silymarin. Silymarin is used as a hepatoprotective agent, but its potential therapeutic use in oncology patients has drawn attention only recently. The aim of this review is to provide comprehensive information on the potential therapeutic effects of milk thistle in oncology patients and potential indications for its use as a supportive therapy either as an anticarcinogenic agent or as an agent that attenuates the side effects of oncological treatments. Evidence of its effects and its safety, and possible interactions with other cancer treatments are emphasized. Available findings are supported mainly by in vitro studies and the results of animal research, but the number of clinical trials in oncology patients is increasing. Based on the results of these studies, milk thistle or silymarin could be beneficial in oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics. Evidence from clinical studies shows that it has mainly beneficial effects in hepatotoxicity and radiotherapy-induced skin and mucosa damage at dosages of 160-600 mg daily.Key words: phytotherapy - drug-herb interactions - cancer - adverse effects - milk thistle - Silybum marianum This publication was written at Masaryk University as part of the project "Experimental and translational pharmacological research and development", number MUNI/A/1063/2016 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2017. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 6. 2017Accepted: 18. 9. 2017.

Factors affecting patient's perception of anticancer treatments side-effects: an observational study.

PubMed

Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio

2014-02-01

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Perceived risk of tamoxifen side effects: a study of the use of absolute frequencies or frequency bands, with or without verbal descriptors.

PubMed

Knapp, Peter; Gardner, Peter H; Raynor, David K; Woolf, Elizabeth; McMillan, Brian

2010-05-01

To investigate the effectiveness of presenting medicine side effect risk information in different forms, including that proposed by UK guidelines [[1] Medicines and Healthcare products Regulatory Agency. Always read the leaflet-Getting the best information with every medicine. (Report of the Committee on Safety of Medicines Working Group on Patient Information). London: The Stationery Office, 2005.]. 134 Cancer Research UK (CRUK) website users were recruited via a 'pop-up'. Using a 2x2 factorial design, participants were randomly allocated to one of four conditions and asked to: imagine they had to take tamoxifen, estimate the risks of 4 side effects, and indicate a presentation mode preference. Those presented with absolute frequencies demonstrated greater accuracy in estimating 2 of 4 side effects, and of any side effect occurring, than those presented with frequency bands. Those presented with combined descriptors were more accurate at estimating the risk of pulmonary embolism than those presented with numeric descriptors only. Absolute frequencies outperform frequency bands when presenting side effect risk information. However, presenting such exact frequencies for every side effect may be much less digestible than all side effects listed under 5 frequency bands. Combined numerical and verbal descriptors may be better than numeric only descriptors when describing infrequent side effects. Information about side effects should be presented in ways that patients prefer, and which result in most accurate risk estimates. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects

PubMed Central

Pei, Yanping; Liu, Huan; Yang, Yi; Yang, Yanwei

2018-01-01

N-Acetylcysteine (NAC), a cysteine prodrug and glutathione (GSH) precursor, has been used for several decades in clinical therapeutic practices as a mucolytic agent and for the treatment of disorders associated with GSH deficiency. Other therapeutic activities of NAC include inhibition of inflammation/NF-κB signaling and expression of proinflammatory cytokines. N-Acetylcysteine is also a nonantibiotic compound possessing antimicrobial property and exerts anticarcinogenic and antimutagenic effects against certain types of cancer. Recently, studies describing potentially important biological and pharmacological activities of NAC have stimulated interests in using NAC-based therapeutics for oral health care. The present review focused on the biological activities of NAC and its potential oral applications. The potential side effects of NAC and formulations for drug delivery were also discussed, with the intent of advancing NAC-associated treatment modalities in oral medicine. PMID:29849877

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

PubMed Central

Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

2015-01-01

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

Classification of ictal and seizure-free HRV signals with focus on lateralization of epilepsy.

PubMed

Behbahani, Soroor; Dabanloo, Nader Jafarnia; Nasrabadi, Ali Motie; Dourado, Antonio

2016-01-01

Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left-sided seizure would result in an ictal bradycardia.

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

PubMed

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study. Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain. © 2017 by the Society for Academic Emergency Medicine.

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D,L-lactide-co-glycolide): effects of polymer structure on in vitro degradation behaviour.

PubMed

Unger, Florian; Wittmar, Matthias; Morell, Frank; Kissel, Thomas

2008-05-01

Branched polyesters of the general structure poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D,L-lactide-co-glycolide) have shown potential for nano- and micro-scale drug delivery systems. Here the in vitro degradation behaviour with a special emphasis on elucidating structure-property relationships is reported. Effects of type and degree of amine substitution as well as PLGA side chain length were considered. In a first set of experiment, the weight loss of solvent cast films of defined size from 19 polymers was measured as a function of incubation in phosphate buffer (pH 7.4) at 37 degrees C over a time of 21 days. A second study was initiated focusing on three selected polymers in a similar set up, but with additional observation of pH influences (pH 2 and pH 9) and determination of water uptake (swelling) and molecular weights during degradation. Scanning electron micrographs have been recorded at selected time points to characterize film specimens morphologically after degradation. Our investigations revealed the potential to influence the degradation of this polymer class by the degree of amine substitution, higher degrees leading to faster erosion. The erosion rate could further be influenced by the type of amine functionality, DEAPA-modified polyesters degrading as fast as or slightly faster than DMAPA-modified polyesters and these degrading faster than DEAEA-PVA-g-PLGA. As a third option the degradation rate could be modified by the PLGA side chain length, shorter side chains leading to faster erosion. As compared to linear PLGA, remarkably shorter degradation times could be achieved by grafting short PLGA side chains onto amine-modified PVA backbones. Erosion times from less than 5 days to more than 4 weeks could be realized by selecting the type of amine functionality, the degree of amine substitution and the PLGA side chain length at the time of synthesis. In addition, the pathway of hydrolytic degradation can be tuned to be either mainly bulk or surface erosion.

Reducing Aversion to Side Effects in Preventive Medical Treatment Decisions

ERIC Educational Resources Information Center

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen M.

2007-01-01

Laypeople tend to be overly sensitive to side effects of treatments that prevent illness, possibly leading them to refuse beneficial therapies. This Internet-based study attempted to reduce such side effect aversion by adding graphic displays to the numerical risk probabilities. It also explored whether graphics reduce side effect aversion by…

Tunneling through superlattices: the effect of anisotropy and kinematic coupling.

PubMed

Halilov, S V; Huang, X Y; Hytha, M; Stephenson, R; Yiptong, A; Takeuchi, H; Cody, N; Mears, R J

2012-12-12

The tunneling of carriers in stratified superlattice systems is analyzed in terms of the constituent effective mass tensor. The focus is on the effects on the tunneling which are caused by the side regions of an intervening barrier. Depending on the covalency and work function in the constituent layers of a superlattice, it is concluded that the kinematics in the regions on either side determined by the effective carrier mass and its interference with the band offset at heterojunctions leads to either a constructive or a destructive effect on the tunneling current. As an example, Si(1-x)Ge(x)/Si and Al(x)Ga(1-x)As/GaAs superlattices are demonstrated to reduce the tunneling current at certain fractional thicknesses and stoichiometries of the constituent slabs without affecting the lateral mobility. The findings show, in general, how manipulation of the carrier's effective mass tensor through stoichiometric/structural modulation of the heterostructure may be used to control the tunneling current through a given potential barrier, given that the characteristic de Broglie wavelength exceeds all the constituent dimensions, thus offering a method complementary to high-k technologies.

Systematic identification of proteins that elicit drug side effects

PubMed Central

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica; Jensen, Lars Juhl; Gross, Cornelius; Gavin, Anne-Claude; Bork, Peer

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug–target relations to identify overrepresented protein–side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations. PMID:23632385

Potential of Endocannabinoids to Control Bladder Pain.

PubMed

Bjorling, Dale E; Wang, Zun-Yi

2018-01-01

Bladder-related pain is one of the most common forms of visceral pain, and visceral pain is among the most common complaints for which patients seek physician consultation. Despite extensive studies of visceral innervation and treatment of visceral pain, opioids remain a mainstay for management of bladder pain. Side effects associated with opioid therapy can profoundly diminish quality of life, and improved options for treatment of bladder pain remain a high priority. Endocannabinoids, primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are endogenously-produced fatty acid ethanolamides with that induce analgesia. Animal experiments have demonstrated that inhibition of enzymes that degrade AEA or 2-AG have the potential to prevent development of visceral and somatic pain. Although experimental results in animal models have been promising, clinical application of this approach has proven difficult. In addition to fatty acid amide hydrolase (FAAH; degrades AEA) and monacylglycerol lipase (MAGL; degrades 2-AG), cyclooxygenase (COX) acts to metabolize endocannabinoids. Another potential limitation of this strategy is that AEA activates pro-nociceptive transient receptor potential vanilloid 1 (TRPV1) channels. Dual inhibitors of FAAH and TRPV1 or FAAH and COX have been synthesized and are currently undergoing preclinical testing for efficacy in providing analgesia. Local inhibition of FAAH or MAGL within the bladder may be viable options to reduce pain associated with cystitis with fewer systemic side effects, but this has not been explored. Further investigation is required before manipulation of the endocannabinoid system can be proven as an efficacious alternative for management of bladder pain.

An Ensemble Approach for Drug Side Effect Prediction

PubMed Central

Jahid, Md Jamiul; Ruan, Jianhua

2014-01-01

In silico prediction of drug side-effects in early stage of drug development is becoming more popular now days, which not only reduces the time for drug design but also reduces the drug development costs. In this article we propose an ensemble approach to predict drug side-effects of drug molecules based on their chemical structure. Our idea originates from the observation that similar drugs have similar side-effects. Based on this observation we design an ensemble approach that combine the results from different classification models where each model is generated by a different set of similar drugs. We applied our approach to 1385 side-effects in the SIDER database for 888 drugs. Results show that our approach outperformed previously published approaches and standard classifiers. Furthermore, we applied our method to a number of uncharacterized drug molecules in DrugBank database and predict their side-effect profiles for future usage. Results from various sources confirm that our method is able to predict the side-effects for uncharacterized drugs and more importantly able to predict rare side-effects which are often ignored by other approaches. The method described in this article can be useful to predict side-effects in drug design in an early stage to reduce experimental cost and time. PMID:25327524

The effects of collision orientation and energy dependence in multinucleon transfer reactions

NASA Astrophysics Data System (ADS)

Li, Jingjing; Li, Cheng; Wen, Peiwei; Zhang, Feng-Shou

2018-05-01

Multinucleon transfer (MNT) reaction 136Xe+208Pb near Coulomb barrier energies are investigated within the dinuclear system (DNS) model. It is found that the collision orientation has an important influence on the mass distributions attributed to the depth of pocket in the driving potential. The calculation results of the isotopic production show that the energy dependence in neutron-deficient side is more sensitive than that in neutron-rich side. The production of the N = 126 isotones are calculated by GRAZING model, DNS+GEMINI model, and ImQMD+GEMINI model, respectively. It demonstrates that MNT reaction is a promising way to produce neutron-rich isotopes in the region of the neutron shell closure N = 126.

The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment.

PubMed

Broström, Anders; Arestedt, Kristofer Franzén; Nilsen, Per; Strömberg, Anna; Ulander, Martin; Svanborg, Eva

2010-12-01

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment. © 2010 European Sleep Research Society.

Currently used and investigational drugs for Cushing´s disease.

PubMed

Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K

2017-01-01

Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.

The role of selective estrogen receptor modulators in the treatment of schizophrenia.

PubMed

Bratek, Agnieszka; Krysta, Krzysztof; Drzyzga, Karolina; Barańska, Justyna; Kucia, Krzysztof

2016-09-01

Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects.

Teaching Spatial Awareness In Small-Sided Games

ERIC Educational Resources Information Center

Phillips, David; Hannon, James C.; Molina, Sergio

2015-01-01

This article supports the use of strategy and tactics at games stage three (how to teach basic offensive and defensive strategy using small-sided games) as a best practices in physical education. Potential learning through game stages three and four (full-sided games) is only possible when teachers have advanced content knowledge to teach the…

Extreme between-study homogeneity in meta-analyses could offer useful insights.

PubMed

Ioannidis, John P A; Trikalinos, Thomas A; Zintzaras, Elias

2006-10-01

Meta-analyses are routinely evaluated for the presence of large between-study heterogeneity. We examined whether it is also important to probe whether there is extreme between-study homogeneity. We used heterogeneity tests with left-sided statistical significance for inference and developed a Monte Carlo simulation test for testing extreme homogeneity in risk ratios across studies, using the empiric distribution of the summary risk ratio and heterogeneity statistic. A left-sided P=0.01 threshold was set for claiming extreme homogeneity to minimize type I error. Among 11,803 meta-analyses with binary contrasts from the Cochrane Library, 143 (1.21%) had left-sided P-value <0.01 for the asymptotic Q statistic and 1,004 (8.50%) had left-sided P-value <0.10. The frequency of extreme between-study homogeneity did not depend on the number of studies in the meta-analyses. We identified examples where extreme between-study homogeneity (left-sided P-value <0.01) could result from various possibilities beyond chance. These included inappropriate statistical inference (asymptotic vs. Monte Carlo), use of a specific effect metric, correlated data or stratification using strong predictors of outcome, and biases and potential fraud. Extreme between-study homogeneity may provide useful insights about a meta-analysis and its constituent studies.

A vortex model for forces and moments on low-aspect-ratio wings in side-slip with experimental validation

PubMed Central

DeVoria, Adam C.

2017-01-01

This paper studies low-aspect-ratio () rectangular wings at high incidence and in side-slip. The main objective is to incorporate the effects of high angle of attack and side-slip into a simplified vortex model for the forces and moments. Experiments are also performed and are used to validate assumptions made in the model. The model asymptotes to the potential flow result of classical aerodynamics for an infinite aspect ratio. The → 0 limit of a rectangular wing is considered with slender body theory, where the side-edge vortices merge into a vortex doublet. Hence, the velocity fields transition from being dominated by a spanwise vorticity monopole ( ≫ 1) to a streamwise vorticity dipole ( ∼ 1). We theoretically derive a spanwise loading distribution that is parabolic instead of elliptic, and this physically represents the additional circulation around the wing that is associated with reattached flow. This is a fundamental feature of wings with a broad-facing leading edge. The experimental measurements of the spanwise circulation closely approximate a parabolic distribution. The vortex model yields very agreeable comparison with direct measurement of the lift and drag, and the roll moment prediction is acceptable for ≤ 1 prior to the roll stall angle and up to side-slip angles of 20°. PMID:28293139

Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

PubMed

Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

2016-02-01

The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity/anticonvulsant effects). Calculated TIs for A-1295120, CMPPE, rac-BHFF, GS39783, and A-1474713 were 5.31x, 5.00x, 4.74x, 3.41x, and 1.83x, respectively, whereas baclofen was <1. The results presented here suggest the DBA/2J mouse AGS test is a potentially useful screening model for detecting PD effects of GABA(B) PAMs and can provide an initial read-out on target-related motor side-effects. Furthermore, an improved TI was observed for PAMs compared to baclofen, indicating the PAM approach may be a viable therapeutic alternative to baclofen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thoracic Injury Risk as a Function of Crash Severity – Car-to-car Side Impact Tests with WorldSID Compared to Real-life Crashes

PubMed Central

Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf

2010-01-01

Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases. The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds. The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures. PMID:21050600

Thoracic Injury Risk as a Function of Crash Severity - Car-to-car Side Impact Tests with WorldSID Compared to Real-life Crashes.

PubMed

Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf

2010-01-01

Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases.The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds.The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures.

The non-target impact of spinosyns on beneficial arthropods.

PubMed

Biondi, Antonio; Mommaerts, Veerle; Smagghe, Guy; Viñuela, Elisa; Zappalà, Lucia; Desneux, Nicolas

2012-12-01

Spinosyn-based products, mostly spinosad, have been widely recommended by extension specialists and agribusiness companies; consequently, they have been used to control various pests in many different cropping systems. Following the worldwide adoption of spinosad-based products for integrated and organic farming, an increasing number of ecotoxicological studies have been published in the past 10 years. These studies are primarily related to the risk assessment of spinosad towards beneficial arthropods. This review takes into account recent data with the aim of (i) highlighting potentially adverse effects of spinosyns on beneficial arthropods (and hence on ecosystem services that they provide in agroecosystems), (ii) clarifying the range of methods used to address spinosyn side effects on biocontrol agents and pollinators in order to provide new insights for the development of more accurate bioassays, (iii) identifying pitfalls when analysing laboratory results to assess field risks and (iv) gaining increasing knowledge on side effects when using spinosad for integrated pest management (IPM) programmes and organic farming. For the first time, a thorough review of possible risks of spinosad and novel spinosyns (such as spinetoram) to beneficial arthropods (notably natural enemies and pollinators) is provided. The acute lethal effect and multiple sublethal effects have been identified in almost all arthropod groups studied. This review will help to optimise the future use of spinosad and new spinosyns in IPM programmes and for organic farming, notably by preventing the possible side effects of spinosyns on beneficial arthropods. Copyright © 2012 Society of Chemical Industry.

CATAPHORETIC CHARGES OF COLLODION PARTICLES AND ANOMALOUS OSMOSIS THROUGH COLLODION MEMBRANES FREE FROM PROTEIN

PubMed Central

Loeb, Jacques

1922-01-01

1. It had been shown in previous papers that when a salt solution is separated from pure water by a collodion membrane, water diffuses through the membrane as if it were positively charged and as if it were attracted by the anion of the salt in solution and repelled by the cation with a force increasing with the valency. In this paper, measurements of the P.D. across the membrane (E) are given, showing that when an electrical effect is added to the purely osmotic effect of the salt solution in the transport of water from the side of pure water to the solution, the latter possesses a considerable negative charge which increases with increasing valency of the anion of the salt and diminishes with increasing valency of the cation. It is also shown that a similar valency effect exists in the diffusion potentials between salt solutions and pure water without the interposition of a membrane. 2. This makes it probable that the driving force for the electrical transport of water from the side of pure water into solution is primarily a diffusion potential. 3. It is shown that the hydrogen ion concentration of the solution affects the transport curves and the diffusion potentials in a similar way. 4. It is shown, however, that the diffusion potential without interposition of the membrane differs in a definite sense from the P.D. across the membrane and that therefore the P.D. across the membrane (E) is a modified diffusion potential. 5. Measurements of the P.D. between collodion particles and aqueous solutions (ε) were made by the method of cataphoresis, which prove that water in contact with collodion particles free from protein practically always assumes a positive charge (except in the presence of salts with trivalent and probably tetravalent cations of a sufficiently high concentration). 6. It is shown that an electrical transport of water from the side of water into the solution is always superposed upon the osmotic transport when the sign of charge of the solution in the potential across the membrane (E) is opposite to that of the water in the P.D. between collodion particle and water (ε); supporting the theoretical deductions made by Bartell. 7. It is shown that the product of the P.D. across the membrane (E) into the cataphoretic P.D. between collodion particles and aqueous solution (ε) accounts in general semiquantitatively for that part of the transport of water into the solution which is due to the electrical forces responsible for anomalous osmosis. PMID:19871981

Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor.

PubMed

Wells, Elizabeth; Kambhampati, Madhuri; Damsker, Jesse M; Gordish-Dressman, Heather; Yadavilli, Sridevi; Becher, Oren J; Gittens, Jamila; Stampar, Mojca; Packer, Roger J; Nazarian, Javad

2017-02-07

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug efficacy, post-treatment behavioral activity and side effects were assessed by treating two cohorts of brain tumor bearing mice with dexamethasone, vamorolone, or vehicle control. Our investigation showed that treatment with vamorolone resulted in a reduction of pro-inflammatory signals in tumor cells in vitro similar to treatment with dexamethasone. Treatment with vamorolone resulted in a better safety profile in comparison to dexamethasone treatment. Vamorolone- treated mice showed similar or better activity and survival when compared to dexamethasone-treated mice. Our data indicate vamorolone is a potential steroid-sparing alternative for treating patients with brain tumors.