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Sample records for inappropriate empiric antifungal

  1. Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

    PubMed

    Hahn-Ast, C; Felder, L; Mayer, K; Mückter, S; Ruhnke, M; Hein, R; Hellmich, M; Schwab, K; Rachow, T; Brossart, P; von Lilienfeld-Toal, M

    2016-05-01

    Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis. PMID:27021301

  2. Impact of Inappropriate Empiric Antimicrobial Therapy on Mortality of Septic Patients with Bacteremia: A Retrospective Study

    PubMed Central

    Lueangarun, Saoraya; Leelarasamee, Amorn

    2012-01-01

    Background. Inappropriate empiric antimicrobials could be a major cause of unfavorable mortality rates in co-morbid patients. This study aimed to assess the prevalence and impact of first-dose and 24-hour inappropriate antimicrobials on mortality rates of bacteremic septic patients. Methods. A retrospective cohort study was employed. Case record forms of patients diagnosed as sepsis, severe sepsis, or septic shock with positive hemoculture during 2009 were retrieved from the medical wards, Siriraj Hospital. Demographic data, antimicrobial use, types of bacteria isolated from blood and susceptibilities, patients' comorbidities, 28-day and overall mortality rates were collected and analyzed. Results. There were 229 cases, mean age (SD) of 63.5 (17.2) years and mean (SD) APACHE II score of 24.7 (6.8). The prevalence of first-dose and 24-hour inappropriate antimicrobials was 29.7% and 25.3%, respectively. The 28-day and overall mortality rates between first-dose inappropriate and appropriate antimicrobial were 67.6% versus 60.2% (P = 0.301) and 75.0% versus 68.3% (P = 0.345), consequently. Patients with septic shock and inappropriate first-dose antimicrobials significantly had higher 28-day mortality rate (61.6% versus 41.9%; P = 0.017). Conclusion. Higher mortality rates in bacteremic septic patients were substantially associated with inappropriate first-dose antimicrobials and 3-hour delayed antimicrobial administration after sepsis diagnosis. PMID:22919379

  3. Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU

    PubMed Central

    2014-01-01

    Background Invasive candidiasis (IC) is a life-threatening ICU-acquired infection. A strong correlation between time to antifungal therapy (AFT) administration and outcome has been established. Empirical therapy benefit should be balanced with the risk of echinocandin overuse. We assessed therefore a decision rule that aimed at guiding empirical therapy. Methods A 45-month prospective cohort study in a teaching medical ICU. All of the patients with suspected IC (uncontrolled sepsis despite broad spectrum antibiotics without any bacterial proven infection in patients with Candida score ≥ 3 points including multifocal Candida sp. colonization) were eligible. The primary endpoint was proven IC diagnosis (i.e., candidemia) following treatment onset. Timing of AFT administration was also investigated in those latter patients. Antifungal therapy step-down and discontinuation was done according to international guidelines in patients with candidemia. Otherwise, echinocandin discontinuation was encouraged in patients without proven IC, excepting when a clinical improvement was achieved without any other explanation that antifungals initiation (i.e., probable IC). In addition, a survival multivariate analysis using a Cox model was conducted. Results Fifty-one patients were given an echinocandin with respect to our decision rule. Among them, candidemia was diagnosed thereafter in 9 patients. Over the same period, antifungal therapy was triggered by candidemia announcement (i.e., definite therapy) in 12 patients who did not fulfill criteria for empirical therapy before. Time elapsed from candidemia onset to echinocandin therapy initiation was shortened (0.4 [0.5] vs. 2.4 [2.8] hours; p = 0.04) when it was given empirically. In addition, 18 patients clinically improved under empirical antifungal therapy without any obvious other explanation, despite IC remained unproven. Moreover, echinocandin exposure duration was independently related to survival in those patients

  4. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia.

    PubMed Central

    Gøtzsche, P. C.; Johansen, H. K.

    1997-01-01

    OBJECTIVE: To determine whether antifungal agents given prophylactically or empirically decrease morbidity and mortality in patients with cancer complicated by neutropenia. DESIGN: Meta-analysis of randomised trials of amphotericin B, various lipid soluble formulations of amphotericin B (for example, AmBisome), fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients with cancer complicated by neutropenia. MAIN OUTCOME MEASURES: Mortality, invasive fungal infection (defined as positive blood culture, oesophageal candidiasis, or lung or deep tissue infection), and colonisation. RESULTS: 24 trials with 2758 randomised patients were reviewed; the total number of deaths was 434. Prophylactic or empirical treatment with antifungals as a group bad no effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14). Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the studies were small and the difference in number of deaths was only 15. Antifungal treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to 0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated (95% confidence interval to 48 to 158) one case of fungal invasion was prevented in surviving patients. CONCLUSIONS: There seems to be no survival benefit of antifungal agents given prophylactically or empirically to patients with cancer complicated by neutropenia. These agents should be restricted to patients with proved infection and those in randomised trials. A large, definitive placebo controlled trial of amphotericin B is needed. PMID:9154027

  5. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J.; Ellanskaya, Irina; Ellanskaya, legal representative, Natalia; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K.; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    2009-09-15

    The invention relates to antifungal compositions and methods for protecting a plant from a fungal pathogen. Compositions including antifungal polypeptides isolated from a fungal fermentation broth are provided.

  6. When inappropriate becomes beneficial.

    PubMed

    Arroja, José David; Zimmermann, Marc

    2015-03-01

    We report the case of a young man who accidentally received a prolonged electric discharge from electrical wires and released the electric source with the help of an inappropriate shock from his implantable cardioverter-defibrillator (ICD), after misinterpretation of the electrical signal by the device as a ventricular tachycardia. This case illustrates the "electrical noise" phenomenon, and underscores the need for precautions for patients with an ICD and their physicians. PMID:25707735

  7. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  8. Antifungal hydrogels

    PubMed Central

    Zumbuehl, Andreas; Ferreira, Lino; Kuhn, Duncan; Astashkina, Anna; Long, Lisa; Yeo, Yoon; Iaconis, Tiffany; Ghannoum, Mahmoud; Fink, Gerald R.; Langer, Robert; Kohane, Daniel S.

    2007-01-01

    Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces. PMID:17664427

  9. The Rasch Model for Achievement Tests--Inappropriate in the Past, Inappropriate Today, Inappropriate Tomorrow.

    ERIC Educational Resources Information Center

    McLean, Leslie D.; Ragsdale, Ronald G.

    1983-01-01

    Robitaille and O'Shea used the Rasch model in developing a set of 40-item mathematics achievement tests. The Rasch model is inappropriate for such a purpose; their article presents the model in a too favorable light and continued application of the model encourages less desirable educational practice and misdirects scarce resources. (BRR)

  10. Conventional management of inappropriate sinus tachycardia.

    PubMed

    Olshansky, Brian; Sullivan, Renee M

    2016-06-01

    Inappropriate sinus tachycardia is a challenging problem to manage. There are limited data on the best method to evaluate and treat the problem. Here, we consider a conventional approach to inappropriate sinus tachycardia. PMID:26164138

  11. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  12. Triazole antifungals: a review.

    PubMed

    Peyton, L R; Gallagher, S; Hashemzadeh, M

    2015-12-01

    Invasive fungal infections and systemic mycosis, whether from nosocomial infection or immunodeficiency, have been on an upward trend for numerous years. Despite advancements in antifungal medication, treatment in certain patients can still be difficult for reasons such as impaired organ function, limited administration routes or poor safety profiles of the available antifungal medications. The growing number of invasive fungal species becoming resistant to current antifungal medications is of appreciable concern. Triazole compounds containing one or more 1,2,4-triazole rings have been shown to contain some of the most potent antifungal properties. Itracon-azole and fluconazole were some of the first triazoles synthesized, but had limitations associated with their use. Second-generation triazoles such as voriconazole, posa-conazole, albaconazole, efinaconazole, ravuconazole and isavuconazole are all derivatives of either itraconazole or fluconazole, and designed to overcome the deficiencies of their parent drugs. The goal of this manuscript is to review antifungal agents derived from triazole. PMID:26798851

  13. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey

    PubMed Central

    Akan, Hamdi; Atilla, Erden

    2016-01-01

    Despite the development of various guidelines, the approach to antifungal treatment in stem cell transplantation centers differs according to country or even between centers. This led to the development of another survey that aims to understand the antifungal treatment policies of Turkish stem cell transplantation centers. Although there has been an increasing trend towards the use of diagnostic-based treatments in Turkey in the last few years, empirical treatment is still the main approach. The practices of the stem cell transplantation centers reflect the general trends and controversies in this area, while there is a considerable use of antifungal combination therapy. PMID:25913124

  14. Teachers' Beliefs about Inappropriate Behaviour: Challenging Attitudes?

    ERIC Educational Resources Information Center

    Grieve, Ann M.

    2009-01-01

    This paper focuses on taking a first step in the process of influencing teachers' attitudes by building a description of beliefs about inappropriate behaviour that can be used in staff development work to provoke dissonance-led change. It describes a study, undertaken in two parts, exploring teachers' attitudes to inclusion, and ascertaining their…

  15. Functional analysis of inappropriate mealtime behaviors.

    PubMed Central

    Piazza, Cathleen C; Fisher, Wayne W; Brown, Kimberly A; Shore, Bridget A; Patel, Meeta R; Katz, Richard M; Sevin, Bart M; Gulotta, Charles S; Blakely-Smith, Audrey

    2003-01-01

    The purpose of the current investigation was to apply the functional analysis described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994) to the inappropriate mealtime behaviors of 15 children who had been referred to an intensive program for the assessment and treatment of severe feeding disorders. During Study 1, we conducted descriptive assessments of children and parents during meals. The results of Study 1 showed that parents used the following consequences for inappropriate mealtime behaviors: coaxing and reprimanding, allowing the child to periodically take a break from or avoid eating, and giving the child preferred food or toys following inappropriate behavior. The effects of these consequences were tested systematically in Study 2 when we conducted analogue functional analyses with the children. During alternating meals, one of the consequences typically used by parents consistently followed inappropriate child behavior. Results indicated that these consequences actually worsened behavior for 10 of the 15 children (67%). These results suggested that the analogue functional analysis described by Iwata et al. may be useful in identifying the environmental events that play a role in feeding disorders. PMID:12858984

  16. Children's Context Inappropriate Anger and Salivary Cortisol

    ERIC Educational Resources Information Center

    Locke, Robin L.; Davidson, Richard J.; Kalin, Ned H.; Goldsmith, H. Hill

    2009-01-01

    Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as…

  17. Antifungal Compounds from Cyanobacteria

    PubMed Central

    Shishido, Tânia K.; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P.; Permi, Perttu; Andreote, Ana P. D.; Fiore, Marli F.; Sivonen, Kaarina

    2015-01-01

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders. PMID:25871291

  18. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  19. Reducing inappropriate accident and emergency department attendances:

    PubMed Central

    Ismail, Sharif A; Gibbons, Daniel C; Gnani, Shamini

    2013-01-01

    Background Inappropriate attendances may account for up to 40% of presentations at accident and emergency (A&E) departments. There is considerable interest from health practitioners and policymakers in interventions to reduce this burden. Aim To review the evidence on primary care service interventions to reduce inappropriate A&E attendances. Design and setting Systematic review of UK and international primary care interventions. Method Studies published in English between 1 January 1986 and 23 August 2011 were identified from PubMed, the NHS Economic Evaluation Database, the Cochrane Collaboration, and Health Technology Assessment databases. The outcome measures were A&E attendances, patient satisfaction, clinical outcome, and intervention cost. Two authors reviewed titles and abstracts of retrieved results, with adjudication of disagreements conducted by the third. Studies were quality assessed using the Scottish Intercollegiate Guidelines Network checklist system where applicable. Results In total, 9916 manuscripts were identified, of which 34 were reviewed. Telephone triage was the single best-evaluated intervention. This resulted in negligible impact on A&E attendance, but exhibited acceptable patient satisfaction and clinical safety; cost effectiveness was uncertain. The limited available evidence suggests that emergency nurse practitioners in community settings and community health centres may reduce A&E attendance. For all other interventions considered in this review (walk-in centres, minor injuries units, and out-of-hours general practice), the effects on A&E attendance, patient outcomes, and cost were inconclusive. Conclusion Studies showed a negligible effect on A&E attendance for all interventions; data on patient outcomes and cost-effectiveness are limited. There is an urgent need to examine all aspects of primary care service interventions that aim to reduce inappropriate A&E attendance. PMID:24351497

  20. Epidemiology and definition of inappropriate sinus tachycardia.

    PubMed

    Pellegrini, Cara N; Scheinman, Melvin M

    2016-06-01

    Inappropriate sinus tachycardia (IST) is a clinical syndrome lacking formal diagnostic criteria. It is generally defined as an elevated resting heart rate (HR; >90-100 bpm) with an exaggerated response to physical or emotional stress and a clearly sinus mechanism. Clinical manifestations are broad from a complete lack of symptoms to incapacitating incessant tachycardia. Now understood to be relatively prevalent, it is observed to have a generally benign prognosis, though symptoms may persist for years. Whether IST is a single discrete entity or a heterogeneous condition with overlap to other syndromes such as postural orthostatic tachycardia syndrome remains a matter of debate. PMID:26310298

  1. Catheter ablation of inappropriate sinus tachycardia.

    PubMed

    Gianni, Carola; Di Biase, Luigi; Mohanty, Sanghamitra; Gökoğlan, Yalçın; Güneş, Mahmut F; Horton, Rodney; Hranitzky, Patrick M; Burkhardt, J David; Natale, Andrea

    2016-06-01

    Catheter ablation for inappropriate sinus tachycardia (IST) is recommended for patients symptomatic for palpitations and refractory to other treatments. The current approach consists in sinus node modification (SNM), achieved by ablation of the cranial part of the sinus node to eliminate faster sinus rates while trying to preserve chronotropic competence. This approach has a limited efficacy, with a very modest long-term clinical success. To overcome this, proper patient selection is crucial and an epicardial approach should always be considered. This brief review will discuss the current role and limitations of catheter ablation in the management of patients with IST. PMID:26310299

  2. Functional analysis and treatment of inappropriate verbal behavior.

    PubMed Central

    Dixon, M R; Benedict, H; Larson, T

    2001-01-01

    The present study examined the possible function of inappropriate verbal behavior of an adult man who had been diagnosed with both mental retardation and psychosis. Results of a functional analysis indicated that inappropriate verbal utterances were maintained by attention. An intervention consisting of the differential reinforcement of appropriate verbal behavior effectively reduced the inappropriate behavior. PMID:11678535

  3. POPI (Pediatrics: Omission of Prescriptions and Inappropriate Prescriptions): Development of a Tool to Identify Inappropriate Prescribing

    PubMed Central

    Prot-Labarthe, Sonia; Weil, Thomas; Angoulvant, François; Boulkedid, Rym; Alberti, Corinne; Bourdon, Olivier

    2014-01-01

    Introduction Rational prescribing for children is an issue for all countries and has been inadequately studied. Inappropriate prescriptions, including drug omissions, are one of the main causes of medication errors in this population. Our aim is to develop a screening tool to identify omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. Methods A selection of diseases was included in the tool using data from social security and hospital statistics. A literature review was done to obtain criteria which could be included in the tool called POPI. A 2-round-Delphi consensus technique was used to establish the content validity of POPI; panelists were asked to rate their level of agreement with each proposition on a 9-point Likert scale and add suggestions if necessary. Results 108 explicit criteria (80 inappropriate prescriptions and 28 omissions) were obtained and submitted to a 16-member expert panel (8 pharmacists, 8 pediatricians hospital-based −50%- or working in community −50%-). Criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology and miscellaneous). Each criterion was accompanied by a concise explanation as to why the practice is potentially inappropriate in pediatrics (including references). Two round of Delphi process were completed via an online questionnaire. 104 out of the 108 criteria submitted to experts were selected after 2 Delphi rounds (79 inappropriate prescriptions and 25 omissions). Discussion Conclusion POPI is the first screening-tool develop to detect inappropriate prescriptions and omissions in pediatrics based on explicit criteria. Inter-user reliability study is necessary before using the tool, and prospective study to assess the effectiveness of POPI is also necessary. PMID:24978045

  4. Syndrome of inappropriate antidiuresis in doxylamine overdose.

    PubMed

    Carrascosa, Miguel F; Caviedes, José-Ramón Salcines; Lucena, M Isabel; Cuadrado-Lavín, Antonio

    2012-01-01

    Doxylamine succinate, an H(1)-antihistamine drug, is commonly used as sleep-inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual doses, it may cause impairment of cognitive and psychomotor performance, anticholinergic effects, agitation and postural hypotension. Besides, since this drug is frequently involved in either accidental or intentional overdoses, it seems relevant to bear in mind other possible toxic effects. We report a case of acute severe hyponatremia in the setting of a syndrome of inappropriate antidiuresis (SIAD), an apparent new adverse effect linked to doxylamine overdose. The Naranjo adverse drug reaction probability scale indicated a probable relationship between doxylamine intake and SIAD development. SIAD may be considered as a potential, serious adverse reaction of doxylamine overdose. Clinicians should consider this aetiological possibility when attending patients suffering from hyponatremia. PMID:23166178

  5. [New antifungal agents: voriconazole and caspofungin].

    PubMed

    Dupont, B

    2003-12-01

    Among new available antifungal agents voriconazole is a new triazole with an intravenous (i.v.) and oral formulation, and caspofungin is an echinocandin, new family with a new mode of action on the cell wall. It is available as an i.v. preparation. Both drugs have a broad spectrum targeting most of the usual pathogens: Candida and Aspergillus, even with low suceptibility or resistance to other antifungals. Voriconazole is also active on Scedosporium and Fusarium. The efficacy of these molecules was established in vitro and in experimental infections in animals either normal or immunosuppressed. Voriconazole is active in oropharyngeal and esophageal candidiasis, in refractory invasive candidiasis and as a first line treatment of invasive aspergillosis with better results than amphotéricine B. It was also effective in scedosporiosis and in fusariosis. Caspofungin is active in oropharyngeal and esophageal candidiasis, in invasive candidiasis ranking among the best drugs in non neutropenic patients. It was shown effective in refractory aspergillosis. As empirical treatment of febrile neutropenic patients, these molecules should probably be restricted to the highest risk-population. Safety is good, side effects are a rare cause of discontinuation of treatment, class specific drug-drug interactions occur with voriconazole. These molecules open an important field of investigations with combination of antifungal agents. PMID:15022787

  6. The risks of inappropriateness in cardiac imaging.

    PubMed

    Picano, Eugenio

    2009-05-01

    The immense clinical and scientific benefits of cardiovascular imaging are well-established, but are also true that 30 to 50% of all examinations are partially or totally inappropriate. Marketing messages, high patient demand and defensive medicine, lead to the vicious circle of the so-called Ulysses syndrome. Mr. Ulysses, a typical middle-aged "worried-well" asymptomatic subject with an A-type coronary personality, a heavy (opium) smoker, leading a stressful life, would be advised to have a cardiological check-up after 10 years of war. After a long journey across imaging laboratories, he will have stress echo, myocardial perfusion scintigraphy, PET-CT, 64-slice CT, and adenosine-MRI performed, with a cumulative cost of >100 times a simple exercise-electrocardiography test and a cumulative radiation dose of >4,000 chest x-rays, with a cancer risk of 1 in 100. Ulysses is tired of useless examinations, exorbitant costs. unaffordable even by the richest society, and unacceptable risks. PMID:19543412

  7. The Risks of Inappropriateness in Cardiac Imaging

    PubMed Central

    Picano, Eugenio

    2009-01-01

    The immense clinical and scientific benefits of cardiovascular imaging are well-established, but are also true that 30 to 50% of all examinations are partially or totally inappropriate. Marketing messages, high patient demand and defensive medicine, lead to the vicious circle of the so-called Ulysses syndrome. Mr. Ulysses, a typical middle-aged “worried-well” asymptomatic subject with an A-type coronary personality, a heavy (opium) smoker, leading a stressful life, would be advised to have a cardiological check-up after 10 years of war. After a long journey across imaging laboratories, he will have stress echo, myocardial perfusion scintigraphy, PET-CT, 64-slice CT, and adenosine-MRI performed, with a cumulative cost of >100 times a simple exercise-electrocardiography test and a cumulative radiation dose of >4,000 chest x-rays, with a cancer risk of 1 in 100. Ulysses is tired of useless examinations, exorbitant costs. unaffordable even by the richest society, and unacceptable risks. PMID:19543412

  8. What to do about Inappropriate Behavior

    NASA Astrophysics Data System (ADS)

    Durand, Bernice

    2011-01-01

    If you believe you are a victim of harassment, bias, or prejudice, your first need is to know what person you should confide in who would be qualified to help you understand and go through the process of resolving your difficult situation. You will be best off if you have an accessible, trustworthy institutional infrastructure in place for dealing with inappropriate behavior. The exact nature of the infrastructure varies among institutions; but it starts with leadership from the top person in every unit, for example the university president, the dean, the department chair, and the research group leader. A good "safety net” structure also includes a reliable system for reporting and addressing problems before they escalate; an institutional "enforcer” who is widely known to mean business; and trainings and frequent publicity about the consequences of such behavior. The components of a good structure, as well as some alternative routes to take if you don't have such a system, will be described in the contexts of different types of institutions; and you will learn the criteria for prohibited behaviors. There will be time for analysis and discussion of scenarios taken from real incidents, altered to protect privacy.

  9. [Porphyria and inappropriate antidiuretic hormone syndrome].

    PubMed

    López Montes, A; Lorenzo, I; Pérez Martínez, J

    2004-01-01

    We report the case of a 37-years-old woman with inappropriate antidiuretic hormone syndrome due to an attack of acute porphyria. The patient was admitted to our hospital for abdominal pain, sleepiness and pink urine. Family and personal history were normal. Seven days before the admission the patient had a laparoscopy operation for endometriosis in her left ovary. The patient had had two normal pregnancies. The physical examination was normal, the skin turgor was good and no edema was present, the blood pressure was 140/90 mmHg. Her serum sodium was 114 mEq/L, serum osmolality 243 mOsm/kg, urine sodium 146 mEq/L and urine osmolality 457 mOsm/kg. Values from laboratory examination revealed a normal peripheral haematogram, a normal kidney function, normal liver, adrenal and thyroid function. The urine tested for amino-levulinic acid, coproporphyrin and uroporphyrin was strongly positive. These findings are compatible with Porphyria Variegata or Coproporphyria Hereditary. A diagnosis of Porphyria acute with SIADH was made, and water fluid restriction, i.v. hypertonic saline infusion and furosemide to correct the hyponatremia was begun. In 1966, lesions of the median eminence of the hypothalamus and both hypothalamic -hypophyseal tracts were described in a patient with Porphyria acute intermittent and SIADH. It was suggested that SIADH occurred because of damage to these areas of the brain from excessive exposure to porphyrins. PMID:15219077

  10. EUCAST breakpoints for antifungals.

    PubMed

    Rodríguez-Tudela, Juan L; Arendrup, Maiken C; Cuenca-Estrella, Manuel; Donnelly, J Peter; Lass-Flörl, Cornelia

    2010-03-01

    Susceptibility testing of fungi and development of interpretative breakpoints has become increasingly important due to the growing incidence of invasive fungal infections, the number and classes of antifungals, and the emerging reports of acquired resistance. The subcommittee on antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST) has developed standards for susceptibility testing of fermentative yeasts and molds as well as proposing breakpoints for fluconazole and voriconazole against Candida. The aim of this work is to describe the EUCAST process of setting breakpoints for antifungals. Five aspects are evaluated during the process of developing breakpoints: 1) the most common dosage used in each European country, 2) the definition of the wild-type population for each target microorganism at the species level and the determination of epidemiological cutoffs, 3) the drug's pharmacokinetics and 4) pharmacodynamics, including Monte Carlo simulations, and 5) the correlation of MICs with clinical outcome of patients treated with the compound. When insufficient data are available (e.g., due to lack of information on the clinical outcome of infections caused by isolates with an elevated MIC), epidemiological cutoff values, rather than breakpoints, are recommended until the necessary information becomes available. PMID:20369073

  11. Reconsidering "The inappropriateness of conventional cephalometrics".

    PubMed

    Bookstein, Fred L

    2016-06-01

    Of all the articles on cephalometrics this journal has published over the last half-century, the one most cited across the scientific literature is the 1979 lecture "The inappropriateness of conventional cephalometrics" by Robert Moyers and me. But the durable salience of this article is perplexing, as its critique was misdirected (it should have been aimed at the craniometrics of the early twentieth century, not merely the roentgenographic extension used in the orthodontic clinic) and its proposed remedies have all failed to establish themselves as methods of any broad utility. When problems highlighted by Moyers and me have been resolved at all, the innovations that resolved them owe to tools very different from those suggested in our article and imported from fields quite a bit farther from biometrics than we expected back in 1979. One of these tools was the creation de novo of a new abstract mathematical construction, statistical shape space, in the 1980s and 1990s; another was a flexible and intuitive new graphic, the thin-plate spline, for meaningfully and suggestively visualizing a wide variety of biological findings in these spaces. On the other hand, many of the complaints Moyers and I enunciated back in 1979, especially those stemming from the disarticulation of morphometrics from the explanatory styles and purposes of clinical medicine, remain unanswered even today. The present essay, a retrospective historical meditation, reviews the context of the 1979 publication, its major themes, and its relevance today. This essay is dedicated to the memory of Robert E. Moyers on the 100th anniversary of the American Journal of Orthodontics and Dentofacial Orthopedics. PMID:27241987

  12. Setting Limits: The Child Who Uses Inappropriate Language

    ERIC Educational Resources Information Center

    Greenberg, Polly

    2004-01-01

    This article discusses how to work with a child who uses inappropriate language. The words inappropriately used by young children are grouped into five categories: (1) names of body parts considered as private, and their nicknames; (2) bathroom words and body products; (3) religion-related words; (4) sexually charged words overheard when adults…

  13. Functional Analysis and Treatment of Multiply Controlled Inappropriate Mealtime Behavior

    ERIC Educational Resources Information Center

    Bachmeyer, Melanie H.; Piazza, Cathleen C.; Fredrick, Laura D.; Reed, Gregory K.; Rivas, Kristi D.; Kadey, Heather J.

    2009-01-01

    Functional analyses identified children whose inappropriate mealtime behavior was maintained by escape and adult attention. Function-based extinction procedures were tested individually and in combination. Attention extinction alone did not result in decreases in inappropriate mealtime behavior or a significant increase in acceptance. By contrast,…

  14. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal...

  15. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal...

  16. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal...

  17. 20 CFR 369.4 - Inappropriate use of the seal.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Inappropriate use of the seal. 369.4 Section... OF THE SEAL OF THE RAILROAD RETIREMENT BOARD § 369.4 Inappropriate use of the seal. The Railroad Retirement Board shall not grant permission for use of the seal in those instances where use of the seal...

  18. Assessing Student Perceptions of Inappropriate and Appropriate Teacher Humor

    ERIC Educational Resources Information Center

    Frymier, Ann Bainbridge; Wanzer, Melissa Bekelja; Wojtaszczyk, Ann M.

    2007-01-01

    This study replicated and extended Wanzer, Frymier, Wojtaszczyk, and Smith's (2006) preliminary typology of appropriate and inappropriate teacher humor and advanced three explanations for differences in interpretations of teacher humor. Students were more likely to view teacher humor as inappropriate when it was perceived as offensive and when it…

  19. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  20. Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

    PubMed Central

    Spampinato, Claudia

    2013-01-01

    The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment of Candida infections is also provided. PMID:23878798

  1. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

    PubMed

    Gupta, Deepa; Jain, D K

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  2. Update on azole antifungals.

    PubMed

    Zonios, Dimitrios I; Bennett, John E

    2008-04-01

    This is a comprehensive, clinically oriented review of the four commercially available triazoles: fluconazole, itraconazole, voriconazole, and posaconazole. Emphasis is placed in pharmacology, drug interactions, adverse events, antifungal activity, and the evolving perspective of their clinical use. Key clinical trials are briefly discussed, and specific drug indications summarized. Fluconazole remains a valuable low-cost choice for the treatment of various fungal infections, including candidiasis and cryptococcosis. It has relatively few drug interactions and is safe but lacks activity against filamentous fungi. The use of itraconazole is historically plagued by erratic bioavailability of the oral capsule, improved with the oral solution. Drug interactions are numerous. Itraconazole exhibits significant activity against Aspergillus and the endemic fungi. Voriconazole has revolutionized the treatment of aspergillosis in severely immunocompromised patients, but its use is compromised by complicated pharmacokinetics, notable drug interactions, and relatively significant adverse events. Finally, posaconazole is the last addition to the azole armamentarium with extended antifungal spectrum, significant activity against the zygomycetes, and, apparently, optimal safety profile. Posaconazole has a significant role for the prophylaxis of invasive fungal infections in severely immunocompromised patients. Multiple daily dosing, a need for fatty foods for absorption, and absence of an intravenous formulation restrict its use to selected populations. PMID:18366001

  3. Recent advances in antifungal chemotherapy.

    PubMed

    Petrikkos, George; Skiada, Anna

    2007-08-01

    For over 50 years, amphotericin B deoxycholate (AmBD) has been the 'gold standard' in antifungal chemotherapy, despite its frequent toxicities. However, improved treatment options for invasive fungal infections (IFIs) have been developed during the last 15 years. Newer antifungal agents, including less toxic lipid preparations of AmBD, triazoles and the echinocandins, have been added to our armamentarium against IFIs. Some of these newer drugs can now replace AmBD as primary therapy (e.g. caspofungin for candidiasis, voriconazole for aspergillosis), whilst others offer new therapeutic options for difficult-to-treat IFIs (e.g. posaconazole for zygomycosis, fusariosis and chromoblastomycosis). It is interesting that extended use of newer antifungals such as fluconazole, despite decreasing the mortality attributed to candidiasis, resulted in selection of species resistant to several antifungals (Candida krusei, Candida glabrata); whilst several publications suggest that prolonged use of voriconazole may expose severely immunocompromised patients to the risk of zygomycosis (breakthrough). On the other hand, the differences in the mode of action of newer antifungals such as echinocandins raise the question whether combination antifungal therapy is more effective than monotherapy. Finally, the availability of an oral formulation with excellent biosafety of several newer antifungals (e.g. posaconazole) makes them candidates for prophylactic or prolonged maintenance therapy. PMID:17524625

  4. Mechanisms of echinocandin antifungal drug resistance

    PubMed Central

    Perlin, David S.

    2015-01-01

    Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall–active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which are frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promote the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin resistance mechanism, along with cellular and clinical factors promoting resistance, will promote more effective strategies to overcome and prevent echinocandin resistance. PMID:26190298

  5. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  6. Antifungal therapy with an emphasis on biofilms

    PubMed Central

    Pierce, Christopher G.; Srinivasan, Anand; Uppuluri, Priya; Ramasubramanian, Anand K.; López-Ribot, José Luis

    2013-01-01

    Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins, constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, microbial communities displaying resistance to most antifungal agents. A better understanding of fungal biofilms provides for new opportunities for the development of urgently needed novel antifungal agents and strategies. PMID:24011516

  7. Comparison of echinocandin antifungals

    PubMed Central

    Eschenauer, Gregory; DePestel, Daryl D; Carver, Peggy L

    2007-01-01

    The incidence of invasive fungal infections, especially those due to Aspergillus spp. and Candida spp., continues to increase. Despite advances in medical practice, the associated mortality from these infections continues to be substantial. The echinocandin antifungals provide clinicians with another treatment option for serious fungal infections. These agents possess a completely novel mechanism of action, are relatively well-tolerated, and have a low potential for serious drug–drug interactions. At the present time, the echinocandins are an option for the treatment of infections due Candida spp (such as esophageal candidiasis, invasive candidiasis, and candidemia). In addition, caspofungin is a viable option for the treatment of refractory aspergillosis. Although micafungin is not Food and Drug Administration-approved for this indication, recent data suggests that it may also be effective. Finally, caspofungin- or micafungin-containing combination therapy should be a consideration for the treatment of severe infections due to Aspergillus spp. Although the echinocandins share many common properties, data regarding their differences are emerging at a rapid pace. Anidulafungin exhibits a unique pharmacokinetic profile, and limited cases have shown a potential far activity in isolates with increased minimum inhibitory concentrations to caspofungin and micafungin. Caspofungin appears to have a slightly higher incidence of side effects and potential for drug–drug interactions. This, combined with some evidence of decreasing susceptibility among some strains of Candida, may lessen its future utility. However, one must take these findings in the context of substantially more data and use with caspofungin compared with the other agents. Micafungin appears to be very similar to caspofungin, with very few obvious differences between the two agents. PMID:18360617

  8. Alternative approaches to antifungal therapies

    PubMed Central

    Mehra, T; Köberle, M; Braunsdorf, C; Mailänder-Sanchez, D; Borelli, C; Schaller, M

    2012-01-01

    The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an aging population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments which exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins, and cathelicidins, as well as novel synthetic peptides. Amongst fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach. PMID:23078400

  9. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  10. Appropriate and Inappropriate Practices for Coaching Female Athletes

    ERIC Educational Resources Information Center

    Bryan, Charity; Sims, Sandra

    2014-01-01

    This article is intended to provide coaches, parents/guardians and school administrators with specific guidelines that identify coaching practices that are in the best interests of the adolescent female athlete (appropriate) and those that are counterproductive or even harmful (inappropriate). These guidelines can be used as a self-assessment for…

  11. Experimental Analysis of Response Covariation among Compliant and Inappropriate Behaviors.

    ERIC Educational Resources Information Center

    Parrish, John M.; And Others

    1986-01-01

    The study investigated the relationship between topographically different child behaviors (compliance and inappropriate activities) in four mentally retarded subjects (aged 3-5) by using a methodology that tests for response covariation. Regardless of the intervention used, the behavior targeted, or the direction manipulated, the nontargeted…

  12. Altering the Inappropriate Comments of a Student with Multiple Disabilities

    ERIC Educational Resources Information Center

    Schoen, Sharon Faith; Thomas, Rachel

    2006-01-01

    This article offers an example of how teachers may successfully use a process for addressing problem behaviors in the classroom. The process includes (1) framing critical questions, (2) collecting relevant data, (3) taking well-researched actions, and (4) reflecting on the impact of these actions. Guided by these steps, the inappropriate comments…

  13. Appropriate and Inappropriate Uses of Humor By Teachers

    ERIC Educational Resources Information Center

    Bekelja Wanzer, Melissa; Bainbridge Frymier, Ann; Wojtaszczyk, Ann M; Smith, Tony

    2006-01-01

    The use of humor in teaching has been linked to learning in several studies, although the research has been equivocal. The various types of humor used by teachers have also been investigated but not in terms of what students view as appropriate and inappropriate uses of humor. Participants in this study were asked to generate examples of…

  14. Inappropriate Student Behavior--A Problem for Student Teachers.

    ERIC Educational Resources Information Center

    Boyce, Ann

    1997-01-01

    Describes a strategy used in a preservice teacher education program to help student teachers and practicum students deal effectively with inappropriate pupil classroom behavior. The three-step strategy helps student teachers effectively identify and modify the behavior of children who misbehave. (SM)

  15. Functional Analysis and Treatment of Inappropriate Sexual Behavior.

    ERIC Educational Resources Information Center

    Fyffe, Christie E.; Kahng, SungWoo; Fittro, Ellen; Russell, David

    2004-01-01

    The results of a functional analysis showed that inappropriate sexual behaviors exhibited by a 9-year-old boy who had been diagnosed with traumatic brain injury were maintained by positive reinforcement in the form of social attention. An intervention consisting of functional communication training and extinction resulted in reduced levels of…

  16. Sexually Inappropriate or Abusive Behaviour among Pupils in Special Schools

    ERIC Educational Resources Information Center

    Fyson, Rachel

    2009-01-01

    In this article, Rachel Fyson of the Centre for Social Work in the School of Sociology and Social Policy at the University of Nottingham reports the findings of a study into sexually inappropriate or abusive behaviour occurring between pupils in special schools in four local authorities in England. The behaviours identified ranged from relatively…

  17. Antifungal Compounds from Piper Species

    PubMed Central

    Xu, Wen-Hui; Li, Xing-Cong

    2013-01-01

    This review documents chemical structures and antifungal activities of 68 compounds isolated from 22 Piper species of the plant family Piperaceae. These compounds include amides, flavonoids, prenylated benzoic acid derivatives, lignans, phenylpropanoids, butenolides, and cyclopentendiones. Some of them may serve as leads for potential pharmaceutical or agricultural fungicide development. PMID:24307889

  18. Antifungal activity of juniper extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sawdust from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane or ethanol and the extracts tested for antifungal activity against four species of wood-rot fungi. These species studied represent the junipers with the greatest potential for co...

  19. AB013. Inappropriate asthma therapy: a tale of two countries

    PubMed Central

    Nibber, Anjan; Belhassen, Manon; Van Ganse, Eric; Ryan, Dermot; Langlois, Carole; Appiagyei, Francis; Skinner, Derek; Laforest, Laurent; Soriano, Joan B.; Price, David

    2016-01-01

    Background Inappropriate prescribing and misuse of asthma medication, have been identified as potentially preventable factors linked to asthma exacerbations and deaths. A recent report by the National Review of Asthma Deaths drew attention to the excessive prescribing of reliever medication, and under-prescribing of controlled medication in the United-Kingdom (UK). The inappropriate prescribing of long-acting beta agonist (LABA) bronchodilator inhalers, as either a monotherapy or without inhaled corticosteroids (ICS) has been highlighted as a major preventable factor of asthma exacerbations and deaths. To determine whether the prevalence of inappropriate LABA therapy use in asthma in the UK and in France has changed over time. Methods Two interval, parallel, population-based cohorts (2007 and 2013), were developed in each country, utilising the UK Optimum Patient Care Research Database and the French Permanent Beneficiaries Sample database. Following inclusion, patients aged 6–40 years were studied over a 12-month period. The use of LABAs without ICS, and ≥2-fold higher use of LABA compared with ICS were investigated. Analyses were stratified by age groups: children (6–13 years) and adults (14–40 years). Results Overall, 39,743 UK and 4,910 French patients were included in 2007 and 14,036 and 5,657 in 2013. In 2013, LABA use without ICS occurred in 0.1% and 1.5% of UK and French adults respectively. This was a marked reduction from 2007 UK and French figures of 0.4% and 2.6% respectively (P<0.05 for both). Excessive use of LABA relative to ICS occurred in 0.2% of UK adults and in 0.7% of French adults in 2013. These percentages represented a decrease from the 2007 figures of 0.6% and 1.4% for UK (P=0.29) and France (P=0.003), respectively. In 2007, LABA inappropriate use was more frequent in French than UK asthmatic children (P<0.0001), but showed a downward trend by time in both countries (0.1% in 2013 in both countries). Conclusions Our study suggests

  20. Syndrome of inappropriate antidiuretic hormone secretion concurrent with liver disease in a dog.

    PubMed

    Kang, Min-Hee; Park, Hee-Myung

    2012-05-01

    A 5-year-old female Chihuahua was presented for acute collapse. Laboratory examinations showed markedly elevated levels of hepatobiliary enzymes. Empiric antibiotic therapy for bacterial infection of the liver was ineffective. The clinical signs worsened with the development of hyponatremia with hypoosmolality and elevated urine sodium levels. The dog was suspected of having acute cholangiohepatitis associated with an immune-mediated disease. Subsequently, it was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) on the basis of the specific disease criteria. Further tests showed normal function of the adrenal and thyroid glands, and MRI and cerebrospinal fluid (CSF) analysis did not show any intracranial diseases. Immunosuppressive therapy and water restriction resolved the clinical signs and improved the SIADH in this dog. This case indicates that SIADH can occur concurrently with suspected immune-mediated liver disease in dogs. PMID:22185769

  1. Training should be the first step toward an antifungal stewardship program.

    PubMed

    Valerio, Maricela; Muñoz, Patricia; Rodríguez-González, Carmen; Sanjurjo, María; Guinea, Jesús; Bouza, Emilio

    2015-04-01

    The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. PMID:25066382

  2. [Overtreatment: Initiatives to identify ineffective and inappropriate medical interventions].

    PubMed

    Wild, Claudia; Mayer, Julia

    2016-04-01

    A growing number of international initiatives rise to the challenge of reduction of medical overuse. Increasingly, these activities are promoted by physicians and clinicians, and aim to identify and avoid inappropriate health interventions. This article places the Choosing Wisely initiative within the context of less well-known activities, 13 all together, and briefly describes their characteristics; in addition, similarities and differences regarding their methods are elaborated. PMID:26883771

  3. Inappropriate use of potent topical glucocorticoids in infants.

    PubMed

    Ozon, Alev; Cetinkaya, Semra; Alikasifoglu, Ayfer; Gonc, E Nazli; Sen, Yaşar; Kandemir, Nurgün

    2007-02-01

    Topical therapy with glucocorticoids (GCs) is used commonly in chronic dermatoses. Side effects are less common compared to systemic use; however, newer potent preparations may have serious side effects. A potential danger is their inappropriate use. Three infants who developed iatrogenic Cushing's syndrome and prolonged adrenal suppression in the course of GC therapy for simple diaper dermatitis are described. One patient also developed steatohepatitis which is uncommon with local GCs. PMID:17396439

  4. Requests for "inappropriate" treatment based on religious beliefs.

    PubMed

    Orr, R D; Genesen, L B

    1997-06-01

    Requests by patients or their families for treatment which the patient's physician considers to be "inappropriate" are becoming more frequent than refusals of treatment which the physician considers appropriate. Such requests are often based on the patient's religious beliefs about the attributes of God (sovereignty, omnipotence), the attributes of persons (sanctity of life), or the individual's personal relationship with God (communication, commands, etc). We present four such cases and discuss some of the basic religious tenets of the three Abrahamic faith traditions as they relate to such requests. We suggest that religious reasons for requesting "inappropriate" treatment are "special" and deserve serious consideration. We offer guidance to assist clinicians and clinical ethicists as they attempt to resolve these conflicts, emphasising the importance of understanding the religious beliefs of the patient/surrogate and suggesting the assistance of a religious interpreter. We suggest open discussion with patients and families of both the clinical situation and the theological basis for these requests. We also suggest that clinicians use additional religious doctrines or principles from patients' own traditions to balance the reasons behind the requests. We conclude that most persistent requests for "inappropriate" treatment should be honoured. PMID:9220325

  5. Reducing inappropriate ESR testing with computerized clinical decision support

    PubMed Central

    Gottheil, Stephanie; Khemani, Ekta; Copley, Katherine; Keeney, Michael; Kinney, Jeff; Chin-Yee, Ian; Gob, Alan

    2016-01-01

    Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering. PMID:27096092

  6. Requests for "inappropriate" treatment based on religious beliefs.

    PubMed Central

    Orr, R D; Genesen, L B

    1997-01-01

    Requests by patients or their families for treatment which the patient's physician considers to be "inappropriate" are becoming more frequent than refusals of treatment which the physician considers appropriate. Such requests are often based on the patient's religious beliefs about the attributes of God (sovereignty, omnipotence), the attributes of persons (sanctity of life), or the individual's personal relationship with God (communication, commands, etc). We present four such cases and discuss some of the basic religious tenets of the three Abrahamic faith traditions as they relate to such requests. We suggest that religious reasons for requesting "inappropriate" treatment are "special" and deserve serious consideration. We offer guidance to assist clinicians and clinical ethicists as they attempt to resolve these conflicts, emphasising the importance of understanding the religious beliefs of the patient/surrogate and suggesting the assistance of a religious interpreter. We suggest open discussion with patients and families of both the clinical situation and the theological basis for these requests. We also suggest that clinicians use additional religious doctrines or principles from patients' own traditions to balance the reasons behind the requests. We conclude that most persistent requests for "inappropriate" treatment should be honoured. PMID:9220325

  7. Reducing inappropriate ESR testing with computerized clinical decision support.

    PubMed

    Gottheil, Stephanie; Khemani, Ekta; Copley, Katherine; Keeney, Michael; Kinney, Jeff; Chin-Yee, Ian; Gob, Alan

    2016-01-01

    Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering. PMID:27096092

  8. Detecting Inappropriate Access to Electronic Health Records Using Collaborative Filtering.

    PubMed

    Menon, Aditya Krishna; Jiang, Xiaoqian; Kim, Jihoon; Vaidya, Jaideep; Ohno-Machado, Lucila

    2014-04-01

    Many healthcare facilities enforce security on their electronic health records (EHRs) through a corrective mechanism: some staff nominally have almost unrestricted access to the records, but there is a strict ex post facto audit process for inappropriate accesses, i.e., accesses that violate the facility's security and privacy policies. This process is inefficient, as each suspicious access has to be reviewed by a security expert, and is purely retrospective, as it occurs after damage may have been incurred. This motivates automated approaches based on machine learning using historical data. Previous attempts at such a system have successfully applied supervised learning models to this end, such as SVMs and logistic regression. While providing benefits over manual auditing, these approaches ignore the identity of the users and patients involved in a record access. Therefore, they cannot exploit the fact that a patient whose record was previously involved in a violation has an increased risk of being involved in a future violation. Motivated by this, in this paper, we propose a collaborative filtering inspired approach to predicting inappropriate accesses. Our solution integrates both explicit and latent features for staff and patients, the latter acting as a personalized "finger-print" based on historical access patterns. The proposed method, when applied to real EHR access data from two tertiary hospitals and a file-access dataset from Amazon, shows not only significantly improved performance compared to existing methods, but also provides insights as to what indicates an inappropriate access. PMID:24683293

  9. A Prototype Antifungal Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hudson, Sarah P.; Mobbs, Ashley N.; Hoare, Todd R.; Iwata, Naomi G.; Fink, Gerald R.

    2011-01-01

    Purpose. To design a contact lens to treat and prevent fungal ocular infections. Methods. Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. Results. Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. Conclusions. An econazole-eluting contact lens could be used as a treatment for fungal ocular infections. PMID:21527380

  10. Advancements in Topical Antifungal Vehicles.

    PubMed

    Kircik, Leon H

    2016-02-01

    The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles. PMID:26885798

  11. Antifungal stilbenoids from Stemona japonica.

    PubMed

    Zhang, Ya-Zhong; Xu, Guo-Bing; Zhang, Tong

    2008-01-01

    Three new dihydrostilbenes, stilbostemins P-R (1-3), and a new dihydrophenanthrene, stemanthrene G (4), were isolated from the roots of Stemona japonica together with three known bibenzyls, 3,5-dihydroxy-2'-methoxy bibenzyl (5), 3,3'-dihydroxy-2,5'-dimethoxy bibenzyl (6), and 3,5,2'-trihydroxy-4-methyl bibenzyl (7). Their structures were elucidated by spectroscopic analyses. Compounds 5 and 6 exhibited strong antifungal activities against Candida albicans. PMID:18636375

  12. Defensins: antifungal lessons from eukaryotes

    PubMed Central

    Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

    2014-01-01

    Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

  13. Evaluation of vaginal antifungal formulations in vivo.

    PubMed Central

    McRipley, R. J.; Erhard, P. J.; Schwind, R. A.; Whitney, R. R.

    1979-01-01

    Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies. PMID:392480

  14. Antibacterial and Antifungal Compounds from Marine Fungi

    PubMed Central

    Xu, Lijian; Meng, Wei; Cao, Cong; Wang, Jian; Shan, Wenjun; Wang, Qinggui

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review. PMID:26042616

  15. Anaerobic Bacteremia: Impact of Inappropriate Therapy on Mortality

    PubMed Central

    Lee, Yangsoon; Park, Yongjung; Kim, Myungsook; Choi, Jun Yong; Yong, Dongeun; Jeong, Seok Hoon

    2016-01-01

    Background Investigation on incidence and mortality of anaerobic bacteremia (AB) is clinically relevant in spite of its infrequent occurrence and not often explored, which report varies according to period and institutions. Therefore, it is necessary to analyze the incidence and risk factors related to mortality and assess clinical outcomes of AB in current aspect. Materials and Methods Characteristics of AB patients and anaerobic bacteria from blood culture at a university hospital in 2012 were reviewed retrospectively. The correlation between risk factors and 28-day patient mortality was analyzed. Results A total of 70 non-duplicated anaerobic bacteria were isolated from blood of 70 bacteremia patients in 2012. The history of cardiovascular disease as host's risk factor was statistically significant (P = 0.0344) in univariate and multivariate analysis. Although the inappropriate therapy was not statistically significant in univariate and multivariate analysis, the survival rate of bacteremia was significantly worse in patients who had inappropriate therapy compared with those underwent appropriate therapy (hazard ratio, 5.4; 95% confidence interval, 1.7–6.9; P = 0.004). The most frequently isolated organism was Bacteroides fragilis (32 isolates, 46%), followed by Bacteroides thetaiotaomicron (10, 14%), and non-perfringens Clostridium (7, 10%). Conclusion The incidence of AB in 2012 was 2.3% (number of AB patients per 100 positive blood culture patients) and the mortality rate in patients with clinically significant AB was 21.4%. In addition, AB was frequently noted in patients having malignancy and the survival rate of AB was significantly worse in patients who received inappropriate therapy compared with those underwent appropriate therapy. PMID:27433379

  16. Medically Inappropriate or Futile Treatment: Deliberation and Justification.

    PubMed

    Misak, Cheryl J; White, Douglas B; Truog, Robert D

    2016-02-01

    This paper reframes the futility debate, moving away from the question "Who decides when to end what is considered to be a medically inappropriate or futile treatment?" and toward the question "How can society make policy that will best account for the multitude of values and conflicts involved in such decision-making?" It offers a pragmatist moral epistemology that provides us with (1) a clear justification of why it is important to take best standards, norms, and physician judgment seriously and (2) a clear justification of why ample opportunity must be made for patients, families, and society to challenge those standards and norms. PMID:26681796

  17. Quetiapine-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone

    PubMed Central

    2016-01-01

    The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can be induced by various conditions, including malignant neoplasms, infections, central nervous system disorders, and numerous drugs. We here report a case of a 65-year-old female patient, treated with quetiapine for schizophrenia, who presented with generalized tonic-clonic seizures and was finally diagnosed with quetiapine-induced SIADH. Quetiapine-associated hyponatremia is extremely uncommon and only a few, relevant reports can be found in the literature. This case underlines the fact that patients on antipsychotic medication and more specifically on quetiapine should be closely monitored and routinely tested for electrolyte disorders. PMID:27034875

  18. Reduction of Inappropriate Behavior with Primary Mentally Handicapped Children Using Teacher Praise, Ignoring, and Parental Consequences.

    ERIC Educational Resources Information Center

    Sandeman, M. G.; McLaughlin, T. F.

    1982-01-01

    The effects of teacher praise, ignoring, time-out, and parental contingencies on the number of inappropriate behaviors of two mentally handicapped (IQ's 55 and 51) male students ages seven and nine were investigated in a one-year study. Both students reduced inappropriate noise and behavior, and the frequency of inappropriate behavior remained…

  19. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis

    PubMed Central

    van der Werf, Marieke J.; Langendam, Miranda W.; Huitric, Emma; Manissero, Davide

    2012-01-01

    We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles. PMID:22005918

  20. The problem of automation: Inappropriate feedback and interaction, not overautomation

    NASA Technical Reports Server (NTRS)

    Norman, Donald A.

    1989-01-01

    As automation increasingly takes its place in industry, especially high-risk industry, it is often blamed for causing harm and increasing the chance of human error when failures occur. It is proposed that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations are performed appropriately under normal conditions, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. When the situations exceed the capabilities of the automatic equipment, then the inadequate feedback leads to difficulties for the human controllers. The problem is that the automation is at an intermediate level of intelligence, powerful enough to take over control that which used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations.

  1. Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital.

    PubMed

    Gamarra, Soledad; Morano, Susana; Dudiuk, Catiana; Mancilla, Estefanía; Nardin, María Elena; de Los Angeles Méndez, Emilce; Garcia-Effron, Guillermo

    2014-10-01

    Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis. PMID:25005365

  2. Antifungals: Mechanism of Action and Drug Resistance.

    PubMed

    Prasad, Rajendra; Shah, Abdul Haseeb; Rawal, Manpreet Kaur

    2016-01-01

    There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise. PMID:26721281

  3. Natural and synthetic peptides with antifungal activity.

    PubMed

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  4. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study. PMID:16641439

  5. Inappropriate prescribing practices: the challenge and opportunity for patient safety.

    PubMed

    Taylor, Laurel K; Kawasumi, Yuko; Bartlett, Gillian; Tamblyn, Robyn

    2005-01-01

    Adverse clinical events related to inappropriate prescribing practices are an important threat to patient safety. Avoidance of inappropriate prescribing in community settings, where the majority of prescriptions are written, offers a major area of opportunity to improve quality of care and outcomes. Electronic medication order entry systems, with automated clinical risk screening and online alerting capabilities, appear as particularly promising enabling tools in such settings. The Medical Office of the Twenty First Century (MOXXI-III) research group is currently utilizing such a system that integrates identification of dosing errors, adverse drug interactions, drug-disease and allergy contraindications and potential toxicity or contraindications based on patient age. This paper characterizes the spectrum of alerts in an urban community of care involving 28 physicians and 32 pharmacies. Over a consecutive nine-month period, alerts were generated in 29% of 22,419 prescriptions, resulting in revised prescriptions in 14% of the alert cases. Drug-disease contraindications were the most common driver of alerts, accounting for 41% of the total and resulting in revised prescriptions in 14% of cases. In contrast, potential dosing errors generated only 8% of all alerts, but resulted in revised prescriptions 23% of the time. Overall, online evidence-based screening and alerting around prescription of medications in a community setting demands confirmation in prescribers' clinical decision making in almost one-third of prescriptions and leads to changed decisions in up to one-quarter of some prescribing categories. Its ultimate determination of clinical relevance to patient safety may, however, have to await more detailed examination of physician response to alerts and patient outcomes as a primary measure of utility. Patient safety is an increasingly recognized challenge and opportunity for stakeholders in improving health care delivery. It involves many issues, including

  6. Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment.

    PubMed

    Weijer, C; Singer, P A; Dickens, B M; Workman, S

    1998-10-01

    Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements. PMID:9805031

  7. Bioethics for clinicians: 16. Dealing with demands for inappropriate treatment

    PubMed Central

    Weijer, C; Singer, P A; Dickens, B M; Workman, S

    1998-01-01

    Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements. PMID:9805031

  8. Antifungal susceptibilities of Paecilomyces species.

    PubMed

    Aguilar, C; Pujol, I; Sala, J; Guarro, J

    1998-07-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  9. Antifungal Susceptibilities of Paecilomyces Species

    PubMed Central

    Aguilar, C.; Pujol, I.; Sala, J.; Guarro, J.

    1998-01-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  10. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  11. Inappropriate intracranial hemodynamics in the natural course of MELAS.

    PubMed

    Nishioka, Junko; Akita, Yukihiro; Yatsuga, Shuichi; Katayama, Koujyu; Matsuishi, Toyojiro; Ishibashi, Masatoshi; Koga, Yasutoshi

    2008-02-01

    The abnormalities of intracranial hemodynamics associated with strokelike episodes in MELAS are variable depend on the time phase from the onset of strokelike episodes and on the progression of the dementia state. To clarify the regional cerebral blood flows (rCBF) in the natural course of MELAS is very important to understand the pathogenic mechanism of this disorder, either cytopathy, angiopathy or both. We analyzed the serial studies of brain statistical parametric mapping (SPM) 99 single photon emission computed tomography (SPECT) in 5 MELAS patients in maximum 10 years interval, who fulfilled the clinical, pathological and genetic criteria of MELAS, and have an A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. SPM is a proven and effective method for the voxel-by-voxel analysis of functional images which show the advantage in its promise of fully automated neurophysiological imaging analysis throughout the whole brain using various statistical analyses. SPECT acquisition was initiated and was reconstructed by iterative algorithm and were processed and analyzed with SPM 99 for Windows software. Statistics were displayed as Z scores (threshold: P < 0.01). The inappropriate intracranial hemodynamics was found not only at the acute but at the interictal phase, and was getting worse as the disease progress. Hypoperfusion in the posterior cingulate cortex was always observed (corrected P < 0.01) in MELAS patients, which is the typical finding reported in Alzheimer's disease. The inappropriate intracranial hemodynamics is a common feature and may be related with mitochondrial angiopathy in the natural course of MELAS. PMID:17664050

  12. Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

    PubMed

    Lagunes, L; Borgatta, B; Martín-Gomez, M T; Rey-Pérez, A; Antonelli, M; Righi, E; Merelli, M; Brugnaro, P; Dimopoulos, G; Garnacho-Montero, J; Colombo, A L; Luzzati, R; Menichetti, F; Muñoz, P; Nucci, M; Scotton, G; Viscoli, C; Tumbarello, M; Bassetti, M; Rello, J

    2016-08-01

    Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies. PMID:27432766

  13. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  14. Antifungal isopimaranes from Hypoestes serpens.

    PubMed

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis. PMID:12943772

  15. Using Precorrection to Manage Inappropriate Academic and Social Behaviors

    ERIC Educational Resources Information Center

    Crosby, Shane; Jolivette, Kristine; Patterson, DaShaunda

    2006-01-01

    This article illustrates a proactive strategy, precorrection, for addressing problem academic and social behaviors with students. Practical classroom scenarios are provided to give teachers a step-by-step guide of how to implement this seven-step preventative strategy. Empirical support for and the benefits of precorrection also are discussed.…

  16. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

    Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141

  17. Association between Physician Specialty and Risk of Prescribing Inappropriate Pill Splitting

    PubMed Central

    Chou, Chia-Yu; Hsu, Chia-Chen; Chiang, Shu-Chiung; Ho, Chin-Chin; Chou, Chia-Lin; Wu, Min-Shan; Chang, Yuh-Lih; Tsai, Han-Yi; Chen, Tzeng-Ji; Chou, Yueh-Ching

    2013-01-01

    Background Prescription errors that occur due to the process of pill splitting are a common medication problem; however, available prescription information involving inappropriate pill splitting and its associated factors is lacking. Methods We retrospectively evaluated a cohort of ambulatory prescriptions involving extended-release or enteric-coated formulations in a Taiwan medical center during a 5-month period in 2010. For this study, those pill splitting prescriptions involving special oral formulations were defined as inappropriate prescriptions. Information obtained included patient demographics, prescriber specialty and prescription details, which were assessed to identify factors associated with inappropriate pill splitting. Results There were 1,252 inappropriate prescriptions identified in this cohort study, representing a prescription frequency for inappropriate pill splitting of 1.0% among 124,300 prescriptions with special oral formulations. Among 35 drugs with special oral formulations in our study, 20 different drugs (57.1%, 20/35) had ever been prescribed to split. Anti-diabetic agents, cardiovascular agents and central nervous system agents were the most common drug classes involved in inappropriate splitting. The rate of inappropriate pill splitting was higher in older (over 65 years of age) patients (1.1%, 832/75,387). Eighty-seven percent (1089/1252) of inappropriate prescriptions were prescribed by internists. The rate of inappropriate pill splitting was highest from endocrinologists (3.4%, 429/12,477), nephrologists (1.3%, 81/6,028) and cardiologists (1.3%, 297/23,531). Multivariate logistic regression analysis revealed that the strongest factor associated with individual specific drug of inappropriate splitting was particular physician specialties. Conclusion This study provides important insights into the inappropriate prescription of special oral formulation related to pill splitting, and helps to aggregate information that can assist

  18. The Prevalence of Antifungal Agents Administration in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Study

    PubMed Central

    Kargar, Mona; Ahmadvand, Alireza; Ahmadvand, Milad; Hadjibabaie, Molouk; Gholami, Kheirollah; Khoee, Seyed Hamid; Javadi, Mohammad Reza; Ghavamzadeh, Ardeshir

    2013-01-01

    Background Invasive fungal infections (IFIs) are chief infectious complications in patients undergoing hematopoietic stem cell transplantation (HSCT). However, the diagnosis of fungal infections is difficult, and often empiric treatment initiates. Since there is no data available on the prevalence of antifungal drugs administration in allogeneic HSCT recipients in Iran, we decided to conduct this study. Methods This study was a retrospective review of records of patients who received allogeneic HSCT in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, between August 2009 and August 2010. Results Sixty (73.1%) patients consist of 41 men (68.3%) with mean age of 26.3 (± 1.2) years received allogeneic HSCT. Patients received prophylaxis with fulconazole however; in 28 patients (46.7%) it was switched to low dose amphotericin B. Fifteen patients (25%) received treatment with antifungal agents. Amphotericin B was the empiric agent administered. In 3 patients treatment was switched to voriconazole. Neither positive culture nor direct microscopic evidence was available from the obtained specimen. Only in one patient the result of serum galactomannan assay was positive. There were no significant differences in neutropenia duration (P value: 0.54), length of hospital stay (P value: 0.27) and number of patients developed graft versus host disease (P value: 0.07) between patients received antifungal agents with those who did not receive treatment. Conclusion In this study HSCT recipients received antifungal agents for prophylaxis. Twenty five percent of patients received treatment with antifungal agents empirically. Improvement in diagnosis of these infections can be helpful and lead to targeted therapy. We suggest larger prospective trials for better assessment of antifungal agent administration. PMID:24505528

  19. Early state research on antifungal natural products.

    PubMed

    Negri, Melyssa; Salci, Tânia P; Shinobu-Mesquita, Cristiane S; Capoci, Isis R G; Svidzinski, Terezinha I E; Kioshima, Erika Seki

    2014-01-01

    Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates. PMID:24609016

  20. When is diagnostic testing inappropriate or irrational? Acceptable regret approach.

    PubMed

    Hozo, Iztok; Djulbegovic, Benjamin

    2008-01-01

    The authors provide a new model within the framework of theories of bounded rationality for the observed physicians' behavior that their ordering of diagnostic tests may not be rational. Contrary to the prevailing thinking, the authors find that physicians do not act irrationally or inappropriately when they order diagnostic tests in usual clinical practice. When acceptable regret (i.e., regret that a decision maker finds tolerable upon making a wrong decision) is taken into account, the authors show that physicians tend to order diagnostic tests at a higher level of pretest probability of disease than predicted by expected utility theory. They also show why physicians tend to overtest when regret about erroneous decisions is extremely small. Finally, they explain variations in the practice of medicine. They demonstrate that in the same clinical situation, different decision makers might have different acceptable regret thresholds for withholding treatment, for ordering a diagnostic test, or for administering treatment. This in turn means that for some decision makers, the most rational strategy is to do nothing, whereas for others, it may be to order a diagnostic test, and still for others, choosing treatment may be the most rational course of action. PMID:18480041

  1. Between two beds: inappropriately delayed discharges from hospitals.

    PubMed

    Holmås, Tor Helge; Islam, Mohammad Kamrul; Kjerstad, Egil

    2013-12-01

    Acknowledging the necessity of a division of labour between hospitals and social care services regarding treatment and care of patients with chronic and complex conditions, is to acknowledge the potential conflict of interests between health care providers. A potentially important conflict is that hospitals prefer comparatively short length of stay (LOS) at hospital, while social care services prefer longer LOS all else equal. Furthermore, inappropriately delayed discharges from hospital, i.e. bed blocking, is costly for society. Our aim is to discuss which factors that may influence bed blocking and to quantify bed blocking costs using individual Norwegian patient data, merged with social care and hospital data. The data allow us to divide hospital LOS into length of appropriate stay (LAS) and length of delay (LOD), the bed blocking period. We find that additional resources allocated to social care services contribute to shorten LOD indicating that social care services may exploit hospital resources as a buffer for insufficient capacity. LAS increases as medical complexity increases indicating hospitals incentives to reduce LOS are softened by considerations related to patients’ medical needs. Bed blocking costs constitute a relatively large share of the total costs of inpatient care. PMID:24122364

  2. Inappropriate eating behavior: a longitudinal study with female adolescents

    PubMed Central

    Fortes, Leonardo de Sousa; Almeida, Sebastião de Sousa; Cipriani, Flávia Marcele; Ferreira, Maria Elisa C.

    2014-01-01

    Objective: To evaluate the inappropriate eating behaviors (IEB) of female adolescents over a one-year period. Methods: 290 adolescents aged between 11 and 14 years old participated in the three research stages (T1: first four months, T2: second four months and T3: third four months). The Eating Attitudes Test (EAT-26) was applied to assess the IEB. Weight and height were measured to calculate body mass index (BMI) in the three study periods. Analysis of variance for repeated measures was used to analyze the data, adjusted for the scores of the Body Shape Questionnaire and the Brazil Economic Classification Criteria. Results: Girls at T1 showed a higher frequency of IEB compared to T2 (p=0.001) and T3 (p=0.001). The findings also indicated higher values for BMI in T3 in relation to T1 (p=0.04). The other comparisons did not show statistically significant differences. Conclusions: IEB scores of female adolescents declined over one year. PMID:24676195

  3. The Prevalence of Inappropriate Image Duplication in Biomedical Research Publications

    PubMed Central

    Casadevall, Arturo; Fang, Ferric C.

    2016-01-01

    ABSTRACT Inaccurate data in scientific papers can result from honest error or intentional falsification. This study attempted to determine the percentage of published papers that contain inappropriate image duplication, a specific type of inaccurate data. The images from a total of 20,621 papers published in 40 scientific journals from 1995 to 2014 were visually screened. Overall, 3.8% of published papers contained problematic figures, with at least half exhibiting features suggestive of deliberate manipulation. The prevalence of papers with problematic images has risen markedly during the past decade. Additional papers written by authors of papers with problematic images had an increased likelihood of containing problematic images as well. As this analysis focused only on one type of data, it is likely that the actual prevalence of inaccurate data in the published literature is higher. The marked variation in the frequency of problematic images among journals suggests that journal practices, such as prepublication image screening, influence the quality of the scientific literature. PMID:27273827

  4. Cefdinir-Induced Hepatotoxicity: Potential Hazards of Inappropriate Antibiotic Use

    PubMed Central

    Chen, Joy

    2008-01-01

    Drug-induced hepatotoxicity is well recognized but can cause some diagnostic problems, particularly if not previously reported. The present case involves a 22-year-old male who presented with jaundice and elevated liver enzymes after a course of cefdinir (Omnicef®) for streptococcal pharyngitis. A diagnosis of drug-induced liver injury was suspected but a liver biopsy was required after his jaundice worsened despite cessation of the presumed offending agent. A short course of steroids was initiated and eventually the jaundice resolved. This case highlights the need to suspect medication-induced liver injury in cases of jaundice, even if not previously reported. In addition, it illustrates the potential for adverse outcomes in situations where antibiotics are used inappropriately or where first line antibiotics are not used for routine infections. We report a case of a young male who developed jaundice associated with cefdinir use with pathological confirmation of moderate cholestasis with portal and lobular mixed inflammation and focal bile duct injury consistent with drug-induced liver injury. PMID:18752027

  5. Turkish high school students' definitions for parallelograms: appropriate or inappropriate?

    NASA Astrophysics Data System (ADS)

    Cansiz Aktaş, Meral

    2016-05-01

    The aim of this study was to investigate the appropriateness of high school students' definitions. The participants in this study were 269 high school students from a public school in Ordu city, which is on the Black Sea coast of Turkey. The participants were asked to write their definitions with no time constraints. In the analysis of the definitions, students' ability to distinguish necessary and sufficient conditions and their ability to use appropriate mathematical terminology were taken into account. The task used in this study enabled us to mirror students' difficulties and inadequacies about their definitions of a parallelogram. The findings indicated that most of the students defined parallelogram inappropriately because they had used incomplete or incorrect statements. On the other hand, for the appropriate definitions, it was found that the number of uneconomical definitions was almost the same as the number of economical ones. At the end of the study, it was suggested that defining activities should be integrated into curriculums explicitly and should be given importance in our mathematic lessons.

  6. Clinical presentation of inappropriate sinus tachycardia and differential diagnosis.

    PubMed

    Peyrol, Michael; Lévy, Samuel

    2016-06-01

    Inappropriate sinus tachycardia (IST) is a syndrome characterized by a sinus tachycardia not related to a medical condition, to a physiological response, or to medication or drugs and associated with symptoms, often invalidating and altering the quality of life of affected patients. It occurs predominantly in adolescents and young adults, and in the female sex. The diagnosis requires a complete work-up in order to exclude other causes of sinus tachycardia and one or several additional tests: 24-h ECG ambulatory recordings, echocardiogram, exercise testing, and autonomous nervous system assessment. It should be differentiated from the postural orthostatic tachycardia syndrome, with which it shares a number of symptoms, and other supraventricular tachycardias originating in the high right atrium. An electrophysiological study should be considered in selected cases in order to differentiate IST from other supraventricular tachycardias. The mechanism is still unclear, and possible etiologies may include intrinsic abnormality of the sinus node, autonomic dysfunction, hypersensitivity of the sinus node to catecholamines, blunted vagal system, or a combination of the above. The authors emphasize the wide spectrum of clinical presentations and the need to better define the IST and the criteria required to ascertain its diagnosis. PMID:26329720

  7. The spectrum of inappropriate pituitary thyrotropin secretion associated with hyperthyroidism

    SciTech Connect

    Gharib, H.; Carpenter, P.C.; Scheithauer, B.W.; Service, F.J.

    1982-09-01

    Two patients with overproduction of thyroid-stimulating hormone (TSH) are described. The first patient, a 25-year-old man with recurrent hyperthyroidism, had a pituitary adenoma and highly elevated levels of TSH. While the patient was receiving 0.3 mg of thyroid daily, and basal TSH level was 161 microM/ml. Despite an increase in the thyroid hormone therapy, serum TSH levels remained elevated. The administration of thyrotropin-releasing hormone (TRH) or dexamethasone resulted in no changes in TSH level. The second patient was an 18-year-old man who had inappropriately elevated levels of TSH 3 months after radioiodine therapy for hyperthyroidism. A gradual increase in thyroid hormone replacement therapy decreased the serum TSH levels from 250 to 14.8 microM/ml. The administration of TRH led to huge increases of TSH. Dexamethasone inhibited basal TSH but not TRH-stimulated TSH levels. The overproduction of TSH was attributed to autonomous, neoplastic secretion in the first case and to partial, selective pituitary thyrotroph resistance to thyroid hormone in the second.

  8. [MIKAMINOM ANTIFUNGAL THERAPY IN NEWBORNS AND INFANTS WITH SURGICAL PATHOLOGY].

    PubMed

    Melnikova, N I; Strogonov, I A; Kartseva, E V; Haritonova, G D; Gliznutsin, O E; Gabulaev, S V; Pulikova, E M

    2016-01-01

    Prolonged empiric and etiotropic therapy of multidrug-resistant or pan-resistant bacterial flora in different gestation age newborns has led to the growth of resistant fungalflora in intencive care units (ICU). According to risk factors and rating scales every child of ICU undergoing the abdominal cavity surgery is threatened the development of a fungal infection and requires antifungal therapy appointment or causal prophylactic. In recent years, before the advent of medications of the group of echinocandins, therapy of invasive fungal infections has been a challenge. Currently alternative drug to diflucane in neonates and infants is micafungine (mycamine) in the dose of 2-8 mg/kg/day, depending on the signs of infestation and severity of the condition. PMID:27192854

  9. Drivers for inappropriate fever management in children: a systematic review.

    PubMed

    Kelly, M; McCarthy, S; O'Sullivan, R; Shiely, F; Larkin, P; Brenner, M; Sahm, L J

    2016-08-01

    Background Fever is one of the most common childhood symptoms and accounts for numerous consultations with healthcare practitioners. It causes much anxiety amongst parents as many struggle with managing a feverish child and find it difficult to assess fever severity. Over- and under-dosing of antipyretics has been reported. Aim of the review The aim of this review was to synthesise qualitative and quantitative evidence on the knowledge, attitudes and beliefs of parents regarding fever and febrile illness in children. Method A systematic search was conducted in ten bibliographic databases from database inception to June 2014. Citation lists of studies and consultation with experts were used as secondary sources to identify further relevant studies. Titles and abstracts were screened for inclusion according to pre-defined inclusion and exclusion criteria. Quantitative studies using a questionnaire were analysed using narrative synthesis. Qualitative studies with a semi-structured interview or focus group methodology were analysed thematically. Results Of the 1565 studies which were screened for inclusion in the review, the final review comprised of 14 studies (three qualitative and 11 quantitative). Three categories emerged from the narrative synthesis of quantitative studies: (i) parental practices; (ii) knowledge; (iii) expectations and information seeking. A further three analytical themes emerged from the qualitative studies: (i) control; (ii) impact on family; (iii) experiences. Conclusion Our review identifies the multifaceted nature of the factors which impact on how parents manage fever and febrile illness in children. A coherent approach to the management of fever and febrile illness needs to be implemented so a consistent message is communicated to parents. Healthcare professionals including pharmacists regularly advise parents on fever management. Information given to parents needs to be timely, consistent and accurate so that inappropriate fever

  10. Potentially inappropriate prescriptions in patients admitted to a psychiatric hospital.

    PubMed

    Soerensen, Ann Lykkegaard; Nielsen, Lars Peter; Poulsen, Birgitte Klindt; Lisby, Marianne; Mainz, Jan

    2016-07-01

    Background Very little is known about the general appropriateness of prescribing for psychiatric patients. Aims To identify prevalence and types of potentially inappropriate prescribing (PIP) of psychotropic and somatic medications, to assess the severity of potential clinical consequences and to identify possible predictive factors of PIP in a sample of adult psychiatric in-patients. Methods A descriptive, cross-sectional design using medication reviews by clinical pharmacologists to identify PIP during a 3-month period. The setting was in-patient units in a psychiatric department of a Danish university hospital during a 3-month period (September 2013-November 2013). Patients medication lists (n = 207) were reviewed at the time of admission and all identified PIPs were assessed for potential consequences by clinical pharmacologists. Results There were 349 PIP identified in 1291 prescriptions. The proportion of patients found to have at least one PIP was 123/207 (59%) and the proportions of patients with at least one PIP assessed to be potentially serious or fatal was 69/207 (33%) and 24/207 (12%), respectively. Interactions between drugs 125/207 (36%) and too high doses of drugs 56/207 (16%) were the most frequent PIP. Predictive factors for PIP were polypharmacy (>5 prescriptions) and having one or more somatic diagnoses. Conclusion PIP is common in psychiatric patients and potentially fatal. Particularly polypharmacy (>5 prescriptions) and concomitant somatic illness were associated with the probability of PIP. Improving the quality of prescribing might benefit from an interprofessional approach and thus better training of physicians and nurses is needed in order to minimize PIP. PMID:26824679

  11. Decreasing Inappropriate Behaviors for Adolescents with Autism Spectrum Disorders Using Modified Social Stories

    ERIC Educational Resources Information Center

    Graetz, Janet E.; Mastropieri, Margo A.; Scruggs, Thomas E.

    2009-01-01

    A multiple baseline design study was implemented to assess the effects of a modified social story intervention on inappropriate social behaviors of three adolescents with moderate autism. Baseline data were collected on inappropriate behaviors that included refusal to stand, use of a high-pitched voice, and placing hands/objects in mouth.…

  12. Impact of a Cybernetic System of Feedback to Physicians on Inappropriate Hospital Use.

    ERIC Educational Resources Information Center

    Studnicki, James; And Others

    1985-01-01

    A cybernetic control program was designed to reduce inappropriate days of hospitalization for Medicare patients in four Western Maryland counties. Hospital stays for patients of 282 physicians were reviewed by physician advisers, with attention to the physician's volume of hospitalized patients and the number of inappropriate days of care.…

  13. Differential Effects of Classroom Lighting on Inappropriate Behaviors in a Severely Mentally Retarded Boy.

    ERIC Educational Resources Information Center

    Fletcher, Donna; Grey, Teresa

    1985-01-01

    A severely mentally retarded 9-year-old boy with a history of inappropriate classroom behaviors was videotaped in his classroom under normal cool white fluorescent and full spectrum florescent lighting. Inappropriate behaviors were considerably less frequent under full spectrum fluorescent lighting. (Author/CL)

  14. Functional Analysis of Inappropriate Social Interactions in Students with Asperger's Syndrome

    ERIC Educational Resources Information Center

    Roantree, Christina F.; Kennedy, Craig H.

    2012-01-01

    We analyzed the inappropriate social interactions of 3 students with Asperger's syndrome whose behavior was maintained by social positive reinforcement. We tested whether inappropriate social behavior was sensitive to social positive reinforcement contingencies and whether such contingencies could be reversed to increase the probability of…

  15. Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study

    PubMed Central

    Morgan, Steven G.; Hunt, Jordan; Rioux, Jocelyn; Proulx, Jeffery; Weymann, Deirdre; Tannenbaum, Cara

    2016-01-01

    Background: Many medications pose greater health risks when prescribed for older adults, compared with available pharmacologic and nonpharmacologic alternatives. We sought to quantify the frequency and cost of potentially inappropriate prescribing for older women and men in Canada. Methods: Using data for 2013 from the National Prescription Drug Utilization Information System database, which contains prescription claims from publicly financed drug plans in all provinces except for Quebec, we identified the frequency of prescribing and cost of potentially inappropriate medications dispensed to provincial drug plan enrollees aged 65 years or more. Potentially inappropriate prescriptions were defined with the use of the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. Results: For the 6 provinces with relatively complete data coverage (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Prince Edward Island), 37% of older people filled 1 or more prescription meeting the Beers Criteria. A higher proportion of women (42%) than men (31%) filled potentially inappropriate prescriptions. The highest rates of prescribing of potentially inappropriate medications were among women aged 85 or more (47%). Benzodiazepines and other hypnotics were the leading contributors to the overall frequency of and sex differences in prescribing of potentially inappropriate drugs among older adults. We estimated that $75 per older Canadian, or $419 million in total, was spent on potentially inappropriate medications outside of hospital settings in 2013. Interpretation: Prescribing of potentially inappropriate medications for older adults is common and costly in Canada, especially for women. Multipronged and well-coordinated strategies to reduce the use and cost of potentially inappropriate drugs would likely generate significant health system savings while simultaneously generating major benefits to

  16. [Inappropriately ordered tests from hepatitis B vaccinated subjects].

    PubMed

    Ozbek, Ozgen Alpay; Oktem, Ibrahim Mehmet Ali

    2010-04-01

    Laboratory testing for viral hepatitis B constitutes a vast burden regarding the cost and the workload for health care system for many countries including ours. There are several reports stating that the cost in question is not always necessary. As a consequence of larger scale vaccination programmes, an increase in unnecessary hepatitis B testing is expected in vaccinated individuals. The present retrospective study aims to determine the rate of inappropriately ordered tests from vaccinated individuals and to discuss the causes and possible solutions of this problem. Laboratory records of 56.349 subjects admitted to Dokuz Eylul University Hospital, Izmir, during 2007 and 2009, were evaluated retrospectively for hepatitis B serological test results. Unnecessary testing was defined as the requests for HBsAg, anti-HBc, anti-HBc IgM, HBeAg and anti-HBe tests from those who had positive anti-HBs and negative anti-HBc results. The cost burden was calculated by taking account the prices recommended by the Department of Social Security. The appropriateness of anti-HBs test orders were not taken into evaluation since specific clinical conditions (immune response disorders, HIV infection, chronic hemodialysis, newborns of HBsAg positive mothers, contact with HBsAg carriers) were not clarified. It was found that among the 17.869 samples tested for both anti-HBs and anti-HBc, 4402 (24.6%) were ordered from subjects who were vaccinated against hepatitis B virus (anti-HBs positive, anti-HBc negative status). Thus, 11.405 (12.9%) tests out of a total of 88.174 hepatitis B tests (HBsAg, anti-HBc, anti-HBc IgM, HBeAg, anti-HBe) were unnecessarily ordered. Social security services and/or individuals paid approximately 59.000 USD for these unnecessary tests in three years, leading to an economic loss of approximately 20.000 USD yearly. Providing appropriate feedback to clinicians and reflex test application (to order a test according to the results of previous tests in accordance to

  17. Systemic antifungal prescribing in neonates and children: outcomes from the Antibiotic Resistance and Prescribing in European Children (ARPEC) Study.

    PubMed

    Lestner, J M; Versporten, A; Doerholt, K; Warris, A; Roilides, E; Sharland, M; Bielicki, J; Goossens, H

    2015-02-01

    The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children

  18. The Association between Inappropriate Weight Control Behaviors and Suicide Ideation and Attempt among Korean Adolescents.

    PubMed

    Lee, Sang Ah; Jang, Suk Yong; Shin, Jaeyong; Ju, Yeong Jun; Nam, Jin Young; Park, Eun Cheol

    2016-10-01

    Suicide is a leading cause of death among adolescents globally, and body weight is also a recognized reason for adolescent suicide. Therefore, we investigated the association between weight control behaviors (WCB) and suicide ideation and attempt, focusing on inappropriate weight control measures. We used data from the 2014 Korea Youth Risk Behavior Web-based Survey, representing a total of 35,224 boys and 34,361 girls aged 12 to 18 years. Adolescents were classified into groups based on WCB: appropriate WCB, inappropriate WCB, and no WCB. We performed logistic regression models to examine associations between WCB and suicide ideation and attempt, controlling for covariates. Both boys and girls with inappropriate WCB were more likely to report suicide ideation and attempt. Underweight and normal weight boys with inappropriate WCB were more likely to think or attempt suicide, and underweight girls with inappropriate WCB were also more likely to attempt suicide. Among five common WCB combinations, the combination of "regular exercise, fasting, eating less" was highly associated with suicide ideation and attempt. We confirmed that inappropriate WCB is associated with suicide ideation and attempt among Korean adolescents. Given the high incidence rate of suicide among adolescents and the adverse effect of inappropriate WCB, encouraging adolescents to control their weight in healthy ways is imperative. PMID:27550479

  19. Sex differences in the risk of receiving potentially inappropriate prescriptions among older adults

    PubMed Central

    Morgan, Steven G.; Weymann, Deirdre; Pratt, Brandy; Smolina, Kate; Gladstone, Emilie J.; Raymond, Colette; Mintzes, Barbara

    2016-01-01

    Objectives: to measure sex differences in the risk of receiving potentially inappropriate prescription drugs and to examine what are the factors that contribute to these differences. Design: a retrospective cohort study. Setting: community setting of British Columbia, Canada. Participants: residents of British Columbia aged 65 and older (n = 660,679). Measurements: we measured 2013 period prevalence of prescription dispensations satisfying the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. We used logistic regressions to test for associations between this outcome and a number of clinical and socioeconomic factors. Results: a larger share of women (31%) than of men (26%) filled one or more potentially inappropriate prescription in the community. The odds of receiving potentially inappropriate prescriptions are associated with several clinical and socioeconomic factors. After controlling for those factors, community-dwelling women were at 16% higher odds of receiving a potentially inappropriate prescription than men (adjusted odds ratio = 1.16, 95% confidence interval = 1.12–1.21). Much of this sex difference stemmed from women's increased odds of receiving potentially inappropriate prescriptions for benzodiazepines and other hypnotics, for tertiary tricyclic antidepressants and for non-selective NSAIDs. Conclusion: there are significant sex differences in older adults' risk of receiving a potentially inappropriate prescription as a result of complex intersections between gender and other social constructs. Appropriate responses will therefore require changes in the information, norms and expectations of both prescribers and patients. PMID:27151390

  20. Antifungal drug discovery: the process and outcomes

    PubMed Central

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  1. New Antifungal Pyranoisoflavone from Ficus tikoua Bur.

    PubMed Central

    Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

    2012-01-01

    Considering the undesirable attributes of synthetic fungicides and the availability of Ficus species in China, the stem of Ficus tikoua Bur. was investigated. One new antifungal pyranoisoflavone, 5,3′,4′-trihydroxy-2″,2″-dimethylpyrano (5″,6″:7,8) isoflavone (1), together with two known isoflavones, wighteone (2) and lupiwighteone (3) (with previously reported antifungal activities), were isolated from ethyl acetate extract by bioassay-guided fractionation. Their structures were determined by spectroscopic analysis, such as NMR (1H-1H COSY, HMQC, HMBC and NOESY), IR, UV and HRMS, as well as ESI-MSn analyses. The antifungal activities of 1–3 against Phytophthora infestans were evaluated by direct spore germination assay, and the IC50 values were 262.442, 198.153 and 90.365 μg·mL−1, respectively. PMID:22837700

  2. Antifungal drug discovery: the process and outcomes.

    PubMed

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that 'repurposing' compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  3. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents

    PubMed Central

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-01-01

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents. PMID:24619221

  4. Inappropriateness of Medication Prescriptions to Elderly Patients in the Primary Care Setting: A Systematic Review

    PubMed Central

    Opondo, Dedan; Eslami, Saied; Visscher, Stefan; de Rooij, Sophia E.; Verheij, Robert; Korevaar, Joke C.; Abu-Hanna, Ameen

    2012-01-01

    Background Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting. Objective The aim of this systematic review is to quantify the extent of inappropriate prescription to elderly persons in the primary care setting. Methods We systematically searched Ovid-Medline and Ovid-EMBASE from 1950 and 1980 respectively to March 2012. Two independent reviewers screened and selected primary studies published in English that measured (in)appropriate medication prescription among elderly persons (>65 years) in the primary care setting. We extracted data sources, instruments for assessing medication prescription appropriateness, and the rate of inappropriate medication prescriptions. We grouped the reported individual medications according to the Anatomical Therapeutic and Chemical (ATC) classification and compared the median rate of inappropriate medication prescription and its range within each therapeutic class. Results We included 19 studies, 14 of which used the Beers criteria as the instrument for assessing appropriateness of prescriptions. The median rate of inappropriate medication prescriptions (IMP) was 20.5% [IQR 18.1 to 25.6%.]. Medications with largest median rate of inappropriate medication prescriptions were propoxyphene 4.52(0.10–23.30)%, doxazosin 3.96 (0.32 15.70)%, diphenhydramine 3.30(0.02–4.40)% and amitriptiline 3.20 (0.05–20.5)% in a decreasing order of IMP rate. Available studies described unequal sets of medications and different measurement tools to estimate the overall prevalence of inappropriate prescription. Conclusions Approximately one in five prescriptions to elderly persons in primary care is inappropropriate despite the attention that has been directed to quality of prescription. Diphenhydramine and amitriptiline are the most common inappropriately prescribed medications with high risk adverse events while propoxyphene and doxazoxin are the most commonly

  5. Antifungal activity of five species of Polygala

    PubMed Central

    Johann, Susana; Mendes, Beatriz G.; Missau, Fabiana C.; de Resende, Maria A.; Pizzolatti, Moacir G.

    2011-01-01

    Crude extracts and fractions of five species of Polygala – P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa – were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC) assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 μg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 μg/mL and 250 μg/mL, respectively) and C. gattii (both with MICs of 250 μg/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 μg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain. PMID:24031724

  6. Screening antifungal activities of selected medicinal plants.

    PubMed

    Quiroga, E N; Sampietro, A R; Vattuone, M A

    2001-01-01

    Plants synthesise a vast array of secondary metabolites that are gaining importance for their biotechnological applications. The antifungal activity of the ethanolic extracts of ten Argentinean plants used in native medicine is reported. Antifungal assays included radial growth inhibition, disk and well diffusion assays and growth inhibition by broth dilution tests. The chosen test fungi were yeasts, microfungi and wood-rot causing Basidiomycetes. Extracts of Larrea divaricata, Zuccagnia punctata and Larrea cuneifolia displayed remarkable activity in the assays against the majority of the test fungi. In addition to the former plants, Prosopanche americana also inhibited yeast growth. PMID:11137353

  7. Inappropriate shocks delivered by implantable cardiac defibrillators during oversensing of activity of diaphagmatic muscle

    PubMed Central

    Babuty, D; Fauchier, L; Cosnay, P

    1999-01-01

    Two cases are reported (both men, one 72 and one 54 years old) of inappropriate shocks delivered by an implantable cardiac defibrillator (ICD) device, which oversensed the myopotentials induced by deep breathing and Valsalva manoeuvre. No damage to leads was associated with the oversensing of myopotentials. The mechanism of the inappropriate shocks was determined using real time electrograms. Modification of the duration of ventricular detection and decrease in sensitivity made it possible to avoid the oversensing of myopotentials and to deliver ICD treatment.

 Keywords: implantable cardiac defibrillator;  inappropriate shocks;  myopotentials PMID:10220554

  8. The Effects of a Token Economy on First Grade Students Inappropriate Social Behavior.

    ERIC Educational Resources Information Center

    Shook, Suzan C.; And Others

    1990-01-01

    Studies the effectiveness of a token economy on specific inappropriate social behaviors of three first grade students. Suggests that token economy systems can be very effective in decreasing disruptive behaviors of primary aged students. (MG)

  9. Cinnamaldehyde and its derivatives, a novel class of antifungal agents.

    PubMed

    Shreaz, Sheikh; Wani, Waseem A; Behbehani, Jawad M; Raja, Vaseem; Irshad, Md; Karched, Maribasappa; Ali, Intzar; Siddiqi, Weqar A; Hun, Lee Ting

    2016-07-01

    The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal. PMID:27259370

  10. Reduction in inappropriate hospital use based on analysis of the causes

    PubMed Central

    2012-01-01

    Background To reduce inappropriate admissions and stays with the application of an improvement cycle in patients admitted to a University Hospital. The secondary objective is to analyze the hospital cost saved by reducing inadequacy after the implementation of measures proposed by the group for improvement. Methods Pre- and post-analysis of a sample of clinical histories studied retrospectively, in which the Appropriateness Evaluation Protocol (AEP) was applied to a representative hospital sample of 1350 clinical histories in two phases. In the first phase the AEP was applied retrospectively to 725 admissions and 1350 stays. The factors associated with inappropriateness were analysed together with the causes, and specific measures were implemented in a bid to reduce inappropriateness. In the second phase the AEP was reapplied to a similar group of clinical histories and the results of the two groups were compared. The cost of inappropriate stays was calculated by cost accounting. Setting: General University Hospital with 426 beds serving a population of 320,000 inhabitants in the centre of Murcia, a city in south-eastern Spain. Results Inappropriate admissions were reduced significantly: 7.4% in the control group and 3.2% in the intervention group. Likewise, inappropriate stays decreased significantly from 24.6% to 10.4%. The cost of inappropriateness in the study sample fell from 147,044 euros to 66,642 euros. The causes of inappropriateness for which corrective measures were adopted were those that showed the most significant decrease. Conclusions It is possible to reduce inadequacy by applying measures based on prior analysis of the situation in each hospital. PMID:23075150

  11. Inappropriate Postural Habits of High School Students from the Municipality of Ceres, Brazil.

    PubMed

    Noll, M; Noll, P Rs; Santos, E M; Silva Neto, A R; Candotti, C T

    2016-02-01

    This study aims to evaluate the prevalence of inappropriate postural habits in students. 827 Brazilian students aged 14 to 19 were evaluated with a self-administered questionnaire. A high prevalence of (>90%) inappropriate habits in sitting postures (on a chair, to write, and at a computer) and picking up an object off the floor was observed, suggesting the need to develop preventive programs. PMID:26897159

  12. Efflux-Mediated Antifungal Drug Resistance†

    PubMed Central

    Cannon, Richard D.; Lamping, Erwin; Holmes, Ann R.; Niimi, Kyoko; Baret, Philippe V.; Keniya, Mikhail V.; Tanabe, Koichi; Niimi, Masakazu; Goffeau, Andre; Monk, Brian C.

    2009-01-01

    Summary: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps. PMID:19366916

  13. Synthetic Multivalent Antifungal Peptides Effective against Fungi

    PubMed Central

    Li, Jianguo; Nandhakumar, Muruganantham; Aung, Thet Tun; Goh, Eunice; Chang, Jamie Ya Ting; Saraswathi, Padhmanaban; Tang, Charles; Safie, Siti Radiah Binte; Lin, Lim Yih; Riezman, Howard; Lei, Zhou; Verma, Chandra S.; Beuerman, Roger W.

    2014-01-01

    Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2–4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. PMID:24498363

  14. Antifungal effect of some spice hydrosols.

    PubMed

    Boyraz, Nuh; Ozcan, Musa

    2005-12-01

    The antifungal effects of rosemary, cumin, sater (savory), basil and pickling herb hydrosols were investigated against Rhizoctonia solani, Fusarium oxysporum f. sp tulipae, Botrytis cinerea and Alternaria citri. Hydrosols of sater and pickling herb showed the most relevant fungicidal activity. PMID:16243447

  15. Emotion Knowledge and Attentional Differences in Preschoolers Showing Context-Inappropriate Anger.

    PubMed

    Locke, Robin L; Lang, Nichole J

    2016-08-01

    Some children show anger inappropriate for the situation based on the predominant incentives, which is called context-inappropriate anger. Children need to attend to and interpret situational incentives for appropriate emotional responses. We examined associations of context-inappropriate anger with emotion recognition and attention problems in 43 preschoolers (42% male; M age = 55.1 months, SD = 4.1). Parents rated context-inappropriate anger across situations. Teachers rated attention problems using the Child Behavior Checklist-Teacher Report Form. Emotion recognition was ability to recognize emotional faces using the Emotion Matching Test. Anger perception bias was indicated by anger to non-anger situations using an adapted Affect Knowledge Test. 28% of children showed context-inappropriate anger, which correlated with lower emotion recognition (β = -.28) and higher attention problems (β = .36). Higher attention problems correlated with more anger perception bias (β = .32). This cross-sectional, correlational study provides preliminary findings that children with context-inappropriate anger showed more attention problems, which suggests that both "problems" tend to covary and associate with deficits or biases in emotion knowledge. PMID:27417387

  16. Utilization of potentially inappropriate medications in elderly patients in a tertiary care teaching hospital in India

    PubMed Central

    Jhaveri, Binit N.; Patel, Tejas K.; Barvaliya, Manish J; Tripathi, Chandrabhanu

    2014-01-01

    Aim: To evaluate the use of potentially inappropriate medicines in elderly inpatients in a tertiary care teaching hospital. Materials and Methods: Retrospective analysis was performed for cases of elderly patients admitted between January 2010 and December 2010. Data on age, gender, diagnosis, duration of hospital stay, treatment, and outcome were collected. Prescriptions were assessed for the use of potentially inappropriate medications in geriatric patients by using American Geriatric Society Beer's criteria (2012) and PRISCUS list (2010). Results: A total of 676 geriatric patients (52.12% females) were admitted in the medicine ward. The average age of geriatric patients was 72.69 years. According to Beer's criteria, at least one inappropriate medicine was prescribed in 590 (87.3%) patients. Metoclopramide (54.3%), alprazolam (9%), diazepam (8%), digoxin > 0.125 mg/day (5%), and diclofenac (3.7%) were the commonly used inappropriate medications. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) in heart and renal failure patients was the commonly identified drug–disease interaction. According to PRISCUS list, at least one inappropriate medication was prescribed in 210 (31.06%) patients. Conclusion: Use of inappropriate medicines is highly prevalent in elderly patients. PMID:25276629

  17. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  18. Prescribing of psychotropics in the elderly: why is it so often inappropriate?

    PubMed

    Mort, Jane R; Aparasu, Rajender R

    2002-01-01

    Psychotropic medications are an important treatment approach to mental health disorders; such disorders are common in the elderly population. Elderly patients are more likely to experience adverse effects from these agents than their younger counterparts due to age-related changes in pharmacodynamic and pharmacokinetic parameters. Because of these factors, inappropriate use of psychotropic medications in elderly patients has become a focus of concern. In general an agent is considered inappropriate if the risk associated with its use exceeds its benefit. Implicit and explicit criteria for inappropriate use of medications in the elderly have been created and include psychotropic agents. These criteria vary in their make-up but the explicit criteria tend to agree that amitriptyline, doxepin, and benzodiazepines that have long half-lives are not appropriate. Although explicit inappropriate medication criteria have been in existence since 1991, elderly patients continue to receive inappropriate psychotropic medications. A wide array of factors may be responsible for this practice. Provider-related causes include deficits in knowledge, confusion due to the lack of a consensus on the inappropriate psychotropic criteria, difficulties in addressing an inappropriate medication started by a previous provider, multiple prescribers and pharmacies involved in the care of a patient, negative perceptions regarding aging, and cost issues. Patients may contribute to the problem by demanding an inappropriate medication. Finally, the healthcare setting may inadvertently contribute to inappropriate prescribing by such policies as restrictive formularies or lack of reimbursement for pharmacists' clinical services. Successful approaches to optimising prescribing have been either educational or administrative. Educational approaches (e.g. one-on-one sessions, academic detailing) seek to influence decision making, while administrative approaches attempt to enforce policies to curtail the

  19. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    PubMed

    Tsunemi, Yuichiro

    2016-01-01

    Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID:27251319

  20. From antidiabetic to antifungal: discovery of highly potent triazole-thiazolidinedione hybrids as novel antifungal agents.

    PubMed

    Wu, Shanchao; Zhang, Yongqiang; He, Xiaomeng; Che, Xiaoying; Wang, Shengzheng; Liu, Yang; Jiang, Yan; Liu, Na; Dong, Guoqiang; Yao, Jianzhong; Miao, Zhenyuan; Wang, Yan; Zhang, Wannian; Sheng, Chunquan

    2014-12-01

    In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15 c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15 μM. Moreover, compounds 15 j and 15 r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C. albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery. PMID:25196996

  1. In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

    PubMed

    Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

    2013-09-01

    The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen. PMID:23496653

  2. Frequent Home Monitoring of ICD Is Effective to Prevent Inappropriate Defibrillator Shock Delivery.

    PubMed

    Bifulco, Paolo; Argenziano, Luigi; Romano, Maria; Cesarelli, Mario; Sansone, Mario; Casella, Stefano; Nardi, Stefano

    2014-01-01

    Recently, in the context of telemedicine, telemonitoring services are gaining attention. They are offered, for example, to patients with implantable cardioverter defibrillators (ICDs). A major problem associated with ICD therapy is the occurrence of inappropriate shocks which impair patients' quality of life and may also be arrhythmogenic. The telemonitoring can provide a valid support to intensify followup visits, in order to improve the prevention of inappropriate defibrillator shock, thus enhancing patient safety. Inappropriate shock generally depends on atrial fibrillation, supraventricular tachycardia, and abnormal sensing (such as those caused by electromagnetic interferences). As a practical example, an unusual case of an ICD patient who risked an inappropriate shock while taking a shower is reported. Continuous remote telemonitoring was able to timely warn cardiologist via GSM-SMS, who were able to detect improper sensing examining the intracardiac electrogram via Web. Patient was promptly contacted and warned to not further come in contact with the hydraulic system and any electrical appliance to prevent an inappropriate defibrillator shock. This demonstrates the effectiveness and usefulness of continuous remote telemonitoring in supporting ICD patients. PMID:24592279

  3. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis.

    PubMed

    Fenske, W; Sandner, B; Christ-Crain, M

    2016-03-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also referred to as syndrome of inappropriate antidiuresis (SIAD), is the most common cause of hyponatremia characterized by extracellular hypotonicity and impaired urine dilution in the absence of any recognizable nonosmotic stimuli for the antidiuretic hormone arginine vasopressin (AVP). Hyponatremia in SIADH is primarily the result of excessive water retention caused by a combination of inappropriate antidiuresis and persistent fluid intake in the presence of impaired osmoregulated inhibition of thirst. It is sometimes aggravated by a sodium deficiency caused by a decreased intake or a secondary natriuresis in response to elevated extracellular volume. Inappropriate antidiuresis usually results from endogenous production of AVP that can be either ectopic (from a malignancy) or eutopic (from the hypothalamus/neurohypophysis). Regardless of its origin, different types of osmotic dysregulation of AVP have been reported with possibly fundamental deviations in treatment need and efficacy. A recent quantitative analysis of 50 patients with SIADH, which underwent serial measurements of copeptin during hypertonic saline infusion, revealed five distinct types of osmoregulatory defect ("type A to E") without affiliation to specific underlying diseases. In addition to apparently impaired osmoregulated inhibition of AVP release in the majority of patients, 12% of patients showed an AVP-independent mechanism of inappropriate antidiuresis, whilst 20% of them presented a reverse relation between hormone release and serum osmolality, presumably related to interrupted nonosmotic inhibitory pathways. The interference of these different types of SIAD with clinical presentation and therapy response will be a relevant subject for future research. PMID:27156760

  4. Photodynamic therapy as an antifungal treatment

    PubMed Central

    LIANG, YI; LU, LI-MING; CHEN, YONG; LIN, YOU-KUN

    2016-01-01

    Photodynamic therapy (PDT) involves the systemic or topical application of a photosensitizer (PS), alongside the selective illumination of the target lesion with light of an appropriate wavelength, in order to promote localized oxidative photodamage and subsequent cell death. Numerous studies have demonstrated that PDT is highly effective in the destruction of fungi in vitro. The mechanism underlying the effects of PDT results from the photons of visible light of an appropriate wavelength interacting with the intracellular molecules of the PS. Reactive species are produced as a result of the oxidative stress caused by the interaction between the visible light and the biological tissue. At present, no antifungal treatment based on PDT has been licensed. However, antifungal PDT is emerging as an area of interest for research. PMID:27347012

  5. Natural Killer Cells and Antifungal Host Response

    PubMed Central

    Schmidt, Stanislaw; Zimmermann, Stefanie-Yvonne; Tramsen, Lars; Koehl, Ulrike

    2013-01-01

    As a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and species in vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clear in vivo data are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies. PMID:23365210

  6. Antifungal activity of 10 Guadeloupean plants.

    PubMed

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. PMID:23280633

  7. Antifungal stewardship in a tertiary-care institution: a bedside intervention.

    PubMed

    Valerio, M; Muñoz, P; Rodríguez, C G; Caliz, B; Padilla, B; Fernández-Cruz, A; Sánchez-Somolinos, M; Gijón, P; Peral, J; Gayoso, J; Frias, I; Salcedo, M; Sanjurjo, M; Bouza, E

    2015-05-01

    Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs. PMID:25748494

  8. Econazole imprinted textiles with antifungal activity.

    PubMed

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. PMID:26883854

  9. Antifungal serum concentration monitoring: an update.

    PubMed

    Goodwin, Megan L; Drew, Richard H

    2008-01-01

    Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole). PMID:17999982

  10. Antifungal activity of Eugenia umbelliflora against dermatophytes.

    PubMed

    Machado, Karina E; Cechinel Filho, Valdir; Cruz, Rosana C B; Meyre-Silva, Christiane; Cruz, Alexandre Bella

    2009-09-01

    Antifungal activities of Eugenia umbelliflora Berg. (Myrtaceae) were tested in vitro against a panel of standard and clinical isolates of human fungal pathogens (dermatophytes and opportunistic saprobes). Methanol extracts of leaves and fruits of E. umbelliflora were separately prepared and partitioned, to yield dichloromethane (DCM), ethyl acetate (EtOAc) and aqueous fractions (Aq). Three compounds (1-3) were obtained from the DCM extract using chromatographic procedures. Antifungal assays were performed using agar dilution techniques. Both extracts (fruits and leaves), their DCM and EtOAc fractions, and compound 2 (betulin and betulinic acid) presented selective antifungal activity against dermatophytes (Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Trichophyton mentagrophytes), with MIC values between 200 and 1000 microg/mL, and interestingly, inhibited 4/5 species with MIC values of < or = 500 microg/mL. The aqueous fractions of fruits and leaves, and compounds 1 (alpha, beta amyrin) and 3 (taraxerol) were inactive up to the maximum concentrations tested (1000 microg/mL). PMID:19831024

  11. Antifungal Activity of Maytenin and Pristimerin

    PubMed Central

    Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

    2012-01-01

    Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

  12. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    PubMed Central

    Ascacio-Valdés, Juan; Burboa, Edgardo; Aguilera-Carbo, Antonio F; Aparicio, Mario; Pérez-Schmidt, Ramón; Rodríguez, Raúl; Aguilar, Cristóbal N

    2013-01-01

    Objective To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica (E. antisyphilitica) Zucc in the wax extraction process. Methods An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16, until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder. An aqueous solution was prepared and treated through ionic exchange liquid chromatography (Q XL) and gel permeation chromatography (G 25). The ellagitannin-rich fraction was thermogravimetrically evaluated (TGA and DTA) to test the thermo-stability of ellagic acid (monomeric unit). Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and, also mass spectroscopy was used to determine the molecular ion. Results The principal functional groups of ellagitannin were determined, the molecular weight was 860.7 g/mol; and an effective antifungal activity against phytopathogenic fungi was demonstrated. Conclusions It can be concluded that the new ellagitannin (860.7 g/mol) isolated from E. antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata, Fusarium oxyzporum, Colletotrichum gloeosporoides and Rhizoctnia solani. PMID:23570015

  13. Current and Emerging Azole Antifungal Agents

    PubMed Central

    Sheehan, Daniel J.; Hitchcock, Christopher A.; Sibley, Carol M.

    1999-01-01

    Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided. PMID:9880474

  14. Hydroxytyrosol expresses antifungal activity in vitro.

    PubMed

    Zoric, Natasa; Horvat, Igor; Kopjar, Nevenka; Vucemilovic, Ante; Kremer, Dario; Tomic, Sinisa; Kosalec, Ivan

    2013-08-01

    Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml⁻¹ and 6.25 mgml⁻¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts. PMID:23721186

  15. Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals.

    PubMed

    Álvarez-Pérez, Sergio; García, Marta E; Peláez, Teresa; Martínez-Nevado, Eva; Blanco, José L

    2016-08-01

    Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended. PMID:27216048

  16. [Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].

    PubMed

    Maeda, T; Takase, M; Ishibashi, A; Yamamoto, T; Sasaki, K; Arika, T; Yokoo, M; Amemiya, K

    1991-02-01

    In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml). PMID:2056447

  17. Make a lasting impression: the neural consequences of re-encountering people who emote inappropriately.

    PubMed

    Bayliss, Andrew P; Naughtin, Claire K; Lipp, Ottmar V; Kritikos, Ada; Dux, Paul E

    2012-12-01

    We can learn about the affective content of the environment by observing the behavior of others; their responses to stimuli tend to be appropriate to the context. To investigate the impact of observing such appropriate, compared with inappropriate, behaviors, we developed a novel behavioral task where participants observed different faces reacting to emotional scenes. We found that affective categorization of a scene was facilitated when it was presented alongside an appropriate facial expression (Experiment 1). Further, we observed that several brain areas in the right hemisphere-the putamen, insula, orbitofrontal cortex, and dorsal anterior cingulate cortex-were more activate when viewing faces that were previously observed emoting inappropriately (Experiment 2). We contend that these areas form a network that codes for the retrieval of affective conflict information generated by observing individuals producing inappropriate emotions. PMID:23095146

  18. [Impact of potentially inappropriate drug usage on health insurance business results].

    PubMed

    Kirschke, Malin; Böhme, Jacqueline

    2014-09-01

    In Germany a list was drawn up that included 83 potentially inappropriate drugs. The PRISCUS list published in 2010 was intended to highlight certain problems in the pharmakotherapy of elderly patients and serve as a support for improved medicine safety. Almost a third of the insurance portfolio of the HALLESCHE Krankenversicherung aged over 75 years takes drugs that are on the PRISCUS list. Benzodiazepine and Z-drugs are taken most frequently. The costs per insurant with potentially inappropriate medication are on average higher than for policyholders who do not take drugs on the PRISCUS list. The costs per insurant are rising, with an increase in the number of PRISCUS agents being taken as well. However, there is still no scientific proof that potentially inappropriate drugs lead to adverse drug events. PMID:25272660

  19. Inappropriate shock for myopotential over-sensing in a patient with subcutaneous ICD.

    PubMed

    Corzani, Alessandro; Ziacchi, Matteo; Biffi, Mauro; Diemberger, Igor; Martignani, Cristian; Boriani, Giuseppe

    2015-01-01

    Inappropriate ICD shocks are common adverse events; they are mainly due to supraventricular arrhythmias and secondly are related to noise, undersensing, oversensing, device malfunctions. We present a case of inappropriate device therapy due to myopotential oversensing in a patient with a subcutaneous ICD (s-ICD). A 58 years old male with an s-ICD during the device interrogation showed a previous episode of suspected sustained ventricular tachycardia at 210 bpm, which was effectively treated with ICD shock. The patient experienced the electrical shock while holding a big gas-cylinder in his arms. The EGM analysis revealed many irregular ventricular signals of low amplitude lasting for 24 s and interrupted by the shock. The device showed no malfunctions. This is the first case report of inappropriate S-ICD shock related to myopotential over-sensing. By recording intracardiac EGM, we demonstrated that the noise was created by the activity of the pectorals muscles. PMID:25820052

  20. Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma

    PubMed Central

    Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung

    2012-01-01

    The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis. PMID:22870060

  1. Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma.

    PubMed

    Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung; Kang, Si-Yong; Yun, Bong-Sik

    2012-06-01

    The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis. PMID:22870060

  2. Antifungal Resistance and New Strategies to Control Fungal Infections

    PubMed Central

    Vandeputte, Patrick; Ferrari, Selene; Coste, Alix T.

    2012-01-01

    Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology. PMID:22187560

  3. Emergency readmissions to paediatric surgery and urology: The impact of inappropriate coding.

    PubMed

    Peeraully, R; Henderson, K; Davies, B

    2016-04-01

    Introduction In England, emergency readmissions within 30 days of hospital discharge after an elective admission are not reimbursed if they do not meet Payment by Results (PbR) exclusion criteria. However, coding errors could inappropriately penalise hospitals. We aimed to assess the accuracy of coding for emergency readmissions. Methods Emergency readmissions attributed to paediatric surgery and urology between September 2012 and August 2014 to our tertiary referral centre were retrospectively reviewed. Payment by Results (PbR) coding data were obtained from the hospital's Family Health Directorate. Clinical details were obtained from contemporaneous records. All readmissions were categorised as appropriately coded (postoperative or nonoperative) or inappropriately coded (planned surgical readmission, unrelated surgical admission, unrelated medical admission or coding error). Results Over the 24-month period, 241 patients were coded as 30-day readmissions, with 143 (59%) meeting the PbR exclusion criteria. Of the remaining 98 (41%) patients, 24 (25%) were inappropriately coded as emergency readmissions. These readmissions resulted in 352 extra bed days, of which 117 (33%) were attributable to inappropriately coded cases. Conclusions One-quarter of non-excluded emergency readmissions were inappropriately coded, accounting for one-third of additional bed days. As a stay on a paediatric ward costs up to £500 a day, the potential cost to our institution due to inappropriate readmission coding was over £50,000. Diagnoses and the reason for admission for each care episode should be accurately documented and coded, and readmission data should be reviewed at a senior clinician level. PMID:26924486

  4. Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA)

    PubMed Central

    Manthey, Leonie; van Veen, Tineke; Giltay, Erik J; Stoop, José E; Neven, Arie Knuistingh; Penninx, Brenda W J H; Zitman, Frans G

    2011-01-01

    AIM Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]= 1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]= 2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]= 2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (β= 0.130) and chronic illnesses (β= 0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use. PMID:21219408

  5. Management of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope

    PubMed Central

    Raj, Satish

    2016-01-01

    Postural tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST) and vasovagal syncope (VVS) are relatively common clinical syndromes that are seen by physicians in several disciplines. They are often not well recognised and are poorly understood by physicians, are associated with significant morbidity and cause significant frustration for both patients and their physicians. The 2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope provides physicians with an introduction to these disorders and initial recommendations on their investigation and treatment. Here we summarise the consensus statement to help physicians in the management of patients with these frequently distressing problems.

  6. Inappropriate implantable cardioverter defibrillator shocks in fractured Sprint Fidelis leads associated with 'appropriate' interrogation.

    PubMed

    Farwell, David; Redpath, Calum; Birnie, David; Gollob, Michael; Lemery, Robert; Posan, Emoke; Green, Martin

    2008-06-01

    We present two patients with fractures within the pace-sense circuit of their Medtronic Sprint Fidelis leads who received inappropriate shocks from their Medtronic defibrillators during device interrogation. This was not simply a coincidence, but due to electromagnetic interference induced within the Sprint Fidelis lead by the device programmer during two-way communication with the defibrillator. Our subsequent investigations have uncovered at least two other similar incidents in Canada. We have also discovered that the Medtronic 'Auto-resume' feature may leave future patients uniquely vulnerable to such inappropriate shocks in the future. PMID:18456645

  7. Evaluation of the supply of antifungal medication for the treatment of vaginal thrush in the community pharmacy setting: a randomized controlled trial

    PubMed Central

    Schneider, Carl R.; Emery, Lyndal; Brostek, Raisa; Clifford, Rhonda M.

    Background The Pharmaceutical Society of Australia have developed "guidance" for the supply of several medicines available without prescription to the general public. Limited research has been published assessing the effect of these guidelines on the provision of medication within the practice of pharmacy. Objective To assess appropriate supply of non-prescription antifungal medications for the treatment of vaginal thrush in community pharmacies, with and without a guideline. A secondary aim was to describe the assessment and counseling provided to patients when requesting this medication. Methods A randomized controlled trial was undertaken whereby two simulated patients conducted visits to 100 randomly selected community pharmacies in a metropolitan region. A product-based request for fluconazole (an oral antifungal that has a guideline was compared to a product-based request for clotrimazole (a topical antifungal without a guideline). The same patient details were used for both requests. Outcome measures of the visits were the appropriateness of supply and referral to a medical practitioner. Results Overall 16% (n=16) of visits resulted in an appropriate outcome; 10% (n=5) of fluconozaole requests compared with 22% (n=11) of clotrimazole requests (chi-square=2.68, p=0.10). There was a difference in the type of assessment performed by pharmacy staff between visits for fluconazole and clotrimazole. A request for clotrimazole resulted in a significant increase in frequency in regards to assessment of the reason for the request (chi-square=8.57, p=0.003), symptom location (chi-square=8.27, p=0.004), and prior history (chi-square=5.09, p=0.02). Conclusions Overall practice was poor, with the majority of pharmacies inappropriately supplying antifungal medication. New strategies are required to improve current practice of community pharmacies for provision of non-prescription antifungals in the treatment of vaginal thrush. PMID:24223077

  8. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02

    PubMed Central

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  9. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02.

    PubMed

    Huh, Chang Ki; Hwang, Tae Yean

    2016-03-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  10. Inappropriate and excessive guilt: instrument validation and developmental differences in relation to depression.

    PubMed

    Tilghman-Osborne, Carlos; Cole, David A; Felton, Julia W

    2012-05-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age. PMID:22086497

  11. Case of inappropriate ADH syndrome: hyponatremia due to polyethylene glycol bowel preparation.

    PubMed

    Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Jae-Young; Kang, Seung Hun; Baeg, Myong Ki; Oh, Hyun Jin

    2014-09-14

    Colonoscopic screening has been reported to reduce deaths from colorectal cancer. Adequate bowel preparation is essential for this and safety is an important issue in choosing the methods. Polyethylene glycol (PEG) is regarded as a safe method for cleansing, especially compared with oral sodium phosphate. Here, we present a case of hyponatremia caused by the syndrome of inappropriate antidiuretic hormone (ADH) syndrome after PEG precolonoscopic cleansing resulting in generalized tonic-clonic seizures. A 62-year-old women had ingested PEG for precolonoscopic bowel cleansing. While waiting for the colonoscopy, she developed a stuporous mentality and generalized tonic-clonic seizures, which did not correlate with brain magnetic resonance imaging. Her serum sodium level was 113 mEq per liter and laboratory analyses were consistent with inappropriate ADH syndrome. Her thyroid and adrenal functions were normal. There were no malignancies, infections, respiratory disorders or central nervous disorders and she had no history of taking either diuretics or other medications, which might have caused inappropriate ADH syndrome. She was treated with 3% hypertonic saline and showed a complete neurological recovery as her sodium levels recovered. Follow-up visits showed the patient to have a normal sodium level without neurologic deficits. This case shows that inappropriate ADH syndrome can be caused by PEG preparation, which implies that physicians have to be aware of the possible side effects of this colonic cleansing approach and mindful of the possible ensuing symptoms. PMID:25232272

  12. Inappropriate and Excessive Guilt: Instrument Validation and Developmental Differences in Relation to Depression

    ERIC Educational Resources Information Center

    Tilghman-Osborne, Carlos; Cole, David A.; Felton, Julia W.

    2012-01-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association ("1994"). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study…

  13. Deceleration Procedures for Inappropriate Social Behaviors with Severely Retarded Ss. Two Papers.

    ERIC Educational Resources Information Center

    Spangler, Robert S.; And Others

    Two papers describe studies to decrease inappropriate social behaviors of severely retarded students. R. Spangler and others in "The Effect of a Time-Out Procedure on the Duration of Tantrum Behavior in a 13-Year-Old Severely Retarded Male S" report on a three phase study in which a combination of verbal instructions and a timeout procedure…

  14. Improving Inappropriate Social Behavior of Autistic Students Using the LISTEN Intervention Strategy

    ERIC Educational Resources Information Center

    Al-Shammari, Zaid; Daniel, Cathy; Faulkner, Paula; Yawkey, Thomas D.

    2010-01-01

    A case study was conducted on the development of the LISTEN intervention strategy for use with autistic students to improve inappropriate social behaviors. The study was conducted in a special education classroom in an autism school in Kuwait. Examination of LISTEN Intervention Strategy applications included: duration of targeted behavior; methods…

  15. Community Services, Issues, and Service Gaps for Individuals with Developmental Disabilities Who Exhibit Inappropriate Sexual Behaviors.

    ERIC Educational Resources Information Center

    Ward, Karen M.; Pfeiffer, Karl T.; Trigler, Jordan S.

    2001-01-01

    A national survey of 243 community agencies evaluated services provided for individuals with developmental disabilities who exhibit high-risk sexual behaviors and identified issues and service gaps. Common offenses were sexual behavior in public situations, inappropriate involvement of others, and involvement of minors. Major issues and problems…

  16. Dysgeusia in symptomatic syndrome of inappropriate antidiuretic hormone secretion: think of lung cancer

    PubMed Central

    Singh, Nishith K; Hayes, Shelbi; Hahs, Seth; Varney, Andrew

    2009-01-01

    The case of a 60-year-old woman who presented with marked dysgeusia to all food and symptomatic syndrome of inappropriate antidiuretic hormone secretion (SIADH) is described. She eventually turned out to have metastatic small cell lung cancer. The case study explores the interesting constellation of dysgeusia, SIADH and lung cancer. PMID:21686989

  17. Use of Inappropriate and Inaccurate Conceptual Knowledge to Solve an Osmosis Problem.

    ERIC Educational Resources Information Center

    Zuckerman, June Trop

    1995-01-01

    Presents correct solutions to an osmosis problem of two high school science students who relied on inaccurate and inappropriate conceptual knowledge. Identifies characteristics of the problem solvers, salient properties of the problem that could contribute to the problem misrepresentation, and spurious correct answers. (27 references) (Author/MKR)

  18. Assertiveness for Librarians Harried by Inappropriate Lecture Hall and Classroom Assignments.

    ERIC Educational Resources Information Center

    Parker, J. Carlyle

    1990-01-01

    Describes problems encountered by public librarians when assisting students with assignments that are difficult or impossible to complete. Examples of librarians' successes in assertive, tactful communication with instructors and a list of solutions to inappropriate assignments are provided. Special emphasis is given to assignments dealing with…

  19. Reducing the Impact of Inappropriate Items on Reviewable Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Yen, Yung-Chin; Ho, Rong-Guey; Liao, Wen-Wei; Chen, Li-Ju

    2012-01-01

    In a test, the testing score would be closer to examinee's actual ability when careless mistakes were corrected. In CAT, however, changing the answer of one item in CAT might cause the following items no longer appropriate for estimating the examinee's ability. These inappropriate items in a reviewable CAT might in turn introduce bias in ability…

  20. Performance Costs when Emotion Tunes Inappropriate Cognitive Abilities: Implications for Mental Resources and Behavior

    ERIC Educational Resources Information Center

    Storbeck, Justin

    2012-01-01

    Emotion tunes cognition, such that approach-motivated positive states promote verbal cognition, whereas withdrawal-motivated negative states promote spatial cognition (Gray, 2001). The current research examined whether self-control resources become depleted and influence subsequent behavior when emotion tunes an inappropriate cognitive tendency.…

  1. Potentially inappropriate prescribing in an Irish elderly population in primary care

    PubMed Central

    Ryan, Cristín; O'Mahony, Denis; Kennedy, Julia; Weedle, Peter; Byrne, Stephen

    2009-01-01

    AIMS Screening tools have been formulated to identify potentially inappropriate prescribing (IP) in older people. Beers' criteria are the most widely used but have disadvantages when used in Europe. New IP screening tools called Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) have been developed to identify potential IP and potential prescribing omissions (PPOs). The aim was to measure the prevalence rates of potential IP and PPOs in primary care using Beers' criteria, STOPP and START. METHODS Case records of 1329 patients ≥65 years old from three general practices in one region of southern Ireland were studied. The mean age ± SD of the patients was 74.9 ± 6.4 years, 60.9% were female. Patients' current diagnoses and prescription medicines were reviewed and the Beers' criteria, STOPP and START tools applied. RESULTS The total number of medicines prescribed was 6684; median number of medicines per patient was five (range 1–19). Overall, Beers' criteria identified 286 potentially inappropriate prescriptions in 18.3% (243) of patients, whilst the corresponding IP rate identified by STOPP was 21.4% (284), in respect of 346 potentially inappropriate prescriptions. A total of 333 PPOs were identified in 22.7% (302) of patients using the START tool. CONCLUSION Potentially inappropriate drug prescribing and errors of drug omission are highly prevalent among older people living in the community. Prevention strategies should involve primary care doctors and community pharmacists. PMID:20002089

  2. Inappropriate fixation of an endotracheal tube causing cuff malfunction resulting in difficult extubation.

    PubMed

    Nag, Deb Sanjay; Samaddar, Devi Prasad

    2016-01-01

    We discuss a case of difficult extubation, due to inadequate deflation of the tracheal tube cuff, despite collapse of the pilot balloon, on its aspiration. This was caused by inadvertent kinking of the pilot balloon tubing due to inappropriate tape fixation of the endotracheal tube. PMID:27591469

  3. Students' Behaviors and Views of Paraphrasing and Inappropriate Textual Borrowing in an EFL Academic Setting

    ERIC Educational Resources Information Center

    Liao, Ming-Tzu; Tseng, Chiung-Ying

    2010-01-01

    This study examines skillful EFL writers' and less skillful writers' EFL performance and perceptions of paraphrasing and inappropriate text borrowing, the extent to which their performance matches perceptions, and the factors behind their problematic text borrowing. Ninety-five postgraduates and undergraduates in Taiwan accomplished a paraphrasing…

  4. Effects of Individualized Video Feedback Combined with Group Parent Training on Inappropriate Maternal Behavior

    ERIC Educational Resources Information Center

    Phaneuf, Leah; McIntyre, Laura Lee

    2007-01-01

    The effects of adding individualized video feedback (IVF) to Webster-Stratton's (2000, 2001) group-based parent training program (GT) were evaluated using a multiple baseline design across four mother-child dyads. During all phases of the study, inappropriate maternal behavior was recorded from videotapes of playtime with their preschoolers with…

  5. Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as clinical presentation of acute intermittent porphyria.

    PubMed

    Valle Feijóo, M L; Bermúdez Sanjurjo, J R; González Vázquez, L; Rey Martínez, M; de la Fuente Aguado, J

    2015-01-01

    Acute intermittent porphyria (AIP) is a rare condition characterized by abdominal pain and a wide range of nonspecific symptoms. We report the case of a woman with abdominal pain and syndrome of inappropriate antidiuretic hormone secretion (SIADH) as clinical presentation of AIP. The diagnosis was achieved through the etiologic study of the SIADH. PMID:25796467

  6. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    ERIC Educational Resources Information Center

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  7. Age-Related Differences in Judgments of Inappropriate Behavior are Related to Humor Style Preferences

    PubMed Central

    Stanley, Jennifer Tehan; Lohani, Monika; Isaacowitz, Derek M.

    2014-01-01

    Identifying social gaffes is important for maintaining relationships. Older adults are less able than young to discriminate between socially appropriate and inappropriate behavior in video clips. One open question is how these social appropriateness ratings relate to potential age differences in the perception of what is actually funny or not. In the present study, young, middle-aged, and older adults were equally able to discriminate between appropriate and inappropriate social behavior in a diverse set of clips relevant to both age groups. However, young and middle-aged adults rated the gaffe clips as funnier than control clips and young adults smiled more during the inappropriate clips than the control clips. Older adults did not show this pattern, suggesting that they did not find the inappropriate clips funny. Additionally, young adults endorsed a more aggressive humor style than middle-aged and older adults and aggressive humor style endorsement mediated age differences in social appropriateness ratings. Results are discussed in terms of possible mechanisms such as cohort differences in humor and developmental prioritization of certain humor styles, as well as the importance of investigating age differences in both abilities and preferences. PMID:25244473

  8. Context-Inappropriate Anger, Emotion Knowledge Deficits, and Negative Social Experiences in Preschool

    ERIC Educational Resources Information Center

    Locke, Robin L.; Miller, Alison L.; Seifer, Ronald; Heinze, Justin E.

    2015-01-01

    This study examined contextually inappropriate (CI) anger in relation to emotion recognition and situation knowledge, negative social experiences, and externalizing behavior among low-income 4-year-olds attending Head Start (n = 134). Approximately 23% showed anger when presented with positive/neutral slides and videos (valence-incongruent CI…

  9. Inappropriate and Excessive Guilt: Instrument Validation and Developmental Differences in Relation to Depression

    PubMed Central

    Tilghman-Osborne, Carlos; Felton, Julia W.

    2014-01-01

    Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age. PMID:22086497

  10. An Action Research Study of Intellectual Disabilities, Inappropriate Behaviors and Learned Helplessness

    ERIC Educational Resources Information Center

    Luper, Elizabeth P. S.; Lockley, Jeannie

    2008-01-01

    This study focused on a population of 36 female patients, aged 25 to 65, who were diagnosed with intellectual disabilities, all of whom had long-standing patterns of inappropriate behaviors. In an attempt to increase more appropriate behaviors in these patients, a set of standardized contingency rules were established. These rules were implemented…

  11. The Effects of a Token Economy System on the Inappropriate Verbalizations of Emotional Support Students.

    ERIC Educational Resources Information Center

    Stover, Karen

    This paper reports on the application of a token economy approach to increase on-task behavior and decrease inappropriate "call-outs" of nine seventh and eighth grade Caucasian male students in a self-containted emotional support classroom. The program included a behavioral contract, token economy "bucks" kept in a classroom bank, and a list of 12…

  12. Neurobrucellosis associated with syndrome of inappropriate antidiuretic hormone with resultant diabetes insipidus and hypothyroidism.

    PubMed

    Sturniolo, Giuseppe; Mondello, Placido; Bruno, Salvatore; Bonfatto, Orsola Elena; Frattima, Sabrina; Albanese, Antonio; Restivo, Roberta; Liberti, Giuseppe; Pasquali, Paolo; Marianelli, Cinzia

    2010-10-01

    Neurological involvement of the central nervous system in brucellosis is uncommon. We describe a rare case of meningoencephalitis due to Brucella melitensis infection, associated with the syndrome of inappropriate antidiuretic hormone secretion and leading to diabetes insipidus and hypothyroidism. Neurobrucellosis, although rare, should be considered in cases of neurological disease of unknown etiology. PMID:20702671

  13. Psychological Factors in Risk Assessment and Management of Inappropriate Sexual Behaviour by Men with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Smith, Mark; Willner, Paul

    2004-01-01

    Aim: This study examined the responses of care managers and direct care staff to vignettes of inappropriate sexual behaviour (ISB) by a man with an intellectual disability. The aim was to identify psychological factors that influenced their assessment of risk and the perceived need for risk management strategies. Method: The vignettes varied in…

  14. Inappropriate speech in a severely retarded child: a case study in language conditioning and generalization

    PubMed Central

    Barton, Elizabeth Spindler

    1970-01-01

    The modification of inappropriate speech, a class of behaviors rather than a limited number of specific examples, is little known in the severely retarded. In this study, operant techniques were used to modify the strikingly bizarre and inappropriate speech of a severely retarded boy. The boy's appropriate verbal responses to questions about magazine pictures were reinforced with candy. When he responded inappropriately, the magazine was withdrawn, and social interaction was discontinued for a 10-sec timeout period. Negative responses were ignored, the next picture displayed, and the next question asked immediately. In 10 sessions, appropriate responses increased from 26% to 86% of all responses. A reversal of reinforcement was then introduced, in which inappropriate responses were reinforced, appropriate responses resulted in timeout, and negative responses were treated as before. This reduced the percentage of appropriate responses to 24%. Subsequent sessions of reinforcement for appropriate responses increased appropriate responses to 96% of all responses. At significant stages in the experiment, a measure of possible generalization was attempted. Although some generalization was recorded, it was minimal: some explanations are discussed. PMID:16795272

  15. Inappropriate overuse of inhaled corticosteroids for COPD patients: impact on health costs and health status.

    PubMed

    de Miguel-Díez, Javier; Carrasco-Garrido, Pilar; Rejas-Gutierrez, Javier; Martín-Centeno, Antonio; Gobartt-Vázquez, Elena; Hernandez-Barrera, Valentín; Gil de, Miguel Angel; Jimenez-Garcia, Rodrigo

    2011-06-01

    The aim of this study was to evaluate the relationship between inappropriate overuse of inhaled corticosteroids and self-reported health status and the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) recruited in the primary-care setting. An observational, crossover, descriptive study was conducted. Patients with stable COPD and aged ≥40 years, evaluated in primary care, were included. Data collected were demographic variables, clinical characteristics, self-reported health status (SF-12), the severity of the illness, treatment, and health-care resource utilization in the past year. The patients were recruited during a period of 3 months (from January 1 to March 31, 2003). Use was considered inappropriate when corticosteroids were prescribed by physicians for patients not meeting criteria for its use as recommended in guidelines. A total of 10,711 patients [75.6% males; mean age = 67.1 (SD = 9.66) years] were evaluated. Disease severity was mild in 35.5% of the cases, moderate in 53.4%, and severe in 11.2%. Among them, 3,697 (34.5%) subjects were prescribed inhaled corticosteroids or drug combinations containing such therapies, with a rate of inappropriate use of 18.2%. Physical health status was significantly lower among patients showing inappropriate corticosteroids use: 37.35 (SD = 9.53) vs. 40.7 (SD = 9.80) (p < 0.05). The annual cost per patient of COPD management was significantly higher in the group with inappropriate inhaled corticosteroids use: 1,590 (SD = 1,834) vs. 1,157 (SD = 1,536) (p < 0.05). Factors statistically associated with inappropriate use of corticosteroids were educational attainment [OR: 2.77 (95% CI: 1.36-5.63) for nonuniversity training], a history of heart disease [OR: 1.42 (95% CI: 1.02-1.97)], depression [OR: 1.47 (95% CI: 1.05-2.05)], any allergy [OR 1.69 (95% CI: 1.13-2.54)], and physical health status [OR 0.97 (95% CI: 0.96-0.98)]. Lack of adherence to the

  16. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  17. Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil

    PubMed Central

    Vieira, Silvia Cristina Heredia; de Paulo, Luis Fernando; Svidzinski, Terezinha Inez Estivaleti; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; de Souza, Amanda; Young, Maria Cláudia Marx; Cortez, Diógenes Aparício Garcia

    2011-01-01

    In vitro activity of the essential oil from Piper diospyrifolium leaves was tested using disk diffusion techniques. The antifungal assay showed significant potencial antifungal activity: the oil was effective against several clinical fungal strains. The majority compounds in the essential oil were identified as sesquiterpenoids by GC-MS and GC-FID techniques. PMID:24031717

  18. Antifungal and antiviral products of marine organisms.

    PubMed

    Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of

  19. The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics

    PubMed Central

    Holloway, Kathleen Anne; Rosella, Laura; Henry, David

    2016-01-01

    Background Inappropriate overuse of antibiotics contributes to antimicrobial resistance (AMR), yet policy implementation to reduce inappropriate antibiotic use is poor in low and middle-income countries. Aims To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies. Materials and Methods Results from independently conducted antibiotic use surveys in countries that did, and did not report implementation of policies to reduce inappropriate antibiotic prescribing, were compared. Survey data on four validated indicators of inappropriate antibiotic use and 16 self-reported policy implementation variables from WHO databases were extracted. The average difference for indicators between countries reporting versus not reporting implementation of specific policies was calculated. For 16 selected policies we regressed the four antibiotic use variables on the numbers of policies the countries reported implementing. Results Data were available for 55 countries. Of 16 policies studied, four (having a national Ministry of Health unit on promoting rational use of medicines, a national drug information centre and provincial and hospital drugs and therapeutics committees) were associated with statistically significant reductions in antibiotic use of ≥20% in upper respiratory infection (URTI). A national strategy to contain antibiotic resistance was associated with a 30% reduction in use of antibiotics in acute diarrheal illness. Policies seemed to be associated with greater effects in antibiotic use for URTI and diarrhea compared with antibiotic use in all patients. There were negative correlations between the numbers of policies reported implemented and the percentage of acute diarrhoea cases treated with antibiotics (r = -0.484, p = 0.007) and the percentage of URTI cases treated with antibiotics (r = -0.472, p = 0.005). Major study limitations were the reliance on self-reported policy

  20. Chemical modification of antifungal polyene macrolide antibiotics

    NASA Astrophysics Data System (ADS)

    Solovieva, S. E.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2011-02-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  1. Histone deacetylases: Targets for antifungal drug development

    PubMed Central

    Kmetzsch, Livia

    2015-01-01

    The interaction of pathogens and its hosts causes a drastic change in the transcriptional landscape in both cells. Among the several mechanisms of gene regulation, transcriptional initiation is probably the main point. In such scenario, the access of transcriptional machinery to promoter is highly regulated by post-translational modification of histones, such as acetylation, phosphorylation and others. Inhibition of histone deacetylases is able to reduce fungal pathogens fitness during infection and, therefore, is currently being considered for the development of new antifungal therapy strategies. PMID:26151486

  2. Combination Antifungal Therapy for Invasive Aspergillosis Revisited

    PubMed Central

    Panackal, Anil A.

    2016-01-01

    Invasive aspergillosis (IA) causes significant morbidity and mortality among immunocompromised hosts. Combination therapy with mold-active triazoles and echinocandins has been used with the hope of improving outcomes over monotherapy, especially in the setting of refractory disease. Herein, I update our prior systematic review and meta-analysis on combination therapy for salvage IA in the context of the recently published randomized clinical trial of combination therapy for primary IA. Clinicians should consider combination antifungals for IA in refractory disease despite immune reconstitution when there are concerns for resistance or pharmacokinetic variability. PMID:27441304

  3. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  4. Emerging Threats in Antifungal-Resistant Fungal Pathogens

    PubMed Central

    Sanglard, Dominique

    2016-01-01

    The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is tempting to combine several drugs to achieve better therapeutic efficacy. In the recent years, several novel resistance patterns have been observed, including antifungal resistance originating from environmental sources in Aspergillus fumigatus and the emergence of simultaneous resistance to different antifungal classes (multidrug resistance) in different Candida species. This review will summarize these current trends. PMID:27014694

  5. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents.

    PubMed

    Chandrika, Nishad Thamban; Shrestha, Sanjib K; Ngo, Huy X; Garneau-Tsodikova, Sylvie

    2016-08-15

    The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested. PMID:27301676

  6. Synergistic Antifungal Effect of Glabridin and Fluconazole

    PubMed Central

    Liu, Wei; Li, Li Ping; Zhang, Jun Dong; Li, Qun; Shen, Hui; Chen, Si Min; He, Li Juan; Yan, Lan; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2014-01-01

    The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents. PMID:25058485

  7. Microbial Biotransformation to Obtain New Antifungals

    PubMed Central

    Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  8. Novel antifungal peptides from Ceylon spinach seeds.

    PubMed

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  9. Antifungal Th Immunity: Growing up in Family

    PubMed Central

    Borghi, Monica; Renga, Giorgia; Puccetti, Matteo; Oikonomou, Vasileios; Palmieri, Melissa; Galosi, Claudia; Bartoli, Andrea; Romani, Luigina

    2014-01-01

    Fungal diseases represent an important paradigm in immunology since they can result from either the lack of recognition or over-activation of the inflammatory response. Current understanding of the pathophysiology underlying fungal infections and diseases highlights the multiple cell populations and cell-signaling pathways involved in these conditions. A systems biology approach that integrates investigations of immunity at the systems-level is required to generate novel insights into this complexity and to decipher the dynamics of the host–fungus interaction. It is becoming clear that a three-way interaction between the host, microbiota, and fungi dictates the types of host–fungus relationship. Tryptophan metabolism helps support this interaction, being exploited by the mammalian host and commensals to increase fitness in response to fungi via resistance and tolerance mechanisms of antifungal immunity. The cellular and molecular mechanisms that provide immune homeostasis with the fungal biota and its possible rupture in fungal infections and diseases will be discussed within the expanding role of antifungal Th cell responses. PMID:25360137

  10. Potentiation of Azole Antifungals by 2-Adamantanamine

    PubMed Central

    Sun, Lingmei; Lister, Ida; Keating, John; Nantel, Andre; Long, Lisa; Ghannoum, Mahmoud; North, Jeffrey; Lee, Richard E.; Coleman, Ken; Dahl, Thomas; Lewis, Kim

    2013-01-01

    Azoles are among the most successful classes of antifungals. They act by inhibiting α-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of Candida albicans. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of C. albicans but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar. In vivo, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (P value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics. PMID:23689724

  11. Resistance to antifungals that target CYP51.

    PubMed

    Parker, Josie E; Warrilow, Andrew G S; Price, Claire L; Mullins, Jonathan G L; Kelly, Diane E; Kelly, Steven L

    2014-10-01

    Fungal diseases are an increasing global burden. Fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. Azole resistance, mediated by several mechanisms including point mutations in the target enzyme (CYP51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. Mutations similar to those seen in clinical isolates as long ago as the 1990s in Candida albicans and later in Aspergillus fumigatus have been identified in agriculturally important fungal species and also wider combinations of point mutations. Recently, evidence that mutations originate in the field and now appear in clinical infections has been suggested. This situation is likely to increase in prevalence as triazole fungicide use continues to rise. Here, we review the progress made in understanding azole resistance found amongst clinically and agriculturally important fungal species focussing on resistance mechanisms associated with CYP51. Biochemical characterisation of wild-type and mutant CYP51 enzymes through ligand binding studies and azole IC50 determinations is an important tool for understanding azole susceptibility and can be used in conjunction with microbiological methods (MIC50 values), molecular biological studies (site-directed mutagenesis) and protein modelling studies to inform future antifungal development with increased specificity for the target enzyme over the host homologue. PMID:25320648

  12. [An update on antifungal susceptibility testing].

    PubMed

    Tapia P, Cecilia V

    2009-04-01

    Due to increasing of invasive fungal infections and emergeney of antifungal drugs resistant fungi, standardized methods of antifungal susceptibility testing (AST) have been developed. The Clinical Laboratory Standards Instutute (CLSI) and the European for Committee Antimicrobial Susceptibility Testing (EUCAST) have guidelines for susceptibility of yeasts by broth microdilution (M27-A2 and E. Dis. 7.1 documents, respectively). Both are equivalent, although they present methodological and interpretative breakpoints differences. In addition, the CLSI have the M38-A (for filamentous fungi) and M44-A (disk diffusion) documents, whereas EUCAST is developing a document for Aspergillus spp. Furthermore, commercial methods are available that display good correlation with the methods of reference such as E-test, Sensititre and Vitek2. The interpretation of the results must be careful because the determination of the minimum inhibitory concentration (CIM) is difficult for fungi, there are host factors involved and not always there is a correlation between MIC and clinical outcome. Due to these methods are laborious and require trained personnel, to ask for AST to a reference laboratory is recommendable. PMID:19621145

  13. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID:26848627

  14. Antifungal drug resistance of oral fungi.

    PubMed

    Niimi, Masakazu; Firth, Norman A; Cannon, Richard D

    2010-02-01

    Fungi comprise a minor component of the oral microbiota but give rise to oral disease in a significant proportion of the population. The most common form of oral fungal disease is oral candidiasis, which has a number of presentations. The mainstay for the treatment of oral candidiasis is the use of polyenes, such as nystatin and amphotericin B, and azoles including miconazole, fluconazole, and itraconazole. Resistance of fungi to polyenes is rare, but some Candida species, such as Candida glabrata and C. krusei, are innately less susceptible to azoles, and C. albicans can acquire azole resistance. The main mechanism of high-level fungal azole resistance, measured in vitro, is energy-dependent drug efflux. Most fungi in the oral cavity, however, are present in multispecies biofilms that typically demonstrate an antifungal resistance phenotype. This resistance is the result of multiple factors including the expression of efflux pumps in the fungal cell membrane, biofilm matrix permeability, and a stress response in the fungal cell. Removal of dental biofilms, or treatments to prevent biofilm development in combination with antifungal drugs, may enable better treatment and prevention of oral fungal disease. PMID:20155503

  15. Microbial Biotransformation to Obtain New Antifungals.

    PubMed

    Bianchini, Luiz F; Arruda, Maria F C; Vieira, Sergio R; Campelo, Patrícia M S; Grégio, Ana M T; Rosa, Edvaldo A R

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called "green chemistry," which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  16. Potentially inappropriate drug prescribing in elderly hospitalized patients: an analysis and comparison of explicit criteria.

    PubMed

    Di Giorgio, Concetta; Provenzani, Alessio; Polidori, Piera

    2016-04-01

    Background The management of therapy in elderly is a critical aspect of primary care. The physio-pathological complexity of the elderly involves the prescription of multiple drugs, exposing them to a higher risk of adverse reactions. Objective Aim of this study was to assess the medication use and (potential) inappropriate medications and prescribing omissions in the elderly before and during hospitalization, according to the main tools in literature described, and their relation to the number of comorbidities. Setting The study was carried out by the Clinical Pharmacists at ISMETT, an Italian Research Institute. Methods The prescriptions of elderly, admitted in ISMETT between January and December 2012, were analyzed. The information about clinical profile of elderly and prescriptions was obtained from the electronic medical records. 2012 Beers criteria, Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment criteria, and Improving Prescribing in the Elderly criteria were used to evaluate the appropriateness of prescriptions. The correlation between the number of comorbidities and the different tools was analyzed with the Spearman correlation coefficient. The frequency analysis was done with the Pearson Chi square test. Main outcome measure Percentage of potentially inappropriate medications and prescribing omissions before/during hospitalization in elderly. Results 1027 elderly were admitted between January and December 2012. At admission and during hospitalization, according to Beers criteria 24 and 49 % of elderly had at least one potentially inappropriate medication, respectively; according to the Screening Tool of Older Person's Prescriptions criteria 21 and 27 %, respectively; according to the Improving Prescribing in the Elderly criteria 28 and 25 %, respectively; and then, according to Screening Tool to Alert doctors to Right Treatment criteria 28 and 33 % had at least one potentially prescribing omission

  17. A prospective determination of the incidence of perceived inappropriate care in critically ill patients

    PubMed Central

    Singal, Rohit K; Sibbald, Robert; Morgan, Brenda; Quinlan, Mel; Parry, Neil; Radford, Michael; Martin, Claudio M

    2014-01-01

    BACKGROUND: Health care providers’ perceptions regarding appropriateness in end-of-life treatments have been widely studied. While nurses and physicians believe that rationing and other cost-related practices sometimes occur in the intensive care unit (ICU), they allege that treatment is often excessive. OBJECTIVE: To prospectively determine the incidence and causes of health care providers’ perceptions regarding appropriateness of end-of-life treatments. METHODS: The present prospective study collected data from patients admitted to the medical-surgical trauma ICU of a 30-bed, Canadian teaching hospital over a three-month period. Daily surveys were completed independently by bedside nurses, charge nurses and attending physician. RESULTS: In total, 5224 of 6558 expected surveys (representing 294 patients) were analyzed, yielding a response rate of 79.7%. The incidence of perceived inappropriate care in the present study was 6.5% (19 of 294 patients), with ongoing treatment for >2 days after this determination occurring in 1% (three of 294 patients). However, at least one caregiver perceived inappropriate care at some point in 110 of 294 (37.5%) patients. In these cases, in which processes to address care were not already underway, respondents believed that important issues resulting in provision of inappropriate treatments included patient-family issues and communication before or in the ICU. Caregivers did not know their patients’ wishes 22% (1129 of 5224) of the time. CONCLUSIONS: Although ongoing inappropriate care appeared to be a rare occurrence, the issue was a concern to at least one caregiver in one-third of cases. Public awareness for end-of-life issues, adequate communication, and up-to-date knowledge and practice in determining the wishes of critically ill patients are potential target areas to improve end-of-life care and reduce inappropriate care in the ICU. A daily, prospective survey of multidisciplinary caregivers, such as the survey used in

  18. Brief Report: Reduction of Inappropriate Vocalizations for a Child with Autism Using a Self-Management Treatment Program.

    ERIC Educational Resources Information Center

    Mancina, Catherine; Tankersley, Melody; Kamps, Debra; Kravits, Tammy; Parrett, Jean

    2000-01-01

    A study examined the effects of a self-management program used to reduce high rates of inappropriate vocalizations (e.g., humming, tongue clucking, perseveration, and echolalic words/phases) in a 12-year-old girl with autism. When self-management was applied to inappropriate vocalizations during leisure, prevocational, and reading tasks, the…

  19. The Nature of All "Inappropriate Referrals" Made to a Countywide Physical Activity Referral Scheme: Implications for Practice

    ERIC Educational Resources Information Center

    Johnston, Lynne Halley; Warwick, Jane; De Ste Croix, Mark; Crone, Diane; Sldford, Adrienne

    2005-01-01

    Objective: The aim of this study was to evaluate the impact of a centralised referral mechanism (CRM) upon the number and type of "inappropriate referrals" made to a countywide physical activity referral scheme. Design: Case study. Method: Phase 1: Hierarchical Content Analysis of 458 "inappropriate referrals" made to a countywide scheme over a…

  20. Identification of antifungal compounds produced by Lactobacillus casei AST18.

    PubMed

    Li, Hongjuan; Liu, Lu; Zhang, Shuwen; Cui, Wenming; Lv, Jiaping

    2012-08-01

    Lactobacillus casei AST18 was screened as an antifungal lactic acid bacteria which we have reported before. In this research, the antifungal properties of cell-free culture filtrate (CCF) from L. casei AST18 were detected, and the antifungal compounds of CCF were prepared by ultrafiltration, and semi-preparative HPLC, and then determined by GC-MS. CCF was sensitive to pH and heat treatment but it was not affected by the treatment of trypsin and pepsin. Through the treatment of ultrafiltration and semi-preparative HPLC there were two parts of CCF which showed antifungal activities: part 1 and part 4. Lactic acid was identified as the main antifungal compound in part 1. In part 4, three small molecular substances were detected with GC-MS. The three potential antifungal substances were cyclo-(Leu-Pro), 2,6-diphenyl-piperidine, and 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a;1',2'-d]pyrazine. The antifungal activity of L. casei AST18 was a synergistic effect of lactic acid and cyclopeptides. PMID:22580887

  1. A Review of Potentially Inappropriate Prescribing in Over 65's in Livinghealth Clinic.

    PubMed

    Sweeney, J; Laoire, F O; Linehan, G; Herlihy, D

    2015-06-01

    Polypharmacy and potentially inappropriate prescribing (PIP) are areas of growing importance and concern. Optimising drug prescribing in older people is challenging and complex at,the individual GP level. At a national level it is an important public health issue for the care and management of the ageing Irish population. The aim of this study was to estimate the prevalence of PIP in Livinghealth Clinic using the STOPP (Screening Tool for Older Persons' Prescribing) criteria and to identify areas of PIP. LHC audits demonstrated PIP levels of between 16% and 29%. Our findings were similar to other studies in that proton pump inhibitors (PPIs) at maximum therapeutic dosage for >8 weeks, and long acting benzodiazepines prescribed for > 1 month, continue to be significant areas of PIP. However, not all identified PIP maybe inappropriate. The STOPP criteria are a useful screening tool for older persons' prescribing, but are best used together with clinical assessment and discretion. PMID:26182803

  2. The 'problem' with automation - Inappropriate feedback and interaction, not 'over-automation'

    NASA Technical Reports Server (NTRS)

    Norman, D. A.

    1990-01-01

    Automation in high-risk industry is often blamed for causing harm and increasing the chance of human error when failures occur. It is proposed that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations are performed appropriately under normal conditions, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. The problem is that the automation is at an intermediate level of intelligence, powerful enough to take over control which used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations.

  3. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle.

    PubMed

    Gabellini, Davide; Green, Michael R; Tupler, Rossella

    2002-08-01

    Facioscapulohumeral muscular dystrophy (FSHD), a common myopathy, is an autosomal dominant disease of unknown molecular mechanism. Almost all FSHD patients carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Here, we find that in FSHD muscle, 4q35 genes located upstream of D4Z4 are inappropriately overexpressed. We show that an element within D4Z4 specifically binds a multiprotein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin. We demonstrate that this multiprotein complex binds D4Z4 in vitro and in vivo and mediates transcriptional repression of 4q35 genes. Based upon these results, we propose that deletion of D4Z4 leads to the inappropriate transcriptional derepression of 4q35 genes resulting in disease. PMID:12176321

  4. Treatment of a patient with dementia and inappropriate sexual behaviors with citalopram.

    PubMed

    Chen, Stephen T

    2010-01-01

    Inappropriate sexual behaviors (ISBs) associated with dementias and their treatment have not been commonly reported in the medical literature. This report presents an elderly male patient with moderately severe dementia and incident onset of ISBs who was treated with citalopram (20-mg daily) and subsequently displayed a reduction in ISBs. A review of the literature suggests that ISBs may be underrecognized and undertreated, and therefore should be actively monitored and treated. PMID:20693867

  5. Tyrosine kinase inhibitor-associated syndrome of inappropriate secretion of anti-diuretic hormone.

    PubMed

    Hill, Jordan; Shields, Jenna; Passero, Vida

    2016-10-01

    Hyponatremia is a common complication among cancer patients. Certain antineoplastic agents have been associated with syndrome of inappropriate secretion of anti-diuretic hormone-induced hyponatremia. The most common agents associated with secretion of anti-diuretic hormone are vinca alkaloids, platinum compounds, and alkylating agents. We report a case of secretion of anti-diuretic hormone associated with tyrosine kinase inhibitors. PMID:26089312

  6. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    PubMed Central

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  7. Pharmacokinetics and Pharmacodynamics of Antifungals in Children: Clinical Implications

    PubMed Central

    Autmizguine, Julie; Guptill, Jeffrey T.; Cohen-Wolkowiez, Michael; Benjamin, Daniel K.; Capparelli, Edmund V.

    2014-01-01

    Invasive fungal disease (IFD) remains life-threatening in premature infants and immunocompromised children despite the recent development of new antifungal agents. Optimal dosing of antifungals is one of the few factors clinicians can control to improve outcomes of IFD. However, dosing in children cannot be extrapolated from adult data because IFD pathophysiology, immune response, and drug disposition differ from adults. We critically examined the literature on pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and highlight recent developments in treating pediatric IFD. To match adult exposure in pediatric patients, dosing adjustment is necessary for almost all antifungals. In young infants, the maturation of renal and metabolic functions occurs rapidly and can significantly influence drug exposure. Fluconazole clearance doubles from birth to 28 days of life and, beyond the neonatal period, agents like fluconazole, voriconazole, and micafungin require higher dosing than in adults due to faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. Pharmacodynamics principles of antifungals mostly rely on in vitro and in vivo models but very few pharmacodynamics studies specifically address IFD in children. Exposure-response relationship may differ in younger children compared with adults, especially in infants with invasive candidiasis who are at higher risk of disseminated disease and meningoencephalitis, and by extension severe neurodevelopmental impairment. Micafungin is the only antifungal agent for which a specific target of exposure was proposed based on a neonatal hematogenous Candida meningoencephalitis animal model. In this review, we found that pediatric data on drug disposition of newer triazoles and echinocandins are lacking, dosing of older antifungals such as fluconazole and amphotericin B products still need optimization in young infants, and that target PK/PD indices need to be

  8. Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate Shocks.

    PubMed

    Lo, Ronald; Al-Ahmad, Amin; Hsia, Henry; Zei, Paul C; Wang, Paul J

    2008-09-01

    Expansion of indications for implantable cardioverter-defibrillators (ICDs) has led to a significant increase in the number of patients receiving ICDs and the number of lives saved because of ICD therapy. However, appropriate or inappropriate shocks are frequent and may result in a significant decrease in quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid conduction, and other supraventricular tachycardias are the most common arrhythmias causing inappropriate therapy. Other causes include oversensing of diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple counting of intracardiac signals, lead fractures or header connection problems, lead chatter or noise, and electromagnetic interference. Strategies to reduce inappropriate therapy using device programming rely on the ability to distinguish supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding therapy for nonsustained ventricular arrhythmias and increasing the role of antitachycardia pacing to terminate ventricular tachycardia are key approaches to reducing shocks for ventricular arrhythmias. Optimal programming holds great promise for decreasing the overall incidence of shock therapy and increasing ICD acceptance. PMID:18814830

  9. Modelling verbal aggression, physical aggression and inappropriate sexual behaviour after acquired brain injury

    PubMed Central

    James, Andrew I. W.; Böhnke, Jan R.; Young, Andrew W.; Lewis, Gary J.

    2015-01-01

    Understanding the underpinnings of behavioural disturbances following brain injury is of considerable importance, but little at present is known about the relationships between different types of behavioural disturbances. Here, we take a novel approach to this issue by using confirmatory factor analysis to elucidate the architecture of verbal aggression, physical aggression and inappropriate sexual behaviour using systematic records made across an eight-week observation period for a large sample (n = 301) of individuals with a range of brain injuries. This approach offers a powerful test of the architecture of these behavioural disturbances by testing the fit between observed behaviours and different theoretical models. We chose models that reflected alternative theoretical perspectives based on generalized disinhibition (Model 1), a difference between aggression and inappropriate sexual behaviour (Model 2), or on the idea that verbal aggression, physical aggression and inappropriate sexual behaviour reflect broadly distinct but correlated clinical phenomena (Model 3). Model 3 provided the best fit to the data indicating that these behaviours can be viewed as distinct, but with substantial overlap. These data are important both for developing models concerning the architecture of behaviour as well as for clinical management in individuals with brain injury. PMID:26136449

  10. Threatening and otherwise inappropriate letters to members of the United States Congress.

    PubMed

    Dietz, P E; Matthews, D B; Martell, D A; Stewart, T M; Hrouda, D R; Warren, J

    1991-09-01

    The authors examine the characteristics of threatening and otherwise inappropriate communications sent to members of the U.S. Congress by a sample of 86 subjects, 20 of whom threatened assassination. We quote excerpts from these letters and provide quantitative data on such variables as the volume, duration, form, and appearance of such communications; the enclosures; the subjects' perceived relationships to the recipients; the thematic content of the communications; and the messages and threats communicated. Comparisons between 43 subjects who pursued encounters with members of Congress and 43 who did not revealed 17 factors associated with such pursuit. In this population, threateners were significantly less likely to pursue an encounter than inappropriate letter writers who did not threaten, regardless of the type of threat or the harm threatened. Inappropriate letters to members of Congress are compared with those directed to Hollywood celebrities. Mentally disordered persons writing to public figures often mention and sometimes threaten public figures other than those to whom the letters are addressed, which raises important issues regarding notification of endangered third parties and the sharing of information among protective agencies. PMID:1955833

  11. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    PubMed

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. PMID:26586600

  12. Neutral red assay in minimum fungicidal concentrations of antifungal agents.

    PubMed

    Fukuda, T; Naka, W; Tajima, S; Nishikawa, T

    1996-01-01

    We assayed the fungicidal effects of antifungal agents using neutral red staining. Fungal elements of Trichophyton mentagrophytes and T. rubrum were treated with various concentrations of antifungal agents in 96-well filtration plates and then stained with neutral red. The amount of neutral red incorporated by the surviving viable cells was determined from the automated spectrophotometric readings at 550 nm. The minimum fungicidal concentrations (MFCs) of antifungal agents determined by this assay correlated well with those determined by conventional assay. This newly developed procedure should provide a rapid, reproducible, quantitative, qualitative and semi-automated susceptibility test for determination of the MFCs of the fungicidal agents. PMID:8912170

  13. Novel drug delivery strategies for improving econazole antifungal action.

    PubMed

    Firooz, Alireza; Nafisi, Shohreh; Maibach, Howard I

    2015-11-10

    Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections. PMID:26383840

  14. Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components.

    PubMed

    Jiang, Hongxia; Wang, Xiaohui; Xiao, Chengze; Wang, Weiyan; Zhao, Xu; Sui, Junkang; Sa, Rongbo; Guo, Tai L; Liu, Xunli

    2015-10-01

    The establishment of safe and effective methods for controlling fungal disease is an urgent issue in agriculture and forestry. Microbiological control of plant disease is expected to achieve better results than use of chemically derived fungicides. This study aimed to establish Brevibacillus laterosporus JX-5 as a potential microbiological control agent of poplar canker. The bacterium was isolated from the poplar rhizosphere and demonstrated significant growth inhibition of several pathogenic fungi in vitro. The antifungal components of Br. laterosporus JX-5 were isolated and identified. The fermentation broth of Br. laterosporus JX-5 and its main antifungal component, designated as component B, reduced Botryosphaeria dothidea associated canker of the excised poplar branch by 70 and 90%, respectively. Component B is considerably heat-stable, adaptable to a broad pH range, and UV-resistant. It could inhibit Bo. dothidea by permeating the fungal membrane, fracturing the nuclei, damaging the cell wall, and eventually killing the pathogenic fungus. The antifungal activity exhibited by Br. laterosporus JX-5 and its bioactive metabolic products indicate its feasibility as a potential biocontrol agent for plant diseases. PMID:26265360

  15. Antifungal Susceptibilities of Bloodstream Isolates of Candida Species from Nine Hospitals in Korea: Application of New Antifungal Breakpoints and Relationship to Antifungal Usage

    PubMed Central

    Won, Eun Jeong; Shin, Jong Hee; Choi, Min Ji; Lee, Wee Gyo; Park, Yeon-Joon; Uh, Young; Kim, Shine-Young; Lee, Mi-Kyung; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

    2015-01-01

    We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ≥4 μg/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman’s correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ≥4 μg/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI. PMID:25706866

  16. Voriconazole: a new triazole antifungal agent.

    PubMed

    Johnson, Leonard B; Kauffman, Carol A

    2003-03-01

    Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi. PMID:12594645

  17. Overview of medically important antifungal azole derivatives.

    PubMed Central

    Fromtling, R A

    1988-01-01

    Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739). PMID:3069196

  18. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID:26826375

  19. Antifungal steroid saponins from Dioscorea cayenensis.

    PubMed

    Sautour, M; Mitaine-Offer, A-C; Miyamoto, T; Dongmo, A; Lacaille-Dubois, M-A

    2004-01-01

    From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive. PMID:14765305

  20. Antifungal activity of fruit pulp extract from Bromelia pinguin.

    PubMed

    Camacho-Hernández, I L; Chávez-Velázquez, J A; Uribe-Beltrán, M J; Ríos-Morgan, A; Delgado-Vargas, F

    2002-08-01

    The methanol extract of the fruit pulp of Bromelia pinguin was evaluated for its antifungal activity. The extract showed a significant activity against some Trichophyton strains, although Candida strains were generally insensitive. PMID:12165338

  1. Research to Identify Effective Antifungal Agents, 1991 Annual Report.

    SciTech Connect

    Schreck, Carl

    1991-09-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990). The objectives of the present study was to evaluate up to 10 candidate fungicides.

  2. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

  3. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  4. Antifungal drug resistance pattern of Candida. spp isolated from vaginitis in Ilam-Iran during 2013-2014

    PubMed Central

    Mohamadi, Jasem; Havasian, Mohamad Reza; Panahi, Jafar; Pakzad, Iraj

    2015-01-01

    Vaginal Candidiasis is the most common and important opportunistic fungal infection in women. By increasing use of antifungal drugs in recent years, it has caused drug resistance. This study aims to evaluate antifungal drugs susceptibility of Candida. spp isolated of women with vaginitis from Ilam-Iran during 2013-2014. samples were collected and cultured from 385 women with vaginitis, then Candida.spp was diagnosed by standard method. Antifungal drug susceptibility test for nystatin 100 unit/disk, fluconazole 10µg/disk, itraconazole 10µg/disk, ketoconazole 10µg/disk, amphotericinB 20µg/disk, clotrimazole 10µg/disk, posaconazole 5µg/disk, and voriconazole 1µg/disk were carried out by M44-A method(CLSI). From all culture positive samples, 150 isolates were Candida albicans and 89 isolates were non-albicans. The resistance to fluconazole, itraconazole, ketoconazole, clotrimazole, voriconazole, posaconazole, nystatin and amphotericin B was 76%, 62%, 72%, 55%, 6%, 7%, 1% and 0%. The highest resistance was seen for fluconazole , itraconazole, and the highest susceptible was seen for nystatin and amphotericin B. These results indicate nystatin and amphotericin B can be used as the first line for empirical therapy of vaginal candidiasis in the district. PMID:26124561

  5. Law of Empires.

    ERIC Educational Resources Information Center

    Martz, Carlton

    2001-01-01

    This issue of "Bill of Rights in Action" explores issues raised by empires and imperial law. The first article, "Clash of Empires: The Fight for North America," looks at the clash of empires and the fight for North America during the 18th century. The second article, "When Roman Law Ruled the Western World," examines Roman Law, which helped hold…

  6. Antioxidant and antifungal activity of Verbena officinalis L. leaves.

    PubMed

    Casanova, E; García-Mina, J M; Calvo, M I

    2008-09-01

    The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform, ethyl acetate and 50% methanolic extracts of Verbena officinalis leaves were investigated. The activity of different fractions of 50% methanolic extract and some isolated compounds were also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered as excellent and readily available sources of natural antifungal and antioxidant compounds. PMID:18498054

  7. Antifungal activity of polymer-based copper nanocomposite coatings

    NASA Astrophysics Data System (ADS)

    Cioffi, Nicola; Torsi, Luisa; Ditaranto, Nicoletta; Sabbatini, Luigia; Zambonin, Pier Giorgio; Tantillo, Giuseppina; Ghibelli, Lina; D'Alessio, Maria; Bleve-Zacheo, Teresa; Traversa, Enrico

    2004-09-01

    Eukaryotes, such as fungi, can be harmful pathogen agents, and the control of their bioactivity is critical as humans are eukaryote organisms, too. Here, copper/polymer nanocomposites are proposed as antifungal spinnable coatings with controlled copper-releasing properties. The tests of the bioactivity show that fungal growth is inhibited on the nanocomposite-coated plates, and the antifungal activity can be modulated by controlling the Cu nanoparticle loading.

  8. Antibacterial and antifungal activity of Indonesian ethnomedical plants.

    PubMed

    Goun, E; Cunningham, G; Chu, D; Nguyen, C; Miles, D

    2003-09-01

    Methylene chloride and methanol extracts of 20 Indonesian plants with ethnomedical uses have been assessed for in vitro antibacterial and antifungal properties by disk diffusion method. Extracts of the six plants: Terminalia catappa, Swietenia mahagoni Jacq., Phyllanthus acuminatus, Ipomoea spp., Tylophora asthmatica and Hyptis brevipes demonstrated high activity in this bioassay system. These findings should stimulate the search for novel, natural product such as new antibacterial and antifungal agents. PMID:12946723

  9. 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

  10. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  11. Update on antifungal drug resistance mechanisms of Aspergillus fumigatus.

    PubMed

    Chamilos, G; Kontoyiannis, D P

    2005-12-01

    Although the arsenal of agents with anti-Aspergillus activity has expanded over the last decade, mortality due to invasive aspergillosis (IA) remains unacceptably high. Aspergillus fumigatus still accounts for the majority of cases of IA; however less susceptible to antifungals non-fumigatus aspergilli began to emerge. Antifungal drug resistance of Aspergillus might partially account for treatment failures. Recent advances in our understanding of mechanisms of antifungal drug action in Aspergillus, along with the standardization of in vitro susceptibility testing methods, has brought resistance testing to the forefront of clinical mycology. In addition, molecular biology has started to shed light on the mechanisms of resistance of A. fumigatus to azoles and the echinocandins, while genome-based assays show promise for high-throughput screening for genotypic antifungal resistance. Several problems remain, however, in the study of this complex area. Large multicenter clinical studies--point prevalence or longitudinal--to capture the incidence and prevalence of antifungal resistance in A. fumigatus isolates are lacking. Correlation of in vitro susceptibility with clinical outcome and susceptibility breakpoints has not been established. In addition, the issue of cross-resistance between the newer triazoles is of concern. Furthermore, in vitro resistance testing for polyenes and echinocandins is difficult, and their mechanisms of resistance are largely unknown. This review examines challenges in the diagnosis, epidemiology, and mechanisms of antifungal drug resistance in A. fumigatus. PMID:16488654

  12. Synthesis and antifungal activity of benzimidazole, benzotriazole and aminothiazole derivatives.

    PubMed

    Khabnadideh, S; Rezaei, Z; Pakshir, K; Zomorodian, K; Ghafari, N

    2012-04-01

    In recent years, the use of antifungal drugs in human medicine has increased, especially with the advent of AIDS epidemic. Efforts have focused on the development of new, less toxic and more efficacious antifungal drugs with novel mechanism of action. The purpose of this study was to synthesize of some new benzimidazole, benzotriazole and aminothiazole derivatives and to evaluate their activity against some species of Candida, Aspergillus and dermatophytes. The desired compounds were synthesized by the reaction of benzimidazole and benzotriazole with bromoalkanes and also by the reaction of an amide derivative of aminothiazole with 2-piperazino-1-ethanol in an efficient solvent in the presence of tetraethyl ammounim bromide or triethylamine) as catalyst. Chemical structures of all the new compounds were confirmed by spectrophotometric methods. Antifungal activities of the new compounds were evaluated by broth micro dilution method as recommended by CLSI. Among the tested compounds, 1-nonyl-1H-benzo[d]imidazole and 1-decyl-1H-benzo[d]imidazole exhibited the best antifungal activities. Of the examined synthetic compounds in different categories, benzimidazole derivatives established better antifungal activities than benzotriazole derivatives, and the piperazine analogue had no significant antifungal effect. PMID:23181082

  13. Oral fungi in HIV: challenges in antifungal therapies.

    PubMed

    Nittayananta, W

    2016-04-01

    Oral candidiasis (OC) caused by Candida species is a common fungal infection among HIV-infected individuals. Despite the wide use of antiretroviral therapy (ART) resulting in a declined prevalence, OC remains the most common oral lesions seen in those living with HIV/AIDS. Various topical and systemic antifungal drugs are available to treat OC. However, due to the patients' immunodeficiency and the nature of OC as biofilm-associated infection, relapse is frequently observed after cessation of antifungal therapy. In addition, long-term antifungal therapy may lead to drug resistance. This review article addressed three major challenges in the treatment of OC in HIV infection including antifungal drug resistance, biofilm-associated infection of OC, and the host underlying immunodeficiency. To reduce the risks of antifungal drug resistance, the author recommends that future studies should focus on herbal plant-derived compounds with antifungal activity that may be used in combination with the drugs. Also, it is recommended that more research should be carried out to explore how to enhance the host innate immunity against oral Candida. PMID:27109279

  14. Role of antifungal agents in the treatment of seborrheic dermatitis.

    PubMed

    Gupta, Aditya K; Nicol, Karyn; Batra, Roma

    2004-01-01

    Seborrheic dermatitis is a superficial fungal disease of the skin, occurring in areas rich in sebaceous glands. It is thought that an association exists between Malassezia yeasts and seborrheic dermatitis. This may, in part, be due to an abnormal or inflammatory immune response to these yeasts. The azoles represent the largest class of antifungals used in the treatment of this disease to date. In addition to their antifungal properties, some azoles, including bifonazole, itraconazole, and ketoconazole, have demonstrated anti-inflammatory activity, which may be beneficial in alleviating symptoms. Other topical antifungal agents, such as the allylamines (terbinafine), benzylamines (butenafine), hydroxypyridones (ciclopirox), and immunomodulators (pimecrolimus and tacrolimus), have also been effective. In addition, recent studies have revealed that tea tree oil (Melaleuca oil), honey, and cinnamic acid have antifungal activity against Malassezia species, which may be of benefit in the treatment of seborrheic dermatitis. In cases where seborrheic dermatitis is widespread, the use of an oral therapy, such as ketoconazole, itraconazole, and terbinafine, may be preferred. Essentially, antifungal therapy reduces the number of yeasts on the skin, leading to an improvement in seborrheic dermatitis. With a wide availability of preparations, including creams, shampoos, and oral formulations, antifungal agents are safe and effective in the treatment of seborrheic dermatitis. PMID:15663338

  15. Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia

    PubMed Central

    Shah, Akash; Ganesan, Prasanth; Radhakrishnan, Venkatraman; Kannan, Krishnarathinam; Rajendranath, Rejiv; Mahajan, Vandana; Vijayakumar, Varalakshmi; Ganesan, Trivadi; Sagar, Tenali Gnana

    2016-01-01

    Background: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. Materials and Methods: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). Results: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. Conclusion: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole. PMID:27051159

  16. A qualitative examination of inappropriate hospital admissions and lengths of stay

    PubMed Central

    Hammond, Christina L; Pinnington, Lorraine L; Phillips, Margaret F

    2009-01-01

    Background Research has shown that a number of patients, with a variety of diagnoses, are admitted to hospital when it is not essential and can remain in hospital unnecessarily. To date, research in this area has been primarily quantitative. The purpose of this study was to explore the perceived causes of inappropriate or prolonged lengths of stay and focuses on a specific population (i.e., patients with long term neurological conditions). We also wanted to identify interventions which might avoid admission or expedite discharge as periods of hospitalisation pose particular risks for this group. Methods Two focus groups were conducted with a convenience sample of eight primary and secondary care clinicians working in the Derbyshire area. Data were analysed using a thematic content approach. Results The participants identified a number of key causes of inappropriate admissions and lengths of stay, including: the limited capacity of health and social care resources; poor communication between primary and secondary care clinicians and the cautiousness of clinicians who manage patients in community settings. The participants also suggested a number of strategies that may prevent inappropriate admissions or reduce length of stay (LoS), including: the introduction of new sub-acute care facilities; the introduction of auxiliary nurses to support specialist nursing staff and patient held summaries of specialist consultations. Conclusion Clinicians in both the secondary and primary care sectors acknowledged that some admissions were unnecessary and some patients remain in hospital for a prolonged period. These events were attributed to problems with the current capacity or structuring of services. It was noted, for example, that there is a shortage of appropriate therapeutic services and that the distribution of beds between community and sub-acute care should be reviewed. PMID:19265547

  17. Inappropriate rightward saccades after right hemisphere damage: Oculomotor analysis and anatomical correlates.

    PubMed

    Bourgeois, Alexia; Chica, Ana B; Migliaccio, Raffaella; Bayle, Dimitri J; Duret, Christophe; Pradat-Diehl, Pascale; Lunven, Marine; Pouget, Pierre; Bartolomeo, Paolo

    2015-07-01

    Patients with right hemisphere damage and visual neglect have severe problems to orient attention towards left-sided objects, often associated with the tendency to produce inappropriate rightward saccades. In its most severe form, this tendency can assume the compulsive character of a rightward deviation of gaze as soon as the visual scene deploys (so-called "magnetic attraction of gaze"). However, little is known about the exact nature of inappropriate rightward saccades, their relation with impaired conscious perception of left-sided stimuli, and their lesional correlates. To explore these issues, we studied three groups of patients with right brain damage: patients with signs of left visual neglect associated to left homonymous hemianopia, neglect patients without hemianopia, and patients without neglect or hemianopia. Participants searched for a gap missing within a target, presented among distractors. Manual responses for target detection were required, while participants were encouraged to move their eyes during search. Endogenous attention could be summoned to the target location by a central cue. All the three groups of patients produced inappropriate rightward saccades, which could not be completely overcome by the endogenous orienting of attention induced by the cues. Anatomical analysis indicated a specific implication of damage to the right frontal eye field and to a long-range white matter tract, the fronto-parietal superior longitudinal fasciculus. Fronto-parietal networks in the right hemisphere appear thus to be essential to integrate covert and overt orienting of attention, and to thoroughly explore space in order to become aware of the multiple competing objects around us. PMID:25930032

  18. On being your own worst enemy: an investigation of socially inappropriate symptoms in Tourette syndrome.

    PubMed

    Eddy, Clare M; Cavanna, Andrea E

    2013-09-01

    Non-obscene socially inappropriate symptoms (NOSIS) in Tourette syndrome (TS) include urges to make insulting remarks about a person's physical characteristics (e.g. "big nose") and other socially disruptive behaviors (e.g. shouting "bomb" at an airport). We aimed to explore the characteristics of NOSIS in TS, and determine whether individuals who experienced NOSIS reported differences to those who did not in terms of quality of life (QoL) and common clinical symptoms. Finally we aimed to identify significant predictors of the presence of NOSIS. Patients were sixty patients with TS from a specialist outpatient clinic. They completed clinical measures assessing NOSIS, QoL, tic severity, premonitory urges for tics, depression, anxiety, obsessions and compulsions, attention problems, coprophenomena and conduct problems. Two-thirds of our sample admitted experiencing urges to make socially inappropriate remarks and/or carry out socially inappropriate actions. However, not all urges led to actions. Obsessions, attention problems, coprolalia and conduct problems were all significantly more common in patients with NOSIS than those without. Moreover, the presence of NOSIS was associated with significantly poorer QoL, and higher scores on measures of tic severity, obsessive-compulsive symptoms, attention problems and premonitory urges. However, only the presence of coprolalia and severity of obsessive-compulsive symptoms and premonitory urges were significant predictors of the presence of NOSIS. Our findings may imply that elevated self-consciousness and obsessionality could comprise risk factors for the development of NOSIS. As NOSIS exert a specific detrimental impact on QoL, these symptoms should be employed as a marker of therapeutic efficacy. PMID:23768869

  19. Polypharmacy, Drug-Drug Interactions, and Potentially Inappropriate Medications in Older HIV-Infected Adults

    PubMed Central

    Greene, Meredith; Steinman, Michael A.; McNicholl, Ian R.; Valcour, Victor

    2014-01-01

    Objectives To describe the frequency of medication-related problems in older HIV-infected adults Design Retrospective chart review Setting And Participants Community dwelling HIV-infected adults age 60 and older and age and sex-matched HIV-uninfected adults Measurements Total number of medications, potentially inappropriate medications as defined by the modified Beers criteria, anticholinergic drug burden as defined by the Anticholinergic Risk Scale, and drug-drug interactions using Lexi-Interact online drug interactions database. Results Of 89 HIV-infected participants, most were Caucasian (91%) and male (94%) with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of 4 were antiretrovirals. At least one potentially inappropriate medication was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two non-antiretroviral medications. We identified 15 participants (17%) with an anticholinergic risk scale score ≥3. In contrast, HIV-uninfected participants were taking a median of 6 medications, 29% had at least one potentially inappropriate medication, and 4% had an anticholinergic risk scale score ≥ 3 (p-value <0.05 for each comparison except p=0.07 for anticholinergic burden). Conclusion HIV-infected older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-uninfected participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use. PMID:24576251

  20. Potentially Inappropriate Medications in Older Adults: Why the Revised Criteria Matter.

    PubMed

    Barenholtz Levy, Hedva; Marcus, Esther-Lee

    2016-07-01

    The 2 most widely used explicit criteria regarding inappropriate medication use in older adults are the American Geriatrics Society's Beers Criteria and the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START). Both documents were updated recently. They are important educational tools that highlight medications for which risks of use may often exceed benefits in older adults and situations in which potentially appropriate medications should be considered for use. The application of these tools has the potential to significantly affect patient care. Thus, it is important for clinicians to be familiar with both documents. PMID:27083921

  1. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study

    PubMed Central

    Lu, Wan-Hsuan; Wen, Yu-Wen; Chen, Liang-Kung; Hsiao, Fei-Yuan

    2015-01-01

    Background: Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. Methods: We used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. Results: The study cohort comprised 59 042 older adults (65–74 yr: 39 358 [66.7%], 75–84 yr: 16 903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65–74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10–2.19), then among those aged 75–84 yr (+1.79, 95% CI 1.70–1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36–1.05). The number of potentially inappropriate medications increased among patients aged 65–74 years (+0.16 [0.15–0.18]) and 75–84 years (+0.09 [0.06–0.08]), but decreased in those aged 85 years and older (−0.15 [−0.26 to −0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5–9 drugs: odds ratio [OR] 1.18, 95% CI 1.12–1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42–1.66) and anticholinergic burden (score 1–2: 1.39, 95% CI 1.31–1.48; ≥ 3: 1.53, 95% CI 1.41–1.66) showed dose–response relations with fracture-specific admission to hospital. Interpretation: The total number of drugs taken (polypharmacy), number of potentially inappropriate

  2. [Inappropriately rough play behaviour and predatory attacks against people by a tomcat. A case report].

    PubMed

    Morber, M; Bartels, A; Erhard, M H

    2013-01-01

    The owner of a 6-months-old tomcat came to seek help because the cat had attacked her face on a near-daily basis. Through a detailed behavioural history, the cat's behaviour was diagnosed as human-directed predatory attack behaviour, play-related aggression and reduced motor as well as emotional self-control. Within a few weeks, behavioural therapy produced a significant improvement. After 5 months of therapy, the cat showed neither predatory attacks nor inappropriately rough or aggressive behaviour in play towards its owner or other humans. PMID:23608967

  3. Tachyarrhythmia Cycle Length in Appropriate versus Inappropriate Defibrillator Shocks in Brugada Syndrome, Early Repolarization Syndrome, or Idiopathic Ventricular Fibrillation

    PubMed Central

    Lee, Woo Seok; Kwon, Chang-Hee; Choi, Jin Hee; Jo, Uk; Kim, Yoo Ri; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Background and Objectives Implantable cardioverter–defibrillators (ICDs) are indicated in patients with Brugada syndrome (BS), early repolarization syndrome (ERS), or idiopathic ventricular fibrillation (IVF) who are at high risk for sudden cardiac death. The optimal ICD programming for reducing inappropriate shocks in these patients remains to be determined. We investigated the difference in the mean cycle length of tachyarrhythmias that activated either appropriate or inappropriate ICD shocks in these three patient groups to determine the optimal ventricular fibrillation (VF) zone for minimizing inappropriate ICD shocks. Subjects and Methods We selected 41 patients (35 men) (mean age±standard deviation=42.6±13.0 year) who received ICD shocks between April 1996 and April 2014 to treat BS (n=24), ERS (n=9), or IVF (n=8). Clinical and ICD interrogation data were retrospectively collected and analyzed for all events with ICD shocks. Results Of the 244 episodes, 180 (73.8%) shocks were appropriate and 64 (26.2%) were inappropriate. The mean cycle lengths of the tachyarrhythmias that activated appropriate and inappropriate shocks were 178.9±28.7 ms and 284.8±24.4 ms, respectively (p<0.001). The cutoff value with the highest sensitivity and specificity for discriminating between appropriate and inappropriate shocks was 235 ms (sensitivity, 98.4%; specificity, 95.6%). When we programmed a single VF zone of ≤270 ms, inappropriate ICD shocks were reduced by 70.5% and appropriate shocks were missed in 1.7% of these patients. Conclusion Programming of a single VF zone of ≤270 ms in patients with BS, ERS, or IVF could reduce inappropriate ICD shocks, with a low risk of missing appropriate shocks. PMID:27014348

  4. Pharmacokinetics of antifungal agents in onychomycoses.

    PubMed

    Debruyne, D; Coquerel, A

    2001-01-01

    Onychomycosis is caused by infection by fungi, mainly dermatophytes and nondermatophyte yeasts or moulds; it affects the fingernails and, more frequently, the toenails. Dermatophytes are responsible for about 90 to 95% of fungal infections. Trichophyton rubrum is the most common dermatophyte; Candida albicans is the major nondermatophyte yeast. Although topical therapy of onchomycosis does not lead to systemic adverse effects or interactions with concomitantly taken drugs, it does not provide high cure rates and requires complete compliance from the patient. At present there are 3 oral antifungal medications that are generally used for the short term treatment of onychomycosis: itraconazole, terbinafine and fluconazole. The persistence of these active drugs in nails allows weekly administration, reduced treatment or a pulse regimen. Good clinical and mycological efficacies are obtained with itraconazole 100 to 200 mg daily, terbinafine 250mg daily for 3 months, or fluconazole 150 mg weekly for at least 6 months. Itraconazole is a synthetic triazole with a broad spectrum of action. It is well absorbed when administered orally and can be detected in nails 1 to 2 weeks after the start of therapy. The nail : plasma ratio stabilises at around 1 by week 18 of treatment. Itraconazole is still detectable in nails 27 weeks after stopping administration. Nail concentrations are higher than the minimum inhibitory concentration (MIC) for most dermatophytes and Candida species from the first month of treatment. The elimination half-life of itraconazole from nails is long, ranging from 32 to 147 days. Terbinafine is a synthetic allylamine that is effective against dermatophytes. Terbinafine is well absorbed from the gastrointestinal tract, and the time to reach effective concentrations in nail is 1 to 2 weeks. The half-life is from 24 to 156 days, explaining the observed persistence of terbinafine in nails for longer than 252 days. Fluconazole is a bis-triazole broad spectrum

  5. Interaction of Common Azole Antifungals with P Glycoprotein

    PubMed Central

    Wang, Er-jia; Lew, Karen; Casciano, Christopher N.; Clement, Robert P.; Johnson, William W.

    2002-01-01

    Both eucaryotic and procaryotic cells are resistant to a large number of antibiotics because of the activities of export transporters. The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics. Observed clinical interactions and some in vitro studies suggest that azole antifungals may interact with P-gp. Such an interaction could both affect the disposition and exposure to azole antifungal therapeutics and partially explain the clinical drug interactions observed with some antifungals. Using a whole-cell assay in which the retention of a marker substrate is evaluated and quantified, we studied the abilities of the most widely prescribed orally administered azole antifungals to inhibit the function of this transporter. In a cell line presenting an overexpressed amount of the human P-gp transporter, itraconazole and ketoconazole inhibited P-gp function with 50% inhibitory concentrations (IC50s) of ∼2 and ∼6 μM, respectively. Cyclosporin A was inhibitory with an IC50 of 1.4 μM in this system. Uniquely, fluconazole had no effect in this assay, a result consistent with known clinical interactions. The effects of these azole antifungals on ATP consumption by P-gp (representing transport activity) were also assessed, and the Km values were congruent with the IC50s. Therefore, exposure of tissue to the azole antifungals may be modulated by human P-gp, and the clinical interactions of azole antifungals with other drugs may be due, in part, to inhibition of P-gp transport. PMID:11751127

  6. New generation azole antifungals in clinical investigation.

    PubMed

    Girmenia, Corrado

    2009-09-01

    Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called 'second generation' triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections. PMID:19678798

  7. Antifungal Hydrolases in Pea Tissue 1

    PubMed Central

    Mauch, Felix; Mauch-Mani, Brigitte; Boller, Thomas

    1988-01-01

    Chitinase and β-1,3-glucanase purified from pea pods acted synergistically in the degradation of fungal cell walls. The antifungal potential of the two enzymes was studied directly by adding protein preparations to paper discs placed on agar plates containing germinated fungal spores. Protein extracts from pea pods infected with Fusarium solani f.sp. phaseoli, which contained high activities of chitinase and β-1,3-glucanase, inhibited growth of 15 out of 18 fungi tested. Protein extracts from uninfected pea pods, which contained low activities of chitinase and β-1,3-glucanase, did not inhibit fungal growth. Purified chitinase and β-1,3-glucanase, tested individually, did not inhibit growth of most of the test fungi. Only Trichoderma viride was inhibited by chitinase alone, and only Fusarium solani f.sp. pisi was inhibited by β-1,3-glucanase alone. However, combinations of purified chitinase and β-1,3-glucanase inhibited all fungi tested as effectively as crude protein extracts containing the same enzyme activities. The pea pathogen, Fusarium solani f.sp. pisi, and the nonpathogen of peas, Fusarium solani f.sp. phaseoli, were similarly strongly inhibited by chitinase and β-1,3-glucanase, indicating that the differential pathogenicity of the two fungi is not due to differential sensitivity to the pea enzymes. Inhibition of fungal growth was caused by the lysis of the hyphal tips. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:16666407

  8. Antifungal activity of plant and bacterial ureases.

    PubMed

    Becker-Ritt, A B; Martinelli, A H S; Mitidieri, S; Feder, V; Wassermann, G E; Santi, L; Vainstein, M H; Oliveira, J T A; Fiuza, L M; Pasquali, G; Carlini, C R

    2007-12-01

    Ureases (EC 3.5.1.5) are nickel-dependent metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Produced by plants, fungi and bacteria, but not by animals, ureases share significant homology and similar mechanisms of catalysis, although differing in quaternary structures. While fungal and plant ureases are homo-oligomeric proteins of 90 kDa subunits, bacterial ureases are multimers of two (e.g. Helicobacter pylori) or three subunit complexes. It has been proposed that in plants these enzymes are involved in nitrogen bioavailability and in protection against pathogens. Previous studies by our group have shown that plant ureases, but not a bacterial (Bacillus pasteurii) urease, display insecticidal activity. Herein we demonstrate that (Glycine max) embryo-specific soybean urease, jackbean (Canavalia ensiformis) major urease and a recombinant H. pylori urease impair growth of selected phytopathogenic fungi at sub-micromolar concentrations. This antifungal property of ureases is not affected by treatment of the proteins with an irreversible inhibitor of the ureolytic activity. Scanning electron microscopy of urease-treated fungi suggests plasmolysis and cell wall injuries. Altogether, our data indicate that ureases probably contribute to the plant arsenal of defense compounds against predators and phytopathogens and that the urease defense mechanism is independent of ammonia release from urea. PMID:17825863

  9. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively. PMID:27002397

  10. Rooting out institutional corruption to manage inappropriate off-label drug use.

    PubMed

    Rodwin, Marc A

    2013-01-01

    Prescribing drugs for uses that the FDA has not approved - off-label drug use - can sometimes be justified but is typically not supported by substantial evidence of effectiveness. At the root of inappropriate off-label drug use lie perverse incentives for pharmaceutical firms and flawed oversight of prescribing physicians. Typical reform proposals such as increased sanctions for manufacturers might reduce the incidence of unjustified off-label use, but they do not remove the source of the problem. Public policy should address the cause and control the practice. To manage inappropriate off-label drug use, off-label prescriptions must be tracked in order to monitor the risks and benefits and the manufacturers' conduct. Even more important, reimbursement rules should be changed so that manufacturers cannot profit from off-label sales. When off-label sales pass a critical threshold, manufacturers should also be required to pay for independent testing of the safety and effectiveness of off-label drug uses and for the FDA to review the evidence. Manufacturers should also finance, under FDA supervision, programs designed to warn physicians and the public about the risks of off-label drug use. PMID:24088156

  11. Excess Baggage for Birds: Inappropriate Placement of Tags on Gannets Changes Flight Patterns

    PubMed Central

    Vandenabeele, Sylvie P.; Grundy, Edward; Friswell, Michael I.; Grogan, Adam; Votier, Stephen C.; Wilson, Rory P.

    2014-01-01

    Devices attached to flying birds can hugely enhance our understanding of their behavioural ecology for periods when they cannot be observed directly. For this, scientists routinely attach units to either birds' backs or their tails. However, inappropriate payload distribution is critical in aircraft and, since birds and planes are subject to the same laws of physics during flight, we considered aircraft aerodynamic constraints to explain flight patterns displayed by northern gannets Sula bassana equipped with (small ca. 14 g) tail- and back-mounted accelerometers and (larger ca. 30 g) tail-mounted GPS units. Tail-mounted GPS-fitted birds showed significantly higher cumulative numbers of flap-glide cycles and a higher pitch angle of the tail than accelerometer-equipped birds, indicating problems with balancing inappropriately placed weights with knock-on consequences relating to energy expenditure. These problems can be addressed by carefully choosing where to place tags on birds according to the mass of the tags and the lifestyle of the subject species. PMID:24671007

  12. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients

    PubMed Central

    Rognstad, Sture; Brekke, Mette; Fetveit, Arne; Spigset, Olav; Wyller, Torgeir Bruun; Straand, Jørund

    2009-01-01

    Objective To establish a clinically relevant list with explicit criteria for pharmacologically inappropriate prescriptions in general practice for elderly people ≥70 years. Design A three-round Delphi process for validating the clinical relevance of suggested criteria (n = 37) for inappropriate prescriptions to elderly patients. Setting A postal consensus process undertaken by a panel of specialists in general practice, clinical pharmacology, and geriatrics. Main outcome measures The Norwegian General Practice (NORGEP) criteria, a relevance-validated list of drugs, drug dosages, and drug combinations to be avoided in the elderly (≤70 years) patients. Results Of the 140 invited panellists, 57 accepted to participate and 47 completed all three rounds of the Delphi process. The panellists reached consensus that 36 of the 37 suggested criteria were clinically relevant for general practice. Relevance of three of the criteria was rated significantly higher in Round 3 than in Round 1. At the end of the Delphi process, a significant difference between the different specialist groups’ scores was seen for only one of the 36 criteria. Conclusion The NORGEP criteria may serve as rules of thumb for general practitioners (GPs) related to their prescribing practice for elderly patients, and as a tool for evaluating the quality of GPs’ prescribing in settings where access to clinical information for individual patients is limited, e.g. in prescription databases and quality improvement interventions. PMID:19462339

  13. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    PubMed

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  14. Antifungal susceptibilities of Candida species isolated from urine culture.

    PubMed

    Toka Özer, Türkan; Durmaz, Süleyman; Yula, Erkan

    2016-09-01

    Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals. PMID:27452427

  15. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles.

    PubMed

    Shinde, Ravikumar Bapurao; Raut, Jayant Shankar; Chauhan, Nitin Mahendra; Karuppayil, Sankunny Mohan

    2013-01-01

    Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p<0.05) in presence of 250μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole. PMID:23602464

  16. In Search of the Holy Grail of Antifungal Therapy

    PubMed Central

    Chapman, Stanley W.; Sullivan, Donna C.; Cleary, John D.

    2008-01-01

    The ideal antifungal agent remains an elusive goal for treatment of life-threatening systemic fungal infections. Such an agent would have broad antifungal activity, low rates of resistance, flexible routes of administration, few associated adverse events, and limited drug-drug interactions. Only three of the seven classes of antifungal agents currently available are suitable for treatment of systemic infection: the polyenes, the azoles, and the echinocandins. None match all the characteristics of an ideal agent, the Holy Grail of antifungal therapy. Academia and industry need to collaborate in the search for new lead antifungal compounds using traditional screening methods as well as the new pharmacogenomics methods. Enhancing efficacy and reducing toxicity of the currently available therapeutic agents is also another important avenue of study. As an example, the Mycosis Research Center at the University of Mississippi Medical Center has identified pyogenic polyenes in commercial preparations of amphotericin B deoxycholate which correlate with infusion related toxicities. A highly purified formulation of amphotericin B appears promising, with a better therapeutic index compared to its parent compound as evidenced by results of in vitro and in vivo studies reviewed in this presentation. PMID:18596853

  17. Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids

    NASA Astrophysics Data System (ADS)

    Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.

    2011-05-01

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.

  18. Antifungal activity of essential oils against selected terverticillate penicillia.

    PubMed

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis. PMID:25780826

  19. Exploring the molecular basis of antifungal synergies using genome-wide approaches

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is a review article summarizing genomic profiling strategies for determining the mechanism of action of antifungal synergies, and highlighting the potential applications of these technologies. Given the limitations of currently available antifungal agents and the development of drug resistance...

  20. Clinical impact of potentially inappropriate medications during hospitalization of acutely ill older patients with multimorbidity

    PubMed Central

    Kersten, Hege; Hvidsten, Lara T; Gløersen, Gløer; Wyller, Torgeir Bruun; Wang-Hansen, Marte Sofie

    2015-01-01

    Objective: To identify potentially inappropriate medications (PIMs), to compare drug changes between geriatric and other medical wards, and to investigate the clinical impact of PIMs in acutely hospitalized older adults. Setting and subjects: Retrospective study of 232 home-dwelling, multimorbid older adults (aged ≥75 years) acutely admitted to Vestfold Hospital Trust, Norway. Main outcome measures. PIMs were identified by Norwegian general practice (NORGEP) criteria and Beers’ 2012 criteria. Clinical correlates were laboratory measures, functional and mental status, physical frailty, and length of stay. Results: Mean (SD) age was 86 (5.7) years, and length of stay was 6.5 (4.8) days. During the stay, the mean number of drugs used regularly changed from 7.8 (3.6) to 7.9 (3.6) (p = 0.22), and drugs used pro re nata (prn) changed from 1.4 (1.6) to 2.0 (1.7) (p < 0.001). The prevalence of any PIM changed from 39.2% to 37.9% (p = 0.076), while anticholinergics and benzodiazepines were reduced significantly (p ≤ 0.02). The geriatric ward reduced drug dosages (p < 0.001) and discontinued PIMs (p < 0.001) significantly more often than other medical wards. No relations between number of PIMS and clinical outcomes were identified, but the concomitant use of ≥3 psychotropic/opioid drugs was associated with reduced hand-grip strength (p ≤ 0.012). Conclusion: Hospitalization did not change polypharmacy or PIMs. Drug treatment was more appropriate on the geriatric than other medical wards. No clinical impact of PIMs was observed, but prescribers should be vigilant about concomitant prescription of ≥3 psychotropics/opioids.KEY POINTSAcute hospitalization of older patients with multimorbidity did not increase polypharmacy or potentially inappropriate medications.Prescription of anticholinergics and benzodiazepines was significantly reduced.The geriatric ward reduced drug dosages and discontinued potentially inappropriate medications more

  1. Antifungal Effect of Chitosan as Ca2+ Channel Blocker

    PubMed Central

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-01-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca2+, whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca2+ gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  2. Survey of small antifungal peptides with chemotherapeutic potential.

    PubMed

    Desbois, Andrew P; Tschörner, David; Coote, Peter J

    2011-08-01

    Many cationic peptides with antimicrobial properties have been isolated from bacteria, fungi, plants, and animals. These peptides vary in molecular size, potency and spectra of activities. This report surveyed the literature to highlight the peptides that have antifungal activity and greatest potential for development as new therapeutic agents. Thus, to be included in the evaluation, each peptide had to fulfil the following criteria: (i) potent antifungal activity, (ii) no, or minimal, mammalian cell toxicity, (iii) of ≤25 amino acids in length, which minimises the costs of synthesis, reduces immunogenicity and enhances bioavailability and stability in vivo, (iv) minimal post-translational modifications (also reduces the production costs). The ~80 peptides that satisfied these criteria are discussed with respect to their structures, mechanisms of antimicrobial action and in vitro and in vivo toxicities. Certainly, some of these small peptides warrant further study and have potential for future exploitation as new antifungal agents. PMID:21470150

  3. Antifungal Effect of Chitosan as Ca(2+) Channel Blocker.

    PubMed

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-06-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca(2+), whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca(2+) gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  4. Comparison of antifungal activities of Vietnamese citrus essential oils.

    PubMed

    Van Hung, Pham; Chi, Pham Thi Lan; Phi, Nguyen Thi Lan

    2013-03-01

    Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries. PMID:22799453

  5. Peptide-based Antifungal Therapies against Emerging Infections

    PubMed Central

    Matejuk, A.; Leng, Q.; Begum, M.D.; Woodle, M.C.; Scaria, P.; Chou, S-T; Mixson, A.J.

    2010-01-01

    Acquired drug resistance to mycotic infections is rapidly emerging as a major medical problem. Opportunistic fungal infections create therapeutic challenges, particularly in high risk immunocompromised patients with AIDS, cancer, and those undergoing transplantation. Higher mortality and/or morbidity rates due to invasive mycosis have been increasing over the last 20 years, and in light of growing resistance to commonly used antibiotics, novel antifungal drugs and approaches are required. Currently there is considerable interest in antifungal peptides that are ubiquitous in plant and animal kingdoms. These small cationic peptides may have specific targets or may be multifunctional in their mechanism of action. On the basis of recent advances in protein engineering and solid phase syntheses, the utility and potential of selected peptides as efficient antifungal drugs with acceptable toxicity profiles are being realized. This review will discuss recent advances in peptide therapy for opportunistic fungal infections. PMID:20495663

  6. Enhancement of Commercial Antifungal Agents by Kojic Acid

    PubMed Central

    Kim, Jong H.; Chang, Perng-Kuang; Chan, Kathleen L.; Faria, Natália C. G.; Mahoney, Noreen; Kim, Young K.; Martins, Maria de L.; Campbell, Bruce C.

    2012-01-01

    Natural compounds that pose no significant medical or environmental side effects are potential sources of antifungal agents, either in their nascent form or as structural backbones for more effective derivatives. Kojic acid (KA) is one such compound. It is a natural by-product of fungal fermentation commonly employed by food and cosmetic industries. We show that KA greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations of commercial medicinal and agricultural antifungal agents, amphotericin B (AMB) and strobilurin, respectively, against pathogenic yeasts and filamentous fungi. Assays using two mitogen-activated protein kinase (MAPK) mutants, i.e., sakAΔ, mpkCΔ, of Aspergillus fumigatus, an agent for human invasive aspergillosis, with hydrogen peroxide (H2O2) or AMB indicate such chemosensitizing activity of KA is most conceivably through disruption of fungal antioxidation systems. KA could be developed as a chemosensitizer to enhance efficacy of certain conventional antifungal drugs or fungicides. PMID:23203038

  7. Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.

    PubMed

    Takahashi, Hidetoshi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

    2014-10-01

    Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm2 and 1 μg/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. PMID:25226792

  8. Inappropriate drug prescribing in older adults: the updated 2002 Beers criteria – a population-based cohort study

    PubMed Central

    van der Hooft, Cornelis S; Jong, Geert W 't; Dieleman, Jeanne P; Verhamme, Katia M C; van der Cammen, Tischa J M; Stricker, Bruno H CH; Sturkenboom, Miriam C J M

    2005-01-01

    Background In 1997, Beers and colleagues developed explicit criteria for potentially inappropriate drug prescribing in ambulatory older adults aged 65 years and over. Several studies have been performed to estimate the prevalence of inappropriate drug prescribing based on these criteria. In 2002, the criteria were updated. Aims To examine the extent and trend of inappropriate drug prescribing to ambulatory older adults in the Netherlands between 1997 and 2001, according to the 1997 and the updated Beers criteria. Methods Data were retrieved from the Integrated Primary Care Information (IPCI) project, a general practice research database with data from computer-based patient records of a group of 150 general practitioners in the Netherlands. All subjects aged 65 and over were included. Prescriptions were classified as inappropriate if they fulfilled the Beers criteria of prescriptions that generally should be avoided in older adults because of a high risk of adverse effects, while also considering dose and comorbidity. Results Between 1997 and 2001, the 1-year risk of receiving at least one inappropriate drug prescription for older adults ranged between 16.8% (95% CI: 16.3–17.3%) and 18.5% (18.3–18.7%) according to the 1997 criteria and between 19.1% (18.6–19.6%) and 20.0% (19.5–20.5%) according to the updated Beers criteria. According to the updated criteria, the most frequently prescribed inappropriate drugs were nitrofurantoin, long-acting benzodiazepines, amitriptyline, promethazine and cimetidine. Temazepam and zolpidem were mostly prescribed in supratherapeutic dose. Conventional NSAIDs in persons with a history of gastric/duodenal ulcer were the most frequently prescribed contra-indicated drugs. Conclusions Prescribing potentially inappropriate prescriptions to ambulatory older people in the Netherlands is substantial. Compared with other studies using the 1997 Beers criteria, inappropriate prescribing to the elderly is lower than in the USA but

  9. Sleeping with the fishes: electromagnetic interference causing an inappropriate implantable cardioverter defibrillator shock

    PubMed Central

    Knight, Hui Min; Cakebread, Holly Elizabeth; Gajendragadkar, Parag Ravindra; Duehmke, Rudolf Martin

    2014-01-01

    A 60-year-old man with a cardiac defibrillator implanted due to previous ventricular fibrillation arrest and ischaemic cardiomyopathy received a shock while cleaning his fish pond. At the time, his immersed arm was close to a submersed water pump, but the patient was asymptomatic. As a result of the shock he lost consciousness, but collapsed backwards, away from the pond. Interrogation of the device revealed a high-frequency artefact that was sensed by the device and triggered a shock. Device parameters were otherwise normal. Subsequently, the submersed water pump was found to be the source of an external alternating current leak and was identified as the likely cause of the inappropriate shock due to electromagnetic interference (EMI). Awareness of potential sources of EMI along with evaluation of data with a detailed clinical history is warranted in all cases. PMID:24879728

  10. Using an Electronic Decision Support Tool to Reduce Inappropriate Polypharmacy and Optimize Medicines: Rationale and Methods

    PubMed Central

    Tordoff, June; Dovey, Susan; Reith, David; Lloyd, Hywel; Tilyard, Murray; Smith, Alesha

    2016-01-01

    Background Polypharmacy and inappropriate continuation of medicines can lead to a significant risk of adverse drug events and drug interactions with patient harm and escalating health care costs as a result. Thorough review of patients’ medications focusing on the need for each drug can reduce the potential for harm. Limitations in performing effective medicine reviews in practice include consultation time constraints and funding for pharmacy services. We will aim to overcome these problems by designing an automatic electronic decision support tool (the medicines optimization/review and evaluation (MORE) module) that is embedded in general practice electronic records systems. The tool will focus on medicines optimization and reducing polypharmacy to aid prescribers in reviewing medicines and improve patient outcomes. Objective The objectives of this study are: (1) to develop an electronic decision support tool to assist prescribers in performing clinical medication reviews with a particular focus on patients experiencing multimorbidity and polypharmacy, and (2) evaluate and assess the use of the electronic decision support tool, providing pilot data on its usefulness in supporting prescribers during consultations with patients. Methods The first three study phases involve development of clinical rules outlining clinical interventions and the creation and validation of the MORE decision support tool. Phase four is a community-based, single-blind, prospective, 6-month controlled trial involving two interventions and two control general practices, matched for practice demographics. We will be measuring the number of times prescribers engage with the tool, total number of interventions suggested by the tool, and total number of times prescribers change medicines in response to recommendations. There will also be prospective follow-up of patients in the intervention group to examine whether changes to medications are upheld, and to determine the number of

  11. Alternatives to potentially inappropriate medications for use in e-prescribing software: triggers and treatment algorithms

    PubMed Central

    Hume, Anne L; Quilliam, Brian J; Goldman, Roberta; Eaton, Charles

    2011-01-01

    Objective To describe the development of evidence-based electronic prescribing (e-prescribing) triggers and treatment algorithms for potentially inappropriate medications (PIMs) for older adults. Design Literature review, expert panel and focus group. Setting Primary care with access to e-prescribing systems. Participants Primary care physicians using e-prescribing systems receiving medication history. Interventions Standardised treatment algorithms for clinicians attempting to prescribe PIMs for older patients. Main outcome measure Development of 15 treatment algorithms suggesting alternative therapies. Results Evidence-based treatment algorithms were well received by primary care physicians. Providing alternatives to PIMs would make it easier for physicians to change decisions at the point of prescribing. Conclusion Prospectively identifying older persons receiving PIMs or with adherence issues and providing feasible interventions may prevent adverse drug events. PMID:21719560

  12. Context-inappropriate anger, emotion knowledge deficits, and negative social experiences in preschool.

    PubMed

    Locke, Robin L; Miller, Alison L; Seifer, Ronald; Heinze, Justin E

    2015-10-01

    This study examined contextually inappropriate (CI) anger in relation to emotion recognition and situation knowledge, negative social experiences, and externalizing behavior among low-income 4-year-olds attending Head Start (n = 134). Approximately 23% showed anger when presented with positive/neutral slides and videos (valence-incongruent CI anger), whereas 40% of children showed anger when presented with negative slides and videos (valence-congruent CI anger). Valence-incongruent CI anger was associated with lower emotion situation knowledge (for boys only), more self-reported peer rejection and loneliness, and greater negative nominations by teachers and peers. Both valence-incongruent and (for boys only) valence-congruent CI anger were positively associated with externalizing behavior. Overall, valence-incongruent CI anger was more strongly associated with negative child outcomes than valence-congruent CI anger. PMID:26376288

  13. Inappropriate preinjury warfarin use in trauma patients: A call for a safety initiative

    PubMed Central

    HH, Hon; Elmously, A; Stehly, CD; Stoltzfus, JC; Granson, MA; Stawicki, SP; Hoey, BA

    2016-01-01

    Introduction: Warfarin continues to be widely prescribed for a variety of conditions. It has been shown that preinjury warfarin may worsen outcomes in trauma patients. We hypothesized that a substantial proportion of injured patients seen at our institution were receiving preinjury warfarin for inappropriate indications and that a significant number of such patients had subtherapeutic or supratherapeutic international normalized ratios as well as increased mortality. Materials and Methods: A retrospective review of registry data from a Level I trauma center was conducted for the period from January 2004 to July 2013. Included were patients aged ≥22 years (based on the youngest recorded patient on warfarin in this study). Abstracted variables included patient age, Injury Severity Score (ISS), Maximum Abbreviated Injury Score for Head (MAISH), mortality, hospital length of stay (HLOS), indication(s) for anticoagulant therapy, admission Glasgow Coma Scale (GCS), and admission international normalized ratio (INR). Suitability of warfarin indication(s) was determined using the most recent American College of Chest Physicians (ACCP) Guidelines. Inappropriate warfarin administration was defined as use inconsistent with these guidelines. For outcome comparisons, a case-control design with 1:1 ratio was used, matching patients taking preinjury warfarin to a random sample of trauma patients who were not taking warfarin. Severe traumatic brain injury (sTBI) was defined as MAISH ≥4. Results: A total of 700 out of 14,583 patients aged ≥22 years were receiving preinjury warfarin (4.8% incidence, WG). This group was age- and ISS-matched with 700 patients (4.8% total sample) who were not taking warfarin (NWG) in a total case-control sample of 1,400. The two groups were similar in age, gender, ISS, and initial GCS. According to the ACCP guidelines, 115/700 (16.4%) patients in the warfarin group were receiving anticoagulation for inappropriate indications. Nearly 65% of the

  14. Reducing inappropriate antibiotic prescribing in the residential care setting: current perspectives

    PubMed Central

    Lim, Ching Jou; Kong, David CM; Stuart, Rhonda L

    2014-01-01

    Residential aged care facilities are increasingly identified as having a high burden of infection, resulting in subsequent antibiotic use, compounded by the complexity of patient demographics and medical care. Of particular concern is the recent emergence of multidrug-resistant organisms among this vulnerable population. Accordingly, antimicrobial stewardship (AMS) programs have started to be introduced into the residential aged care facilities setting to promote judicious antimicrobial use. However, to successfully implement AMS programs, there are unique challenges pertaining to this resource-limited setting that need to be addressed. In this review, we summarize the epidemiology of infections in this population and review studies that explore antibiotic use and prescribing patterns. Specific attention is paid to issues relating to inappropriate or suboptimal antibiotic prescribing to guide future AMS interventions. PMID:24477218

  15. Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

    PubMed Central

    Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

    2008-01-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

  16. [Severe nutritional deficiencies in young infants with inappropriate plant milk consumption].

    PubMed

    Le Louer, B; Lemale, J; Garcette, K; Orzechowski, C; Chalvon, A; Girardet, J-P; Tounian, P

    2014-05-01

    Over the past few years, we have observed increasing consumption of inappropriate plant milks as an alternative to infant milk formula. Some families believe that foods labeled as natural are the most healthy and an appropriate nutritional choice. However, their composition does not respect European recommendations. They are always hypocaloric and protein, vitamin, and mineral concentrations are inadequate. The aim of this study was to report severe nutritional complications after inappropriate plant milk consumption. Between 2008 and 2011, we studied severe nutritional deficiencies caused by consumption of plant milks bought in health food stores or online shops. Infants were identified in our centers and examined through medical history, physical examination, and laboratory testing. Nine cases of infants aged from 4 to 14 months were observed. In all cases, these milks were used as an alternative to milk formulas for supposed cow's milk allergy. At diagnosis, four patients were aged 6 months or less. They had received plant milk exclusively for 1-3 months. The beverages consumed were rice, soya, almond and sweet chestnut milks. In three cases, infants presented severe protein-calorie malnutrition with substantial hypoalbuminemia (<20 g/L) and diffuse edema. In the other cases, the nutritional disorders were revealed by a refractory status epilepticus related to severe hypocalcemia (one case), growth arrest of both height and weight secondary to insufficient caloric intake (five cases), and severe cutaneous involvement (one case). Five children had severe iron deficiency anemia (<70 g/L), three children had a very low 25-hydroxy vitamin D level (nutritional rickets), and two had severe hyponatremia (<130 mmoL/L). Milk alternative beverages expose infants to severe nutritional deficiencies. Serious complications can occur. Early, exclusive, and extended use is riskier. These diseases are preventable, and parental education should be provided. Statutory measures

  17. Identification of inappropriate medication use in elderly patients with frequent emergency department visits

    PubMed Central

    Wong, Jeffrey; Marr, Patricia; Kwan, Debbie; Meiyappan, Soumia; Adcock, Lesley

    2014-01-01

    Objective: To determine the demographic and health care characteristics of elderly family health team patients who are frequent emergency department (ED) users, focusing on potentially inappropriate medications (PIMs) and access to primary care services. Design: Cross-sectional retrospective chart review. Setting: Academic family medicine clinic in Toronto, Ontario. Participants: A total of 46 elderly patients (age >65 years) with 4 or more visits to a University Health Network–affiliated ED between April 1, 2010, and March 31, 2011. Main outcome measures: Using the validated STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions) criteria, PIMs were identified. The primary objective was to determine whether PIMs were associated with more frequent ED use. The secondary objective was to determine whether patients who had previously undergone a clinic pharmacist-led medication review had fewer PIMs. We also determined the health characteristics of these patients at the time of their last ED visit of the study period. Utilization of primary care resources, both prior to and after ED visits, was determined. Results: Sixty-five percent of patients were taking at least 1 PIM. The total number of PIMs in the study population was 71. Having more PIMs was significantly correlated with a higher number of ED visits (r = 0.32, p < 0.05). Patients with a previous medication review had a similar number of PIMs compared with those without a review. The mean number of concurrent medications was 12.1 and the mean Charlson Comorbidity Index score was 3.7. Significant delay between hospital discharge and primary care follow-up (median 13 days) was observed. Conclusion: Elderly patients who are more frequent ED users have a greater number of PIMs. Primary care resources appear to be underused in this population. PMID:25360151

  18. Atmospheric pressure cold plasma as an antifungal therapy

    NASA Astrophysics Data System (ADS)

    Sun, Peng; Sun, Yi; Wu, Haiyan; Zhu, Weidong; Lopez, Jose L.; Liu, Wei; Zhang, Jue; Li, Ruoyu; Fang, Jing

    2011-01-01

    A microhollow cathode based, direct-current, atmospheric pressure, He/O2 (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

  19. Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action.

    PubMed

    Rosen, Theodore; Stein Gold, Linda F

    2016-03-01

    In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals. PMID:27074700

  20. Recent advances in topical formulation carriers of antifungal agents.

    PubMed

    Bseiso, Eman Ahmed; Nasr, Maha; Sammour, Omaima; Abd El Gawad, Nabaweya A

    2015-01-01

    Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles. PMID:26261140

  1. Atmospheric pressure cold plasma as an antifungal therapy

    SciTech Connect

    Sun Peng; Wu Haiyan; Sun Yi; Liu Wei; Li Ruoyu; Zhu Weidong; Lopez, Jose L.; Zhang Jue; Fang Jing

    2011-01-10

    A microhollow cathode based, direct-current, atmospheric pressure, He/O{sub 2} (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

  2. Antifungal activity of three mouth rinses--in vitro study.

    PubMed

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans. PMID:16758789

  3. Fungal virulence genes as targets for antifungal chemotherapy.

    PubMed Central

    Perfect, J R

    1996-01-01

    Fungal virulence genes have now met the age of molecular pathogenesis. The definition of virulence genes needs to be broad so that it encompasses the focus on molecular antifungal targets and vaccine epitopes. However, in the broad but simple definition of a virulence gene, there will be many complex genetic and host interactions which investigators will need to carefully define. Nevertheless, with the increasing numbers of serious fungal infections produced by old and newly reported organisms, the paucity of present antifungal drugs, and the likelihood of increasing drug resistance, the need for investigations into understanding fungal virulence at the molecular level has never been more important. PMID:8807043

  4. Inappropriate use of commercial Antinuclear Antibody Testing in a community-based US hospital: a retrospective study.

    PubMed

    Mohammed, Abdul S; Boddu, Prajwal; Mael, David; Samee, Mohammed; Villines, Dana

    2016-01-01

    Healthcare providers use antinuclear antibodies (ANAs) to screen and diagnose patients with autoimmune diseases. In the recent years, commercial multiplex ANA kits have emerged as a convenient and fast diagnostic method. Diagnostic testing should follow sequenced algorithms: initial screen followed by specific antibody analysis. Second-level testing as an initial screen for autoimmune disease is inappropriate. We reviewed 68 patients with ANA comprehensive panels over a 6-month period from May 2015 to October 2015. We assessed appropriateness and estimated incurred losses from inappropriate testing. We found 92.6% (63 out of 68) of the ANA comprehensive panel results to be negative. Incurred losses from inappropriate ANA comprehensive panel testing were $66,000. Physicians should become familiar with ANA-sequenced diagnostic algorithms to avoid unnecessary higher level testing. PMID:27609725

  5. Candida tropicalis as a Predominant Isolate from Clinical Specimens and its Antifungal Susceptibility Pattern in a Tertiary Care Hospital in Southern India

    PubMed Central

    Mohanram, Kalyani

    2015-01-01

    Background The incidence of infections caused by Candida species has increased considerably over the past three decades mainly due to the rise of the AIDS epidemic, an increasingly aged population, higher numbers of immunocompromised patients and the more widespread use of indwelling medical devices. Candida tropicalis is emerging pathogenic yeast among non-albicans species. Recently drug-resistant C.tropicalis was also reported in hospitals. Aim and Objective The present study aimed to isolate and speciate C. tropicalis from various clinical samples and to determine its antifungal susceptibility profile. Materials and Methods Clinical samples such as urine, blood, exudates and vaginal swab which were submitted to the Microbiology laboratory during the year 2013 were screened for the growth of Candidia species, which then identified as C.tropicalis by the routine microbiological procedures such as germ tube formation, assimilation and fermentation of sugars and colony color on HICHROM Candida agar. Antifungal susceptibility was performed by disc diffusion method with the drugs Amphotericin-B, Itraconazole, Ketaconazole and Fluconazole on C. tropicalis isolates. Results A total number of 112 Candida isolates were isolated during the year 2012 from various clinical specimens. Among them 61 (54.3%) were identified as C.tropicalis. All the C. tropicalis isolates were sensitive to Amphotericin-B (100%) but 23 isolates (37.7%) were resistant to Fluconazole. Conclusion We conclude that identification of Candida species is important to know the prevalent species in the clinical setup and routine antifungal susceptibility should be performed to avoid inappropriate treatment. PMID:26393128

  6. Potentially inappropriate prescribing in institutionalised older patients in Spain: the STOPP-START criteria compared with the Beers criteria

    PubMed Central

    Ubeda, Amalia; Ferrándiz, Luisa; Maicas, Nuria; Gomez, Cristina; Bonet, Montserrat; Peris, Jose E.

    Objective The aims of this study were to identify potentially inappropriate prescribing using the Beers and STOPP criteria. The START criteria were applied to detect prescription omission in the geriatric population. We compared the utility of these criteria in institutionalised older people. Methods Descriptive study reviewing the medication and clinical records of 81 residents (aged 65 years and more) by pharmacists in a nursing home in the Lleida region (Spain). Results The mean patients’'age was 84 (SD=8) years, with an average of 5 drugs per resident (total prescriptions: 416 medicines). The Beers criteria identified potentially inappropriate medication use in 25% of patients and 48% of patients used at least 1 inappropriate medication according to STOPP criteria. The most frequent potentially inappropriate medications for both criteria were long-acting benzodiazepines and NSAIDs. START detected 58 potential prescribing omissions in 44% of patients. Calcium-vitamin D supplementation in osteoporosis was the most frequent rule (15%), but omissions corresponding to the cardiovascular system implied 23% of patients. Conclusions The STOPP-START criteria reveal that potentially inappropriate prescribing (PIP) is a highly prevalent problem among Spanish nursing home residents, and a statistically significant positive correlation was found between the number of medicines prescribed and the number of PIP detected in this study. The STOPP criteria detect a larger number of PI medications in this geriatric population than the Beers criteria. The prescribing omissions detected by the START criteria are relevant and require intervention. Pharmacists’ review of medications may help identify potentially inappropriate prescribing and, through an interdisciplinary approach, working with physicians may improve prescribing practices among geriatric residents of nursing homes. PMID:24155822

  7. Antifungal Activities of SCY-078 (MK-3118) and Standard Antifungal Agents against Clinical Non-Aspergillus Mold Isolates

    PubMed Central

    Lamoth, Frédéric

    2015-01-01

    The limited armamentarium of active and oral antifungal drugs against emerging non-Aspergillus molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-d-glucan synthase inhibitor SCY-078 were tested in vitro against 135 clinical non-Aspergillus mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against Mucoromycotina and Fusarium spp. However, SCY-078 was highly active against Paecilomyces variotii and was the only compound displaying some activity against notoriously panresistant Scedosporium prolificans. PMID:25896696

  8. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology

    PubMed Central

    Ashbee, H. Ruth; Barnes, Rosemary A.; Johnson, Elizabeth M.; Richardson, Malcolm D.; Gorton, Rebecca; Hope, William W.

    2014-01-01

    The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics–pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents. PMID:24379304

  9. [Recent advances in the study of antifungal lead compounds with new chemical scaffolds].

    PubMed

    Shao, Lü-cheng; Sheng, Chun-quan; Zhang, Wan-nian

    2007-11-01

    In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized. PMID:18300466

  10. Non-Empirical Confirmation

    NASA Astrophysics Data System (ADS)

    Dawid, Richard

    2016-06-01

    In fundamental physics today, some theories are taken to be probably viable despite a lack of strong (or any) empirical confirmation. This situation suggests, I argue, an extension of the concept of theory confirmation that allows for confirmation by observations that are not predicted by the theory in question. "Non-empirical confirmation", as I call the latter form of confirmation, plays a more conspicuous role today than in earlier periods of physics. It has always constituted a significant albeit implicit element of the assessment of physical theory, however, that has not been adequately accounted for in canonical reconstructions of the scientific method. The talk discusses the core argumentative structure of non-empirical confirmation, analyses the concept’s reliance on the empirical testability of the theories in question and addresses some worries that have been raised in its regard.

  11. Enhancement of commercial antifungal agents by kojic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kojic acid (KA), a natural by-product of fungal fermentation, is a commonly used food and cosmetic additive. We show that KA increases activity of amphotericin B and strobilurin, medical and agricultural antifungal agents, respectively, possibly targeting the fungal antioxidative system. KA shows pr...

  12. Simplifungin and Valsafungins, Antifungal Antibiotics of Fungal Origin.

    PubMed

    Ishijima, Hiroyuki; Uchida, Ryuji; Ohtawa, Masaki; Kondo, Ariko; Nagai, Kenichiro; Shima, Keisuke; Nonaka, Kenichi; Masuma, Rokuro; Iwamoto, Susumu; Onodera, Hideyuki; Nagamitsu, Tohru; Tomoda, Hiroshi

    2016-09-01

    The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision-induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 μg/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively. PMID:27400027

  13. Successful management of renal mucormycosis with antifungal therapy and drainage

    PubMed Central

    Devana, Sudheer K.; Bora, Girdhar S.; Mavuduru, Ravimohan S.; Panwar, Pankaj; Kakkar, Nandita; Mandal, Arup K.

    2016-01-01

    We report a case of isolated extensive renal mucormycosis in an immunocompetent adult, who was successfully managed conservatively without surgical debridement. To the best of our knowledge, this is the first case where antifungal therapy alone was sufficient even with such an extensive involvement. PMID:27127360

  14. Antifungal activity of heartwood extracts from three Juniperus species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heartwood samples from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane, ethanol and methanol and the hexane and ethanol extracts were tested for antifungal activity against four species of wood-rot fungi. These three species represent the ...

  15. Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs

    PubMed Central

    Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M. A.; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E.; Casadevall, Arturo

    2015-01-01

    The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. PMID:26711773

  16. Chemosensitization as a means to augment commercial antifungal agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is growing list of papers on antimycotic chemosensitization and the mechanisms by which they function. Currently, antifungal agents used in agriculture and in human or veterinary medicine are confronted by a number of obstacles, the main one being continual development of resistance to one, or...

  17. Prediction of antifungal activity of gemini imidazolium compounds.

    PubMed

    Pałkowski, Łukasz; Błaszczyński, Jerzy; Skrzypczak, Andrzej; Błaszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Kożuszko, Sylwia; Gospodarek, Eugenia; Słowiński, Roman; Krysiński, Jerzy

    2015-01-01

    The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds. PMID:25961015

  18. In vitro antifungal activity of Schizozygia coffaeoides bail. (Apocynaceae) extracts.

    PubMed

    Kariba, R M; Siboe, G M; Dossaji, S F

    2001-01-01

    Leaf extracts of Schizozygia coffaeoides were investigated for antifungal activity using the disc diffusion assay technique. Petroleum ether 40-60 degrees C, dichloromethane-ethyl acetate (1:1) and methanol extracts were fungitoxic to Trichophyton mentagrophytes, Microsporum gypseum, Cladosporium cucumerinum and Candida albicans. The extracts were fungistatic in action. PMID:11137346

  19. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

    Pałkowski, Łukasz; Błaszczyński, Jerzy; Skrzypczak, Andrzej; Błaszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Kożuszko, Sylwia; Gospodarek, Eugenia; Słowiński, Roman; Krysiński, Jerzy

    2015-01-01

    The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds. PMID:25961015

  20. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

    PubMed

    Hufford, C D; Sharma, A S; Oguntimein, B O

    1980-10-01

    Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina. PMID:7420287

  1. Research to Identify Effective Antifungal Agents, 1992 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-03-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990 and Schreck et al. 1991). The objectives of the present study were to select and evaluate up to 10 candidate fungicides.

  2. [Antifungal activity of 5-benzilidene pyrrolone and furanone derivatives].

    PubMed

    de Carvalho, M G; Pitta, I da R; Galdino, S L; Takaki, G de C; Bergé, G

    1989-01-01

    The antifungal activity against Neurospora crassa of some 5-benzilidene pyrrolone and furanone derivatives was realised. Relations between the structure and this biological activity are established with Fujita-Ban and Hansch methods. The preponderant part of lipophilicity, resonance effect and E or Z configurations have been showed. PMID:2535109

  3. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    PubMed

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  4. Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs.

    PubMed

    Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M A; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E; Casadevall, Arturo; Gonçalves, Teresa

    2016-03-01

    The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. PMID:26711773

  5. Antifungal Lock Therapy with Liposomal Amphotericin B: A Prospective Trial.

    PubMed

    McGhee, William; Michaels, Marian G; Martin, Judith M; Mazariegos, George V; Green, Michael

    2016-03-01

    We conducted a prospective pilot study to evaluate the potential role of combined systemic antifungal and liposomal amphotericin B lock therapy in children with intestinal insufficiency with fungal catheter-related bloodstream infections whose central venous catheters had not been removed. Our results provide supportive evidence for the conduct of larger clinical trials to confirm the efficacy and safety of this approach. PMID:26908494

  6. Determination of antifungal, biochemical and physiological features of Trichoderma koningiopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trichoderma koningiopsis is a species that has been recently identified and has not yet been published, but is in press. Due to the absence of reported data on this species, antifungal, biochemical and physiological features were analyzed for the Trichoderma koningiopsis strain isolated from root se...

  7. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  8. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  9. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  10. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  11. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  12. Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy

    PubMed Central

    Meletiadis, Joseph; Chanock, Stephen; Walsh, Thomas J.

    2006-01-01

    Pharmacogenomics is defined as the study of the impacts of heritable traits on pharmacology and toxicology. Candidate genes with potential pharmacogenomic importance include drug transporters involved in absorption and excretion, phase I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II enzymes (e.g., glucuronosyltransferases) contributing to metabolism, and those molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the distribution of antifungal compounds. By using the tools of population genetics to define interindividual differences in drug absorption, distribution, metabolism, and excretion, pharmacogenomic models for genetic variations in antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become especially important in the treatment of immunocompromised patients or those with persistent or refractory mycoses that cannot be explained by elevated MICs and where rational dosage optimization of the antifungal agent may be particularly critical. Pharmacogenomics has the potential to shift the paradigm of therapy and to improve the selection of antifungal compounds and adjustment of dosage based upon individual variations in drug absorption, metabolism, and excretion. PMID:17041143

  13. Antifungal activities of nine traditional Mexican medicinal plants.

    PubMed

    Navarro García, V M; Gonzalez, A; Fuentes, M; Aviles, M; Rios, M Y; Zepeda, G; Rojas, M G

    2003-07-01

    Eighteen plant extracts from nine traditional Mexican medicinal plants were tested for antifungal activity against two dermatophyte fungal species (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and Annona cherimolia. PMID:12787958

  14. Identification and biological activity of antifungal saponins from shallot ( Allium cepa L. Aggregatum group).

    PubMed

    Teshima, Yoshiki; Ikeda, Tsuyoshi; Imada, Kiyoshi; Sasaki, Kazunori; El-Sayed, Magdi A; Shigyo, Masayoshi; Tanaka, Shuhei; Ito, Shin-Ichi

    2013-08-01

    The n-butanol extract of shallot basal plates and roots showed antifungal activity against plant pathogenic fungi. The purified compounds from the extract were examined for antifungal activity to determine the predominant antifungal compounds in the extract. Two major antifungal compounds purified were determined to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal activity against a wide range of fungi. The products of acid hydrolysis of ALA showed a reduced antifungal activity, suggesting that the compound's sugar chain is essential for its antifungal activity. Fungal cells treated with ALA showed rapid production of reactive oxygen species. The fungicidal action of ALA was partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide anion generation in the fungal cells may be related to the compound's action. Inoculation experiments showed that ALA protected strawberry plants against Colletotrichum gloeosporioides , indicating that ALA has the potential to control anthracnose of the plant. PMID:24138065

  15. Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

    PubMed

    Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. PMID:26680221

  16. [Empiric treatment of pyelonephritis].

    PubMed

    Iarovoĭ, S K; Shimanovskiĭ, N L; Kareva, E N

    2011-01-01

    The article analyses the most typical clinical situations in empirical treatment of pyelonephritis including situations with comorbid severe diseases: decompensated diabetes mellitus, chronic renal failure, HIV-infection. Choice of antibacterial medicines for empiric treatment of pyelonephritis is based on the results of the latest studies of antibioticoresistance of pyelonephritis pathogens as well as on specific features of pharmacokinetics and pharmacodynamics of antibacterial drugs. PMID:21815461

  17. Persistent syndrome of inappropriate antidiuretic hormone secretion following traumatic brain injury

    PubMed Central

    Dick, Michael; Kumareswaran, Kavita; Hamblin, Peter Shane; Topliss, Duncan J

    2015-01-01

    Summary The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case reports describing chronic SIADH and all resolved within 12 months, except for one case complicated by meningo-encephalitis. Persistent symptomatic hyponatremia due to chronic SIADH was present for 4 years following a TBI in a previously well 32-year-old man. Hyponatremia consistent with SIADH initially occurred in the immediate period following a high-speed motorbike accident in 2010. There were associated complications of post-traumatic amnesia and mild cognitive deficits. Normalization of serum sodium was achieved initially with fluid restriction. However, this was not sustained and he subsequently required a permanent 1.2 l restriction to maintain near normal sodium levels. Multiple episodes of acute symptomatic hyponatremia requiring hospitalization occurred over the following years when he repeatedly stopped the fluid restriction. Given the ongoing nature of his hyponatremia and difficulties complying with strict fluid restriction, demeclocycline was commenced in 2014. Normal sodium levels without fluid restriction have been maintained for 6 months since starting demeclocycline. This case illustrates an important long-term effect of TBI, the challenges of complying with permanent fluid restrictions and the potential role of demeclocycline in patients with chronic hyponatremia due to SIADH. Learning points Hyponatraemia due to SIADH commonly occurs after TBI, but is usually mild and transient. Chronic hyponatraemia due to SIADH following TBI is a rare but important complication. It likely results from damage to the pituitary stalk or posterior pituitary causing inappropriate non-osmotic hypersecretion of ADH. First line management of SIADH is generally fluid restriction, but hypertonic saline may be required in severe cases. Adherence to long-term fluid restriction is challenging

  18. In Vitro Antifungal Activities against Moulds Isolated from Dermatological Specimens

    PubMed Central

    Mohd Nizam, Tzar; Binting, Rabiatul Adawiyah AG.; Mohd Saari, Shafika; Kumar, Thivyananthini Vijaya; Muhammad, Marianayati; Satim, Hartini; Yusoff, Hamidah; Santhanam, Jacinta

    2016-01-01

    Background This study aimed to determine the minimum inhibitory concentrations (MICs) of various antifungal agents against moulds isolated from dermatological specimens. Methods We identified 29 moulds from dermatological specimens between October 2012 and March 2013 by conventional methods. We performed antifungal susceptibility testing on six antifungal agents, amphotericin B, clotrimazole, itraconazole, ketoconazole, miconazole and terbinafine, according to the Clinical and Laboratory Standards Institute guidelines contained in the M38-A2 document. Results Most antifungal agents were active against the dermatophytes, except for terbinafine against Trichophyton rubrum (geometric mean MIC, MICGM 3.17 μg/mL). The dematiaceous moulds were relatively susceptible to amphotericin B and azoles (MICGM 0.17–0.34 μg/mL), but not to terbinafine (MICGM 3.62 μg/mL). Septate hyaline moulds showed variable results between the relatively more susceptible Aspergillus spp. (MICGM 0.25–4 μg/mL) and the more resistant Fusarium spp. (MICGM 5.66–32 μg/mL). The zygomycetes were susceptible to amphotericin B (MICGM 0.5 μg/mL) and clotrimazole (MICGM 0.08 μg/mL), but not to other azoles (MICGM 2.52–4 μg/mL). Conclusion Amphotericin B and clotrimazole were the most effective antifungal agents against all moulds excepting Fusarium spp., while terbinafine was useful against dermatophytes (except T. rubrum) and Aspergillus spp. However, a larger study is required to draw more solid conclusions. PMID:27418867

  19. Sporothrix schenckii complex in Iran: Molecular identification and antifungal susceptibility.

    PubMed

    Mahmoudi, Shahram; Zaini, Farideh; Kordbacheh, Parivash; Safara, Mahin; Heidari, Mansour

    2016-08-01

    Sporotrichosis is a global subcutaneous fungal infection caused by the Sporothrix schenckii complex. Sporotrichosis is an uncommon infection in Iran, and there have been no phenotypic, molecular typing or antifungal susceptibility studies of Sporothrix species. This study aimed to identify nine Iranian isolates of the S. schenckii complex to the species level using colony morphology, carbohydrate assimilation tests, and PCR-sequencing of the calmodulin gene. The antifungal susceptibilities of these Sporothrix isolates to five antifungal agents (amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and terbinafine (TRB)) were also evaluated according to the M27-A3 and M38-A2 protocols of the Clinical and Laboratory Standards Institute for yeast and mycelial phases, respectively. Five of seven clinical isolates were identified as S. schenckii, and two clinical and two environmental isolates were identified as S. globosa. This is the first report of S. globosa in Iran. There was significant agreement (73%) between the results of the phenotypic and genotypic identification methods. TRB and ITC were the most effective antifungals against the Sporothrix isolates. The minimum inhibitory concentration (MIC) values of TRB for the yeast and mycelial phases of S. schenckii differed significantly. There was also a significant difference in the minimum fungicidal concentration (MFC) values of AMB and TRB for the two phases. Considering the low efficacy of VRC and FLC and the wide MIC ranges of AMB (1-16 μg/ml and 1-8 μg/ml for yeast and mycelial forms, respectively) observed in the present study, in vitro antifungal susceptibility testing should be performed to determine appropriate therapeutic regimens. PMID:26933207

  20. Evaluation of the antifungal activity and modulation between Cajanus cajan (L.) Millsp. leaves and roots ethanolic extracts and conventional antifungals

    PubMed Central

    Brito, Samara A.; Rodrigues, Fabíola F. G.; Campos, Adriana R.; da Costa, José G. M.

    2012-01-01

    Background: The use and investigation of natural products with antimicrobial activity from vegeral source have been reported by several researchers. Cajanus cajan (Fabaceae) is a multiple use specie mainly as human food. In popular medicine, diverse parts of the plant are used as sedative and to treat cough, hepatitis, and diabetes. Materials and Methods: This study shows the characterization of secondary metabolites present in ehtanolic extracts from leaves and roots of Cajanus cajan by phytochemical prospection. The evaluation of the antifungal activity was performed by the microdilution method, and from the subinhibitory concentrations (MIC 1/8) the modulatory activity of antifungical (fluconazole and ketoconazole) was analyzed by the direct contact assay against C. albicans ATCC40006, Candida krusei ATCC 6538 and Candida tropicalis ATCC 40042. Results: The results showed the presence of tannins, flavonoids, and alkaloids in both extracts as the clinically relevant antifungal activity. The modulatory potential is presented by the antifungal tested against yeasts. Conclusion: The extracts studied here have demonstrated to be a new therapeutic source to treat these microorganism-associated diseases. PMID:22701281

  1. A nutrition support team led by general surgeons decreases inappropriate use of total parenteral nutrition on a surgical service.

    PubMed

    Saalwachter, A R; Evans, H L; Willcutts, K F; O'Donnell, K B; Radigan, A E; McElearney, S T; Smith, R L; Chong, T W; Schirmer, B D; Pruett, T L; Sawyer, R G

    2004-12-01

    The purpose of this study was to decrease the number of inappropriate orders for total parenteral nutrition (TPN) in surgical patients. From February 1999 through November 2000 and between July 2001 and June 2002, the surgeon-guided adult nutrition support team (NST) at a university hospital monitored new TPN orders for appropriateness and specific indication. In April 1999, the NST was given authority to discontinue inappropriate TPN orders. Indications, based on the American Society for Parenteral and Enteral Nutrition (ASPEN) standards, included short gut, severe pancreatitis, severe malnutrition/catabolism with inability to enterally feed > or =5 days, inability to enterally feed >50 per cent of nutritional needs > or =9 days, enterocutaneous fistula, intra-abdominal leak, bowel obstruction, chylothorax, ischemic bowel, hemodynamic instability, massive gastrointestinal bleed, and lack of abdominal wall integrity. The number of inappropriate TPN orders declined from 62/194 (32.0%) in the first 11 months of the study to 22/168 (13.1%) in the second 11 months (P < 0.0001). This number further declined to 17/215 (7.9%) in the final 12 months of data collection, but compared to the second 11 months, this decrease was not statistically significant (P = 0.1347). The involvement of a surgical NST was associated with a reduction in inappropriate TPN orders without a change in overall use. PMID:15663055

  2. The Use of Inappropriate Feeding Practices by Rural Parents and Their Effect on Preschoolers' Fruit and Vegetable Preferences and Intake

    ERIC Educational Resources Information Center

    Bante, Holly; Elliott, Michael; Harrod, Amanda; Haire-Joshu, Debra

    2008-01-01

    Objective: To describe the frequency of inappropriate feeding practices used by parents of preschoolers and the impact on a child's preference for and intake of fruits and vegetables (FV). Design: Cross-sectional analysis of baseline data from a telephone interview. Setting: A community-based program in rural southeastern Missouri. Participants:…

  3. Unipolar ventricular pacing reduces inappropriate shocks from a separate cardioverter defibrillator in a post-Fontan patient.

    PubMed

    Cohen, Mitchell I; Jedeikin, Roy; Pfeiffer, Sharon; Pedersen, Scott

    2006-04-01

    This report describes a 20-year-old man with complex congenital heart disease and inappropriate epicardial implantable cardioverter defibrillator (ICD) shocks secondary to double counting of ventricular-paced spikes and QRS complexes from a separate bipolar epicardial dual-chamber pacemaker. Adjusting to a unipolar paced-ventricular mode resolved any double counting via pacemaker-ICD interaction. PMID:16627457

  4. Group Contingencies, Randomization of Reinforcers, and Criteria for Reinforcement, Self-Monitoring, and Peer Feedback on Reducing Inappropriate Classroom Behavior

    ERIC Educational Resources Information Center

    Coogan, Brenda Anne; Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.

    2007-01-01

    Considerable research has demonstrated the effectiveness of interdependent and unknown dependent group contingencies on reducing inappropriate classroom behavior. Several investigators have focused on the addition of self-monitoring and peer feedback to these interdependent and unknown dependent group contingencies in order to further improve…

  5. [Multiple inappropriate defibrillator shocks due to insulation failure of a Biotronik Linox defibrillator lead with externalized conductor].

    PubMed

    Elfarra, Hamdi; Moosdorf, Rainer; Rybinski, Leszek; Grimm, Wolfram

    2016-03-01

    In this article the case of a patient who received a total of 35 inappropriate defibrillator shocks due to insulation failure with externalized conductor of a Biotronik Linox® lead is described. The implanted defibrillator was immediately inactivated and the failed lead was extracted using a laser sheath system. PMID:26848762

  6. Nontechnical Strategies To Reduce Children's Exposure to Inappropriate Material on the Internet. Summary of a Workshop (December 13, 2000).

    ERIC Educational Resources Information Center

    Iannotta, Joah G., Ed.

    In response to a Congressional mandate in conjunction with the Protection of Children from Sexual Predators Act of 1998, a committee of experts was formed to explore both technical and nontechnical strategies for protecting children from pornography and other inappropriate Internet content. This book summarizes a workshop held in December 2000 to…

  7. "Normal" and "Inappropriate" Childhood Sexual Behaviours: Findings from a Delphi Study of Professionals in the United Kingdom

    ERIC Educational Resources Information Center

    Vosmer, Susanne; Hackett, Simon; Callanan, Margie

    2009-01-01

    This paper presents the results of a three-stage Delphi study examining the current level of consensus among 24 professionals in the United Kingdom regarding definitions of and distinctions between normal, inappropriate and sexually abusive behaviours in children under 10 years, as well as factors influencing their views. Although firm conclusions…

  8. The Perils of Being a Male Primary/Junior Teacher: Vulnerability and Accusations of Inappropriate Contact with Students

    ERIC Educational Resources Information Center

    Parr, Michael; Gosse, Douglas

    2011-01-01

    There is a perceived shortage of male teachers in education, particularly at the primary/junior (P/J) level where male teachers in Canada account for a dwindling minority. Included among the many factors inhibiting males from becoming P/J teachers are perceptions that males might be unduly vulnerable to false accusations of inappropriate conduct…

  9. (In)appropriate Personal Pronoun Use in Political Science: A Qualitative Study and a Proposed Heuristic for Future Research

    ERIC Educational Resources Information Center

    Harwood, Nigel

    2006-01-01

    This article describes five political scientists' interview-based accounts of appropriate and inappropriate use of the pronouns "I" and "we" in academic writing. The informants talked about pronoun use with reference to one of their own journal articles and also by referring to other informants' texts. Beliefs about appropriate and inappropriate…

  10. Two Children with Multiple Disabilities Increase Adaptive Object Manipulation and Reduce Inappropriate Behavior via a Technology-Assisted Program

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Didden, Robert; Oliva, Doretta; Campodonico, Francesca

    2010-01-01

    Persons with severe to profound multiple disabilities, such as intellectual, visual, and motor disabilities, may be characterized by low levels of adaptive engagement with the environment. They may also display forms of inappropriate, stereotypical behavior (like hand mouthing, that is, putting their fingers into or over their mouths) or…

  11. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

    PubMed

    2015-11-01

    The 2015 American Geriatrics Society (AGS) Beers Criteria are presented. Like the 2012 AGS Beers Criteria, they include lists of potentially inappropriate medications to be avoided in older adults. New to the criteria are lists of select drugs that should be avoided or have their dose adjusted based on the individual's kidney function and select drug-drug interactions documented to be associated with harms in older adults. The specific aim was to have a 13-member interdisciplinary panel of experts in geriatric care and pharmacotherapy update the 2012 AGS Beers Criteria using a modified Delphi method to systematically review and grade the evidence and reach a consensus on each existing and new criterion. The process followed an evidence-based approach using Institute of Medicine standards. The 2015 AGS Beers Criteria are applicable to all older adults with the exclusion of those in palliative and hospice care. Careful application of the criteria by health professionals, consumers, payors, and health systems should lead to closer monitoring of drug use in older adults. PMID:26446832

  12. The relative merits of therapies being developed to tackle inappropriate ('self'-directed) complement activation.

    PubMed

    Antwi-Baffour, Samuel; Kyeremeh, Ransford; Adjei, Jonathan Kofi; Aryeh, Claudia; Kpentey, George

    2016-12-01

    The complement system is an enzyme cascade that helps defend against infection. Many complement proteins occur in serum as inactive enzyme precursors or reside on cell surfaces. Complement components have many biologic functions and their activation can eventually damage the plasma membranes of cells and some bacteria. Although a direct link between complement activation and autoimmune diseases has not been found, there is increasing evidence that complement activation significantly contributes to the pathogenesis of a large number of inflammatory diseases that may have autoimmune linkage. The inhibition of complement may therefore be very important in a variety of autoimmune diseases since their activation may be detrimental to the individual involved. However, a complete and long-term inhibition of complement may have some contra side effects such as increased susceptibility to infection. The site of complement activation will, however, determine the type of inhibitor to be used, its route of application and dosage level. Compared with conventional drugs, complement inhibitors may be the best option for treatment of autoimmune diseases. The review takes a critical look at the relative merits of therapies being developed to tackle inappropriate complement activation that are likely to result in sporadic autoimmune diseases or worsen already existing one. It covers the complement system, general aspects of complement inhibition therapy, therapeutic strategies and examples of complement inhibitors. It concludes by highlighting on the possibility that a better inhibitor of complement activation when found will help provide a formidable treatment for autoimmune diseases as well as preventing one. PMID:26935316

  13. [The treament of hyponatremia secundary to the syndrome of inappropriate antidiuretic hormone secretion].

    PubMed

    Runkle, Isabelle; Villabona, Carles; Navarro, Andrés; Pose, Antonio; Formiga, Francesc; Tejedor, Alberto; Poch, Esteban

    2013-12-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most frequent cause of hyponatremia in a hospital setting. However, detailed protocols and algorithms for its management are lacking. Our objective was to develop 2 consensus algorithms for the therapy of hyponatremia due to SIADH in hospitalized patients. A multidisciplinary group made up of 2 endocrinologists, 2 nephrologists, 2 internists, and one hospital pharmacist held meetings over the period of a year. The group worked under the auspices of the European Hyponatremia Network and the corresponding Spanish medical societies. Therapeutic proposals were based on widely-accepted recommendations, expert opinion and consensus guidelines, as well as on the authors' personal experience. Two algorithms were developed. Algorithm 1 addresses acute correction of hyponatremia posing as a medical emergency, and is applicable to both severe euvolemic and hypovolemic hyponatremia. The mainstay of this algorithm is the iv use of 3% hypertonic saline solution. Specific infusion rates are proposed, as are steps to avoid or reverse overcorrection of serum sodium levels. Algorithm 2 is directed to the therapy of SIADH-induced mild or moderate, non-acute hyponatremia. It addresses when and how to use fluid restriction, solute, furosemide, and tolvaptan to achieve eunatremia in patients with SIADH. Two complementary strategies were elaborated to treat SIADH-induced hyponatremia in an attempt to increase awareness of its importance, simplify its therapy, and improve prognosis. PMID:24169317

  14. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    PubMed Central

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  15. Safeguarding Older Adults From Inappropriate Over-the-Counter Medications: The Role of Community Pharmacists

    PubMed Central

    Chui, Michelle A.; Stone, Jamie A.; Martin, Beth A.; Croes, Kenneth D.; Thorpe, Joshua M.

    2014-01-01

    Purpose of the Study: To elicit the thought process or mental model that community pharmacists use when making recommendations on over-the-counter (OTC) medications to older adults and to elicit the current practices of community pharmacists in providing information, advice, and counseling to older adults about potentially inappropriate OTC medications. Design and Methods: Three separate focus groups with pharmacists were conducted with 5 to 8 pharmacists per group. A vignette about an elderly woman seeking an OTC sleep aid was used to elicit information that pharmacists seek to establish when making a recommendation. Focus groups were recorded, transcribed verbatim, and analyzed for themes using the initial and focused coding methods of grounded theory. Results: Community pharmacists’ mental models were characterized by 2 similarities: a similarity in what community pharmacists seek to establish about patients and a similarity in when community pharmacists seek to establish it—the sequence in which they try to learn key details about patients. It was identified that pharmacists gather specific information about the patient’s medication profile, health conditions, characteristics of the problem, and past treatments in order to make a recommendation. Community pharmacists recommended behavioral modifications and seeing their physician prior to recommending an OTC sleep aid, primarily due to medication safety concerns. Implications: Pharmacists can play a key role in assisting older adults to select and use OTC medications. PMID:24197014

  16. 78 FR 6316 - Empire Pipeline, Inc. (Empire); Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Empire Pipeline, Inc. (Empire); Notice of Filing Take notice that on November 29, 2012 Empire Pipeline Company (Empire) submitted a request for a waiver of the...

  17. Antifungal effects of citronella oil against Aspergillus niger ATCC 16404.

    PubMed

    Li, Wen-Ru; Shi, Qing-Shan; Ouyang, You-Sheng; Chen, Yi-Ben; Duan, Shun-Shan

    2013-08-01

    Essential oils are aromatic oily liquids obtained from some aromatic plant materials. Certain essential oils such as citronella oil contain antifungal activity, but the antifungal effect is still unknown. In this study, we explored the antifungal effect of citronella oil with Aspergillus niger ATCC 16404. The antifungal activity of citronella oil on conidia of A. niger was determined by poisoned food technique, broth dilution method, and disc volatility method. Experimental results indicated that the citronella oil has strong antifungal activity: 0.125 (v/v) and 0.25 % (v/v) citronella oil inhibited the growth of 5 × 10⁵ spore/ml conidia separately for 7 and 28 days while 0.5 % (v/v) citronella oil could completely kill the conidia of 5 × 10⁵ spore/ml. Moreover, the fungicidal kinetic curves revealed that more than 90 % conidia (initial concentration is 5 × 10⁵ spore/ml) were killed in all the treatments with 0.125 to 2 % citronella oil after 24 h. Furthermore, with increase of citronella oil concentration and treatment time, the antifungal activity was increased correspondingly. The 0.5 % (v/v) concentration of citronella oil was a threshold to kill the conidia thoroughly. The surviving conidia treated with 0.5 to 2 % citronella oil decreased by an order of magnitude every day, and no fungus survived after 10 days. With light microscope, scanning electron microscope, and transmission electron microscope, we found that citronella oil could lead to irreversible alteration of the hyphae and conidia. Based on our observation, we hypothesized that the citronella oil destroyed the cell wall of the A. niger hyphae, passed through the cell membrane, penetrated into the cytoplasm, and acted on the main organelles. Subsequently, the hyphae was collapsed and squashed due to large cytoplasm loss, and the organelles were severely destroyed. Similarly, citronella oil could lead to the rupture of hard cell wall and then act on the sporoplasm to kill the

  18. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

    PubMed Central

    O'Mahony, Denis; O'Sullivan, David; Byrne, Stephen; O'Connor, Marie Noelle; Ryan, Cristin; Gallagher, Paul

    2015-01-01

    Purpose: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts. PMID:25324330

  19. The Syndrome of Inappropriate Secretion of Anti-Diuretic Hormone (SIADH) and Brucellosis.

    PubMed

    Bala, Keziban Aslı; Doğan, Murat; Kaba, Sultan; Akbayram, Sinan; Aslan, Oktay; Kocaman, Selami; Bayhan, Gülsüm İclal; Üstyol, Lokman; Demir, Nihat

    2016-01-01

    BACKGROUND Our study aimed to demonstrate the frequency of the syndrome of inappropriate ADH secretion (SIADH) and associated factors during the course of brucellosis in children and adolescents. MATERIAL AND METHODS The study included children and adolescents aged 0-18 years old diagnosed with brucellosis between 2012 and 2014. The data were collected from patient charts. The diagnosis of brucellosis was made based on titrations >1:160 in standard Wright tube agglutination tests and/or positive culture tests. SIADH diagnosis was made based on the following criteria: euvolemic hyponatremia, serum Na+ <135 mmol/L, presence of serum hypoosmolarity (serum osmolarity <275 mOsm/L), increased urinary sodium (>25 mmol/L with normal dietary salt intake), low uric acid (<2 mg/dL), absence of kidney, thyroid or adrenal disease, and any anti-diuretic use. RESULTS The study included 160 children and adolescents with mean age of 9.58±3.95 years (range: 2-18 years) including 70 girls (43.8%) and 90 boys (56.2%). When the patients were stratified based on SIADH, it was found that SIADH was present in 35 patients (21.9%). SIADH was associated with elevated glucose (p<0.001), ALT (p<0.05), AST (p<0.05), LDH (p<0.001), CRP (p<0.001), and MPV (p<0.001); and decreased potassium (p<0.05), chloride (p<0.001), albumin (p<0.001), total protein (p<0.05), and hemoglobin (p<0.05) levels. CONCLUSIONS Our study reports on the frequency, clinical characteristics, predisposing factors, and management of SIADH that can develop in children and adolescents diagnosed with brucellosis. PMID:27590789

  20. Fulminate Hepatic Failure in a 5 Year Old Female after Inappropriate Acetaminophen Treatment

    PubMed Central

    Kasmi, Irena; Sallabanda, Sashenka; Kasmi, Gentian

    2015-01-01

    BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/L. Patient totally recovered within 29 days. CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction.

  1. Inappropriate publication of trial results and potential for allegations of illegal share dealing.

    PubMed

    Freestone, D S; Mitchell, H

    1993-04-24

    There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any

  2. Inappropriate Drug Use in People with Cognitive Impairment and Dementia: A Systematic Review

    PubMed Central

    Johnell, Kristina

    2015-01-01

    The aim of this systematic review was to identify, assess and summarize studies about potentially inappropriate drug use (IDU) in cognitive impairment and dementia and to present findings about whether cognitive impairment and dementia are associated with IDU. The search was made in Medline/PubMed using free terms in the title or abstract. The inclusion criteria were: English language, published until 1 March 2014, original quantitative study and assessment of overall IDU with a consensus based summarized measure. Exclusion criteria were: focus on specific patient group (other than cognitive impairment or dementia), focus on specific drug class and failure to present a prevalence measure of IDU or an effect estimate (i.e. odds ratio). Of the initial 182 studies found in Medline, 22 articles fulfilled the criteria. Most studies used the Beers criteria for assessment of IDU. Prevalence of IDU among individuals with cognitive impairment or dementia ranged from 10.2% to 56.4% and was higher in nursing home settings than in community-dwelling samples. Most studies reported a lower likelihood of IDU in case of cognitive impairment or dementia. To conclude, IDU is highly prevalent among persons with cognitive impairment and dementia, although these conditions seem to be associated with a lower probability of IDU. This might reflect an awareness among clinicians of cautious prescribing to this vulnerable group of patients. More studies on large cohorts of persons with cognitive impairment and dementia are needed to draw conclusions about optimal drug prescribing to this frail group of older persons. PMID:26054404

  3. Independent review of inappropriate identification, storage and treatment methods of polychlorinated biphenyl waste streams

    SciTech Connect

    1997-07-01

    The purpose of the review was to evaluate incidents involving the inappropriate identification, storage, and treatment methods associated with polychlorinated biphenyl (PCB) waste streams originating from the V-tank system at the Test Area North (TAN). The team was instructed to perform a comprehensive review of Lockheed Martin Idaho Technologies Company (LMITCO`s) compliance programs related to these incidents to assess the adequacy and effectiveness of the management program in all respects including: adequacy of the waste management program in meeting all LMITCO requirements and regulations; adequacy of policies, plans, and procedures in addressing and implementing all federal and state requirements and regulations; and compliance status of LMITCO, LMITCO contract team members, and LMITCO contract/team member subcontractor personnel with established PCB management policies, plans, and procedures. The V-Tanks are part of an intermediate waste disposal system and are located at the Technical Support Facility (TSF) at TAN at the Idaho National Engineering and Environmental Laboratory (INEEL). The IRT evaluated how a waste was characterized, managed, and information was documented; however, they did not take control of wastes or ensure followup was performed on all waste streams that may have been generated from the V-Tanks. The team has also subsequently learned that the Environmental Restoration (ER) program is revising the plans for the decontamination and decommissioning of the intermediate waste disposal system based on new information listed and PCB wastes. The team has not reviewed those in-process changes. The source of PCB in the V-Tank is suspected to be a spill of hydraulic fluid in 1968.

  4. Long-term Cognitive and Functional Effects of Potentially Inappropriate Medications in Older Women

    PubMed Central

    2014-01-01

    Background. The use of potentially inappropriate medications in older adults can lead to known adverse drug events, but long-term effects are less clear. We therefore conducted a prospective cohort study of older women to determine whether PIM use is associated with risk of functional impairment or low cognitive performance. Methods. We followed up 1,429 community-dwelling women (≥75 years) for a period of 5 years at four clinical sites in the United States. The primary predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes included scores on a battery of six cognitive tests at follow-up and having one or more incident impairments in instrumental activities of daily living. Regression models were adjusted for baseline age, race, education, smoking, physical activity, a modified Charlson Comorbidity Index, and cognitive score. Results. The mean ± SD age of women at baseline was 83.2 ± 3.3. In multivariate models, baseline PIM use and higher ACB scores were significantly associated with poorer performance in category fluency (PIM: p = .01; ACB: p = .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p = .04). Both PIM use (odds ratio [OR]: 1.36 [1.05–1.75]) and higher ACB scores (OR: 1.11 [1.04–1.19]) were also strongly associated with incident functional impairment. Conclusions. The results provide suggestive evidence that PIM use and increased anticholinergic load may be associated with risk of functional impairment and low cognitive performance. More cautious selection of medications in older adults may reduce these potential risks. PMID:24293516

  5. Factors associated with inappropriate weight loss attempts by early adolescent girls in Japan.

    PubMed

    Sugawara, A; Sato, M; Totsuka, K; Saito, K; Kodama, S; Fukushi, A; Yamanashi, Y; Matsushima, E; Fujiwara, Y; Suzuki, E; Kondo, K; Yamamoto, S; Sone, H

    2011-09-01

    Attempting to lose weight by normal or underweight adolescent girls is a serious issue in many countries. It has been reported that the mode of attempted weight loss does not differ between normal weight and overweight girls. These inappropriate weight loss attempts (IWLA) by normal or underweight adolescent girls is associated with various health issues, but factors associated with IWLA have only been marginally elucidated. In this study, we applied a single multivariate regression analysis to clarify independent factors for IWLA. Study subjects were 134 pairs of early adolescent girls (aged 12-15) and their mothers. In addition to IWLA, many factors including height, weight, body image, perceived weight status, depressive symptoms, media influence and self-esteem were surveyed in both mothers and daughters and subjected to multivariate analysis. Approximately half of girls surveyed had IWLA, even though all were of normal weight and 62.9% knew that they were of normal weight. IWLA were independently associated with depressive symptoms (OR (95% CI); 2.80 (1.21-6.50), p=0.016) independent of actual or perceived weight status. Factors significantly associated with IWLA by the girls were percentage deviation of weight from standard weight (%DW) and media influence on the girls themselves, and media influence on and self-esteem of their mothers. IWLA, which were frequently observed among early adolescent girls even among those of normal weight, were closely related to depressive status. IWLA were significantly associated with not only factors related to the girls (1.09 (1.04-1.14), p=0.001), but also with maternal psychological factors (1.06 (1.00-1.13), p=0.035) conveyed by the media. Future prospective or interventional studies are required to clarify whether these factors could be targeted in an effort to prevent IWLA. PMID:22290031

  6. Patients Aged 80 Years or Older are Encountered More Potentially Inappropriate Medication Use

    PubMed Central

    Mo, Li; Ding, Ding; Pu, Shi-Yun; Liu, Qin-Hui; Li, Hong; Dong, Bi-Rong; Yang, Xiao-Yan; He, Jin-Han

    2016-01-01

    Background: Polypharmacy and potentially inappropriate medications (PIMs) are prominent prescribing issues in elderly patients. This study was to investigate the different prevalence of PIM use in elderly inpatients between 65–79 years of age and 80 years or older, who were discharged from Geriatric Department in West China Hospital. Methods: A large-scale cohort of 1796 inpatients aged 65 years or over was recruited. Respectively, 618 patients were 65–79 years and 1178 patients were 80 years or older. Updated 2012 Beers Criteria by the American Geriatric Society was applied to assess the use of PIM among the investigated samples. Results: A review of the prescribed medications identified 686 patients aged 80 years or older consumed at least one PIM giving a rate of 58.2%. Conversely, 268 (43.4%) patients aged 65–79 years consumed at least one PIM (χ2 = 40.18, P < 0.001). Patients aged 80 years or older had higher hospitalization expenses, length of stay, co-morbidities, medical prescription, and mortality than patients aged 65–79 years (all with P < 0.001). Patients aged 80 years or older were prescribed with more benzodiazepines, drugs with strong anticholinergic properties, megestrol, antipsychotics, theophylline, and aspirin. In multiple regression analysis, PIM use was significantly associated with female gender, age, number of diagnostic disease, and number of prescribed medication. Conclusions: The finding from this study revealed that inpatients aged 80 years or older encountered more PIM use than those aged 65–79 years. Anticholinergic properties, megestrol, antipsychotics, theophylline, and aspirin are medications that often prescribed to inpatients aged 80 years or older. Doctors should carefully choose drugs for the elderly, especially the elderly aged 80 years or older. PMID:26712428

  7. Inappropriate Feeding Behaviors and Dietary Intakes in Children with FASD or Probable PAE

    PubMed Central

    Werts, Rachel L.; Van Calcar, Sandra C.; Wargowski, David S.; Smith, Susan M.

    2013-01-01

    Background Prenatal alcohol exposure (PAE) is a leading cause of significant neurobehavioral and neurocognitive deficits. Its potential consequences for eating behaviors, nutritional status and other nutritional issues in childhood have received little attention. Methods Nineteen children (11 male, 8 female) of mean age 9.6 years, referred for FASD screening and assessment, were analyzed with physical exams and caregiver questionnaires to identify possible abnormalities in food and eating behaviors. Fourteen children contributed 24-hour diet recalls and were assessed for nutritional status. Results Seventy-nine percent of participants were diagnosed with FASD and 63.2% had confirmed PAE. Fifty percent of females were overweight or obese, whereas 37% of males had reduced stature, weight, or BMI for their age. Recurring feeding problems included constant snacking (36.8%), lack of satiety (26.3%), and picky eating/poor appetite (31.6%). None had oral feeding problems. Constipation was common (26.3%). Macronutrient intakes were largely normal but sugar consumption was excessive (140%-190% of recommendations) in 57% of subjects. Vitamin A intake exceeded the Upper Limit for 64% of participants, whereas ≥50% had intakes <80% of RDAs for choline, vitamin E, potassium, β-carotene, and essential fatty acids; 100% had vitamin D intakes <80% of the RDA. Conclusions PAE may be associated with altered acquisition and distribution of body mass with increasing age. Disordered eating was common. The increased feeding behaviors surrounding lack of satiety suggest self-regulation may be altered. Constipation could reflect low dietary fiber or altered gastrointestinal function. These exploratory data suggest that children with PAE may be at risk for nutritional deficiencies, which are influenced by inappropriate food preferences, disordered eating patterns, medication use, and the stressful dynamics surrounding food preparation and mealtime. PMID:24164456

  8. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea.

    PubMed

    Decaux, G; Brimioulle, S; Genette, F; Mockel, J

    1980-07-01

    Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p less than 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p less than 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p less than 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the "salt-losing" tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin-induced SIADH. in both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (less than 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks. It is concluded that urea is a good alternative in the treatment of patients with SIADH who presented with persistent hyponatremia despite the restriction of water intake. PMID:7386514

  9. A Comparison of Immediate Feedback Delivered Via an FM Headset versus Delayed Feedback on the Inappropriate Verbalizations of a Student with ADHD.

    ERIC Educational Resources Information Center

    Price, Anne T.; Martella, Ronald C.; Marchand-Martella, Nancy E.; Cleanthous, Charalambos C.

    2002-01-01

    The effects of immediate feedback provided through a wireless headphone FM transmission system were compared to the effects of delayed feedback on inappropriate verbalizations of a 10-year-old with attention deficit/hyperactivity disorder. Results indicate that inappropriate verbalizations decreased during both conditions, although the decrease…

  10. Antifungal activity of biflavones from Taxus baccata and Ginkgo biloba.

    PubMed

    Krauze-Baranowska, Mirosława; Wiwart, Marian

    2003-01-01

    Bilobetin and 4'''-O-methylamentoflavone were isolated and identified in the needles of Taxus baccata, for the first time in this species. The antifungal activity of biflavones from T. baccata and Ginkgo biloba, namely amentoflavone, 7-O-methylamentoflavone, bilobetin, ginkgetin, sciadopitysin and 2,3-dihydrosciadopitysin towards the fungi Alternaria alternata, Fusarium culmorum, Cladosporium oxysporum was determined employing computer-aided image analysis couplet to a microscope. Bilobetin exhibited a significant antifungal activity with values of ED50 14, 11 and 17 microM respectively. This compound completely inhibited the growth of germinating tubes of Cladosporium oxysporum and Fusarium culmorum at a concentration 100 microM. Activity of ginkgetin and 7-O-methylamentoflavone towards Alternaria alternata was stronger than that of bilobetin. Moreover, slight structural changes in the cell wall of Alternaria alternata exposed to ginkgetin at concentration of 200 microM were observed. PMID:12622229

  11. Design, synthesis and antifungal activity of novel furancarboxamide derivatives.

    PubMed

    Wen, Fang; Jin, Hong; Tao, Ke; Hou, Taiping

    2016-09-14

    Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L(-1). Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L(-1). This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides. PMID:27191618

  12. Conventional and alternative antifungal therapies to oral candidiasis

    PubMed Central

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-01-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis. PMID:24031562

  13. Synthesis, characterization, and antifungal activity of novel quaternary chitosan derivatives.

    PubMed

    Li, Rongchun; Guo, Zhanyong; Jiang, Pingan

    2010-09-01

    Three novel quaternary chitosan derivatives were successfully synthesized by reaction of chloracetyl chitosan (CACS) with pyridine (PACS), 4-(5-chloro-2-hydroxybenzylideneamino)-pyridine (CHPACS), and 4-(5-bromo-2-hydroxybenzylideneamino)-pyridine (BHPACS). The chemical structure of the prepared chitosan derivatives was confirmed by Fourier transform infrared (FT-IR) and (13)C nuclear magnetic resonance ((13)C NMR) and their antifungal activity against Cladosporium cucumerinum, Monilinia fructicola, Colletotrichum lagenarium, and Fusarium oxysporum was assessed. Comparing with the antifungal activity of chitosan, CACS, and PACS, CHPACS and BHPACS exhibited obviously better inhibitory effects, which should be related to the synergistic reaction of chitosan itself with the grafted 2-[4-(5-chloro-2-hydroxybenzylideneamino)-pyridyl]acetyl and 2-[4-(5-bromo-2-hydroxybenzylideneamino)-pyridyl]acetyl. PMID:20615498

  14. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    PubMed Central

    Zhang, Xiaohui; Jacob, Melissa R; Rao, R Ranga; Wang, Yan-Hong; Agarwal, Ameeta K; Newman, David J; Khan, Ikhlas A; Clark, Alice M; Li, Xing-Cong

    2013-01-01

    Screening natural product extracts from the National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Using LC–MS analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins J (1) and K (2), were isolated from the deep-water sponge Microscleroderma herdmani, along with microsclerodermins A (3) and B (4), previously isolated from an unidentified Microscleroderma species. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. In vitro antifungal testing showed that the four compounds possessed strong activities against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. PMID:23936761

  15. Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species.

    PubMed

    Paredes, Katihuska; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2016-04-01

    Scopulariopsisis an emerging opportunistic fungus characterized by its high resistance to antifungal therapies. We have developed a murine model of disseminated infection in immunosuppressed animals by intravenous inoculation ofScopulariopsis brevicaulisandScopulariopsis brumptii, the most clinically relevant species, in order to evaluate their virulence and their responses to conventional antifungal treatments. Survival and tissue burden studies showed thatS. brumptiiwas more virulent thanS. brevicaulis The three drugs tested, liposomal amphotericin B, posaconazole, and voriconazole, prolonged the survival of mice infected withS. brumptii, but none showed efficacy againstS. brevicaulis The different therapies were only able to modestly reduce the fungal burden of infected tissue; however, in general, despite the high serum levels reached, they showed poor efficacy in the treatment of the infection. Unfortunately, the most effective therapy forScopulariopsisinfections remains unresolved. PMID:26787688

  16. Rondonin an antifungal peptide from spider (Acanthoscurria rondoniae) haemolymph

    PubMed Central

    Riciluca, K.C.T.; Sayegh, R.S.R.; Melo, R.L.; Silva, P.I.

    2012-01-01

    Antimicrobial activities were detected in the haemolymph of the spider Acanthoscurrria rondoniae. A novel antifungal peptide, rondonin, was purified by reverse phase high performance liquid chromatography (RP-HPLC). Rondonin has an amino acid sequence of IIIQYEGHKH and a molecular mass of 1236.776 Da. This peptide has identity to a C-terminal fragment of the “d” subunit of haemocyanin from the spiders Eurypelma californicum and Acanthoscurria gomesiana. A synthetic peptide mimicking rondonin had identical characteristics to those of the isolated material, confirming its sequence. The synthetic peptide was active only against fungus. These data led us to conclude that the antifungal activity detected in the plasma of these spiders is the result of enzymatic processing of a protein that delivers oxygen in the haemolymph of many chelicerate. Several studies have suggested that haemocyanins are involved in the arthropod immune system, and the activity of this haemocyanin fragment reinforces this idea. PMID:24371568

  17. Empires of the Mind

    ERIC Educational Resources Information Center

    Jackson, Shirley Ann

    2007-01-01

    In this article, the author discusses the challenge of educating students for service and leadership in this flat and integrated world, yet asymmetrical and unstable. She says that the future is now and educators have the opportunity and responsibility to create the environments that foster the empires of the mind, and to ensure that the future…

  18. Empirical Research without Certainty

    ERIC Educational Resources Information Center

    Floden, Robert E.

    2009-01-01

    In this essay, Robert Floden reviews three recent volumes in the Philosophy, Theory, and Educational Research series that address the philosophical implications of three "isms"-- postpositivism, pragmatism, and poststructuralism--for empirical educational research. These volumes, written by D.C. Phillips, Gert J.J. Biesta, and Michael A. Peters,…

  19. Empirical quantum mechanics

    NASA Astrophysics Data System (ADS)

    Nishimura, Hirokazu

    1996-06-01

    Machida and Namiki developed a many-Hilbert-spaces formalism for dealing with the interaction between a quantum object and a measuring apparatus. Their mathematically rugged formalism was polished first by Araki from an operator-algebraic standpoint and then by Ozawa for Boolean quantum mechanics, which approaches a quantum system with a compatible family of continuous superselection rules from a notable and perspicacious viewpoint. On the other hand, Foulis and Randall set up a formal theory for the empirical foundation of all sciences, at the hub of which lies the notion of a manual of operations. They deem an operation as the set of possible outcomes and put down a manual of operations at a family of partially overlapping operations. Their notion of a manual of operations was incorporated into a category-theoretic standpoint into that of a manual of Boolean locales by Nishimura, who looked upon an operation as the complete Boolean algebra of observable events. Considering a family of Hilbert spaces not over a single Boolean locale but over a manual of Boolean locales as a whole, Ozawa's Boolean quantum mechanics is elevated into empirical quantum mechanics, which is, roughly speaking, the study of quantum systems with incompatible families of continuous superselection rules. To this end, we are obliged to develop empirical Hilbert space theory. In particular, empirical versions of the square root lemma for bounded positive operators, the spectral theorem for (possibly unbounded) self-adjoint operators, and Stone's theorem for one-parameter unitary groups are established.

  20. Auditory Imagery: Empirical Findings

    ERIC Educational Resources Information Center

    Hubbard, Timothy L.

    2010-01-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d)…

  1. Synthesis of Novel Pyrimethanil Grafted Chitosan Derivatives with Enhanced Antifungal Activity.

    PubMed

    Li, Yan; Liu, Song; Qin, Yukun; Xing, Ronge; Chen, Xiaolin; Li, Kecheng; Li, Pengcheng

    2016-01-01

    In this study, three pyrimethanil grafted chitosan (PML-g-CS) derivatives were obtained. The structures of the conjugates were confirmed by FT-IR, (1)H NMR, and EA. The grafting ratios were measured by HPLC. Antifungal properties of pyrimethanil grafted chitosan (PML-g-CS) derivatives against the plant pathogenic fungi Rhizoctonia solani and Gibberella zeae were investigated at concentrations of 100, 200, and 400 mg/L. The PML-g-CS derivatives showed enhanced antifungal activity in comparison with chitosan. The PML-g-CS-1 showed the best antifungal activity against R. solani, whose antifungal index was 58.32%. The PML-g-CS-2 showed the best antifungal activity against G. zeae, whose antifungal index was 53.48%. The conjugation of chitosan and pyrimethanil showed synergistic effect. The PML-g-CS derivatives we developed showed potential for further study and application in crop protection. PMID:27529072

  2. In Vitro Screening of 10 Edible Thai Plants for Potential Antifungal Properties

    PubMed Central

    Luplertlop, Natthanej

    2014-01-01

    Growing rates of fungal infections and increasing resistance against standard antifungal drugs can cause serious health problems. There is, therefore, increasing interest in the potential use of medicinal plants as novel antifungal agents. This study investigates the antifungal properties of crude plant extracts from ten medicinal plant species. Crude samples were extracted using the hot water extraction process. The minimum inhibitory concentrations (MIC) and diameter zone of inhibition were determined in each extract against ten fungal strains, and fluconazole was used as a positive control. The cytotoxicity of crude extracts on in vitro human skin fibroblast (HSF) cell models was determined by MTT assay. Of the ten crude extracts, Psidium guajava L. exhibited the highest antifungal activity, diameter zone of inhibition, and percentage HSF cell viability. Although all extracts exhibited antifungal activity, Psidium guajava L. had the greatest potential for developing antifungal treatments. PMID:24516502

  3. The fungal resistome: a risk and an opportunity for the development of novel antifungal therapies.

    PubMed

    Reales-Calderón, Jose A; Molero, Gloria; Gil, Concha; Martínez, José L

    2016-08-01

    The risks for toxicity of novel antifungal compounds, together with the emergence of resistance, makes the use of inhibitors of resistance, in combination with antifungal compounds, a suitable strategy for developing novel antifungal formulations. Among them, inhibitors of efflux pumps are suitable candidates. Increasing drug influx or interfering with the stress response may also improve the efficacy of antifungals. Therapies as induction of fungal apoptosis or immunostimulation are also good strategies for reducing the risks for resistance and to improve antifungals' efficacy. Understanding the effect of the acquisition of resistance on the fungal physiology and determining the collateral sensitivity networks are useful for the development of novel strategies based on combination of antifungals for improving the efficacy of the therapy. PMID:27485839

  4. Synthesis of Novel Pyrimethanil Grafted Chitosan Derivatives with Enhanced Antifungal Activity

    PubMed Central

    Liu, Song; Xing, Ronge; Chen, Xiaolin

    2016-01-01

    In this study, three pyrimethanil grafted chitosan (PML-g-CS) derivatives were obtained. The structures of the conjugates were confirmed by FT-IR, 1H NMR, and EA. The grafting ratios were measured by HPLC. Antifungal properties of pyrimethanil grafted chitosan (PML-g-CS) derivatives against the plant pathogenic fungi Rhizoctonia solani and Gibberella zeae were investigated at concentrations of 100, 200, and 400 mg/L. The PML-g-CS derivatives showed enhanced antifungal activity in comparison with chitosan. The PML-g-CS-1 showed the best antifungal activity against R. solani, whose antifungal index was 58.32%. The PML-g-CS-2 showed the best antifungal activity against G. zeae, whose antifungal index was 53.48%. The conjugation of chitosan and pyrimethanil showed synergistic effect. The PML-g-CS derivatives we developed showed potential for further study and application in crop protection. PMID:27529072

  5. Analysis of the efficiency and costs of antifungal prophylaxis and mycological diagnostics in patients undergoing allogeneic haematopoietic cell transplantation: "real life" evaluation.

    PubMed

    Bertz, Hartmut; Drognitz, Kathrin; Finke, Jürgen

    2016-02-01

    Antifungal prophylaxis/therapy (AP/AT) raises the cost of allogeneic haematopoietic cell transplantation (alloHCT). Its efficacy, different approaches for AP/AT, diagnostic measures and cost-effectiveness must still be evaluated. In 2010, we conducted a prospective study with 106 consecutive patients receiving an alloHCT analysing AP/AT, choice and costs of diagnostics applied including CT scans, galactomannan (Gal) and β-D-glucan (β-D) testing. Antifungal prophylaxis in 91 patients consisted of fluconazole (FLU) or L-AMB (AmBisome™ 1 or 3 mg/kg/day b.w.), and antifungal therapy had to be initiated in 38 % of the FLU/L-AMB-1-mg patients but in none with L-AMB 3 mg. Empirical AT consisted of L-AMB 1 mg/kg (n = 12) and preemptive AT of L-AMB 3 mg/kg (n = 17) and proved very efficacious with no further antifungal drug escalation in 89.6 %. Mean costs of diagnostic measures were 402 €/alloHCT; however, only 22 % of the CT scans, 4 % of β-D and 3 % of galactomannan testing were positive. We detected one proven, 17 probable and 14 possible fungal infections. Due to the German diagnosis-related group system with additional compensation, all our AP/AT strategies were adequately reimbursed. While clinical symptoms and CT scans are the most commonly used, inexpensive decision-making tools for starting AT, the expensive laboratory diagnostic procedures are ineffective; we have therefore discontinued regular GAL/β-D testing and changed our AP in patients at risk. PMID:26627891

  6. Persistence of histoplasma in adrenals 7 years after antifungal therapy

    PubMed Central

    Kothari, Deepak; Chopra, Shweta; Bhardwaj, Minakshi; Ajmani, Ajay K.; Kulshreshtha, Bindu

    2013-01-01

    Adrenal histoplasmosis is an uncommon cause for adrenal insufficiency. The duration of treatment for adrenal histoplasmosis is not clear. Existing treatment regimens advocate antifungals given for periods ranging from 6 months to 2 years. We report here a rare case who showed persistence of histoplasma in adrenal biopsy 7 years after being initially treated with itraconazole for 9 months. This calls for a prolonged therapy with regular review of adrenal morphology and histology in these patients. PMID:23869317

  7. Restricticin, a novel glycine-containing antifungal agent.

    PubMed

    Schwartz, R E; Dufresne, C; Flor, J E; Kempf, A J; Wilson, K E; Lam, T; Onishi, J; Milligan, J; Fromtling, R A; Abruzzo, G K

    1991-05-01

    Restricticin (1) is a naturally-occurring antifungal agent which contains triene, pyran and glycine ester functionalities and is unrelated to any previously known family of natural products. This unstable compound, as well as its corresponding N,N-dimethyl derivative (2), have been produced and isolated from both solid and liquid fermentations of Penicillium restrictum. The desglycyl hydrolysis product, restrictinol (3), was produced via the hydrolysis of pure restricticin and as an artifact of the isolation of restricticin. PMID:2061189

  8. Antifungal methylphenone derivatives and 5-methylcoumarins from Mutisia friesiana.

    PubMed

    Viturro, Carmen I; de la Fuente, Juana R; Maier, Marta S

    2003-01-01

    In addition to the known mutisicoumarin A, the aerial parts of the shrub Mutisia friesiana afforded five new methylphenones, two new 5-methylcoumarins and a new related chromone. Their structures were elucidated by spectroscopic methods 13C NMR data for mutisicoumarin A are reported for the first time. Mutisiphenones A and B and mutisicoumarin A showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum. PMID:12939040

  9. Antifungal and larvicidal cordiaquinones from the roots of Cordia curassavica.

    PubMed

    Ioset, J R; Marston, A; Gupta, M P; Hostettmann, K

    2000-03-01

    In addition to the known cordiaquinones A and B, two novel meroterpenoid naphthoquinones, named cordiaquinones J and K, have been isolated from the roots of Cordia curassavica. Their structures were elucidated by spectrometric methods including EI, D/CI mass spectrometry, 1H, 13C and 2D-NMR experiments. The four naphthoquinones demonstrated antifungal activities against Cladosporium cucumerinum, Candida albicans and toxic properties against larvae of the yellow fever-transmitting mosquito Aedes aegypti. PMID:10724189

  10. Antifungal Activity of Ellagic Acid In Vitro and In Vivo.

    PubMed

    Li, Zhi-Jian; Guo, Xin; Dawuti, Gulina; Aibai, Silafu

    2015-07-01

    Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti-inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38-A and M27-A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC-based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α-demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm(2) ) significantly enhanced the cure rate in a guinea-pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. PMID:25919446

  11. New and emerging antifungal agents: impact on respiratory infections.

    PubMed

    Feldmesser, Marta

    2003-01-01

    Fungal pathogens are increasingly important causes of respiratory disease, yet the number of antifungal agents available for clinical use is limited. Use of amphotericin B deoxycholate is hampered by severe toxicity. Triazole agents currently available have significant drug interactions; fluconazole has a limited spectrum of activity and itraconazole was, until recently, available only in oral formulations with limited bioavailability. The development of resistance to all three agents is increasingly being recognized and some filamentous fungi are resistant to the action of all of these agents. In the past few years, new antifungal agents and new formulations of existing agents have become available.The use of liposomal amphotericin B preparations is associated with reduced, but still substantial, rates of nephrotoxicity and infusion-related reactions. An intravenous formulation of itraconazole has been introduced, and several new triazole agents have been developed, with the view of identifying agents that have enhanced potency, broader spectra of action and improved pharmacodynamic properties. One of these, voriconazole, has completed large-scale clinical trials. In addition, caspofungin, the first of a new class of agents, the echinocandins, which inhibit cell wall glucan synthesis, was approved for use in the US in 2001 as salvage therapy for invasive aspergillosis. It is hoped that the availability of these agents will have a significant impact on the morbidity and mortality of fungal respiratory infections. However, at the present time, our ability to assess their impact is limited by the problematic nature of conducting trials for antifungal therapy. PMID:14719990

  12. Antifungal defensins and their role in plant defense.

    PubMed

    Lacerda, Ariane F; Vasconcelos, Erico A R; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term "plant defensin," after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  13. Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

    PubMed

    Casanova, Bruna B; Muniz, Mauro N; de Oliveira, Thayse; de Oliveira, Luís Flavio; Machado, Michel M; Fuentefria, Alexandre M; Gosmann, Grace; Gnoatto, Simone C B

    2015-01-01

    Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents. PMID:26007181

  14. Design, Synthesis, and Antifungal Activity of New α-Aminophosphonates

    PubMed Central

    Rezaei, Zahra; Khabnadideh, Soghra; Zomorodian, Kamiar; Pakshir, Keyvan; Nadali, Setareh; Mohtashami, Nadia; Faghih Mirzaei, Ehsan

    2011-01-01

    α-Aminophosphonates are bioisosteres of amino acids and have several pharmacological activities. These compounds have been synthesized by various routes from reaction between amine, aldehyde, and phosphite compounds. In order to synthesize α-aminophosphonates, catalytic effect of CuCl2 was compared with FeCl3. Also all designed structures as well as griseofulvin were docked into the active site of microtubule (1JFF), using Autodock program. The results showed that the reactions were carried out in the presence of CuCl2 in lower yields, and also the time of reaction was longer in comparison with FeCl3. The chemical structures of the new compounds were confirmed by spectral analyses. The compounds were investigated for antifungal activity against several fungi in comparison with griseofulvin. An indole-derived bis(α-aminophosphonates) with the best negative ΔG in docking study showed maximum antifungal activity against Microsporum canis, and other investigated compounds did not have a good antifungal activity. PMID:25954522

  15. Antifungal and cytotoxic activities of Nannorrhops ritchiana roots extract.

    PubMed

    Rashid, Rehana; Mukhtar, Farah; Khan, Abida

    2014-01-01

    This atudy was designed to evaluate the antifungal and cytotoxic activities of the Nannorrhops ritchiana (Mazari Palm) 80% methanol extract (NR-M) and its four crude extracts i.e., petroleum ether (NR-A), dichloromethane (NR-B), ethyl acetate (NR-C) and butanol (NR-D). The antifungal activity was determined by agar tube dilution method against nine fungal strains; Aspergillus flavus, Trichophyton longifusis, Trichophyton mentagrophytes, Aspergillus flavus and Microsporum canis were susceptible to the extracts with percentage inhibition of (70-80%). Extracts exhibited significant and good antifungal activity against various fungal strains. The results were deduced by comparing with those for miconazole, amphotericin B and ketoconazole as standard drugs. The fractions of methanolic extract were assayed for their brine shrimp cytotoxic activity. They exhibited low toxicity with LC50 values ranging from 285.7 to 4350.75 μg/mL at the concentration of obtained results warrant follow up through bioassay guided isolation of the active principles, future antiinfectious research. PMID:25362807

  16. Antifungal Properties of Chenopodium ambrosioides Essential Oil Against Candida Species

    PubMed Central

    Chekem, Marie Stéphanie Goka; Lunga, Paul Keilah; Tamokou, Jean De Dieu; Kuiate, Jules Roger; Tane, Pierre; Vilarem, Gerard; Cerny, Muriel

    2010-01-01

    The essential oil of the aerial part (leaves, flowers and stem) of Chenopodium ambrosioides was obtained by hydrodistillation and its chemical composition analyzed by GC and GC/MS, which permitted the identification of 14 components, representing 98.8% of the total oil. Major components were α-terpinene (51.3%), p-cymene (23.4%) and p-mentha-1,8-diène (15.3%). The antifungal properties of this essential oil were investigated in vitro by the well diffusion and broth microdilution methods. The in vitro antifungal activity was concentration dependent and minimum inhibitory concentration values varied from 0.25 to 2 mg/mL. The in vivo antifungal activity was evaluated on an induced vaginal candidiasis rat model. The in vivo activity of the oil on mice vaginal candidiasis was not dose-dependent. Indeed, all the three tested doses; 0.1%, 1% and 10% led to the recovery of mice from the induced infection after 12 days of treatment. The effect of the essential oil on C. albicans ATCC 1663 fatty acid profile was studied. This oil has a relatively important dose-dependent effect on the fatty acids profile.

  17. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

  18. Cytotoxic, trypanocidal, and antifungal activities of Eugenia jambolana L.

    PubMed

    dos Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin A; Coutinho, Henrique D M

    2012-01-01

    Chagas' disease, caused by Trypanosoma cruzi, is considered a public health problem. Nowadays, chemotherapy is the only available treatment for this disease, and the drugs currently used, nifurtimox and benzonidazole, present high toxicity levels. Alternatives for replacing these drugs are natural extracts from Eugenia jambolana, a plant used in traditional medicine because of its antimicrobial and biological activities. An ethanol extract from E. jambolana was prepared. To research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1×10(5)/mL in 200 μL of tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used. To examine antifungal activity, Candida albicans, Candida tropicalis, and Candida krusei were used. This is the first record of trypanocide activity for E. jambolana. The effective concentration capable of killing 50% of the parasites was 56.42 μg/mL. The minimum inhibitory concentration was ≤1,024 μg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with the ethanol extract of E. jambolana. Thus our results indicate that E. jambolana could be a source of plant-derived natural products with anti-epimastigote and antifungal modifying activity with moderate toxicity. PMID:21877946

  19. In vitro Antifungal Activity of Luliconazole against Trichophyton spp.

    PubMed

    Maeda, Jun; Nanjoh, Yasuko; Koga, Hiroyasu; Toga, Tetsuo; Makimura, Koichi; Tsuboi, Ryoji

    2016-01-01

    The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of luliconazole against Trichophyton rubrum (14 strains) and Trichophyton mentagrophytes (14 strains), which are the most common cause of tinea, were compared with those of 6 topical antifungal drugs of lanoconazole, bifonazole, efinaconazole, liranaftate, naftifine and terbinafine. Luliconazole showed the most potent antifungal activity (MIC90 =0.00098 μg/ml and MFC90 =0.0078 μg/ml) among the compounds tested against the two species. Efinaconazole and bifonazole, the drug of azole-class, showed a large MFC/MIC ratio. On the other hand, these ratios of luliconazole and lanoconazole were as small as those of liranaftate, naftifine and terbinafine which are thought to possess fungicidal mechanism. These results suggest that luliconazole possesses fungicidal activity against both species of Trichophyton. In this study, we found that luliconazole had the most potent antifungal activity among the major topical antimycotics used in Japan and the US. Luliconazole would be the best-in-class drug for dermatophytosis in clinics. PMID:26936346

  20. New constitutive latex osmotin-like proteins lacking antifungal activity.

    PubMed

    Freitas, Cleverson D T; Silva, Maria Z R; Bruno-Moreno, Frederico; Monteiro-Moreira, Ana C O; Moreira, Renato A; Ramos, Márcio V

    2015-11-01

    Proteins that share similar primary sequences to the protein originally described in salt-stressed tobacco cells have been named osmotins. So far, only two osmotin-like proteins were purified and characterized of latex fluids. Osmotin from Carica papaya latex is an inducible protein lacking antifungal activity, whereas the Calotropis procera latex osmotin is a constitutive antifungal protein. To get additional insights into this subject, we investigated osmotins in latex fluids of five species. Two potential osmotin-like proteins in Cryptostegia grandiflora and Plumeria rubra latex were detected by immunological cross-reactivity with polyclonal antibodies produced against the C. procera latex osmotin (CpOsm) by ELISA, Dot Blot and Western Blot assays. Osmotin-like proteins were not detected in the latex of Thevetia peruviana, Himatanthus drasticus and healthy Carica papaya fruits. Later, the two new osmotin-like proteins were purified through immunoaffinity chromatography with anti-CpOsm immobilized antibodies. Worth noting the chromatographic efficiency allowed for the purification of the osmotin-like protein belonging to H. drasticus latex, which was not detectable by immunoassays. The identification of the purified proteins was confirmed after MS/MS analyses of their tryptic digests. It is concluded that the constitutive osmotin-like proteins reported here share structural similarities to CpOsm. However, unlike CpOsm, they did not exhibit antifungal activity against Fusarium solani and Colletotrichum gloeosporioides. These results suggest that osmotins of different latex sources may be involved in distinct physiological or defensive events. PMID:26231325

  1. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

    PubMed Central

    Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

    2012-01-01

    Background Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Methods Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. Results The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. Conclusion The present work has developed a new biocompatible antifungal PMMA denture base material. PMID:22969297

  2. Antifungal activity of topical microemulsion containing a thiophene derivative

    PubMed Central

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270–540 μg.mL−1) and good activity against C. neoformans (MIC = 17 μg.mL−1). Candida species were susceptible to ME-5CN05 (70–140 μg.mL−1), but C. neoformans was much more, presenting a MIC value of 2.2 μg.mL−1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans. PMID:25242940

  3. In vitro antifungal activities of luliconazole, a new topical imidazole.

    PubMed

    Koga, Hiroyasu; Nanjoh, Yasuko; Makimura, Koichi; Tsuboi, Ryoji

    2009-01-01

    Luliconazole is a topical antifungal drug newly developed in Japan. The present study compares the in vitro antifungal activity of luliconazole against clinically important dermatomycotic fungi with that of other representative antifungal drugs. The reference drugs chosen were five classes of nine topical agents, i.e., allylamine (terbinafine), thiocarbamate (liranaftate), benzylamine (butenafine), morpholine (amorolfine), and azole (ketoconazole, clotrimazole, neticonazole, miconazole and bifonazole). The minimum inhibitory concentrations (MIC) of luliconazole and the reference drugs against Trichophyton spp. (T. rubrum, T. mentagrophytes and T. tonsurans) and Candida albicans were measured by the standardized broth microdilution method. Luliconazole demonstrated greater potency against Trichophyton spp. (MIC range:

  4. Antifungal activities and chemical composition of some medicinal plants.

    PubMed

    Mohammadi, A; Nazari, H; Imani, S; Amrollahi, H

    2014-06-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists and natural-products scientists are combing the earth for phytochemicals and leads, which could be developed for treatment of infectious diseases. The aim of this study was to investigate the antifungal activities of the essential oils of some medicinal plants such as Stachys pubescens, Thymus kotschyanus, Thymus daenensis and Bupleurum falcatum against Fusarium oxysporum, Aspergillus flavus and Alternaria alternata. The essential oils were used to evaluate their MICs and MFCs compared to the amphotricin B as a standard drug. The essential oils were also analyzed by GC/MS. Essential oils isolated from the S. pubescens, T. kotschyanus and B. falcatum showed strong antifungal activities. The essential oil of T. daenensis exhibited a moderate activity against the selected fungi in comparison with the other plants' essential oils. In addition, the results showed that 26, 23, 22 and 15 components were identified from the essential oils of T. kotschyanus, S. pubescens, T. daenensis and B. falcatum, respectively. These oils exhibited a noticeable antifungal activity against the selected fungi. Regarding obtained results and that natural antimicrobial substances are inexpensive and have fewer side effects, they convey potential for implementation in fungal pathogenic systems. PMID:24768063

  5. Antifungal defensins and their role in plant defense

    PubMed Central

    Lacerda, Ariane F.; Vasconcelos, Érico A. R.; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F.

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term “plant defensin,” after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  6. An overview of antifungal peptides derived from insect.

    PubMed

    Faruck, Mohammad Omer; Yusof, Faridah; Chowdhury, Silvia

    2016-06-01

    Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases. PMID:26093218

  7. Innovative phytosynthesized silver nanoarchitectures with enhanced antifungal and antioxidant properties

    NASA Astrophysics Data System (ADS)

    Ortan, Alina; Fierascu, Irina; Ungureanu, Camelia; Fierascu, Radu Claudiu; Avramescu, Sorin Marius; Dumitrescu, Ovidiu; Dinu-Pirvu, Cristina Elena

    2015-12-01

    While in the early era of nanotechnology, nanoparticles of noble metals were obtained through expensive methods, using toxic chemical reagents, in the last decade attempts are made to obtain the desired chemical composition, size, morphology, and other properties by eco and green synthesis, using plants. The aim of this paper is to compare two extraction methods (hydroalcoholic extraction and microwave extraction) used to phytosynthesize silver nanoparticles, in terms of nanoparticle (NP) morphology, antioxidant, and antifungal action, using an European native plant, Anthriscus cerefolium (L.) Hoffm. The extracts and the obtained NPs were characterized by modern analytical techniques (GC-MS, UV-Vis, SEM, TEM) and by phytochemical assays (total flavonoids, total terpenoids and total phenolic content). The antifungal activity (evaluated using the Kirby-Bauer method, against Aspergillus niger and Penicillium hirsutum) and the antioxidant activity (determined by the DPPH assay and a chemiluminescence assay) revealed notable differences between the samples, differences due to the extraction procedure followed. Also, preliminary studies regarding the stability and the toxicity of the nanoparticles are presented. By using the microwave-assisted extraction, not only smaller particles (less than 10 nm) were obtained, but also with better antifungal and antioxidant properties than the ones obtained by classical extraction.

  8. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry. PMID:26593505

  9. Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis

    PubMed Central

    Boisard, Séverine; Le Ray, Anne-Marie; Landreau, Anne; Kempf, Marie; Cassisa, Viviane; Flurin, Catherine; Richomme, Pascal

    2015-01-01

    During this study, the in vitro antifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains including Staphylococcus aureus. Organic extracts showed a significant antifungal activity against C. albicans and C. glabrata (MIC80 between 16 and 31 µg/mL) but only a weak activity towards A. fumigatus (MIC80 = 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially against S. aureus (SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100 30–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study. PMID:25873978

  10. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

  11. Antifungal susceptibility patterns of a global collection of fungal isolates: results of the SENTRY Antifungal Surveillance Program (2013).

    PubMed

    Castanheira, Mariana; Messer, Shawn A; Rhomberg, Paul R; Pfaller, Michael A

    2016-06-01

    Among 1846 fungal clinical isolates from 31 countries, echinocandin resistance in Candida spp. ranged from 0.0% to 2.8% (highest for anidulafungin versus Candida glabrata), and fluconazole resistance was noted among 11.9% and 11.6% of the C. glabrata and Candida tropicalis, respectively. Two isolates of Aspergillus fumigatus displayed elevated MICs for itraconazole and carried cyp51a mutations encoding TR34 L98H. All Cryptococcus neoformans had azole MIC values below epidemiological cutoff values. The increasing resistance among certain species and more frequent reports of breakthrough infections in patients undergoing antifungal therapy highlights the importance of antifungal surveillance to guide therapy for patients with invasive fungal infections. PMID:27061369

  12. Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

    PubMed

    Delarze, Eric; Sanglard, Dominique

    2015-11-01

    A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments. PMID:26690338

  13. Monosubstituted Benzene Derivatives from Fruits of Ficus hirta and Their Antifungal Activity against Phytopathogen Penicillium italicum.

    PubMed

    Wan, Chunpeng; Han, Jianxin; Chen, Chuying; Yao, Liangliang; Chen, Jinyin; Yuan, Tao

    2016-07-20

    Ficus hirta, a widely consumed food by Hakka people, has been reported to show potent antifungal activity against phytopathogen Penicillium italicum. However, there is no report of chemical constituents responsible for the antifungal activity. In the current study, nine monosubstituted benzene derivatives, including three new derivatives (1-3), were isolated from the fruits of F. hirta. The structures of these isolates were elucidated on the basis of the analysis of spectroscopic data (mass spectrometry and nuclear magnetic resonance). All of the isolates were evaluated for antifungal activities against P. italicum. At an equivalent concentration, compound 1 exhibited stronger antifungal activity than that of the ethanol extract of F. hirta fruits. PMID:27381890

  14. Response to Hypothetical Social Scenarios in Individuals with Traumatic Brain Injury Who Present Inappropriate Social Behavior: A Preliminary Report

    PubMed Central

    Gagnon, Jean; Henry, Anne; Decoste, François-Pierre; Ouellette, Michel; McDuff, Pierre; Daelman, Sacha

    2013-01-01

    Background: Very little research thus far has examined the decision making that underlies inappropriate social behavior (ISB) post-TBI (traumatic brain injury). Objectives: To verify the usefulness of a new instrument, the Social Responding Task, for investigating whether, in social decision making, individuals with TBI, who present inappropriate social behavior (ISB), have difficulty anticipating their own feelings of embarrassment and others’ angry reactions following an ISB. Methods: Seven subjects with TBI presenting with inappropriate social behavior (TBI-ISB), 10 presenting with appropriate social behavior (TBI-ASB), and 15 healthy controls were given 12 hypothetical scenarios three times, each time ending with a different behavioral response. Subjects were asked to gauge the likelihood of their displaying the behavior in that situation (part A) and of it being followed by an angry reaction from the other or by feelings of embarrassment in themselves (part B). Results: TBI-ISB subjects scored higher than TBI-ASB and healthy controls on a scale of likelihood of displaying an ISB. Results regarding expectations of angry reactions from others and feelings of embarrassment after an ISB were similar among groups. Negative correlations between endorsement of an inappropriate behavior and anticipation of negative emotional consequences were significant for both TBI-ASB and control subjects, but not for TBI-ISB subjects. Conclusions: Results suggest that the TBI-ISB participants were likely to endorse an ISB despite being able to anticipate a negative emotional response in themselves or others, suggesting that there were other explanations for their poor behavior. A self-reported likely response to hypothetical social scenarios can be a useful approach for studying the neurocognitive processes behind the poor choices of individuals with TBI-ISB, but the task needs further validation studies. A comprehensive discussion follows on the underlying mechanisms affecting

  15. The health workforce crisis in Bangladesh: shortage, inappropriate skill-mix and inequitable distribution

    PubMed Central

    2011-01-01

    revealed the number of faith/traditional healers, homeopaths (qualified and non-qualified) and basic care providers. Conclusions Bangladesh is suffering from a severe HRH crisis--in terms of a shortage of qualified providers, an inappropriate skills-mix and inequity in distribution--which requires immediate attention from policy makers. PMID:21255446

  16. The Landscape of Inappropriate Laboratory Testing: A 15-Year Meta-Analysis

    PubMed Central

    Zhi, Ming; Ding, Eric L.; Theisen-Toupal, Jesse; Whelan, Julia; Arnaout, Ramy

    2013-01-01

    Background Laboratory testing is the single highest-volume medical activity and drives clinical decision-making across medicine. However, the overall landscape of inappropriate testing, which is thought to be dominated by repeat testing, is unclear. Systematic differences in initial vs. repeat testing, measurement criteria, and other factors would suggest new priorities for improving laboratory testing. Methods A multi-database systematic review was performed on published studies from 1997–2012 using strict inclusion and exclusion criteria. Over- vs. underutilization, initial vs. repeat testing, low- vs. high-volume testing, subjective vs. objective appropriateness criteria, and restrictive vs. permissive appropriateness criteria, among other factors, were assessed. Results Overall mean rates of over- and underutilization were 20.6% (95% CI 16.2–24.9%) and 44.8% (95% CI 33.8–55.8%). Overutilization during initial testing (43.9%; 95% CI 35.4–52.5%) was six times higher than during repeat testing (7.4%; 95% CI 2.5–12.3%; P for stratum difference <0.001). Overutilization of low-volume tests (32.2%; 95% CI 25.0–39.4%) was three times that of high-volume tests (10.2%; 95% CI 2.6–17.7%; P<0.001). Overutilization measured according to restrictive criteria (44.2%; 95% CI 36.8–51.6%) was three times higher than for permissive criteria (12.0%; 95% CI 8.0–16.0%; P<0.001). Overutilization measured using subjective criteria (29.0%; 95% CI 21.9–36.1%) was nearly twice as high as for objective criteria (16.1%; 95% CI 11.0–21.2%; P = 0.004). Together, these factors explained over half (54%) of the overall variability in overutilization. There were no statistically significant differences between studies from the United States vs. elsewhere (P = 0.38) or among chemistry, hematology, microbiology, and molecular tests (P = 0.05–0.65) and no robust statistically significant trends over time. Conclusions The landscape of overutilization varies

  17. Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates

    PubMed Central

    Andersen, Kari-Mette; Kristoffersen, Anne Karin; Ingebretsen, André; Vikholt, Katharina Johnsen; Örtengren, Ulf Thore; Olsen, Ingar; Enersen, Morten; Gaustad, Peter

    2016-01-01

    Background Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections. Objectives To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK®2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility. Design A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK®2) and mass spectrometry (MALDI–TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests®. Results Using VITEK®2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L. Conclusions Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high

  18. Displays of inappropriate sexual behaviour by patients with progressive cognitive impairment: the forgotten form of challenging behaviour?

    PubMed

    Stubbs, B

    2011-09-01

    Persons with progressive cognitive impairment such as dementia or Alzheimer's disease may display an array of challenging behaviours. For instance, levels of agitation and aggression have been reported as high as 33% in home-dwelling individuals and 80% in those residing in institutions. One form of challenging behaviour that may be displayed by this group is inappropriate sexual behaviour (ISB), but it is often overshadowed by other behaviours such as aggression. Inappropriate sexual behaviour involves any verbal of physical action of a sexual nature which is displayed in an inappropriate social context. Examples of ISB include: exposure of genitals in public/ward environments, 'groping' of nurses and masturbation in public areas. It has been estimated that the prevalence of ISB ranges from 2% to 17% of individuals with progressive cognitive impairment. Although it is less frequent than other challenging behaviours, it still may have significant deleterious effects on the victim's health. This paper is a review of the available literature on the nature, effects and management of ISB in persons with progressive cognitive impairment. Possible avenues for future research are also explored. PMID:21848594

  19. Children under the age of two are more likely to watch inappropriate background media than older children

    PubMed Central

    Tomopoulos, Suzy; Brockmeyer Cates, Carolyn; Dreyer, Benard P; Fierman, Arthur H; Berkule, Samantha B; Mendelsohn, Alan L

    2014-01-01

    Aim To establish whether young children watched foreground electronic media or background media that was not aimed at them or was inappropriate for their age. Methods We performed a longitudinal analysis of mother-infant dyads participating in a larger parenting study. The primary dependent variable was maternal reports of watching habits from media diaries at six, 14, 24 and 36 months. Independent variables were child age, programme content and whether the programme was turned on specifically for the child. Results We analysed 3,570 programme exposures in 527 children, mostly from television. Children were significantly more likely to actually watch programmes if they were older, if the content was coded as “educational-young child” or if the parent tuned on the programme specifically so the child could watch it. Children under the age of two were more likely than older children to watch background media that featured age-inappropriate content or had not been turned on for them to watch (30% versus 16% of programmes; AOR = 2.19, [95%CI 1.82-2.65]). Conclusions Young children under the age of two frequently watch background media that has age-inappropriate content or has not been turned on for them to watch. PMID:24812713

  20. Use of potentially inappropriate medications in hospitalized elderly at a teaching hospital: A comparison between Beers 2003 and 2012 criteria

    PubMed Central

    Momin, Taufik G.; Pandya, Rushi N.; Rana, Devang A.; Patel, Varsha J.

    2013-01-01

    Objectives: To detect the prevalence and pattern of use of Potentially inappropriate medications (PIMs) in hospitalized elderly patients of a tertiary care teaching hospital using Beers 2012 criteria and to compare the same with Beers 2003 criteria. Materials and Methods: Prescriptions of the elderly patients aged 65 years and above were collected from the medicine ward and analyzed. PIMs were identified with help of Beers 2003 and Beers 2012 criteria and comparison was made between the two criteria. Predictors associated with use of PIM were identified using bivariate and multivariate logistic regression analysis. Results: A total of 210 patients received 2,267 drugs. According to Beers 2003 criteria, 60 (28.57%) elderly patients received at least one PIM and 2.9% drugs were prescribed inappropriately. According to Beers 2012 criteria, 84 (40%) elderly received at least one PIM while 22 (10.47%) received multiple PIMs and about 5% drugs were prescribed inappropriately. The most commonly prescribed PIM was mineral oil-liquid paraffin (30, 14.3%) followed by spironolactone (25, 11.9%), digoxin (19, 9%), and benzodiazepines (14, 6.7%). There was a significant association between the number of patients receiving more than six drugs and the use of PIMs (P < 0.01). Use of more than 10 drugs was a significant predictor for use of PIMs in the elderly. Conclusion: The study shows high prevalence of prescribing PIMs in hospitalized elderly patients. Beers 2012 criteria are more effective in identifying PIMs than Beers 2003 criteria. PMID:24347769

  1. Glycosidic activities of Candida albicans after action of vegetable latex saps (natural antifungals) and isoconazole (synthetic antifungal).

    PubMed

    Giordani, R; Moulin-Traffort, J; Régli, P

    1991-01-01

    Glycosidic activities have been examined in Candida albicans grown on medium culture containing latex sap (natural antifungal) or isoconazole (synthetic antifungal). The different types of utilized latex sap were those of Lactuca sativa (latex exuded from articulated laticifers) and Asclepias curassavica (latex flowing from non-articulated laticifers). The same enzyme assays were performed on C. albicans grown without antifungal compounds. Except for alpha-arabinosidase, all glycosidase activities were increased when C. albicans was grown in medium supplemented with L. sativa latex sap. The most stimulated activities were those of beta-fucosidase, alpha-galactosidase, alpha- and beta-glucosidase, alpha- and beta-mannosidase, acetyl-beta-glucosaminidase. The presence of A. curassavica latex sap in culture medium produced similar results: the most stimulated activities were those of alpha-mannosidase, alpha-galactosidase, acetyl-beta-glucosaminidase and beta-fucosidase. Electron microscope observations suggested a correlation between this stimulation of glycosidic activities and the fungal cell wall breakdown. For comparison the presence of isoconazole in culture medium yields no increase in glycosidic activities and no ultrastructural modification of fungal cell wall. The mode of action of latex saps in cell wall breakdown is discussed. PMID:1922192

  2. Antifungal activities of three different Lactobacillus species and their production of antifungal carboxylic acids in wheat sourdough.

    PubMed

    Axel, Claudia; Brosnan, Brid; Zannini, Emanuele; Peyer, Lorenzo C; Furey, Ambrose; Coffey, Aidan; Arendt, Elke K

    2016-02-01

    This study was undertaken to assess the antifungal performance of three different Lactobacillus species.Experiments were conducted in vitro and in situ to extend the shelf life of wheat bread. Standard sourdough analyses were performed characterising acidity and carbohydrate levels. Overall, the strains showed good inhibition in vitro against the indicator mould Fusarium culmorum TMW4.2043. Sourdough bread fermented with Lactobacillus amylovorus DSM19280 performed best in the in situ shelf life experiment. An average shelf life extension of six more mould-free days was reached when compared to the non-acidified control bread. A range of antifungal-active acids like 3-phenyllactic acid, 4-hydroxyphenyllactic acid and 2-hydroxyisocaproic acid in quantities between 0.1 and 360 mg/kg were present in the freeze-dried sourdoughs. Their concentration differed greatly amongst the species.However, a higher concentration of these compounds could not completely justify the growth inhibition of environmental moulds. In particular, although Lb. reuteri R29 produced the highest total concentration of these active compounds in the sourdough, its addition to bread did not result in a longest shelf life. Nevertheless, when the artificial compounds were spiked into a chemically acidified dough, it succeeded in a longer shelf life (+25 %) than achieved only by acidifying the dough. This provides evidence of their contribution to the antifungal activity and their synergy in concentration levels far below their single minimal inhibition concentrations under acidic conditions. PMID:26481620

  3. Some Antifungal Properties of Sorbic Acid Extracted from Berries of Rowan (Sorbus Aucuparia).

    ERIC Educational Resources Information Center

    Brunner, Ulrich

    1985-01-01

    The food preservative sorbic acid can be extracted from Eurasian mountain ash berries (commercially available) and used to show antifungal properties in microbiological investigations. Techniques for extraction, purification, ultraviolet analysis, and experiments displaying antifungal activity are described. A systematic search for similar…

  4. Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.

    PubMed

    Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

    2014-08-01

    Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage. PMID:24750809

  5. Antifungal activities of the leaves of three Pistacia species grown in Turkey.

    PubMed

    Kordali, S; Cakir, A; Zengin, H; Duru, M E

    2003-02-01

    The crude extracts obtained from the leaves of Pistacia vera, Pistacia terebinthus and Pistacia lentiscus were tested for antifungal activities against three pathogenic agricultural fungi, Phythium ultimum, Rhizoctania solani and Fusarium sambucinum. The extracts significantly inhibited the growth of P. ultimum and R. solani. However, the antifungal activity was not observed against F. sambucinum. PMID:12628416

  6. Anti-fungal activities of medicinal plants extracts of Ivorian pharmacopoeia

    PubMed Central

    Mathieu, Kra Adou Koffi; Marcel, Ahon Gnamien; Djè, Djo-Bi; Sitapha, Ouattara; Adama, Coulibaly; Joseph, Djaman Allico

    2014-01-01

    Aim: This study was to evaluate in vitro anti-fungal activity of aqueous and hydroethanolic from medicinal plants extracts collected in Côte d’Ivoire. Materials and Methods: Plants extracts were prepared by homogenization and separately incorporated to Sabouraud agar using the agar slanted double dilution method. Ketoconazole was used as standards for anti-fungal assay. The anti-fungal tests were performed by sowing 1000 cells of Candida albicans on the previously prepared medium culture. Anti-fungal activity was determined by evaluating anti-fungal parameters values (minimal fungicidal concentrations [MFC] and IC50). Results: The results showed that all extracts possessed anti-fungal activities whose levels vary from plant species to another. Eight of them had a satisfactory anti-candidosic activity and extracts from Terminalia species were the most active. Among them the Terminalia superba extracts generated the strongest activities (MFC = 0.0975 mg/mL). Compared with ketoconazole (MFC = 0.390 mg/mL), the T. superba extracts, aqueous (MFC = 0.195 mg/mL) and hydroethanolic (0.0975 mg/mL) were successively twice and four times more active. The worst anti-fungal activity (MFC = 1600 mg/mL) was obtained with the Guarea cedrata aqueous extract. Conclusion: All medicinal plants extracts produced anti-fungal activities, and T. superba was the most active. PMID:26401367

  7. Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil

    PubMed Central

    Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

    2008-01-01

    This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested. PMID:24031180

  8. Optimization of Spore and Antifungal Lipopeptide Production during the Solid State Fermentation of Bacillus subtilis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus subtilis strain TrigoCor 1448 was grown on wheat middlings in 0.5-liter solid state fermentation (SSF) bioreactors for the production of an antifungal biological control agent. Total antifungal activity was quantified using a 96-well microplate bioassay against the plant pathogen Fusarium ...

  9. Antifungal activities of Hedychium essential oils and plant extracts against mycotoxigenic fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-derived antifungal compounds are preferred to chemicals to reduce the risk of toxic effects on humans, livestock and the environment. Essential oil extracted from rhizomes and plant extracts of ornamental ginger lily (Hedychium spp.) were evaluated for their antifungal activity against two fu...

  10. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant ...

  11. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...

  12. Thiophene congeners of morpholine and allylamine type antifungals--syntheses and biological activities.

    PubMed

    Bracher, F; Papke, T

    1995-08-01

    A thiophene analogue 8 of the antifungal drug amorolfine (1) was prepared starting from the alcohol 5. In addition, congeners of naftifine, terbinafine and butenafine, in which the naphthalene ring is replaced by a branched thienylalkyl group, wee synthesized. Of the four drug analogues only compound 9, related to terbinafine, showed significant antifungal activity. PMID:7568314

  13. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrazone derivatives possess good antifungal and insecticidal activities and their structure are used in pesticide design. In the present study, ten hydrazone derivatives (2a-j) were evaluated for their antifungal activity against Colletotrichum, Botrytis, Fusarium and Phomopsis species and for the...

  14. Antifungal activity of gold nanoparticles prepared by solvothermal method

    SciTech Connect

    Ahmad, Tokeer; Wani, Irshad A.; Lone, Irfan H.; Ganguly, Aparna; Manzoor, Nikhat; Ahmad, Aijaz; Ahmed, Jahangeer; Al-Shihri, Ayed S.

    2013-01-15

    Graphical abstract: Gold nanoparticles (7 and 15 nm) of very high surface area (329 and 269 m{sup 2}/g) have been successfully synthesized through solvothermal method by using tin chloride and sodium borohydride as reducing agents. As-prepared gold nanoparticles shows very excellent antifungal activity against Candida isolates and activity increases with decrease in the particle size. Display Omitted Highlights: ► Effect of reducing agents on the morphology of gold nanoparticles. ► Highly uniform and monodisperse gold nanoparticles (7 nm). ► Highest surface area of gold nanoparticles (329 m{sup 2/}g). ► Excellent antifungal activity of gold nanoparticles against Candida strains. -- Abstract: Gold nanoparticles have been successfully synthesized by solvothermal method using SnCl{sub 2} and NaBH{sub 4} as reducing agents. X-ray diffraction studies show highly crystalline and monophasic nature of the gold nanoparticles with face centred cubic structure. The transmission electron microscopic studies show the formation of nearly spherical gold nanoparticles of average size of 15 nm using SnCl{sub 2}, however, NaBH{sub 4} produced highly uniform, monodispersed and spherical gold nanoparticles of average grain size of 7 nm. A high surface area of 329 m{sup 2}/g for 7 nm and 269 m{sup 2}/g for 15 nm gold nanoparticles was observed. UV–vis studies assert the excitations over the visible region due to transverse and longitudinal surface plasmon modes. The gold nanoparticles exhibit excellent size dependant antifungal activity and greater biocidal action against Candida isolates for 7 nm sized gold nanoparticles restricting the transmembrane H{sup +} efflux of the Candida species than 15 nm sized gold nanoparticles.

  15. Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings.

    PubMed

    Boehm, Ryan D; Daniels, Justin; Stafslien, Shane; Nasir, Adnan; Lefebvre, Joe; Narayan, Roger J

    2015-01-01

    In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 μm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions. PMID:25732934

  16. Antifungal activity of the local complement system in cerebral aspergillosis.

    PubMed

    Rambach, Günter; Hagleitner, Magdalena; Mohsenipour, Iradj; Lass-Flörl, Cornelia; Maier, Hans; Würzner, Reinhard; Dierich, Manfred P; Speth, Cornelia

    2005-10-01

    Dissemination of aspergillosis into the central nervous system is associated with nearly 100% mortality. To study the reasons for the antifungal immune failure we analyzed the efficacy of cerebral complement to combat the fungus Aspergillus. Incubation of Aspergillus in non-inflammatory cerebrospinal fluid (CSF) revealed that complement levels were sufficient to obtain a deposition on the surface, but opsonization was much weaker than in serum. Consequently complement deposition from normal CSF on fungal surface stimulated a very low phagocytic activity of microglia, granulocytes, monocytes and macrophages compared to stimulation by conidia opsonized in serum. Similarly, opsonization of Aspergillus by CSF was not sufficient to induce an oxidative burst in infiltrating granulocytes, whereas conidia opsonized in serum induced a clear respiratory signal. Thus, granulocytes were capable of considerably reducing the viability of serum-opsonized Aspergillus conidia, but not of conidia opsonized in CSF. The limited efficacy of antifungal attack by cerebral complement can be partly compensated by enhanced synthesis, leading to elevated complement concentrations in CSF derived from a patient with cerebral aspergillosis. This inflammatory CSF was able to induce (i) a higher complement deposition on the Aspergillus surface than non-inflammatory CSF, (ii) an accumulation of complement activation products and (iii) an increase in phagocytic and killing activity of infiltrating granulocytes. However, levels and efficacy of the serum-derived complement were not reached. These data indicate that low local complement synthesis and activation may represent a central reason for the insufficient antifungal defense in the brain and the high mortality rate of cerebral aspergillosis. PMID:16027023

  17. Heterologous expression of new antifungal chitinase from wheat.

    PubMed

    Singh, Arpita; Kirubakaran, S Isaac; Sakthivel, N

    2007-11-01

    Chitinases (EC 3.2.1.14) have been grouped into seven classes (class I-VII) on the basis of their structural properties. Chitinases expressed during plant-microbe interaction are involved in defense responses of host plant against pathogens. In the present investigation, chitinase gene from wheat has been subcloned and overexpressed in Escherichia coli BL-21 (DE3). Molecular phylogeny analyses of wheat chitinase indicated that it belongs to an acidic form of class VII chitinase (glycosyl hydrolase family 19) and shows 77% identity with other wheat chitinase of class IV and low level identity to other plant chitinases. The three-dimensional structural model of wheat chitinase showed the presence of 10 alpha-helices, 3 beta-strands, 21 loop turns and the presence of 6 cysteine residues that are responsible for the formation of 3 disulphide bridges. The active site residues (Glu94 and Glu103) may be suggested for its antifungal activity. Expression of chitinase (33 kDa) was confirmed by SDS-PAGE and Western hybridization analyses. The yield of purified chitinase was 20 mg/L with chitinase activity of 1.9 U/mg. Purified chitinase exerted a broad-spectrum antifungal activity against Colletotrichum falcatum (red rot of sugarcane) Pestalotia theae (leaf spot of tea), Rhizoctonia solani (sheath blight of rice), Sarocladium oryzae (sheath rot of rice) Alternaria sp. (grain discoloration of rice) and Fusarium sp. (scab of rye). Due to its innate antifungal potential wheat chitinase can be used to enhance fungal-resistance in crop plants. PMID:17697785

  18. New ethacridine derivatives as the potential antifungal and antibacterial preparations.

    PubMed

    Petrikaite, Vilma; Tarasevicius, Eduardas; Pavilonis, Alvydas

    2007-01-01

    Until the 20th century fungal infections were rather easy cured, and the need of new antifungal drugs was low. However, low choice of antifungal preparations, their toxicity, limited spectrum of action, and ability to produce resistant strains show the need of new effective medicines for systemic fungal diseases in nowadays. Our goal of research was to synthesize new antimicrobial compounds containing three or more pharmacophores in one molecule. The initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S-demethylation to yield 2-amino-substituted thiazolidinones. Ethacridine, nitrofuran aldehydes and nitrobenzene aldehyde as pharmacophoric amino or aldehyde group having compounds have been used. Antimicrobial (antifungal) activity of the new compounds was screened in vitro in these bacterial cultures: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 33499 and fungal cultures: Candida albicans ATCC 60193, Candida glabrata, Candida krusei, Candida kefyr ATCC 8614, Candida tropicalis ATCC 8302, Candida parapsilosis. Results showed that the new compounds were significantly more effective as antimicrobial agents than initial preparation ethacridine. Ethacridine derivatives were not only effective against numerous gram-positive and some gram-negative bacteria, but the spectrum of action has been discovered against fungi. Minimal fungistatic concentration varies in the range 10.0-750 microg/mL and antibacterial concentration is in the range 62.5-1000 microg/mL. Compound 2a having nitrofuryl substituent in the fifth position of tiazolidine cycle was the most active of synthesized ethacridine compounds. The obtained results gave the opportunity to separate the perspective group of potential antiinfective compounds. PMID:17895642

  19. Antifungal activity of topical microemulsion containing a thiophene derivative.

    PubMed

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 μg . mL(-1)) and good activity against C. neoformans (MIC = 17 μg . mL(-1)). Candida species were susceptible to ME-5CN05 (70-140 μg . mL(-1)), but C. neoformans was much more, presenting a MIC value of 2.2 μg . mL(-1). The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans. PMID:25242940

  20. Characterization of a new antifungal lipid transfer protein from wheat.

    PubMed

    Kirubakaran, S Isaac; Begum, S Mubarak; Ulaganathan, K; Sakthivel, N

    2008-10-01

    Lipid transfer proteins (LTPs) are members of the family of pathogenesis-related proteins (PR-14) that are believed to be involved in plant defense responses. In this study, a novel gene Ltp 3F1 encoding an antifungal protein from wheat (Sumai 3) was subcloned, overexpressed in Escherichia coli BL-21 (DE3) and enriched using ammonium sulfate fractionation followed by gel permeation chromatography. Molecular phylogeny analyses of wheat Ltp 3F1 gene showed a strong identity to other plant LTPs. Predicted three-dimensional structural model showed the presence of 6 alpha-helices and 9 loop turns. The active site catalytic residues Gly30, Pro50, Ala52 and Cys55 may be suggested for catalyzing the reaction involved in lipid binding. SDS-PAGE analysis confirmed the production of recombinant fusion protein. The LTP fusion protein exhibited a broad-spectrum antifungal activity against Alternaria sp., Rhizoctonia solani, Curvularia lunata, Bipolaris oryzae, Cylindrocladium scoparium, Botrytis cinerea and Sarocladium oryzae. Gene cassette with cyanamide hydratase (cah) marker and Ltp 3F1 gene was constructed for genetic transformation in tobacco. Efficient regeneration was achieved in selective media amended with cyanamide. Transgenic plants with normal phenotype were obtained. Results of PCR and Southern, Northern and Western hybridization analyses confirmed the integration and expression of genes in transgenic plants. Experiments with detached leaves from transgenic tobacco expressing Ltp 3F1 gene showed fungal resistance. Due to the innate potential of broad-spectrum antifungal activity, wheat Ltp 3F1 gene can be used to enhance resistance against fungi in crop plants. PMID:18595724

  1. Antifungal and Antioxidant Activities of Pyrrolidone Thiosemicarbazone Complexes

    PubMed Central

    Al-Amiery, Ahmed A.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2012-01-01

    Metal complexes of (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L) with Cu(II), Co(II), and Ni(II) chlorides were tested against selected types of fungi and were found to have significant antifungal activities. The free-radical-scavenging ability of the metal complexes was determined by their interaction with the stable free radical 2,2′′-diphenyl-1-picrylhydrazyl, and all the compounds showed encouraging antioxidant activities. DFT calculations of the Cu complex were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms. PMID:22400016

  2. Antifungal and antibacterial naphthoquinones from Newbouldia laevis roots.

    PubMed

    Gafner, S; Wolfender, J L; Nianga, M; Stoeckli-Evans, H; Hostettmann, K

    1996-07-01

    From a dichloromethane extract of Newbouldia laevis roots, four new (6-hydroxydehydroiso-alpha-lapachone, 7-hydroxydehydroiso-alpha-lapachone, 5,7-dihydroxydehydroiso-alpha-lapachone and 3-hydroxy-5-methoxydehydroiso-alpha-lapachone) and six known naphthoquinones have been isolated. Their structures were established by spectroscopic methods (UV, EI mass spectrometry, 1H and 13C NMR) and that of 7-hydroxydehydroiso-alpha-lapachone was confirmed by X-ray crystallography. All naphthoquinones showed antifungal activity against Cladosporium cucumerinum and Candida albicans, and activity against the bacteria Bacillus subtilis and Escherichia coli. PMID:9397206

  3. An antifungal naphthoquinone, xanthones and secoiridoids from Swertia calycina.

    PubMed

    Rodriguez, S; Wolfender, J L; Hakizamungu, E; Hostettmann, K

    1995-08-01

    A chemical and biological screening of 25 species of the Gentianaceae family has been undertaken. Both methanolic and dichloromethane extracts of Swertia calycina exhibited a strong antifungal activity against Cladosporium cucumerinum and Candida albicans. The compound responsible for this activity has been isolated and identified as 2-methoxy-1,4-naphthoquinone. It is the first naphthoquinone to be described in Gentianaceae species. LC-UV and LC-TSP-MS analysis of the crude extracts of Swertia calycina also allowed on-line identification of six known xanthones and secoiridoids. PMID:7480185

  4. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed

    Liu, S C; Oguntimein, B; Hufford, C D; Clark, A M

    1990-04-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

  5. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed Central

    Liu, S C; Oguntimein, B; Hufford, C D; Clark, A M

    1990-01-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

  6. Trichoharzianol, a new antifungal from Trichoderma harzianum F031.

    PubMed

    Jeerapong, Chotika; Phupong, Worrapong; Bangrak, Phuwadol; Intana, Warin; Tuchinda, Patoomratana

    2015-04-15

    A new decalin derivative, trichoharzianol (1), together with three known compounds, eujavanicol A (2), 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (3), and 4,6-dihydroxy-5-methylphthalide (4), were isolated from Trichoderma harzianum F031. For the first time, compounds 2-4 were reported from the Trichoderma species. Their structures were characterized by spectroscopic methods. Trichoharzianol (1) showed the highest antifungal activity against Colletotrichum gloeosporioides, with a minimum inhibitory concentration (MIC) of 128 μg/mL. PMID:25817439

  7. Azole antifungal agents related to naftifine and butenafine.

    PubMed

    Castellano, S; La Colla, P; Musiu, C; Stefancich, G

    2000-06-01

    The methyl group of naftifine (1) and butenafine (2) was replaced by an azolic nucleus to obtain the new compounds 3-8 which exhibit the characteristics of both allylamine (or benzylamine) and azole antifungals. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. Among these, compounds 5, 6, and 8 were found to inhibit the growth of dermatophytes with a potency comparable to that of naftifine. The synthetic sequence includes the preparation of aminoazole Schiff bases, reduction, and alkylation of the corresponding secondary amines. PMID:10909187

  8. Mechanism of Action of Efinaconazole, a Novel Triazole Antifungal Agent

    PubMed Central

    Nagashima, Maria; Shibanushi, Toshiyuki; Iwata, Atsushi; Kangawa, Yumi; Inui, Fumie; Siu, William J. Jo; Pillai, Radhakrishnan; Nishiyama, Yayoi

    2013-01-01

    The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4α-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14α-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

  9. Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

    PubMed Central

    Asner, Sandra A.; Giulieri, Stefano; Diezi, Manuel; Marchetti, Oscar

    2015-01-01

    Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5

  10. The effects of Paenibacillus polymyxa E681 on antifungal and crack remediation of cement paste.

    PubMed

    Park, Sung-Jin; Park, Seung-Hwan; Ghim, Sa-Youl

    2014-10-01

    This study investigated the antifungal effects of cement paste containing Paenibacillus polymyxa E681 against Aspergillus niger, a deleterious fungus commonly found in cement buildings and structures. To test the antifungal effects, cement paste containing P. polymyxa E681 was neutralized by CO2 gas, and the fungal growth inhibition was examined according to the clear zone around the cement specimen. In addition to the antifungal effects of the cement paste added with bacteria, calcium crystal precipitation of P. polymyxa E681 was examined by qualitative and quantitative analyses. The cement paste containing P. polymyxa E681 showed strong antifungal effects but fusA mutant (deficient in fusaricidin synthesis) showed no antifungal activity. Crack sealing of the cement paste treated with P. polymyxa E681 was captured by light microscope showed fungal growth inhibition and crack repairing in cement paste. PMID:24824950

  11. Detection and partial characterization of antifungal bioactivity from the secretions of the medicinal maggot, Lucilia sericata.

    PubMed

    Evans, Rhys; Dudley, Ed; Nigam, Yamni

    2015-01-01

    The antibacterial properties of the excretions/secretions (ES) of the medicinal maggot, Lucilia sericata have long been known and the effectiveness of maggot debridement therapy in relation to the clearance of bacteria from the surface of wounds has been the source of much research over recent years. Less well known, however, are the antifungal properties of L. sericata ES. Here, we show by means of the colony forming unit assay and optical density assays, that L. sericata native ES possess significant antifungal properties and appears to possess a highly heat stable, freeze/thaw, and lyophilization resistant antifungal component. We also show that the antifungal activity present in the native ES consists of a number of antifungal components present in three fraction masses consisting of >10, 10-0.5, and <0.5 kDa, with the greatest level of activity being seen in the <0.5 kDa fraction. PMID:25847128

  12. An overview about the medical use of antifungals in Portugal in the last years.

    PubMed

    Manuel da S Azevedo, Maria; Cruz, Luisa; Pina-Vaz, Cidália; Gonçalves-Rodrigues, Acácio

    2016-05-01

    Despite the introduction of new antifungal agents, the frequency of invasive and mucocutaneous fungal infections as well as resistance to antifungal drugs continues to increase. Over 300 million persons are infected annually with fungi. Resistance to antimicrobials is one of today's major health threats. Can the possible causes of fungal antimicrobial resistance be understood and prevented to minimize risks to public health. We provide an overview of antifungal drug use in European countries, particularly Portugal. We reviewed prescriptions for and over-the-counter sales (OTC) of azoles in Portuguese pharmacies and in alternative shops. We conclude that in Portugal, azole antifungal sales, as well as medical prescribed azoles are very high. The Portuguese population consumes more antifungal drugs per capita than others in Europe. PMID:26865319

  13. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

    PubMed Central

    Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

    2015-01-01

    Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections. PMID:26048362

  14. Less is more: a project to reduce the number of PIMs (potentially inappropriate medications) on an elderly care ward

    PubMed Central

    Aung, Tin Htun; Judith Beck, Adèle; Siese, Thomas; Berrisford, Richard

    2016-01-01

    Potentially inappropriate prescribing in healthcare of the elderly (HCE) is associated with avoidable adverse drug events (ADEs).1,2 A recent set of prescribing criteria has been designed and validated, called “Screening Tool of Older Persons' Prescriptions” (STOPP), to rationalise prescribing in hospitalised patients on HCE wards.1,3 The aim of this quality improvement project was to identify how many potentially inappropriate medications (PIMs) were prescribed on these wards, and remove them. This was executed by implementing a ward round checklist, which incorporated STOPP criteria, for the twice weekly, consultant led ward rounds. This quality improvement project was carried out over four months. In a pilot study, we identified eight inappropriate medical prescriptions among 148 medications (5.4% ) prescribed on one ward. After applying a checklist for a structured ward round, we reviewed the medications prescribed on that ward, and found 10 PIMs out of 192 (5.2% ). Utilising the increasingly recognised “plan, do, study, act” (PDSA) cycle,4 we implemented departmental teaching and meetings with other members of the multidisciplinary team, which raised awareness of PIMs among junior doctors, as well as involving our pharmacists in drug chart screening. During this process we continued with a further six cycles on a bi-weekly basis, and saw a gradual decrease in PIM to 1.5%. In conclusion, a structured ward round, facilitated by a checklist that included review of drug charts based on STOPP criteria, demonstrated a considerable reduction of PIMs. It would be interesting to apply this quality improvement project to non-HCE wards, including general surgical wards or adult psychiatry wards, as a means of not only reducing the effects of ADEs, but also the expenditure associated with unnecessary drug prescriptions, and the costs associated with additional care arising from associated ADEs. PMID:27096089

  15. Empirical microeconomics action functionals

    NASA Astrophysics Data System (ADS)

    Baaquie, Belal E.; Du, Xin; Tanputraman, Winson

    2015-06-01

    A statistical generalization of microeconomics has been made in Baaquie (2013), where the market price of every traded commodity, at each instant of time, is considered to be an independent random variable. The dynamics of commodity market prices is modeled by an action functional-and the focus of this paper is to empirically determine the action functionals for different commodities. The correlation functions of the model are defined using a Feynman path integral. The model is calibrated using the unequal time correlation of the market commodity prices as well as their cubic and quartic moments using a perturbation expansion. The consistency of the perturbation expansion is verified by a numerical evaluation of the path integral. Nine commodities drawn from the energy, metal and grain sectors are studied and their market behavior is described by the model to an accuracy of over 90% using only six parameters. The paper empirically establishes the existence of the action functional for commodity prices that was postulated to exist in Baaquie (2013).

  16. Differential antifungal and calcium channel-blocking activity among structurally related plant defensins.

    PubMed

    Spelbrink, Robert G; Dilmac, Nejmi; Allen, Aron; Smith, Thomas J; Shah, Dilip M; Hockerman, Gregory H

    2004-08-01

    Plant defensins are a family of small Cys-rich antifungal proteins that play important roles in plant defense against invading fungi. Structures of several plant defensins share a Cys-stabilized alpha/beta-motif. Structural determinants in plant defensins that govern their antifungal activity and the mechanisms by which they inhibit fungal growth remain unclear. Alfalfa (Medicago sativa) seed defensin, MsDef1, strongly inhibits the growth of Fusarium graminearum in vitro, and its antifungal activity is markedly reduced in the presence of Ca(2+). By contrast, MtDef2 from Medicago truncatula, which shares 65% amino acid sequence identity with MsDef1, lacks antifungal activity against F. graminearum. Characterization of the in vitro antifungal activity of the chimeras containing portions of the MsDef1 and MtDef2 proteins shows that the major determinants of antifungal activity reside in the carboxy-terminal region (amino acids 31-45) of MsDef1. We further define the active site by demonstrating that the Arg at position 38 of MsDef1 is critical for its antifungal activity. Furthermore, we have found for the first time, to our knowledge, that MsDef1 blocks the mammalian L-type Ca(2+) channel in a manner akin to a virally encoded and structurally unrelated antifungal toxin KP4 from Ustilago maydis, whereas structurally similar MtDef2 and the radish (Raphanus sativus) seed defensin Rs-AFP2 fail to block the L-type Ca(2+) channel. From these results, we speculate that the two unrelated antifungal proteins, KP4 and MsDef1, have evolutionarily converged upon the same molecular target, whereas the two structurally related antifungal plant defensins, MtDef2 and Rs-AFP2, have diverged to attack different targets in fungi. PMID:15299136

  17. Antifungal activity of Lactobacillus against Microsporum canis, Microsporum gypseum and Epidermophyton floccosum

    PubMed Central

    Guo, Jiahui; Brosnan, Brid; Furey, Ambrose; Arendt, Elke; Murphy, Padraigin; Coffey, Aidan

    2012-01-01

    A total of 220 lactic acid bacteria isolates were screened for antifungal activity using Aspergillus fumigatus and Aspergillus niger as the target strains. Four Lactobacillus strains exhibited strong inhibitory activity on agar surfaces. All four were also identified as having strong inhibitory activity against the human pathogenic fungi Microsporum canis, Microsporum gypseum and Epidermophyton floccosum. One of the four lactobacilli, namely Lb. reuteri ee1p exhibited the most inhibition against dermatophytes. Cell-free culture supernatants of Lb. reuteri ee1p and of the non-antifungal Lb. reuteri M13 were freeze-dried and used to access and compare antifungal activity in agar plate assays and microtiter plate assays. Addition of the Lb. reuteri ee1p freeze-dried cell-free supernatant powder into the agar medium at concentrations greater than 2% inhibited all fungal colony growth. Addition of the powder at 5% to liquid cultures caused complete inhibition of fungal growth on the basis of turbidity. Freeze-dried supernatant of the non-antifungal Lb. reuteri M13 at the same concentrations had a much lesser effect. As Lb. reuteri M13 is very similar to the antifungal strain ee1p in terms of growth rate and final pH in liquid culture, and as it has little antifungal activity, it is clear that other antifungal compounds must be specifically produced (or produced at higher levels) by the anti-dermatophyte strain Lb. reuteri ee1p. Reuterin was undetectable in all four antifungal strains. The cell free supernatant of Lb. reuteri ee1p was analyzed by LC-FTMS using an Accela LC coupled to an LTQ Orbitrap XL mass spectrometer. The high mass accuracy spectrum produced by compounds in the Lb. reuteri ee1p strain was compared with both a multianalyte chromatogram and individual spectra of standard anti-fungal compounds, which are known to be produced by lactic acid bacteria. Ten antifungal metabolites were detected. PMID:22539027

  18. Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

    PubMed

    Lamas, Cristina; del Pozo, Carlos; Villabona, Carles

    2014-04-01

    Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring. PMID:24588923

  19. Inappropriate Shock Delivered By Implantable Cardioverter Defibrillator - Cardiac Resynchronization Therapy (ICD-CRT) Due To Myopotential Oversensing

    PubMed Central

    Barakpour, Hamid; Emkanjoo, Zahra; Alizadeh, Abolfath; Sadr-Ameli, Mohammad Ali

    2009-01-01

    The clinical efficacy of ICD-CRT therapy depends on accurate sensing of intracardiac signals and sensing algorithms. We report the occurrence of sensing abnormality in a patient with ICD-CRT. In this patient, oversensing of myopotentials during strenuous muscular activity resulted in an inappropriate ICD-CRT discharge. Although modern ICDs are highly effective in detecting and terminating malignant tachyarrhythmias, their detection specificity must be improved. It is possible to find the mechanism of arrhythmia by EGM. Simple device reprogramming make it possible to avoid the oversensing of myopotentials. PMID:19165363

  20. [Onset of Syndrome of Inappropriate Secretion of Antidiuretic Hormone in a Gastric Cancer Patient on SOX Treatment].

    PubMed

    Goto, Yoshinori; Wakita, Shigenori; Yoshimitsu, Masashi; Inagaki, Satoko; Kobayashi, Takeshi; Kaneko, Shuichi

    2015-12-01

    A 78-year-old man with advanced gastric cancer was treated with S-1 and oxaliplatin chemotherapy. He developed hiccups and nausea, and was diagnosed with hyponatremia (serum Na: 120 mEq/L) on day 6 of the first treatment course. Because of his increased urinary Na excretion and relatively high ADH values, he was subsequently diagnosed with chemotherapy-induced syndrome of inappropriate secretion of antidiuretic hormone. The patient recovered after an infusion of hypertonic saline. Although S-1 was restarted, hyponatremia did not recur. We suspected adverse drug reactions to ACE inhibitors and K-sparing diuretics in our case of hyponatremia. PMID:26809306

  1. Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris.

    PubMed

    Wong, Jack H; Ng, Tzi Bun; Wang, Hexiang; Sze, Stephen Cho Wing; Zhang, Kalin Yanbo; Li, Qi; Lu, Xiaoxu

    2011-03-15

    Cordymin, an antifungal peptide with a molecular mass of 10,906 Da and an N-terminal amino acid sequence distinct from those of previously reported proteins, was purified from the medicinal mushroom Cordyceps militaris. The isolation protocol comprised ion exchange chromatography of the aqueous extract on SP-Sepharose and Mono S and gel filtration on Superdex 75 by a fast protein liquid chromatography system. Cordymin was adsorbed on both cation exchangers. The peptide inhibited mycelial growth in Bipolaris maydis, Mycosphaerella arachidicola, Rhizoctonia solani and Candida albicans with an IC(50) of 50 μM, 10 μM, 80 μM, and 0.75 mM, respectively. However, there was no effect on Aspergillus fumigatus, Fusarium oxysporum and Valsa mali when tested up to 2 mM. The antifungal activity of the peptide was stable up to 100°C and in the pH range 6-13, and unaffected by 10 mM Zn(2+) and 10 mM Mg(2+). Cordymin inhibited HIV-1 reverse transcriptase with an IC(50) of 55 μM. Cordymin displayed antiproliferative activity toward breast cancer cells (MCF-7) but there was no effect on colon cancer cells (HT-29). There was no mitogenic activity toward mouse spleen cells and no nitric oxide inducing activity toward mouse macrophages when tested up to 1 mM. PMID:20739167

  2. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES.

    PubMed

    Biasi-Garbin, Renata Perugini; Demitto, Fernanda de Oliveira; Amaral, Renata Claro Ribeiro do; Ferreira, Magda Rhayanny Assunção; Soares, Luiz Alberto Lira; Svidzinski, Terezinha Inez Estivalet; Baeza, Lilian Cristiane; Yamada-Ogatta, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytes ATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  3. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    SciTech Connect

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  4. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    PubMed

    Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

    2012-01-01

    This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in phosphoglycerides (PGLs) composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

  5. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity

    PubMed Central

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L.; Avery, Simon V.

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  6. A novel antifungal protein of Bacillus subtilis B25.

    PubMed

    Tan, Zhiqiong; Lin, Baoying; Zhang, Rongyi

    2013-01-01

    Bacillus subtilis B25 was isolated from banana rhizosphere soil. It has been confirmed for B25 to have stronger antagonism against Fusarium oxysporum f.sp.cubense, Additionally B25 has good inhibitory to plant pathogens, including Corynespora cassiicola, Alternaria solani, Botrytis cinerea and Colletotrichum gloeosporioides on potato dextrose agar (PDA) plates. The antagonistic substance can be extracted from cell-free culture broth supernatants by 70% (w/v) (NH4)2 SO4 saturation. Clear blank band was observed between the protein and a pathogen. The examination of antagonistic mechanism under light microscope showed that the antifungal protein of B25 appeared to inhibit pathogens by leading to mycelium and spores tumescence, distortion, abnormality. The isolation procedure comprised ion exchange chromatography on DEAE-Sephadex Fast Flow and gel filtration chromatography on SephadexG-100. The purified antifungal fraction showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The active fraction was identified by NanoLC-ESI-MS/MS The amino acid sequences of 17 peptides segments were obtained. The analysis of the protein suggested that it was a hypothetical protein (gi154685475), with a relative molecular mass of 38708.67 Da and isoelectric point (pI) of 5.63. PMID:24255843

  7. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.

    PubMed

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L; Avery, Simon V

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  8. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals.

    PubMed

    Akhtar, Nida; Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  9. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

    PubMed Central

    Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  10. Antifungal activity of lectins against yeast of vaginal secretion

    PubMed Central

    Gomes, Bruno Severo; Siqueira, Ana Beatriz Sotero; de Cássia Carvalho Maia, Rita; Giampaoli, Viviana; Teixeira, Edson Holanda; Arruda, Francisco Vassiliepe Sousa; do Nascimento, Kyria Santiago; de Lima, Adriana Nunes; Souza-Motta, Cristina Maria; Cavada, Benildo Sousa; Porto, Ana Lúcia Figueiredo

    2012-01-01

    Lectins are carbohydrate-binding proteins of non-imune origin. This group of proteins is distributed widely in nature and they have been found in viruses, microorganisms, plants and animals. Lectins of plants have been isolated and characterized according to their chemical, physical-chemical, structural and biological properties. Among their biological activities, we can stress its fungicidal action. It has been previously described the effect of the lectins Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the growth of yeasts isolated from vaginal secretions. In the present work the experiments were carried out in microtiter plates and the results interpreted by both methods: visual observations and a microplate reader at 530nm. The lectin concentrations varied from 0.5 to 256μg/mL, and the inoculum was established between 65-70% of trammitance. All yeast samples isolated from vaginal secretion were evaluated taxonomically, where were observed macroscopic and microscopic characteristics to each species. The LSL lectin did not demonstrate any antifungal activity to any isolate studied. The other lectins DRL, ConBr and DvioL, showed antifungal potential against yeast isolated from vaginal secretion. These findings offering offer a promising field of investigation to develop new therapeutic strategies against vaginal yeast infections, collaborating to improve women's health. PMID:24031889

  11. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES

    PubMed Central

    BIASI-GARBIN, Renata Perugini; DEMITTO, Fernanda de Oliveira; do AMARAL, Renata Claro Ribeiro; FERREIRA, Magda Rhayanny Assunção; SOARES, Luiz Alberto Lira; SVIDZINSKI, Terezinha Inez Estivalet; BAEZA, Lilian Cristiane; YAMADA-OGATTA, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytesATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  12. Antifungal Enantiomeric Styrylpyrones from Sanrafaelia ruffonammari and Ophrypetalum odoratum.

    PubMed

    Malebo, Hamisi M; Kihampa, Charles; Mgina, Clarence A; Sung'hwa, Fortunatus; Waibel, Reiner; Jonker, Stephan A; Nkunya, Mayunga H H

    2014-04-01

    Phytochemical investigation of Sanrafaelia ruffonammari Verd and Ophrypetalum odoratum Diels that belongs to the rare genera confined to East African coastal forests led to the isolation of enantiomeric styrylpyrone dimer, (±)-5-methoxy-7-phenyl-[4-methoxy-2-pyronyl]-1-(E)-styryl-2-oxabicyclo-[4.2.0]-octa-4-en-3-one (1) alongside (+)-6-styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the enantiomeric (+)- (3) and (-)-6-styryl-7,8-dihydroxy-4-methoxypyran-2-ones (4). Their structures were established by means of spectroscopic methods. In this paper we reveal for the first time the occurrence of styrylpyrones in East African biodiversity. (+)-6-Styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the dihydroxystyrylpyrone enantiomer (3) showed in vitro antifungal activity against Candida albicans at a concentration of 24.4 and 26.2 µM with zones of inhibition of 17 and 9 mm, respectively. Compound 2 exhibited strong activity in the brine shrimp test with LC50 = 1.7 µg/mL. Their high cytotoxic and antifungal activities render them candidates for further scientific attention for drug development programs against cancer and microbial infections. PMID:24859289

  13. Benzoic acid derivatives with improved antifungal activity: Design, synthesis, structure-activity relationship (SAR) and CYP53 docking studies.

    PubMed

    Berne, Sabina; Kovačič, Lidija; Sova, Matej; Kraševec, Nada; Gobec, Stanislav; Križaj, Igor; Komel, Radovan

    2015-08-01

    Previously, we identified CYP53 as a fungal-specific target of natural phenolic antifungal compounds and discovered several inhibitors with antifungal properties. In this study, we performed similarity-based virtual screening and synthesis to obtain benzoic acid-derived compounds and assessed their antifungal activity against Cochliobolus lunatus, Aspergillus niger and Pleurotus ostreatus. In addition, we generated structural models of CYP53 enzyme and used them in docking trials with 40 selected compounds. Finally, we explored CYP53-ligand interactions and identified structural elements conferring increased antifungal activity to facilitate the development of potential new antifungal agents that specifically target CYP53 enzymes of animal and plant pathogenic fungi. PMID:26154240

  14. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme.

    PubMed

    Arendrup, M C; Dzajic, E; Jensen, R H; Johansen, H K; Kjaeldgaard, P; Knudsen, J D; Kristensen, L; Leitz, C; Lemming, L E; Nielsen, L; Olesen, B; Rosenvinge, F S; Røder, B L; Schønheyder, H C

    2013-08-01

    Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes. PMID:23607326

  15. Correlation between Antifungal Susceptibilities of Coccidioides immitis In Vitro and Antifungal Treatment with Caspofungin in a Mouse Model

    PubMed Central

    González, Gloria M.; Tijerina, Rolando; Najvar, Laura K.; Bocanegra, Rosie; Luther, Michael; Rinaldi, Michael G.; Graybill, John R.

    2001-01-01

    Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis. In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines. Two C. immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains were used for animal studies. Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers. Mice infected with strain 98-449 (48-h MIC, 8 μg/ml; 48-h MEC, 0.125 μg/ml) showed 100% survival to day 50 when treated with caspofungin at ≥1 mg/kg. Mice infected with strain 98-571 (48-h MIC, 64 μg/ml; 48-h MEC, 0.125 μg/ml) displayed ≥80% survival when the treatment was caspofungin at ≥5 mg/kg. Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate. When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains. A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing. Caspofungin may have a role in the treatment of coccidioidomycosis. PMID:11353637

  16. Antifungal treatment in allergic bronchopulmonary aspergillosis with and without cystic fibrosis: a systematic review.

    PubMed

    Moreira, A S; Silva, D; Ferreira, A Reis; Delgado, L

    2014-10-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA. PMID:24809846

  17. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    PubMed

    Desnos-Ollivier, Marie; Robert, Vincent; Raoux-Barbot, Dorothée; Groenewald, Marizeth; Dromer, Françoise

    2012-01-01

    New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites) were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes). Interestingly, geometric mean minimum inhibitory concentrations (MICs) of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001). Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens. PMID:22396754

  18. A novel 96-well gel-based assay for determining antifungal activity against filamentous fungi.

    PubMed

    Troskie, Anscha Mari; Vlok, Nicolas Maré; Rautenbach, Marina

    2012-12-01

    In recent years the global rise in antibiotic resistance and environmental consciousness lead to a renewed fervour to find and develop novel antibiotics, including antifungals. However, the influence of the environment on antifungal activity is often disregarded and many in vitro assays may cause the activity of certain antifungals to be overestimated or underestimated. The general antifungal test assays that are economically accessible to the majority of scientists primarily rely on visual examination or on spectrophotometric analysis. The effect of certain morphogenic antifungals, which may lead to hyperbranching of filamentous fungi, unfortunately renders these methods unreliable. To minimise the difficulties experienced as a result of hyperbranching, we developed a straightforward, economical 96-well gel-based method, independent of spectrophotometric analysis, for highly repeatable determination of antifungal activity. For the calculation of inhibition parameters, this method relies on the visualisation of assay results by digitisation. The antifungal activity results from our novel micro-gel dilution assay are comparable to that of the micro-broth dilution assay used as standard reference test of The Clinical and Laboratory Standard Institute. Furthermore, our economical assay is multifunctional as it permits microscopic analysis of the preserved assay results, as well as rendering highly reliable data. PMID:23089670

  19. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex.

    PubMed

    Cordeiro, Rossana de Aguiar; Macedo, Ramila de Brito; Teixeira, Carlos Eduardo Cordeiro; Marques, Francisca Jakelyne de Farias; Bandeira, Tereza de Jesus Pinheiro Gomes; Moreira, José Luciano Bezerra; Brilhante, Raimunda Sâmia Nogueira; Rocha, Marcos Fábio Gadelha; Sidrim, José Júlio Costa

    2014-07-01

    Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs. PMID:24722799

  20. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

  1. In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections

    PubMed Central

    Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera

    2014-01-01

    Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737

  2. Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.

    PubMed Central

    Santos, Karla K.A.; Matias, Edinardo F.F.; Tintino, Saulo R.; Souza, Celestina E.S.; Braga, Maria F.B.M.; Guedes, Gláucia M.M.; Costa, José G.M.; Menezes, Irwin R.A.

    2013-01-01

    Abstract Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

  3. Clauraila E from the roots of Clausena harmandiana and antifungal activity against Pythium insidiosum.

    PubMed

    Sriphana, Uraiwan; Thongsri, Yordhathai; Prariyachatigul, Chularut; Pakawatchai, Chaveng; Yenjai, Chavi

    2013-09-01

    A new carbazole alkaloid named clauraila E (1) together with 8 known compounds were isolated from the methanol extract of the roots of Clausena harmandiana. All compounds were evaluated for antifungal activity against Pythium insidiosum using disc diffusion assay. Pythium insidiosum is a fungus-like microorganism, for which antifungals available now are not effective. It was found that compounds 3, 6, 7 and 9 could inhibit the mycelia growth of P. insidiosum. The results show convincingly that they may be lead to compounds for the development of probiotic or novel antifungal drugs. PMID:23595552

  4. Enhancement of the antifungal activity of antimicrobial drugs by Eugenia uniflora L.

    PubMed

    Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique Douglas Melo

    2013-07-01

    Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

  5. Update from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance.

    PubMed

    Albataineh, Mohammad T; Sutton, Deanna A; Fothergill, Annette W; Wiederhold, Nathan P

    2016-03-01

    Despite the availability of new diagnostic assays and broad-spectrum antifungal agents, invasive fungal infections remain a significant challenge to clinicians and are associated with marked morbidity and mortality. In addition, the number of etiologic agents of invasive mycoses has increased accompanied by an expansion in the immunocompromised patient populations, and the use of molecular tools for fungal identification and characterization has resulted in the discovery of several cryptic species. This article reviews various methods used to identify fungi and perform antifungal susceptibility testing in the clinical laboratory. Recent developments in antifungal resistance are also discussed. PMID:26739605

  6. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  7. Relation between detection rate and inappropriate shocks in single versus dual chamber cardioverter-defibrillator - an analysis from the OPTION trial.

    PubMed

    Kolb, Christof; Sturmer, Marcio; Babuty, Dominique; Sick, Peter; Davy, Jean Marc; Molon, Giulio; Schwab, Jörg Otto; Mantovani, Giuseppe; Wickliffe, Andrew; Lennerz, Carsten; Semmler, Verena; Siot, Pierre-Henri; Reif, Sebastian

    2016-01-01

    The programming of implantable cardioverter-defibrillators (ICDs) influences inappropriate shock rates. The aim of the study is to analyse rates of patients with appropriate and inappropriate shocks according to detection zones in the OPTION trial. All patients received dual chamber (DC) ICDs randomly assigned to be programmed either to single chamber (SC) or to DC settings including PARAD+ algorithm. In a post-hoc analysis, rates of patients with inappropriate and appropriate shocks were calculated for shocks triggered at heart rates ≥170 bpm (ventricular tachycardia zone) and at rates ≥200 bpm (ventricular fibrillation zone). In the SC group, higher rates of patients with total and inappropriate shocks were delivered at heart rates ≥170 bpm than at rates ≥200 bpm (total shocks: 21.1% vs. 16.6%; p = 0.002; inappropriate shocks: 7.6% vs. 4.5%, p = 0.016; appropriate shocks: 15.2% vs. 13.5%; p = n.s.). No such differences were observed in the DC group (total shocks: 14.3% vs. 12.6%; p = n.s.; inappropriate shocks: 3.9% vs. 3.6%; p = n.s.; appropriate shocks: 12.2% vs. 10.4%; p = n.s.). The higher frequency of patients with total shocks with SC settings than with DC settings that benefit from PARAD+ was driven by a higher percentage of patients with inappropriate shocks in the VT zone (170-200 bpm) in the SC population. PMID:26892534

  8. Relation between detection rate and inappropriate shocks in single versus dual chamber cardioverter-defibrillator – an analysis from the OPTION trial

    PubMed Central

    Kolb, Christof; Sturmer, Marcio; Babuty, Dominique; Sick, Peter; Davy, Jean Marc; Molon, Giulio; Schwab, Jörg Otto; Mantovani, Giuseppe; Wickliffe, Andrew; Lennerz, Carsten; Semmler, Verena; Siot, Pierre-Henri; Reif , Sebastian

    2016-01-01

    The programming of implantable cardioverter-defibrillators (ICDs) influences inappropriate shock rates. The aim of the study is to analyse rates of patients with appropriate and inappropriate shocks according to detection zones in the OPTION trial. All patients received dual chamber (DC) ICDs randomly assigned to be programmed either to single chamber (SC) or to DC settings including PARAD+ algorithm. In a post-hoc analysis, rates of patients with inappropriate and appropriate shocks were calculated for shocks triggered at heart rates ≥170 bpm (ventricular tachycardia zone) and at rates ≥200 bpm (ventricular fibrillation zone). In the SC group, higher rates of patients with total and inappropriate shocks were delivered at heart rates ≥170 bpm than at rates ≥200 bpm (total shocks: 21.1% vs. 16.6%; p = 0.002; inappropriate shocks: 7.6% vs. 4.5%, p = 0.016; appropriate shocks: 15.2% vs. 13.5%; p = n.s.). No such differences were observed in the DC group (total shocks: 14.3% vs. 12.6%; p = n.s.; inappropriate shocks: 3.9% vs. 3.6%; p = n.s.; appropriate shocks: 12.2% vs. 10.4%; p = n.s.). The higher frequency of patients with total shocks with SC settings than with DC settings that benefit from PARAD+ was driven by a higher percentage of patients with inappropriate shocks in the VT zone (170–200 bpm) in the SC population. PMID:26892534

  9. Auditory imagery: empirical findings.

    PubMed

    Hubbard, Timothy L

    2010-03-01

    The empirical literature on auditory imagery is reviewed. Data on (a) imagery for auditory features (pitch, timbre, loudness), (b) imagery for complex nonverbal auditory stimuli (musical contour, melody, harmony, tempo, notational audiation, environmental sounds), (c) imagery for verbal stimuli (speech, text, in dreams, interior monologue), (d) auditory imagery's relationship to perception and memory (detection, encoding, recall, mnemonic properties, phonological loop), and (e) individual differences in auditory imagery (in vividness, musical ability and experience, synesthesia, musical hallucinosis, schizophrenia, amusia) are considered. It is concluded that auditory imagery (a) preserves many structural and temporal properties of auditory stimuli, (b) can facilitate auditory discrimination but interfere with auditory detection, (c) involves many of the same brain areas as auditory perception, (d) is often but not necessarily influenced by subvocalization, (e) involves semantically interpreted information and expectancies, (f) involves depictive components and descriptive components, (g) can function as a mnemonic but is distinct from rehearsal, and (h) is related to musical ability and experience (although the mechanisms of that relationship are not clear). PMID:20192565

  10. Acetoxychavicol Acetate, an Antifungal Component of Alpinia galanga1.

    PubMed

    Janssen, A M; Scheffer, J J

    1985-12-01

    The essential oils from fresh and dried rhizomes of ALPINIA GALANGA showed an antimicrobial activity against gram-positive bacteria, a yeast and some dermatophytes, using the agar overlay technique. The main components of the oils were also tested and terpinen-4-ol was found most active. An N-pentane/diethyl ether extract of dried rhizomes was active against TRICHOPHYTON MENTAGROPHYTES. 1'-Acetoxychavicol acetate, 1'-acetoxyeugenol acetate and 1'-hydroxychavicol acetate identified by MS and NMR were found in the antifungally active fractions obtained by LSC. Acetoxychavicol acetate was active against the seven fungi tested and its MIC value for dermatophytes ranged from 50 to 250 microg/ml. Dried sliced rhizomes contained 1.5% of this compound. The compound was not found in rhizomes of ALPINIA OFFICINARUM, ZINGIBER OFFICINALE and KAEMPFERIA GALANGA. PMID:17345272

  11. Antifungal activity of silver nanoparticles obtained by green synthesis.

    PubMed

    Mallmann, Eduardo José J; Cunha, Francisco Afrânio; Castro, Bruno N M F; Maciel, Auberson Martins; Menezes, Everardo Albuquerque; Fechine, Pierre Basílio Almeida

    2015-01-01

    Silver nanoparticles (AgNPs) are metal structures at the nanoscale. AgNPs have exhibited antimicrobial activities against fungi and bacteria; however synthesis of AgNPs can generate toxic waste during the reaction process. Accordingly, new routes using non-toxic compounds have been researched. The proposal of the present study was to synthesize AgNPs using ribose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer. The antifungal activity of these particles against C. albicans and C. tropicalis was also evaluated. Stable nanoparticles 12.5 ± 4.9 nm (mean ± SD) in size were obtained, which showed high activity against Candida spp. and could represent an alternative for fungal infection treatment. PMID:25923897

  12. A lectin with antifungal activity from the mussel Crenomytilus grayanus.

    PubMed

    Chikalovets, Irina V; Chernikov, Oleg V; Pivkin, Mikhail V; Molchanova, Valentina I; Litovchenko, Alina P; Li, Wei; Lukyanov, Pavel A

    2015-02-01

    Lectins (carbohydrate-binding proteins) are well known to actively participate in the defense functions of vertebrates and invertebrates where they play an important role in the recognition of foreign particles. In this study, we investigated of in vitro antifungal activity of lectin from the mussel Crenomytilus grayanus (CGL). Enzyme-linked immunosorbent assay indicated that CGL was predominantly detectable in tissues of mantle and to a lesser degree in the tissues of muscle, hepatopancreas, gill and hemocytes. After challenged by Pichia pastoris the level of CGL was upregulated and reached the maximum level at 12 h post challenge and recovered to the original level at 24 h. The lectin was capable of inhibiting the germination of spores and hyphal growth in the fungi. All these results indicated that CGL is involved in the innate immune response in mollusc animals. PMID:25482060

  13. Partial identification of antifungal compounds from Punica granatum peel extracts.

    PubMed

    Glazer, Ira; Masaphy, Segula; Marciano, Prosper; Bar-Ilan, Igal; Holland, Doron; Kerem, Zohar; Amir, Rachel

    2012-05-16

    Aqueous extracts of pomegranate peels were assayed in vitro for their antifungal activity against six rot fungi that cause fruit and vegetable decay during storage. The growth rates of Alternaria alternata , Stemphylium botryosum , and Fusarium spp. were significantly inhibited by the extracts. The growth rates were negatively correlated with the levels of total polyphenolic compounds in the extract and particularly with punicalagins, the major ellagitannins in pomegranate peels. Ellagitannins were also found to be the main compounds in the bioactive fractions using bioautograms, and punicalagins were identified as the main bioactive compounds using chromatographic separation. These results suggest that ellagitannins, and more specifically punicalagins, which are the dominant compounds in pomegranate peels, may be used as a control agent of storage diseases and to reduce the use of synthetic fungicides. PMID:22533815

  14. Pavietin, a coumarin from Aesculus pavia with antifungal activity.

    PubMed

    Curir, Paolo; Galeotti, Francesco; Dolci, Marcello; Barile, Elisa; Lanzotti, Virginia

    2007-10-01

    A new prenylated coumarin, S-6-[2-(hydroxymethyl)butoxy]-7-hydroxy-4-methyl-2 H-chromen-2-one ( 1), named pavietin, has been isolated from the leaves of an Aesculus pavia genotype along with three known flavonol glycosides, quercetin 3- O-alpha-rhamnoside (quercitrin, 2), quercetin 3- O-alpha-arabinoside ( 3), and isorhamnetin 3- O-alpha-arabinoside (distichin, 4). The chemical structure of compound 1 was determined by chemical and spectroscopic methods, inclusive of UV, MS, and 1D and 2D NMR experiments. It showed appreciable antimicrobial properties against several pathogens, displaying a significant antifungal activity toward one of the main fungal parasites of Aesculus species, Guignardia aesculi. The same biological tests performed with a mixture of flavonoids 2- 4 resulted in weak or no activity. Compound 1 was undetectable in Aesculus hippocastanum, a closely related species lacking resistance to fungal pathogens. The possible role of 1 in plant resistance is discussed. PMID:17914881

  15. Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

    PubMed Central

    Rex, John H.; Pfaller, Michael A.; Walsh, Thomas J.; Chaturvedi, Vishnu; Espinel-Ingroff, Ana; Ghannoum, Mahmoud A.; Gosey, Linda L.; Odds, Frank C.; Rinaldi, Michael G.; Sheehan, Daniel J.; Warnock, David W.

    2001-01-01

    Development of standardized antifungal susceptibility testing methods has been the focus of intensive research for the last 15 years. Reference methods for yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of these methods provides researchers not only with standardized methods for testing but also with an understanding of the variables that affect interlaboratory reproducibility. With this knowledge, we have now moved into the phase of (i) demonstrating the clinical value (or lack thereof) of standardized methods, (ii) developing modifications to these reference methods that address specific problems, and (iii) developing reliable commercial test kits. Clinically relevant testing is now available for selected fungi and drugs: Candida spp. against fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B; Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful testing procedures is the current focus of research in this area. PMID:11585779

  16. [Chalcones and their heterocyclic analogs as potential antifungal chemotherapeutic agents].

    PubMed

    Opletalová, V; Sedivý, D

    1999-11-01

    Chalcones and their heterocyclic analogues show various biological effects, e.g. anti-inflammatory, antitumour, antibacterial, antituberculous, antiviral, antiprotozoal, gastroprotective, and others. The present review discusses in greater detail the fungistatic and fungicide properties of these compounds and presents also their chemical structures. The mechanism of antifungal effects of chalcones and their analogues has not been investigated in greater detail. Due to the presence of a reactive ketovinyl moiety in the molecule the compounds of this type are able to react with the thiol groups of enzymes. It cannot be excluded that chalcones interfere with the normal function of the membranes of fungi and moulds. Further investigation of chemical, physical, and biological properties of chalcones and their analogues could lead to the elucidation of the mechanism of their action and finding of effective fungicidal and fungistatic agents in this group of organic substances. PMID:10748740

  17. Medical claims and current applications of the potent echinocandin antifungals.

    PubMed

    Smith, Leif; Lu, Shi-En

    2010-01-01

    Echinocandins are an interesting group of antifungals that were originally discovered in the early 1970s. They are a group of lipopeptides produced by fungi which consists of a large number of structural analogs of echinocandin B, the first echinocandin to be structurally characterized. All clinically used echinocandins are produced semi-synthetically. The cyclic peptide nuclear core is retained while the acyl chain is replaced to minimize toxicity and expand their spectrum of activity. It was not until 2002 with the introduction of caspofungin (Cancidas) into the clinics that their true worth was realized. Since the introduction of caspofungin, two other echinocandins, micafungin (Mycamine) and anidulafungin (Eraxis) have been introduced. They all function by inhibiting an enzyme unique for fungal cell wall production, which presumably accounts for their minimal side-effects. In this review, topics pertaining to their production, structural diversity, and use in the clinic along with the recent patents are discussed. PMID:19929842

  18. Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

    PubMed Central

    Kouznetsov, Vladímir V.; Zacchino, Susana A.; Sortino, Maximiliano; Vargas Méndez, Leonor Y.; Gupta, Mahabir P.

    2012-01-01

    Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC50 < 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. PMID:23264936

  19. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID:26827629

  20. Characterization of Chitosan Nanofiber Sheets for Antifungal Application

    PubMed Central

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young’s modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young’s modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046