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Sample records for capecitabine-induced cardiotoxicity case

  1. Capecitabine-induced cardiotoxicity: more evidence or clinical approaches to protect the patients' heart?

    Directory of Open Access Journals (Sweden)

    Fontanella C

    2014-09-01

    Full Text Available Caterina Fontanella,1 Marianna Aita,1 Marika Cinausero,1 Giuseppe Aprile,1 Maria Grazia Baldin,2 Veronica Dusi,3 Chiara Lestuzzi,4 Gianpiero Fasola,1 Fabio Puglisi1,5 1Department of Oncology, University Hospital of Udine, Udine, Italy; 2Department of Cardiology, Palmanova General Hospital, Palmanova, Italy; 3Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 4Department of Cardiology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy; 5Department of Medical and Biological Sciences, University of Udine, Udine, Italy Abstract: Fluoropyrimidines, such as capecitabine and 5-fluorouracil, may cause cardiac toxicity. In recent years, the incidence of this side effect has increased and it is expected to further rise due to the population aging and the disproportionate incidence of breast and gastrointestinal cancers in older individuals. The spectrum of cardiac manifestations includes different signs and symptoms and the diagnosis may be difficult. Here, we report the case of a 43-year-old woman with advanced breast cancer who was rechallenged with a capecitabine-based regimen after experiencing a cardiac adverse event during the first fluoropyrimidine exposure. This real-practice case serves as a springboard for discussion about the current evidence on differential diagnosis of capecitabine-related cardiac toxicity, its risk factors, and the underpinning mechanisms of early onset. Moreover, we discussed whether a rechallenge with fluoropyrimidines could be safe in patients who had experienced a previous cardiac adverse event. Keywords: risk factors, clinical manifestation, rechallenge

  2. Capecitabine cardiac toxicity presenting as effort angina: a case report.

    Science.gov (United States)

    Lestuzzi, Chiara; Crivellari, Diana; Rigo, Fausto; Viel, Elda; Meneguzzo, Nereo

    2010-09-01

    We report a case of capecitabine-induced cardiotoxicity (effort angina) in a woman with metastatic breast carcinoma. Due to cancer progression, rechallenge of therapy with capecitabine was attempted, using several strategies in order to prevent cardiotoxicity. The most (even if not fully) effective strategy was reducing capecitabine dosage together with nitrates, calcium-channel blockers and trimetazidine therapy. PMID:20093950

  3. Capecitabine-induced ventricular fibrillation arrest: Possible Kounis syndrome.

    Science.gov (United States)

    Kido, Kazuhiko; Adams, Val R; Morehead, Richard S; Flannery, Alexander H

    2016-04-01

    We report the case of capecitabine-induced ventricular fibrillation arrest, possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid resection, was started on adjuvant capecitabine approximately five months prior to presentation of cardiac arrest secondary to ventricular fibrillation. An electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and the patient was taken emergently to the cardiac catheterization laboratory. The catheterization revealed no angiographically significant stenosis and coronary artery disease was ruled out. After ruling out other causes of cardiac arrest, the working diagnosis was capecitabine-induced ventricular fibrillation arrest. As such, an inflammatory work up was sent to evaluate for the possibility of a capecitabine hypersensitivity, or Kounis syndrome, and is the first documented report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability scale indicates a probable adverse effect due to capecitabine with seven points. A case of capecitabine-induced ventricular fibrillation arrest is reported, with a potential for type 1 Kounis syndrome as an underlying pathology supported by immunologic work up. PMID:25870182

  4. Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

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    Tabchi S

    2014-05-01

    Full Text Available A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

  5. Paracetamol cardiotoxicity.

    OpenAIRE

    Armour, A.; Slater, S D

    1993-01-01

    A 29 year old man with a significant paracetamol overdose was found to have an abnormal electrocardiograph which, in the absence of hepatic encephalopathy, was considered due to a direct cardiotoxic effect of the drug. A functional coronary insufficiency resulting from inhibition of endothelium-derived relaxing factor secondary to depletion of sulphydryl groups is postulated, and it is suggested that in paracetamol poisoning evidence of cardiotoxicity alone may be sufficient justification for...

  6. Role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity: two cases and review of the literature.

    Science.gov (United States)

    Gallucci, Giuseppina; Tartarone, Alfredo; Tocchetti, Carlo Gabriele; Bochicchio, Anna Maria; Coccaro, Mariarosa; Capobianco, Alba; Maurea, Nicola; Improta, Giuseppina; Zupa, Angela; Aieta, Michele

    2013-01-01

    Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support. PMID:23252570

  7. A Case of Trastuzumab-Associated Cardiomyopathy Presenting as an Acute Coronary Syndrome: Acute Trastuzumab Cardiotoxicity

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    Sylvana Hidalgo

    2013-01-01

    Full Text Available Trastuzumab is a monoclonal antibody highly effective in the treatment of several cancers, but its use is associated with cardiac toxicity which usually responds to cessation of the drug and/or medical therapy. We present an unusual case of acute cardiac toxicity temporally related to administration of trastuzumab in which the clinical presentation suggested an acute coronary syndrome. Coronary angiography, however, demonstrated minimal epicardial disease, but new wall motion abnormalities. Furthermore, the patient did not respond to withdrawal of the drug or medical therapy for heart failure.

  8. Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management.

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    Layoun, Michael E; Wickramasinghe, Chanaka D; Peralta, Maria V; Yang, Eric H

    2016-06-01

    Fluoropyrimidines-5-fluorouracil (5-FU) and capecitabine-have been implicated as cardiotoxic chemotherapy agents. This rare, albeit potentially serious toxicity has been described in nearly four decades of case reports, case series, and in vitro modeling; however, there is a paucity in clinical trials and prospective analyses focused on cardioprotective strategies and cardiotoxic surveillance of these agents. While much attention has focused on the well-known cardiac toxicity of anthracyclines and monoclonal antibody agents such as trastuzumab, fluoropyrimidines remain one of the most common causes of chemotherapy-associated cardiotoxicity. The introduction of capecitabine, an oral prodrug of 5-FU, has made the treatment of solid tumors more convenient along with a subsequent rise in documented cardiotoxic cases. This review discusses the symptomatology, clinical manifestations, and proposed molecular mechanisms that attempt to describe the heterogeneous spectrum of fluoropyrimidine-induced cardiotoxicity. Four case examples showcasing the varied manifestations of cardiotoxicity are presented. Finally, several proposed management strategies for cardiotoxicity and post-hospital course precautions are discussed. PMID:27113369

  9. Duxorubicin-induced cardiotoxicity

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    Mukund Joshi

    2015-02-01

    Full Text Available The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the and ldquo;toxicity that affects the heart. and rdquo; This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX, cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the

  10. Capecitabine Induced Multifocal Leukoencephalopathy: Do We Have Always to Switch off the Chemotherapy?

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    Anastasia Bougea

    2016-01-01

    Full Text Available Capecitabine is a well tolerated and safe 5-fluorouracil agent for adjuvant, neoadjuvant chemotherapy or metastatic cases. Neurological side effects require discontinuation of chemotherapy. We report this unique case of a 50-year-old female, who presented an isolated episode of dysarthria and ataxia under bevacizumab, capecitabine, and oxaliplatin treatment due to reversible multifocal leukoencephalopathy that did not recur after readministration of chemotherapy.

  11. Capecitabine Induced Multifocal Leukoencephalopathy: Do We Have Always to Switch off the Chemotherapy?

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    Bougea, Anastasia; Voskou, Panagiota; Kilidireas, Constantinos; Andreadou, Elisabeth

    2016-01-01

    Capecitabine is a well tolerated and safe 5-fluorouracil agent for adjuvant, neoadjuvant chemotherapy or metastatic cases. Neurological side effects require discontinuation of chemotherapy. We report this unique case of a 50-year-old female, who presented an isolated episode of dysarthria and ataxia under bevacizumab, capecitabine, and oxaliplatin treatment due to reversible multifocal leukoencephalopathy that did not recur after readministration of chemotherapy. PMID:26966603

  12. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

    DEFF Research Database (Denmark)

    Nielsen, Karin; Polk, Anne; Nielsen, Dorte Lisbet;

    2014-01-01

    infusion. Furthermore a 13-fold increase in N-terminal Pro Brain Natriuretic Peptide (NT-pro-BNP) occurred during infusion. No subjective cardiac symptoms were described, but the findings were interpreted as cardiotoxicity. Case report 2 presents a 64-year old woman with a medical history of hypertension...... and hyperlipidemia as well as an incidental finding of negative T-waves in electrocardiogram years before 5-FU treatment. No subjective cardiac symptoms were described during infusion, but approximately 12 hours after infusion she suffered from cardiac arrest but was revived. Subsequent analysis of...

  13. Mechanisms of Cardiotoxicity and the Development of Heart Failure.

    Science.gov (United States)

    Lee, Christopher S

    2015-12-01

    Cardiotoxicity is a broad term that refers to the negative effects of toxic substances on the heart. Cancer drugs can cause cardiotoxicity by effects on heart cells, thromboembolic events, and/or hypertension that can lead to heart failure. Rheumatoid arthritis biologics may interfere with ischemic preconditioning and cause/worsen heart failure. Long-term and heavy alcohol use can result in oxidative stress, apoptosis, and decreased contractile protein function. Cocaine use results in sympathetic nervous system stimulation of heart and smooth muscle cells and leads to cardiotoxicity and evolution of heart failure. The definition of cardiotoxicity is likely to evolve along with knowledge about detecting subclinical myocardial injury. PMID:26567492

  14. Cardiotoxicity of oncologic treatment of breast cancer

    International Nuclear Information System (INIS)

    Cardiac affectation by neoplastic diseases may be due to the heart invasion produced by itself tumor, compression of the heart and / or great vessels by noncardiac neoplasms, most commonly embolization and therapeutic purposes antitumor. Cancer treatment has experienced significant progress in recent decades by the great expansion of chemotherapeutic agents and the refinement of radiotherapy techniques; however, many of the most effective drugs antineoplastic and thoracic irradiation cause both acute and chronic cardiotoxicity. Thus, the long-term monitoring of patients receiving anthracycline drugs Crucial in the therapy of many neoplasms, demonstrates clinical heart failure in 4.5 to 7% of patients, increasing the incidence of defects in the cardiac function over time. Its pathogenesis is likely included in the formation of free radicals, alterations calcium transport, dysfunction or adrenergic amines glass release active. Dex razoxane is the only clinically used cardio protective marketed for selected group of patients with breast cancer, it is necessary development of new agents that protect the cardiotoxicity of this group of drugs and reduce morbidity and secondary mortality to them. In this work, the tracking shows 4 patients with breast cancer who had received treatment with anthracyclines and the cardiotoxic manifestation suffered, resulting in changes in their treatment, and in one of the patients was used cardio protective medication

  15. Radionuclide methods of diagnosing anthracycline - induced cardiotoxity

    International Nuclear Information System (INIS)

    Anthracycline chemotherapeutic agents play an important role in tumor treatment owing to their high therapeutic efficiency but at the same time they cause lesions to healthy tissues and organs among which cardiotoxity is the most significant. Radionuclide diagnostic methods are widely used in diagnosing heart damage against the background of therapy with anthracyclines. Radionuclide ventriculography is implemented in practice as a routine procedure for serial evaluation of LVFI (left ventricular filling index) and regional myocardial kinetics monitoring. The obtained results are used for individual assessment of the cumulative dose of the anthracycline antineoplastic agent administered. However, the method has low prognostic value regarding the severity of myocardial impairment on account of its late positiveness. Researches along these lines are focused on radiopharmaceuticals accumulating in the myocardial cell and mirroring its perfusion, innervation and vitality, such as 111In-antimyosin, 123I-MIBG and 99mTc-MIBI. Investigations using the aforementioned radiopharmaceuticals disclose the mechanisms of myocardial cell damage under the effect of anthracyclines, becoming positive before clinical manifestation of cardiotoxicity. Their implementation in the routine practice lags behind because of insufficient studies on the issue

  16. Phytochemicals that counteract the cardiotoxic side effects of cancer chemotherapy

    OpenAIRE

    Anita Piasek; Agnieszka Bartoszek; Jacek Namieśnik

    2009-01-01

    Almost all clinically used antitumor drugs exhibit toxic side effects affecting heart function. Because of cardiotoxicity during anticancer chemotherapy, effective doses of cytostatics have to be limited, which may worsen antitumor efficacy. The cardiotoxicity induced by cytostatics of the anthracycline group in particular results, among others, from massive stimulation of ROS. It has therefore been suggested that some phytochemicals with high antioxidant potential, when administered together...

  17. CE: Cardiotoxicity and Breast Cancer as Late Effects of Pediatric and Adolescent Hodgkin Lymphoma Treatment.

    Science.gov (United States)

    Lee Candela, Joanne

    2016-04-01

    : The American Cancer Society estimates that in 2014 nearly 16,000 U.S. children and adolescents developed cancer, and in roughly 1,200 of these cases the cancer was Hodgkin lymphoma (HL). The great majority of these patients will survive, joining the thousands who have been diagnosed and treated successfully in decades past. Nurses' familiarity with and attention to the late effects of the chemotherapy and radiation therapy used to treat HL, which include breast cancer as well as cardiotoxicity and its sequelae, are essential in helping these patients maintain their overall health. PMID:26974745

  18. CARDIOTOXICITY ANTIPSYCHOTICS: MORPHO-ELECTROCARDIOGRAPHIC ASSOCIATIONS

    Directory of Open Access Journals (Sweden)

    V. P. Volkov

    2015-12-01

    Full Text Available Aim. To study the morphological and functional heart disorders in patients with different duration of antipsychotic treatment. Material and methods. Medical documents of 78 deceased schizophrenic patients treated with antipsychotic drugs were studied. The patients were split into 4 groups depending on duration of neuroleptic treatment: group 1 — <10 years, group 2 — 11-20 years; group 3 — 21-30 years, group 4 — >30 years. ECG-disorders and left ventricular morphometric data were analyzed. Сorrelation analysis of myocardium morphological changes and electrophysiological disorders was performed. Results. The dependence of morphometric myocardium changes on the treatment duration was found: increase in stromal-parenchymal ratio (from 9.9±4.1% to 80.0±10.1% in groups 1 and 4, respectively, in specific volume of atrophied cardiomyocytes (from 8.0±3.8% to 45.1±12.6% in groups 1 and 4, respectively, in specific volume of degenerative cardiomyocytes (from 5.2±3.1% to 35.2±12.1% in groups 1 and 4, respectively. Increased incidence of extrasystole detection (from 2.2% to 11.2% in groups 1 and 2, respectively, as well as left anterior fascicular block (from 1.1% to 25.9% in groups 1 and 2, respectively and left ventricle hypertrophy (from 2.2% to 18.5% in groups 1 and 4, respectively were found. A strong positive correlation (r=0.88–0.99 was revealed between antipsychotic treatment duration and ECG disorders, as well as between morphological myocardium state and ECG disorders. Conclusion. Awareness about the neuroleptic-depended ECG changes is necessary for early diagnosis, secondary prevention and correction of existing heart disorders due to cardiotoxic side effects of antipsychotic drugs.

  19. Nuclear imaging in detection and monitoring of cardiotoxicity

    Institute of Scientific and Technical Information of China (English)

    Carmen; D’Amore; Paola; Gargiulo; Stefania; Paolillo; Angela; Maria; Pellegrino; Tiziana; Formisano; Antonio; Mariniello; Giuseppe; DellaRatta; Elisabetta; Iardino; Marianna; D’Amato; Lucia; La; Mura; Irma; Fabiani; Flavia; Fusco; Pasquale; Perrone; Filardi

    2014-01-01

    Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient’s management and outcome.The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents.Left ventricular dysfunction is the most typical manifestation and can lead to heart failure.Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage,but it identifies a late manifestation of myocardial injury.Early non-invasive imaging techniques are needed for the diagnosis and monitoringof cardiotoxic effects.Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment,greater attention is focused on new nuclear cardiologic techniques,which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation.The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage,focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.

  20. Crocin treatment prevents doxorubicin-induced cardiotoxicity in rats.

    Science.gov (United States)

    Razmaraii, Nasser; Babaei, Hossein; Mohajjel Nayebi, Alireza; Assadnassab, Gholamreza; Ashrafi Helan, Javad; Azarmi, Yadollah

    2016-07-15

    Doxorubicin (DOX)-induced cardiotoxicity is well-known as a serious complication of chemotherapy in patients with cancer. It is unknown whether crocin (CRO), main component of Crocus sativus L. (Saffron), could reduce the severity of DOX-induced cardiotoxicity. Therefore, this study was undertaken to assess the protective impact of CRO on DOX-induced cardiotoxicity in rats. The rats were divided into four groups: control, DOX (2mg/kg/48h, for 12days), and CRO groups that receiving DOX as in group 2 and CRO (20 and 40mg/kg/24h, for 20days) starting 4days prior to first DOX injection and throughout the study. Echocardiographic, electrocardiographic and hemodynamic studies, along with histopathological examination and MTT test were carried out. Our findings demonstrate that DOX resulted in cardiotoxicity manifested by decreased the left ventricular (LV) systolic and diastolic pressures, rate of rise/drop of LV pressure, ejection fraction, fractional shortening and contractility index, as compared to control group. In addition, histopathological analysis of heart confirmed adverse structural changes in myocardial cells following DOX administration. The results also showed that CRO treatment significantly improved DOX-induced heart damage, structural changes in the myocardium and ventricular function. In addition, CRO did not affect the in vitro antitumor activity of DOX. Taken together, our data confirm that CRO is protective against cardiovascular-related disorders produced by DOX, and clinical studies are needed to examine these findings in human. PMID:27297631

  1. Colchicine cardiotoxicity following ingestion of Gloriosa superba tubers.

    OpenAIRE

    Mendis, S.

    1989-01-01

    The clinical features of colchicine toxicity in a patient following ingestion of Gloriosa superba tubers are described. Gastroenteritis, acute renal failure, cardiotoxicity and haematological abnormalities were the main toxic manifestations. There was no hypotension and no neurological manifestations. Electrocardiographic changes were noteworthy and have not been reported previously.

  2. Hesperidin Alleviates Doxorubicin-Induced Cardiotoxicity in Rats

    International Nuclear Information System (INIS)

    Background: Doxorubicin (DOX) is a potent chemotherapeutic agent used in the treatment of several tumors but its cardiac toxicity prevents its use at a maximum dose, representing an important problem. Increased reactive oxygen species (ROS) and imbalance in nitric oxide (NO) production have been implicated in the cardiotoxicity of doxorubicin. Hesperidin is a citrus bioflavonoid that possesses a potent antioxidant and NO modulating activities. Objectives: Therefore, the aim of this study was to investigate the possible protective role of hesperidin against doxorubicin-induced cardiac toxicity. Methods: Four groups of animals were used in this study. First group served as a control and injected with the vehicle. Second group was given 200 mg/kg of hesperidin orally for seven consecutive days. The third group was injected with a single dose (20 mg/kg) of doxorubicin intraperitoneally and was sacrificed after 48 h. The fourth group was treated with hesperidin for seven days but on day five, 1-hour after hesperidin treatment, rats were injected with the single dose of doxorubicin. On day seven, the rats were scarified by decapitation. Blood was collected and processed for determination of serum lactate dehydrogenase (LDH), creatine kinase (CK) and NO. The hearts were removed and processed for both histopathological examination and determination of oxidative stress parameters like reduced glutathione (GSH), lipid peroxide (TBARS) levels and superoxide dismutase (SOD) activity. Results: Our results showed that doxorubicin produced severe cardiotoxicity as indicated from increase in serum LDH, CK activities and NO level. Histopathological examination of DOX-treated rats revealed degenerative changes in heart tissues. The significant decrease in GSH levels, SOD activity and increase in TBARS levels, indi- cated that DOX-induced cardiotoxicity was mediated through ROS generation. On the other hand, pretreatment of rats with hesperidin protected cardiac tissues against the

  3. Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paweorn Angsutararux

    2015-01-01

    Full Text Available Chemotherapy-induced cardiotoxicity is a serious complication that poses a serious threat to life and limits the clinical use of various chemotherapeutic agents, particularly the anthracyclines. Understanding molecular mechanisms of chemotherapy-induced cardiotoxicity is a key to effective preventive strategies and improved chemotherapy regimen. Although no reliable and effective preventive treatment has become available, numerous evidence demonstrates that chemotherapy-induced cardiotoxicity involves the generation of reactive oxygen species (ROS. This review provides an overview of the roles of oxidative stress in chemotherapy-induced cardiotoxicity using doxorubicin, which is one of the most effective chemotherapeutic agents against a wide range of cancers, as an example. Current understanding in the molecular mechanisms of ROS-mediated cardiotoxicity will be explored and discussed, with emphasis on cardiomyocyte apoptosis leading to cardiomyopathy. The review will conclude with perspectives on model development needed to facilitate further progress and understanding on chemotherapy-induced cardiotoxicity.

  4. Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors.

    Science.gov (United States)

    Bobesh, Karyakulam Andrews; Renuka, Janupally; Srilakshmi, Rudraraju Reshma; Yellanki, Swapna; Kulkarni, Pushkar; Yogeeswari, Perumal; Sriram, Dharmarajan

    2016-01-01

    Recently numerous non-fluoroquinolone-based bacterial type II topoisomerase inhibitors from both the GyrA and GyrB classes have been reported as antibacterial agents. Inhibitors of the GyrA class include aminopiperidine-based novel bacterial type II topoisomerase inhibitors (NBTIs). However, inhibition of the cardiac ion channel remains a serious liability for the aminopiperidine based NBTIs. In this paper we replaced central aminopiperidine linker with piperazine moiety and tested for its biological activity. We developed a series of twenty four compounds with a piperazine linker 1-(2-(piperazin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one, by following a multistep protocol. Among them compound 4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)-N-(4-nitrophenyl)piperazine-1-carboxamide (11) was the most promising inhibitor with Mycobacterium tuberculosis (MTB) DNA gyrase enzyme supercoiling IC50 of 0.29±0.22μM, with a good MTB MIC of 3.45μM. These kind of compounds retains good potency and showed reduced cardiotoxicity compared to aminopiperidines. PMID:26678175

  5. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Science.gov (United States)

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  6. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Vistisen, Kirsten; Vaage-Nilsen, Merete;

    2014-01-01

    Med for articles in English using the search terms: 5-FU OR 5-fluorouracil OR capecitabine AND cardiotoxicity. Papers evaluating the pathophysiology of this cardiotoxicity were included. RESULTS: We identified 27 articles of 26 studies concerning the pathophysiology of 5-FU-induced cardiotoxicity. The...... transfer oxygen resulting in myocardial ischemia. CONCLUSIONS: There is no evidence for a single mechanism responsible for 5-FU-induced cardiotoxicity, and the underlying mechanisms might be multifactorial. Further research is needed to elucidate the pathogenesis of this side effect....

  7. Subacute Cardiotoxicity of Yessotoxin: In Vitro and in Vivo Studies.

    Science.gov (United States)

    Ferreiro, Sara F; Vilariño, Natalia; Carrera, Cristina; Louzao, M Carmen; Cantalapiedra, Antonio G; Santamarina, Germán; Cifuentes, J Manuel; Vieira, Andrés C; Botana, Luis M

    2016-06-20

    Yessotoxin (YTX) is a marine phycotoxin produced by dinoflagellates and accumulated in filter feeding shellfish. Although no human intoxication episodes have been reported, YTX content in shellfish is regulated by many food safety authorities due to their worldwide distribution. YTXs have been related to ultrastructural heart damage in vivo, but the functional consequences in the long term have not been evaluated. In this study, we explored the accumulative cardiotoxic potential of YTX in vitro and in vivo. Preliminary in vitro evaluation of cardiotoxicity was based on the effect on hERG (human ether-a-go-go related gene) channel trafficking. In vivo experiments were performed in rats that received repeated administrations of YTX followed by recordings of electrocardiograms, arterial blood pressure, plasmatic cardiac biomarkers, and analysis of myocardium structure and ultrastructure. Our results showed that an exposure to 100 nM YTX for 12 or 24 h caused an increase of extracellular surface hERG channels. Furthermore, remarkable bradycardia and hypotension, structural heart alterations, and increased plasma levels of tissue inhibitor of metalloproteinases-1 were observed in rats after four intraperitoneal injections of YTX at doses of 50 or 70 μg/kg that were administered every 4 days along a period of 15 days. Therefore, and for the first time, YTX-induced subacute cardiotoxicity is supported by evidence of cardiovascular function alterations related to its repeated administration. Considering international criteria for marine toxin risk estimation and that the regulatory limit for YTX has been recently raised in many countries, YTX cardiotoxicity might pose a health risk to humans and especially to people with previous cardiovascular risk. PMID:27104637

  8. Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity

    OpenAIRE

    Chung, Woo-Baek; Youn, Ho-Joong

    2016-01-01

    Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicit...

  9. In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae

    Directory of Open Access Journals (Sweden)

    Jinfeng Liang

    2016-02-01

    Full Text Available Sodium aescinate (SA is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro, which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio, we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence, as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC10. Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time- and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development.

  10. A cell culture assay for the detection of cardiotoxicity

    International Nuclear Information System (INIS)

    An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. The authors propose the use of shock protein formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing shock protein formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of shock proteins. Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes shock protein formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce shock protein synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive

  11. A cell culture assay for the detection of cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Loew-Friedrich, Iv.; von Bredow, F.; Schoeppe, W. (Department of Nephrology, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main (Germany))

    1991-04-01

    An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. The authors propose the use of shock protein formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing shock protein formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of shock proteins. Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes shock protein formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce shock protein synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive.

  12. 5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection.

    Science.gov (United States)

    Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

    2015-01-01

    A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. PMID:25935919

  13. Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy

    NARCIS (Netherlands)

    E.C. van Dalen; H.J.H. van der Pal; H.N. Caron; L.C.M. Kremer

    2006-01-01

    Background The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline dosage schedules (i.e. peak doses and infusion durations) have been studied. Objectives The primary objective was to determine the occ

  14. Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Sachin Diwadkar

    2016-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

  15. Rehabilitative exercise in a rat model of doxorubicin cardiotoxicity.

    Science.gov (United States)

    Hydock, David S; Lien, Chia-Ying; Jensen, Brock T; Parry, Traci L; Schneider, Carole M; Hayward, Reid

    2012-12-01

    The use of exercise to minimize doxorubicin (DOX)-induced cardiotoxicity is gaining attention. However, very few clinically relevant reports exist investigating the effects of exercise performed during and following DOX treatments. The purpose of this study, therefore, was to examine the effects of voluntary wheel running during and following DOX treatment using two models of late-onset DOX cardiotoxicity in the rat. Female Sprague-Dawley rats received either DOX or saline injections using one of two separate treatment regimens. These regimens involved either daily or weekly DOX injections with cumulative doses for both protocols totaling 15 mg/kg. Daily DOX injections were 1 mg/kg and lasted for 15 consecutive days while weekly DOX injections were 2.5 mg/kg and lasted for six consecutive weeks with control animals receiving matched saline injection regimens. Immediately following the initial DOX/saline injection, animals were randomly housed in cages with voluntary running wheels or standard rat cages throughout DOX/saline treatments and continued until reaching 10 weeks. Cardiac function was then assessed using echocardiography and an isolated working heart model, and myosin heavy chain (MHC) isoform distribution was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When compared wth controls, daily DOX treatment resulted in reduced running wheel distances at weeks 2-10 (P blood flow velocities, left ventricular developed pressure and MHC isoform expression. In conclusion, the overall reduced volume of activity during and following daily and weekly DOX treatments attenuated DOX-induced cardiac dysfunction suggesting that low-volume endurance training may be an effective rehabilitative approach in minimizing DOX cardiotoxicity in cancer patients. PMID:23354407

  16. Animal Models in Studies of Cardiotoxicity Side Effects from Antiblastic Drugs in Patients and Occupational Exposed Workers

    Directory of Open Access Journals (Sweden)

    Monica Lamberti

    2014-01-01

    Full Text Available Cardiotoxicity is an important side effect of cytotoxic drugs and may be a risk factor of long-term morbidity for both patients during therapy and also for staff exposed during the phases of manipulation of antiblastic drugs. The mechanism of cardiotoxicity studied in vitro and in vivo essentially concerns the formation of free radicals leading to oxidative stress, with apoptosis of cardiac cells or immunologic reactions, but other mechanisms may play a role in antiblastic-induced cardiotoxicity. Actually, some new cytotoxic drugs like trastuzumab and cyclopentenyl cytosine show cardiotoxic effects. In this report we discuss the different mechanisms of cardiotoxicity induced by antiblastic drugs assessed using animal models.

  17. Berberine attenuates doxorubicin-induced cardiotoxicity in mice.

    Science.gov (United States)

    Zhao, X; Zhang, J; Tong, N; Liao, X; Wang, E; Li, Z; Luo, Y; Zuo, H

    2011-01-01

    This study investigated the effects of berberine, a natural alkaloid, on doxorubicin-induced cardiotoxicity in mice. Mice were injected intraperitoneally with saline 10 ml/kg (n = 10), doxorubicin 2.5 mg/kg (n = 10), 60 mg/kg berberine 1 h before doxorubicin 2.5 mg/kg (n = 10), or 60 mg/kg berberine alone (n = 10) every other day for 14 days. Body weight, general condition and mortality were recorded over the 14-day study period. Electro cardiography was performed before the start of treatment and after 14 days and plasma lactate dehydrogenase (LDH) activity was measured after 14 days. At the end of the study period the heart was excised and examined histologically. An increase in mortality, an initial decrease in body weight, increased LDH activity, prolongation of QRS duration and increased myocardial injury were seen in the doxorubicin-treated group compared with the saline control group. These changes were significantly attenuated by pretreatment with berberine. The study suggests that berberine may have a potential protective role against doxorubicin-induced cardiotoxicity in mice. PMID:22117972

  18. Phytochemicals that counteract the cardiotoxic side effects of cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Anita Piasek

    2009-04-01

    Full Text Available Almost all clinically used antitumor drugs exhibit toxic side effects affecting heart function. Because of cardiotoxicity during anticancer chemotherapy, effective doses of cytostatics have to be limited, which may worsen antitumor efficacy. The cardiotoxicity induced by cytostatics of the anthracycline group in particular results, among others, from massive stimulation of ROS. It has therefore been suggested that some phytochemicals with high antioxidant potential, when administered together with antitumor agents, could decrease the toxic side effects of chemotherapy and reduce the risk of heart failure. This review summarizes findings of studies undertaken to identify edible plants or phytochemicals isolated from them displaying cardioprotective properties during chemotherapy. Such properties have been shown for such foods as grapes, garlic, tomato, spinach, and beetroot. A protective role on the heart is also displayed by melatonin (a hormone synthesized by the pineal gland, but also present in many edible plants, chalcones (precursors of all known flavonoids, some herbal dietary supplements, vitamins A, C, and E, selenium, and semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER. Although to date only a limited number of investigations have been carried out, their results suggest that dietary intervention with antioxidants found in edible plants may be a safe and effective way of alleviating the toxicity of anticancer chemotherapy and preventing heart failure.

  19. Molecular mechanisms of cardiotoxicity of gefitinib in vivo and in vitro rat cardiomyocyte: Role of apoptosis and oxidative stress.

    Science.gov (United States)

    Korashy, Hesham M; Attafi, Ibraheem M; Ansari, Mushtaq A; Assiri, Mohammed A; Belali, Osamah M; Ahmad, Sheik F; Al-Alallah, Ibrahim A; Anazi, Fawaz E Al; Alhaider, Abdulqader A

    2016-06-11

    Gefitinib (GEF) is a multi-targeted tyrosine kinase inhibitor with anti-cancer properties, yet few cases of cardiotoxicity has been reported as a significant side effect associated with GEF treatment. The main purpose of this study was to investigate the potential cardiotoxic effect of GEF and the possible mechanisms involved using in vivo and in vitro rat cardiomyocyte model. Treatment of rat cardiomyocyte H9c2 cell line with GEF (0, 1, 5, and 10μM) caused cardiomyocyte death and upregulation of hypertrophic gene markers, such as brain natriuretic peptides (BNP) and Beta-myosin heavy chain (β-MHC) in a concentration-dependent manner at the mRNA and protein levels associated with an increase in the percentage of hypertrophied cardiac cells. Mechanistically, GEF treatment caused proportional and concentration-dependent increases in the mRNA and protein expression levels of apoptotic markers caspase-3 and p53 which was accompanied with marked increases in the percentage of H9c2 cells underwent apoptosis/necrosis as compared to control. In addition, oxidative stress marker (heme oxygenase-1, HO-1) and the formation of reactive oxygen species were increased in response to GEF treatment. At the in vivo level, treatment of Wistar albino rats for 21days with GEF (20 and 30mg/kg) significantly increased the cardiac enzymes (CK, CKmb, and LDH) levels associated with histopathological changes indicative of cardiotoxicity. Similarly, in vivo GEF treatment increased the mRNA and protein levels of BNP and β-MHC whereas inhibited the antihypertrophoic gene (α-MHC) associated with increased the percentage of hypertrophied cells. Furthermore, the mRNA and protein expression levels of caspase-3, p53, and HO-1 genes and the percentage of apoptotic cells were significantly increased by GEF treatment, which was more pronounced at the 30mg/kg dose. In conclusion, GEF induces cardiotoxicity and cardiac hypertrophy in vivo and in vitro rat model through cardiac apoptotic cell death

  20. Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper

    DEFF Research Database (Denmark)

    Aapro, M; Bernard-Marty, C; Brain, E G C;

    2011-01-01

    and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening...

  1. BNP predicts chemotherapy-related cardiotoxicity and death

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Hasbak, Philip; Kjaer, Andreas

    2014-01-01

    ) or death in a population of anthracycline-treated cancer patients. METHODS: We prospectively followed 333 cancer patients referred to our department for routine monitoring of LVEF with MUGA and measurement of BNP, January-December 2004. Study end points were hospitalization for CHF and death during...... overall death. In multivariate Cox analysis both BNP and LVEF were independent predictors of CHF while age remained the only independent predictor of overall death. CONCLUSION: In cancer patients treated with cardiotoxic chemotherapy both BNP and LVEF can significantly predict subsequent hospitalization...... with CHF. In addition, BNP and not LVEF has a prognostic value in detecting overall death. This prospective study based on the hitherto largest study population supports BNP as a clinical relevant method for monitoring chemotherapy-related cardiac failure and death....

  2. Antiarrhythmic effect of disulfiram in various cardiotoxic models.

    Science.gov (United States)

    Fossa, A A; Carlson, G P

    1983-01-01

    Disulfiram has been shown to decrease the incidence of arrhythmias in rabbits exposed to trichloroethylene. In this study additional cardiotoxic models were used to evaluate disulfiram's antiarrhythmogenicity. Disulfiram (7.5 mg/kg, i.v.) significantly decreased the time spent in arrhythmia compared to control rabbits, 120-180 s following intravenous administration of 4 mg/kg barium chloride. This was very similar to the effect of quinidine sulfate (10 mg/kg, i.v.) used as a positive control. In ouabain-induced arrhythmias, disulfiram treatment (400 mg/kg, i.p.) did not significantly alter the arrhythmogenic or lethal doses of a ouabain infusion. Quinidine, however, significantly increased the arrhythmogenic dose 86% and the lethal dose 44% compared to control. In vitro studies demonstrated that disulfiram (1 X 10(-4) and 3 X 10(-4) M) significantly depressed the myocardial contractility of rat ventricular strips compared to polyethylene glycol 400 controls. PMID:6836004

  3. Dietary trans fats enhance doxorubicin-induced cardiotoxicity in mice.

    Science.gov (United States)

    Mong, Mei-chin; Hsia, Te-chun; Yin, Mei-chin

    2013-10-01

    This study investigated the combined effects of trans fat diet (TFD) and doxorubicin upon cardiac oxidative, inflammatory, and coagulatory stress. TFD increased trans fatty acid deposit in heart (P TFD plus doxorubicin treatment elevated activities of plasminogen activator inhibitor-1, lactate dehydrogenase, and creatine phosphokinase (P TFD or doxorubicin treatment alone (P TFD alone increased cardiac nuclear factor kappa B (NF-κB) activity (P 0.05). Doxorubicin treatment alone augmented cardiac activity, mRNA expression, and protein production of NF-κB and MAPK (P TFD plus doxorubicin treatment further upregulated cardiac expression of NF-κB p65, p-p38, and p-ERK1/2 (P TFD exacerbates doxorubicin-induced cardiotoxicity. PMID:24024564

  4. Life-threatening cardiotoxicity due to chronic oral phenytoin overdose

    Directory of Open Access Journals (Sweden)

    Su Chih-Min

    2009-01-01

    Full Text Available Severe cardiac adverse effects are often related to intravenous phenytoin overdose. However, there is no reported cardiotoxicity resulting from oral overdose of phenytoin. We report a patient with post-traumatic epilepsy who received oral phenytoin for five months and developed life-threatening junctional bradycardia, with his serum phenytoin level reaching up to 91µg/mL. The patient was successfully treated with temporary transvenous pacemaker implantation for his severe bradycardia and hypotension. To our knowledge, our patient had the most serious cardiovascular toxicity ever reported with chronic oral phenytoin overdose. From emergency department (ED physician′s perspective, when a patient with dysrhythmias and cardiovascular collapse is presented to the ED, severe phenytoin overdose should be considered in patients on oral phenytoin with hyperbilirubinemia, hypoalbuminemia, and severe electrolyte imbalance.

  5. Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

    Energy Technology Data Exchange (ETDEWEB)

    Guimarães, Sarita Lígia Pessoa de Melo Machado [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Brandão, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Andrade, Luciana Raposo [Hospital Santa Joana, Recife, PE (Brazil); Maia, Rafael José Coelho [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Markman Filho, Brivaldo [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil)

    2015-09-15

    Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 ({sup 123}I-mIBG) seems to precede the drop in left ventricular ejection fraction. To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline. Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2). Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02). In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with {sup 123}I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity.

  6. Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

    International Nuclear Information System (INIS)

    Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 (123I-mIBG) seems to precede the drop in left ventricular ejection fraction. To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline. Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of 123I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2). Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of 123I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of 123I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of 123I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of 123I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02). In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with 123I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity

  7. Cardiotoxicity of cancer therapeutics: current issues in screening, prevention and therapy

    Directory of Open Access Journals (Sweden)

    Richard Joseph Sheppard

    2013-03-01

    Full Text Available In the context of modern cancer chemotherapeutics, cancer survivors are living longer and being exposed to potential comorbidities related to non-cancer side effects of such treatments. With close monitoring of cancer patients receiving potentially cardiotoxic medical therapies, oncologists and cardiologists alike are identifying patients in both clinical and subclinical phases of cardiovascular disease related to such chemotherapies. Specifically, cardiotoxicity at the level of the myocardium and potential for the development of heart failure are becoming a growing concern with increasing survival of cancer patients.Traditional chemotherapeutic agents used commonly in the treatment of breast cancer and hematologic malignancies, such as anthracyclines and HER-2 antagonists, are well known to be associated with cardiovascular sequelae. Patients often present without symptoms and an abnormal cardiac imaging study performed as part of routine evaluation of patients receiving cardiotoxic therapies. Additionally, patients can present with signs and symptoms of cardiovascular disease months to years after receiving the chemotherapies. As the understanding of the physiology underlying the various cancers has grown, therapies have been developed that target specific molecules that represent key aspects of physiologic pathways responsible for cancer growth. Inhibition of these pathways, such as those involving tyrosine kinases, has lead to the potential for cardiotoxicity as well. In view of the potential cardiotoxicity of specific chemotherapies, there is a growing interest in identifying patients who are at risk of cardiotoxicity prior to becoming symptomatic or developing cardiotoxicity that may limit the use of potentially life-saving chemotherapy agents. Serological markers and novel cardiac imaging techniques have become the source of many investigations with the goal of screening patients for pre-clinical cardiotoxicity. Additionally, studies have

  8. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity.

    Science.gov (United States)

    Lotrionte, Marzia; Biondi-Zoccai, Giuseppe; Abbate, Antonio; Lanzetta, Gaetano; D'Ascenzo, Fabrizio; Malavasi, Vincenzo; Peruzzi, Mariangela; Frati, Giacomo; Palazzoni, Giovanni

    2013-12-15

    The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a systematic review and meta-analysis on incidence and predictors of anthracycline chemotherapy in patients with cancer. Databases were searched for pertinent studies. Meta-analytic pooling with random-effects methods was performed for incidence estimates, while relying on descriptive statistics for prevalence and strength of association of predictors. From 16,054 retrieved citations, 18 studies reporting on 49,017 patients with cancer were included, with 22,815 treated with anthracyclines. After a median follow-up of 9 years, clinically overt cardiotoxicity occurred in 6% (95% confidence interval 3% to 9%), whereas subclinical cardiotoxicity developed in 18% (95% confidence interval 12% to 24%). Appraisal of independent risk factors of cardiotoxicity showed that cumulative anthracycline dose was most consistently reported as an accurate and robust predictor of cardiotoxicity, with an acceptable prognostic role also for chest radiotherapy, African-American ethnicity, very young or very old age, diabetes, hypertension, very high or very low body weight, or severe co-morbidities. In conclusion, despite ongoing refinements in chemotherapy regimens, anthracyclines still pose a significant risk of cardiotoxicity, especially in those requiring a high cumulative dose or chest radiotherapy. PMID:24075281

  9. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

    Directory of Open Access Journals (Sweden)

    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day combined with mildronate (MD, 200 mg/kg/day and PLC (250 mg/kg/day, respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day. IFO significantly increased serum creatinine, blood urea nitrogen (BUN, urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB, lactate dehydrogenase (LDH, intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS in cardiac tissues and significantly decreased adenosine triphosphate (ATP and total carnitine and reduced glutathione (GSH content in cardiac tissues. In carnitine

  10. Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model.

    Science.gov (United States)

    Sayed-Ahmed, Mohamed M; Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4(th), 5(th) and 6(th) groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine

  11. Cardiotoxicity of Senna occidentalis in sheep (Ovis aries)

    Science.gov (United States)

    Lopes, D.I.S.; Sousa, M.G.; Ramos, A.T.; Maruo, V.M.

    2016-01-01

    The cardiotoxicity of Coffee senna (Senna occidentalis) was investigated in sheep that were fed diets containing its seeds, which are recognized as the most poisonous part of such weed. Dianthrone, the main toxic component of S. occidentalis, is known to impair mitochondrial oxidative phosphorylation, leading to myofiber degeneration. In this study, fifteen ewes were fed 0%, 2% or 4% of seeds of S. occidentalis for 63 days. Non-specific markers of myocyte injury and electrocardiograms were undertaken at baseline, and at 14, 35, and 63 days after the animals were first fed the diets, while histopathology of heart samples was performed at the very end of the study. Our results showed an increase in serum AST and LDH over time, while CK-MB did not change significantly. Changes that could be ascribed to myocardial damage were not documented in the electrocardiograms. Cardiac histopathology demonstrated only mild-to-moderate vacuolar degeneration, myofiber edema and disarray, structural disorganization, and cellular necrosis. In conclusion, S. occidentalis caused myocardial fiber degeneration in a dose-dependent fashion, but the electrocardiogram was not able to identify these lesions non-invasively. Because the markers of myofiber injury used in this study lack specificity, they may not be used to support cardiac impairment objectively, despite some of them did change over time. PMID:26894038

  12. The Protective Role of Phenolic Compounds Against Doxorubicin-induced Cardiotoxicity: A Comprehensive Review.

    Science.gov (United States)

    Razavi-Azarkhiavi, Kamal; Iranshahy, Milad; Sahebkar, Amirhossein; Shirani, Kobra; Karimi, Gholamreza

    2016-01-01

    Although doxorubicin (DOX) is among the most widely used anticancer agents, its clinical application is hampered owing to its cardiotoxicity. Adjuvant therapy with an antioxidant has been suggested as a promising strategy to reduce DOX-induced adverse effects. In this context, many phenolic compounds have been reported to protect against DOX-induced cardiotoxicity. The cardioprotective effects of phenolic compounds are exerted via multiple mechanisms including inhibition of reactive oxygen species generation, apoptosis, NF-κB, p53, mitochondrial dysfunction, and DNA damage. In this review, we present a summary of the in vitro, in vivo, and clinical findings on the protective mechanisms of phenolic compounds against DOX-induced cardiotoxicity. PMID:27341037

  13. Anthracycline-related cardiotoxicity: risk factors and therapeutic options in childhood cancers

    Directory of Open Access Journals (Sweden)

    NADIA PUMA

    2008-04-01

    Full Text Available Anthracyclines play an important role in chemotherapeutic regimens for a wide spectrum of childhood tumors, but they can cause cytotoxic damage to cardiac cells, especially in combination with radiotherapy. Furthermore, cardiotoxicity increases with the cumulative dose and may lead to congestive heart failure and cardiomyopathy. Other factors, including age, pre-existing cardiac disease, length of follow-up, gender, route of administration, concomitant exposure to some chemotherapeutic drugs, trisomy 21 and black race, play a role in increasing the risk of cardiac dysfunction. The prevention of anthracycline-induced cardiotoxicity is mandatory as children are expected to survive for decades after being cured of their cancer. The purpose of this work is to point out the major risk factors of cardiotoxicity in children and to summarize some strategies to limit or prevent this complication and to treat the development of acute heart failure.

  14. Partially reversible bortezomib-induced cardiotoxicity: an unusual cause of acute cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Marcelle G. Meseeha

    2015-12-01

    Full Text Available Chemotherapy-associated cardiotoxicity can present as a spectrum from arrhythmia to acute congestive heart failure. Unlike anthracyclines, proteasome inhibitors – for example, bortezomib – are not notorious for causing cardiotoxicity in absence of pre-existing cardiac dysfunction or without concomitant use of other cardiotoxic agents. We describe a 66-year-old woman with end-stage renal disease who developed acute dyspnea hours after a third treatment with bortezomib for IgG kappa myeloma. The Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5 between bortezomib and acute left ventricular dysfunction. Patients receiving proteasome inhibitors should be closely monitored for evidence of cardiac dysfunction during treatment.

  15. The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review

    International Nuclear Information System (INIS)

    The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity. Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses. One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality. This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection

  16. Doxorubicin-induced cardiotoxicity in mice; protection by silymarin

    Directory of Open Access Journals (Sweden)

    Heba Abdelnasser Aniss a, Ashraf El Metwally Said b, Ibrahim Helmy El Sayed c, Camelia AdLy

    2012-07-01

    Full Text Available Background: despite its vast utility in clinical oncology, the use of doxorubicin is limited by a potentially fatal cardiomyopathy and congestive heart failure. Free radical formation and antioxidants depletion are mechanisms proposed for this cardiomyopathy. The aim of this study is to compare the potential antioxidative protective effect of silymarin on doxorubicin-induced cardiotoxicity in experimental mice. Materials and methods: four groups (ten animals in each group of experimental mice were used as follows: Group 1, mice received only saline (intraperitoneally and served as a negative control group; Group 2, mice received doxorubicin (intraperitoneally, 5 mg/kg body weight in three equal injections over a period of two weeks for a cumulative dose of 15 mg/kg body weight; Group 3, mice orally administrated silymarin (200 mg/day/kg body weight respectively, through an intragastric feeding tube over a period of three weeks; Group 4, mice treated orally with silymarin plus intraperitoneally doxorubicin administration with the same protocol of groups 3 and 4. Serum lactate dehydrogenase (LDH, creatine phosphokinase (CPK, aspartate aminotransferase (ASAT, alanine aminotransferase (ALAT, malondialdehyde (MDA, total nitric oxide (NO, cardiac reduced glutathione (GSH, superoxide dismutase (SOD, glutathione peroxidase (GPx and catalase (CAT were measured in all tested groups. Results: doxorubicin elevated the activities of LDH, CPK, AST, ALT, MDA and NO in the cardiac tissue. Cardiac antioxidant enzymes activities SOD and CAT also increased while GPx activity was decreased. Pre-co-treatment with silymarin prevented the changes induced by doxorubicin administration. These findings demonstrate the cardio-protective effect of silymarin on cardiac antioxidant status during doxorubicin induced cardiac damage in mice. Conclusion: silymarin could be recommended for further investigation as potentially new indication for clinical application.

  17. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management.

    Science.gov (United States)

    Curigliano, Giuseppe; Cardinale, Daniela; Dent, Susan; Criscitiello, Carmen; Aseyev, Olexiy; Lenihan, Daniel; Cipolla, Carlo Maria

    2016-07-01

    Answer questions and earn CME/CNE Cancer and heart disease are the leading causes of morbidity and mortality in the industrialized world. Modern treatment strategies have led to an improvement in the chances of surviving a diagnosis of cancer; however, these gains can come at a cost. Patients may experience adverse cardiovascular events related to their cancer treatment or as a result of an exacerbation of underlying cardiovascular disease. With longer periods of survival, late effects of cancer treatment may become clinically evident years or decades after completion of therapy. Current cancer therapy incorporates multiple agents whose deleterious cardiac effects may be additive or synergistic. Cardiac dysfunction may result from agents that can result in myocyte destruction, such as with anthracycline use, or from agents that appear to transiently affect left ventricular contractility. In addition, cancer treatment may be associated with other cardiac events, such as severe treatment-induced hypertension and vasospastic and thromboembolic ischemia, as well as rhythm disturbances, including QTc prolongation, that may be rarely life-threatening. Early and late effects of chest radiation can lead to radiation-induced heart disease, including pericardial disease, myocardial fibrosis, cardiomyopathy, coronary artery disease, valvular disease, and arrhythmias, in the setting of myocardial fibrosis. The discipline of cardio-oncology has developed in response to the combined decision making necessary to optimize the care of cancer patients, whether they are receiving active treatment or are long-term survivors. Strategies to prevent or mitigate cardiovascular damage from cancer treatment are needed to provide the best cancer care. This review will focus on the common cardiovascular issues that may arise during or after cancer therapy, the detection and monitoring of cardiovascular injury, and the best management principles to protect against or minimize cardiotoxicity

  18. Perflurooctanoic acid induces developmental cardiotoxicity in chicken embryos and hatchlings

    International Nuclear Information System (INIS)

    investigate mechanisms of PFOA-induced developmental cardiotoxicity.

  19. MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Holmgren, Gustav; Synnergren, Jane; Andersson, Christian X; Lindahl, Anders; Sartipy, Peter

    2016-08-01

    Anthracyclines, such as doxorubicin, are well-established, highly efficient anti-neoplastic drugs used for treatment of a variety of cancers, including solid tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin has, however, been hampered by severe cardiotoxic side-effects. In order to prevent or reverse negative side-effects of doxorubicin, it is important to find early biomarkers of heart injury and drug-induced cardiotoxicity. The high stability under extreme conditions, presence in various body fluids, and tissue-specificity, makes microRNAs very suitable as clinical biomarkers. The present study aimed towards evaluating the early and late effects of doxorubicin on the microRNA expression in cardiomyocytes derived from human pluripotent stem cells. We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a, miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are differentially expressed upon, and after, treatment with doxorubicin. Investigation of the biological relevance of the identified microRNAs revealed connections to cardiomyocyte function and cardiotoxicity, thus supporting the findings of these microRNAs as potential biomarkers for drug-induced cardiotoxicity. PMID:27033315

  20. Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Issam Salouege

    2014-01-01

    Conclusion: We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.

  1. Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Shao-hui ZHANG; Wen-quan WANG; Jia-ling WANG

    2009-01-01

    Aim: To test the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) on doxorubicin (DOX)-induced cardiotoxicity. Methods: We used neonate rat cardiomyocytes and an acute mouse model of DOX-induced cardiotoxicity to examine the protective effect of THSG.Results: In the mouse model, administration of THSG significantly reduced DOX-induced cardiotoxicity, including animal mortality, histo-pathological changes, and levels of serum creatine kinase (CK) and lactate dehydrogenase (LDH). Moreover, THSG was able to attenuate the increased malondialdehyde (MDA) and decreased reduced glutathione (GSH) caused by DOX. In in vitro studies, THSG 10-300 μmol/L ameliorated DOX-induced cardiomyocyte apoptosis in a concentration-dependent manner. Further studies showed that THSG inhibited reactive oxygen species (ROS) generation and prevented DOX-induced loss of mitochondrial membrane potential, caspase-3 activation and upregulation of Bax protein expression. We observed a protective response against damage after DOX treatment. The level of Bcl-2 protein was increased. Additionally, THSG inhibited a DOX-induced [Ca~(2+)] increase.Conclusion: These results showed that THSG protected against DOX-induced cardiotoxicity by decreasing ROS generation and intracel-lular [Ca~(2+)] and by inhibiting apoptotic signaling pathways.

  2. Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, J.D., E-mail: jennifer.cohen@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Babiarz, J.E., E-mail: joshua.babiarz@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Abrams, R.M., E-mail: rory.abrams@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Guo, L., E-mail: liang.guo@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Kameoka, S., E-mail: sei.kameoka@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Chiao, E., E-mail: eric.chiao@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Taunton, J., E-mail: taunton@cmp.ucsf.edu [Howard Hughes Medical Institute, Cellular and Molecular Pharmacology, University California San Francisco, San Francisco, CA 94158 (United States); Kolaja, K.L., E-mail: kyle.kolaja@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2011-11-15

    Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC{sub 50} in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 {mu}M concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 {mu}M. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity. -- Highlights: Black-Right-Pointing-Pointer Cytoxic effect of sunitinib on human stem cell derived cardiomyocytes Black

  3. Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Zhi-yong [Department of Pharmacy, Affiliated Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); School of Pharmacy, Shanghai Jiao Tong University, 200240 Shanghai (China); Wan, Li-li; Yang, Quan-jun; Han, Yong-long; Li, Yan; Yu, Qi [Department of Pharmacy, Affiliated Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); Guo, Cheng, E-mail: guochengphd@yahoo.com.cn [Department of Pharmacy, Affiliated Sixth People' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China); School of Pharmacy, Shanghai Jiao Tong University, 200240 Shanghai (China); Li, Xiao, E-mail: lixiao3326@yahoo.com.cn [Department of Hematology, Affiliated Sixth people' s Hospital, Shanghai Jiao Tong University, 200233 Shanghai (China)

    2013-10-01

    Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague–Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5 mg/kg) alone, and DOX co-administrated with either 20 or 40 mg/kg nilotinib. Blood was withdrawn at 12 time points till 72 h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC–MS–MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40 mg/kg nilotinib increased the AUC{sub 0–t} and C{sub max} of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40 mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40 mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart.

  4. Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib

    International Nuclear Information System (INIS)

    Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague–Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5 mg/kg) alone, and DOX co-administrated with either 20 or 40 mg/kg nilotinib. Blood was withdrawn at 12 time points till 72 h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC–MS–MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40 mg/kg nilotinib increased the AUC0–t and Cmax of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40 mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40 mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart

  5. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

  6. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography.

    Science.gov (United States)

    Oliveira, Maira S; Melo, Marcos B; Carvalho, Juliana L; Melo, Isabela M; Lavor, Mario Sl; Gomes, Dawidson A; de Goes, Alfredo M; Melo, Marilia M

    2013-01-01

    Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investigated to improve heart function in toxic cardiomyopathy. This work aimed to assess early cardiac function improvement after treatments with either flavonoid extract from Camellia sinensis or mesenchymal stem cells in Dox cardiotoxicity using strain echocardiography. Twenty Wistar rats were randomly assigned to four groups. They received water (control, Dox, Dox + stem cells) or 100 mg/kg C. sinensis extract (Dox + C. sinensis) via gavage, daily, for four weeks. Animals also received saline (control) or 5 mg/kg doxorubicin (Dox, Dox + C. sinensis, Dox + stem cells) via intraperitoneal injection, weekly, for four weeks. Stem cells were injected (3 × 10(6) cells) through tail vein prior the beginning of the experiment (Dox + stem cells). Animals were evaluated by hematological, electrocardiography, echocardiography, and histopathological examinations. Dox cardiotoxicity was only diagnosed with strain echocardiography, detecting a decrease in ventricular function. C. sinensis extract did not prevent ventricular dysfunction induced by Dox. However, strain echocardiography examination revealed that Dox cardiotoxicity was significantly suppressed in rats treated with stem cells. In conclusion, strain echocardiography was able to detect precocity signs of heart failure and stem cell therapy showed cardioprotection effect against Dox cardiotoxicity. PMID:23459697

  7. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Merchant, Michael L. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Division of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40292 (United States); Prough, Russell A. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States); Williams, Jessica D. [University of Cincinnati College of Medicine, Internal Medicine, Cincinnati, OH 45267 (United States); Prabhu, Sumanth D. [Division of Cardiovascular Disease, University of Alabama-Birmingham, Birmingham, AL 35294 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States)

    2015-06-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  8. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    International Nuclear Information System (INIS)

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  9. Cardioprotective effect of Solanum nigrum against doxorubicin induced cardiotoxicity-an experimental study

    OpenAIRE

    Privy Varshney; Pinki Vishwakarma; Monica Sharma; Manish Saini; Shaily Bhatt; Ganesh Singh,; Saxena, K. K.

    2016-01-01

    Background: Solanum nigrum (S.nigrum) a medicinal herb is widely used in the Indian system of medicine for treatment of various ailments. The methanolic extract of S.nigrum berries had shown cardio protective and antioxidant effect. However, so far aqueous extract of S.nigrum is not scientifically evaluated for its cardio protective potential. Hence the present study was designed to find out cardio protective role of S.nigrum against doxorubicin induced cardiotoxicity. Methods: Seventy two...

  10. [Prevention of neuro- and cardiotoxic side effects of tuberculosis chemotherapy with noopept].

    Science.gov (United States)

    Mordyk, A V; Lysov, A V; Kondria, A V; Gol'dzon, M A; Khlebova, N V

    2009-01-01

    The study evaluated clinical efficiency of noopept used to prevent adverse side effects of antituberculous agents. It included 60 patients with newly diagnosed respiratory tuberculosis. Those in group 1 (n = 30) received 10 mg of noopept twice daily during the first month. The treatment promoted functional normalization of vegetative nervous system and antioxidative systems, reduced manifestations of anxiety, decreased frequency of adverse neuro- and cardiotoxic responses to antituberculous drugs. PMID:19565831

  11. Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats

    OpenAIRE

    Issam Salouege; Ridha Ben Ali; Dorra Ben Saïd; Noomen Elkadri; Nadia Kourda; Mohamed Lakhal; Anis Klouz

    2014-01-01

    Objectives: This work is aimed on the study of doxorubicin cardiotoxicity and hepatotoxicity in rats and the evaluation of protective effect of trimetazidine administrated concomitantly with doxorubicin for 3 days. Materials and Methods: Male Wistar rats used were subjected to different types of treatment (3 days); A: Control, B: Doxorubicin treatment and C: Trimetazidine and doxorubicin treatment. After sacrifice, tissular distribution of doxorubicin, cardiac scintigraphy, histological e...

  12. Cardiotoxicity of Doxorubicin. A Study of Methods and Protective Interventions in Rat Models

    OpenAIRE

    Hole, Lisa Drange

    2015-01-01

    Introduction: The clinical use of anthracyclines, like doxorubicin, is a double-edged sword. On one side, anthracyclines play an undisputed key role in the treatment of many neoplastic diseases. On the other side; administration of anthracyclines induces cardiomyopathy and congestive heart failure usually refractory to common medications. Therefore, interventions to reduce the cardiotoxicity of doxorubicin are important and clinically relevant, and research should be performed ...

  13. The ex vivo neurotoxic, myotoxic and cardiotoxic activity of cucurbituril-based macrocyclic drug delivery vehicles

    OpenAIRE

    Oun, Rabbab; Floriano, Rafael S.; Isaacs, Lyle; Rowan, Edward G.; Wheate, Nial J.

    2014-01-01

    The cucurbituril family of drug delivery vehicles have been examined for their tissue specific toxicity using ex vivo models. Cucurbit[6]uril (CB[6]), cucurbit[7]uril (CB[7]) and the linear cucurbituril-derivative Motor2 were examined for their neuro-, myo- and cardiotoxic activity and compared with β-cyclodextrin. The protective effect of drug encapsulation by CB[7] was also examined on the platinum-based anticancer drug cisplatin. The results show that none of the cucurbiturils have statist...

  14. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography

    OpenAIRE

    Maira S. Oliveira; Melo, Marcos B.; Carvalho, Juliana L; Melo, Isabela M; Lavor, Mario SL; Gomes, Dawidson A.; de Goes, Alfredo M; Melo, Marilia M

    2013-01-01

    Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investig...

  15. Doxorubicin-induced carbonylation and degradation of cardiac myosin binding protein C promote cardiotoxicity

    OpenAIRE

    Aryal, Baikuntha; Jeong, Jinsook; Rao, V. Ashutosh

    2014-01-01

    Doxorubicin is one of the most successful anticancer agents. However, 10–30% of all treated patients experience a dose-limiting cardiac adverse event. Oxidative stress is partly responsible for the cardiotoxicity because the heart does not possess required antioxidant mechanisms. Protein oxidation by carbonylation is irreversible and marks proteins for loss of function and degradation. Using proteomics and MS, we identified and investigated cardiac myosin binding protein (MyBPC) as being sele...

  16. Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy.

    Science.gov (United States)

    Li, Shengke; Chan, Judy Yuet-Wa; Li, Yan; Bardelang, David; Zheng, Jun; Yew, Wing Wai; Chan, Denise Pui-Chung; Lee, Simon Ming Yuen; Wang, Ruibing

    2016-08-21

    Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient. PMID:27439674

  17. EVALUATION OF CONCOMITANT TREATMENT OF SIMVASTATIN AND ZINGIBER OFFICINALE IN DOXORUBICIN INDUCED CARDIOTOXICITY IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Khatib N.A

    2011-02-01

    Full Text Available The present study was aimed to evaluate the combined effects of simvastatin (SIM and ethanol extract of Zingiber officinale (ZO in doxorubicin (DOX induced cardiotoxicity in Wistar rats. DOX 10 mg/kg i.p single dose to causes cardiac damage and increases the levels of cardiac biomarker enzymes viz. ALT, AST, LDH and CKMB. In addition, a significant rise in HR, ST- segment and alterations in ECG patterns were observed in DOX treated group. SIM (1.8 mg/kg & 3.6 mg/kg and ZO (200 mg/kg & 400 mg/kg alone and in combination were given to rats as pretreatment for 30 days orally. Pretreatment with SIM and ZO alone significantly (P<0.001 reduced the elevated serum biomarker enzyme levels and ECG alterations in DOX induced cardiotoxic rats. But, combined pretreatment with SIM and ZO normalized the biochemical parameters and ECG changes in DOX induced cardiotoxic rats. The result obtained from the present study indicates concomitant pretreatment of SIM and ZO showed significant improvement than single treatment.

  18. Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

    International Nuclear Information System (INIS)

    In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

  19. Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity

    Science.gov (United States)

    Ojha, Shreesh; Al Taee, Hasan; Goyal, Sameer; Mahajan, Umesh B.; Patil, Chandrgouda R.; Arya, D. S.; Rajesh, Mohanraj

    2016-01-01

    Doxorubicin (DOX) is a potent and widely used anthracycline antibiotic for the treatment of several malignancies. Unfortunately, the clinical utility of DOX is often restricted due to the elicitation of organ toxicity. Particularly, the increased risk for the development of dilated cardiomyopathy by DOX among the cancer survivors warrants major attention from the physicians as well as researchers to develop adjuvant agents to neutralize the noxious effects of DOX on the healthy myocardium. Despite these pitfalls, the use of traditional cytotoxic drugs continues to be the mainstay treatment for several types of cancer. Recently, phytochemicals have gained attention for their anticancer, chemopreventive, and cardioprotective activities. The ideal cardioprotective agents should not compromise the clinical efficacy of DOX and should be devoid of cumulative or irreversible toxicity on the naïve tissues. Furthermore, adjuvants possessing synergistic anticancer activity and quelling of chemoresistance would significantly enhance the clinical utility in combating DOX-induced cardiotoxicity. The present review renders an overview of cardioprotective effects of plant-derived small molecules and their purported mechanisms against DOX-induced cardiotoxicity. Phytochemicals serve as the reservoirs of pharmacophore which can be utilized as templates for developing safe and potential novel cardioprotective agents in combating DOX-induced cardiotoxicity. PMID:27313831

  20. Novel insights in pathophysiology of antiblastic drugs-induced cardiotoxicity and cardioprotection.

    Science.gov (United States)

    Deidda, Martino; Madonna, Rosalinda; Mango, Ruggiero; Pagliaro, Pasquale; Bassareo, Pier P; Cugusi, Lucia; Romano, Silvio; Penco, Maria; Romeo, Francesco; Mercuro, Giuseppe

    2016-05-01

    Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab. Because of this unresolved issue, investigators are searching for alternative therapeutic strategies. In this article, we present state-of-the-art technology with regard to the genomic and epigenetic mechanisms underlying cardiotoxicity and cardioprotection, the role of anticancer in influencing the redox (reduction/oxidation) balance and the function of stem cells in the repair/regeneration of the adult heart. These findings, although not immediately transferable to clinical applications, form the basis for the development of personalized medicine based on the prevention of cardiotoxicity with the use of genetic testing. Proteomics, metabolomics and investigations on reactive oxygen species-dependent pathways, particularly those that interact with the production of NO and energy metabolism, appear to be promising for the identification of early markers of cardiotoxicity and for the development of cardioprotective agents. Finally, autologous cardiac stem and progenitor cells may represent future contributions in the field of myocardial protection and recovery in the context of antiblastic therapy. PMID:27183528

  1. Cardioprotective effect of Urtica parviflora leaf extract against doxorubicin-induced cardiotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    N.R.Barman; Prasanna K.Kar; Prakash K.Hazam; Himadri S.Pal; Arvind Kumar; Sanjib Bhattacharya; Pallab K.Haldar

    2013-01-01

    AIM:The present study evaluated the cardioprotective property of the hydroethanol extract of Urtica parviflora leaf material (EEUP) against doxorubicin-induced cardiotoxicity in rats.METHODS:Cardiotoxicity was produced by doxorubicin administration (15 mg·kg-1 i.p.for 21 days).The rats received EEUP at 200 and 400 mg·kg-1 b.w.(i.p.) daily for 21 days,After 24 h,serum cardiac biomarkers,i.e.creatine phosphokinase (CPK) and lactate dehydrogenase (LDH); serum lipid profiles,like high density lipoprotein (HDL),low density lipoprotein (LDL) and triglyceride (TG); serum biochemical parameters,viz.aspartate aminotransferase (AST),alanine transaminase (ALT) and alkaline phosphatase (ALP); myocardial antioxidant parameters,viz.malondialdehyde (MDA),superoxide dismutase (SOD),catalase (CAT) and reduced glutathione (GSH) were measured.RESULTS:EEUP treatment significantly (P < 0.01) and dose dependently protected the myocardium by decreasing the elevated level of MDA; elevating the diminished levels of GSH,SOD,CAT and HDL,with a concomitant decrease in the elevated levels of HDL,LDL,and TG.EEUP also significantly (P <0.01) reduced the increased activities of AST,ALT,ALP,CPK and LDH.The results revealed that EEUP demonstrated dose dependent cardioprotective efficacy by restoration of the serum biomarkers profile and antioxidant property.CONCLUSION:From the present study,U.parviflora leaf extract showed promising cardioprotective effect against doxorubicin-induced cardiotoxicity in Wistar rats.

  2. A Novel Method for Evaluating the Cardiotoxicity of Traditional Chinese Medicine Compatibility by Using Support Vector Machine Model Combined with Metabonomics

    Science.gov (United States)

    Li, Yubo; Zhou, Haonan; Xie, Jiabin; Ally, Mayassa Salum; Hou, Zhiguo; Xu, Yanyan

    2016-01-01

    Traditional biochemical and histopathological tests have been used to evaluate the safety of traditional Chinese medicine (TCM) compatibility for a long time. But these methods lack high sensitivity and specificity. In the previous study, we have found ten biomarkers related to cardiotoxicity and established a support vector machine (SVM) prediction model. Results showed a good sensitivity and specificity. Therefore, in this study, we used SVM model combined with metabonomics UPLC/Q-TOF-MS technology to build a rapid and sensitivity and specificity method to predict the cardiotoxicity of TCM compatibility. This study firstly applied SVM model to the prediction of cardiotoxicity in TCM compatibility containing Aconiti Lateralis Radix Praeparata and further identified whether the cardiotoxicity increased after Aconiti Lateralis Radix Praeparata combined with other TCM. This study provides a new idea for studying the evaluation of the cardiotoxicity caused by compatibility of TCM.

  3. The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Vefki Gürhan Kadıköylü

    2010-06-01

    Full Text Available Objective: Amifostine (AMI has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations.Materials and Methods: Thirty-six rats were divided into six groups (n=6 in each. Control rats were given intraperitoneal (i.p. serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups. Results: The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA levels increased in MITO groups compared to controls. Catalase and glutathione (GSH levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower. Conclusion: MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO-induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation.

  4. Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis

    OpenAIRE

    Mina Thabet Kelleni; Entesar Farghaly Amin; Aly Mohamed Abdelrahman

    2015-01-01

    Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin pro...

  5. EVALUATION OF CONCOMITANT TREATMENT OF SIMVASTATIN AND ZINGIBER OFFICINALE IN DOXORUBICIN INDUCED CARDIOTOXICITY IN WISTAR RATS

    OpenAIRE

    Khatib N.A; Medi Swathi; Patel Jignesh

    2011-01-01

    The present study was aimed to evaluate the combined effects of simvastatin (SIM) and ethanol extract of Zingiber officinale (ZO) in doxorubicin (DOX) induced cardiotoxicity in Wistar rats. DOX 10 mg/kg i.p single dose to causes cardiac damage and increases the levels of cardiac biomarker enzymes viz. ALT, AST, LDH and CKMB. In addition, a significant rise in HR, ST- segment and alterations in ECG patterns were observed in DOX treated group. SIM (1.8 mg/kg & 3.6 mg/kg) and ZO (200 mg/kg & 400...

  6. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    International Nuclear Information System (INIS)

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  7. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity

    International Nuclear Information System (INIS)

    There is an overwhelming weight of evidence that certifies cardiac troponin (cTn) as the preferred, defacto, translational, safety biomarker for myocardial injury in cardiotoxicity. As well as being the gold standard for cardiac injury in man, it has been widely used for clinical assessment and monitoring of cardiac toxicity in humans being treated for cancer. Furthermore, several dozen preclinical published studies have directly confirmed its effectiveness in laboratory animals for assessment of cardiotoxicity. It is gradually being reverse translated from human into animal use as a safety biomarker. Its use is especially merited whenever there is any safety signal indicating potential cardiotoxicity and its required inclusion as a routine biomarker in preclinical safety studies seems on the horizon. There are some considerations that are unique to use of cTn assays in animals. Lack of awareness of these has, historically, significantly inhibited the introduction of cTn as a safety biomarker in preclinical toxicology. Firstly, cross-species reactivity is usually but not always high. Secondly, there is a background of cardiac injury that needs to be controlled for, including spontaneous cardiomyopathy in Sprague Dawley rats, and inappropriate blood collection methods. Also, there are faster kinetics of clearance in rats than for humans. Also, coincident muscle injury is frequent with cardiotoxicity and requires a skeletal muscle biomarker. Because cTn assays were developed for detection of gross cardiac necrosis, such as occurs with myocardial infarct, the more sensitive assays should be used for preclinical studies. However, analytic sensitivity is higher for standard preclinical studies than for clinical diagnostic testing because of use of concurrent controls and use of batch analysis that eliminates interassay variability. No other biomarker of myocardial injury comes close to cTn in effectiveness, including CK-MB, LDH-1 and 2, myoglobin, and FABP3. In addition

  8. Iodine and tritium labelling of curarizing and cardiotoxic agents. Study of the conformation of toxic polypeptides extracted from snake venom

    International Nuclear Information System (INIS)

    A short review of present-day knowledge on the action mechanism of toxic snake venom polypeptides is followed by a study of the radioactive labelling of some toxic compounds. Those dealt with more especially are Naja nigricollis α toxin and Laticauda semifasciata b erabutoxin, then (+) tubocurarin, a non-peptidic curarizing alkaloid, and two cardiotoxic polypeptides: cytotoxin II and cardiotoxin γ extracted from the venom of Naja naja and Naja nigricollis respectively. The labelling principle is based on the specific fixation of one or more iodine atoms then tritium substitution of the halogen by catalytic hydrogenolysis. As predicted from titration of the aromatic groups the halogenation process, obtained by addition of iodine monochloride, takes place sometimes on the phenolic nuclei and sometimes on the imidazole nuclei, the position of which targets within each sequence has been identified. From results of the study of reactivity towards iodine combined with those of basic titration, the accessibility of several aromatic nuclei has also been defined. Each iodinated polypeptide is then hydrogenolysed in the presence of tritium gas giving a specific activity between 4 and 27 Ci/mmole according to the compound treated. In all cases the biological potential and physical properties of the radioactive material obtained by the above titration process remained intact. An example of the bonding kinetics of short toxins with the partially purified choligenic receptor is given in the special case of tritiated b erabutoxin. The affinity of this toxin for its receptor target is strong, though slightly less so than that of tritiated Naja nigricollis α toxin

  9. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  10. H2S-Donating Doxorubicins May Overcome Cardiotoxicity and Multidrug Resistance.

    Science.gov (United States)

    Chegaev, Konstantin; Rolando, Barbara; Cortese, Daniela; Gazzano, Elena; Buondonno, Ilaria; Lazzarato, Loretta; Fanelli, Marilù; Hattinger, Claudia M; Serra, Massimo; Riganti, Chiara; Fruttero, Roberta; Ghigo, Dario; Gasco, Alberto

    2016-05-26

    Doxorubicin (DOXO) is one of the most effective antineoplastic agents in clinical practice. Its use is limited by acute and chronic side effects, in particular by its cardiotoxicity and by the rapid development of resistance to it. As part of a program aimed at developing new DOXO derivatives endowed with reduced cardiotoxicity, and active against DOXO-resistant tumor cells, a series of H2S-releasing DOXOs (H2S-DOXOs) were obtained by combining DOXO with appropriate H2S donor substructures. The resulting compounds were studied on H9c2 cardiomyocytes and in DOXO-sensitive U-2OS osteosarcoma cells, as well as in related cell variants with increasing degrees of DOXO-resistance. Differently from DOXO, most of the products were not toxic at 5 μM concentration on H9c2 cells. A few of them triggered high activity on the cancer cells. H2S-DOXOs 10 and 11 emerged as the most interesting members of the series. The capacity of 10 to impair Pgp transporter is also discussed. PMID:27120394

  11. Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

    International Nuclear Information System (INIS)

    Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O2 consumption with half-maximal inhibitory concentrations (IC5) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

  12. [Evaluation of acute cardiotoxicity from the combination cyclophosphamide-mitoxantrone-5-fluorouracil (CMF) with Holter ECG].

    Science.gov (United States)

    Doria, G; Cangemi, F; Tosto, A; Platania, F; Circo, A; Motta, S; Tralongo, P; Aiello, R A; Failla, G

    1990-05-01

    By making use of a twenty-four hour Holter monitoring, it as been possible to compute the acute cardiotoxicity of the cyclophosphamide + mitoxantrone + 5-fluorouracil (CNF) association in twenty oncologic patients (pts) each of whom being immune from organic cardiopathy emerging clinically and at their first cycle of chemotherapy. The following parameters have been computed: meaningful changes in the heart frequency; premature atrial and ventricular depolarizations, both as a first appearance and as a clear growth in the number; the ST dislocation entity; malignant ventricular arrhythmias. The administration of CNF at the doses of: 600 mg/m2 of cyclophosphamide, 12 mg/m2 of mitoxantrone and 600 mg/m2 of 5-fluorouracil , has caused a meaningful increase in the heart frequency on 6 pts (30%), an increase of premature atrial depolarization on 4 pts (20%) with an appearance ex novo on 2 pts (10%), an increase of premature ventricular depolarization, without any passing to superior Lown classes, on 2 pts (10%) with an appearance ex novo on 3 pts (15%). Although the results in the study point out a frequency percentage of simple hyperkinetic arrhythmias equal to the 55%, the lack of more serious hyperkinetic arrhythmias and of intense disorders of ventricular repolarization testified to a synergic effect as a determining factor on the acute cardiotoxicity of the previously discussed association, in our opinion. PMID:2234455

  13. In vivo and in vitro assessment of the role of glutathione antioxidant system in anthracycline-induced cardiotoxicity

    Czech Academy of Sciences Publication Activity Database

    Vávrová, A.; Popelová, O.; Štěrba, M.; Jirkovský, E.; Hašková, P.; Mertlíková-Kaiserová, Helena; Geršl, V.; Šimůnek, T.

    2011-01-01

    Roč. 85, č. 5 (2011), s. 525-535. ISSN 0340-5761 Grant ostatní: GA ČR(CZ) GA305/09/0416 Institutional research plan: CEZ:AV0Z40550506 Keywords : anthracycline cardiotoxicity * daunorubicin * glutathione * glutathione peroxidase * glutathione peroxidase Subject RIV: CE - Biochemistry Impact factor: 4.674, year: 2011

  14. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    Guenancia, Charles [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Li, Na [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Hachet, Olivier [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Rigal, Eve [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cottin, Yves [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Dutartre, Patrick; Rochette, Luc [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Vergely, Catherine, E-mail: cvergely@u-bourgogne.fr [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France)

    2015-04-15

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

  15. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

    International Nuclear Information System (INIS)

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

  16. Potential Effects of Pomegranate on Lipid Peroxidation and Pro-inflammatory Changes in Daunorubicin-induced Cardiotoxicity in Rats

    Science.gov (United States)

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Daunorubicin-induced acute cardiotoxicity caused by oxidative stress and free radical formation. Pomegranate possessed a significant in vitro free radical scavenging activity. Therefore, the aim of this study was estimations of the role of pomegranate effects in daunorubicin-induced cardiotoxicity. Methods: A total of 21 Sprague male rats were allocated into three groups, seven animals in each group. Group A: Control group received distilled water. Group B: Treated group with daunorubicin 20 mg/kg via intraperitoneal injection daily for the 12th day for total cumulative dose of 240 mg/kg. Group C: Pretreatment group with pomegranate 25 mg/kg for 6 days orally, then daunorubicin 20 mg/kg administrated concomitantly for the next 6 days with a cumulative dose of 120 mg/kg. Cardiac troponin I([cTn I] pg/ml), malondialdehyde (MDA) (ng/ml), interleukin 17 (IL-17 pg/ml), and cardiac lactate dehydrogenase (LDH) (pm/ml), all these biomarkers were used to measure the severity of cardiotoxicity. Results: Daunorubicin at a dose of 20 mg/kg lead to pronounced cardiac damage that reflected on through elevations of serum cTn and serum LDH levels significantly P Pomegranate pretreatment demonstrated a significant cardioprotection from daunorubicin-induced cardiotoxicity; it attenuated the cardiac damage through reduction of cTn, LDH, MDA, and serum IL-17 level significantly P Pomegranate demonstrated significant cardioprotection in daunorubicin-induced cardiotoxicity through reduction of oxidative stress, lipid peroxidation, pro-inflammatory, and cardiac injury biomarkers. PMID:27413516

  17. Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats

    Directory of Open Access Journals (Sweden)

    Dragojević-Simić Viktorija

    2013-01-01

    Full Text Available Background/Aim. Amifostine (AMI is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX in male Wistar rats. Methods. AMI (300 mg/kg ip was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv. The evaluation of DOXinduced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme α-hydroxybutirate dehydrogenase - α- HBDH, as well as the histopathological and ultrastructural analysis of the heart tissue. Results. AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and α-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 ± 18.37 vs 167.70 ± 44.24; 771.42 ± 161.99 vs 1057.00 ± 300.00; 3230.00 ± 1031.73 vs 4243.10 ± 904.06; 202.57 ± 42.46 vs 294.90 ± 80.20 UI/l, respectively, and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS from 2.62 ± 0.51 to 1.62 ± 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg. The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats. Conclusion. AMI provided a significant protection against DOX

  18. Methanolic leaf extract of Parkia biglobosa protects against doxorubicin-induced cardiotoxicity in rats

    Directory of Open Access Journals (Sweden)

    K Komolafe

    2013-07-01

    Full Text Available Summary. Aqueous-methanolic leaf extract of Parkia biglobosa (PBE was investigated for its effects on doxorubicin-induced cardiotoxicity and phytochemical constituents. Adult albino rats weighing (200g-220g were pretreated with ramipril (10mg/kg/day or PBE (25 mg/kg, 50 mg/kg, 75 mg/kg and 100 mg/kg/day by gavage for 14 consecutive days before receiving single intraperitoneal (i.p dose of doxorubicin (15mg/kg on the 13th day.  Animals were sacrificed twenty hours after the last administration and the heart homogenate and serum were analysed for biochemical indices of oxidative stress, tissue markers of cardiotoxicity and serum lipid profile. Results revealed the presence of saponins, tannins, cardiac glycosides, total flavonoid (121.30±3.2 mg Quercetin equivalent, total phenol (55.40±1.2 mg gallic acid equivalent, and dose-dependent reduction of iron-induced MDA formation in rat’s heart by PBE. Doxorubicin caused significant elevations (P<0.05 of cardiac MDA, serum creatine kinase-MB, lactate dehydrogenase, aspartate aminotransferase and dyslipidemia while causing significant reduction in the levels/or activities of cardiac reduced glutathione, glutathione peroxidase, glutathione S-transferase  and superoxide dismutase. Pretreatment with PBE prevented most of these derangements in a comparable manner to that of ramipril. It may be concluded from the study that PBE can protect against doxorubicin-induced toxicity probably via antioxidative and antihyperlipidemic mechanisms.Industrial relevance. The use of plants and plant-products will continue to find relevance in the treatment and management of numerous diseases and /or pathological conditions especially in the low-income countries due to the ready accessibility and inexpensive nature of these materials.  Parkia biglobosa (Jacq. Benth., is a common and widespread tree in tropical Africa where it is used for timber and food and also with popular ethnomedicinal applications in the

  19. Modulation of synergistic cardiotoxicity of doxorubicin and radiation therapy by propionyl l-carnitine

    International Nuclear Information System (INIS)

    Combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy. However, the combination of Doxorubicin (DOX) and irradiation (IRR) may be more cardiotoxic than either agent. Propionyl-L-carnitine (PLC) is a naturally occurring derivative of L-carnitine that has been considered in the treatment of many forms of cardiomyopathies. In this study, the possible mechanism (S) whereby PLC couls protect against DOX and/or IRR-induced cardiomyopathy were carried out. Administration of DOX as a single dose (5 mg/Kg) or cumulative dose (15 and 25 mg/kg divided into 3 and 5 equal doses 5 mg/kg each, every other day) resulted in significant and dose dependent increase in serum cardiac enzymes (CPK, GOT and LDH) in rat, MDA level and nitric oxide in heart tissue and dose dependent decrease in the antioxidant enzymes (SOD) and GSHPx). Whole body irradiation (2 Gy) induced similar effect to DOX. Combination of DOX and IRR resulted in marked elevation in cardiac enzymes and MDA level and remarkable decrease in the antioxidant enzymes . PLC (250 mg/kg, for 9 days) before DOX and /or IRR induced significant increase in the activity of SOD and GSHPx and significantly decreased the level of MDA and nitric oxide in rat cardiac tissue and the activity of cardiac enzymes in rat serum. Also, DOX-induced dose dependent increase in AC/FC ratio above the normal value (0.4) in serum and heart tissue. Combination of DOX and IRR increased the ratio. Administration of PLC to DOX and/or IRR resulted in partial reversal of DOX induced increase in the AC/FC ratio except for the highest cumulative dose (25 mg/kg) in serum. Dox induced dose-dependent increase in DOX concentration in serum and heart tissue. Administration of PLC decreased DOX concentration in heart with an increase in DOX concentration in serum. IRR did not alter DOX concentration. Worth mentioning os that PLC had no effect on the antitumor activity of DOX and/ or IRR in solid

  20. Multiple impairments of cutaneous nociceptor function induced by cardiotoxic doses of Adriamycin in the rat.

    Science.gov (United States)

    Boros, Krisztina; Jancsó, Gábor; Dux, Mária; Fekécs, Zoltán; Bencsik, Péter; Oszlács, Orsolya; Katona, Márta; Ferdinandy, Péter; Nógrádi, Antal; Sántha, Péter

    2016-09-01

    Besides their deleterious action on cardiac muscle, anthracycline-type cytostatic agents exert significant neurotoxic effects on primary sensory neurons. Since cardiac sensory nerves confer protective effects on heart muscle and share common traits with cutaneous chemosensitive nerves, this study examined the effects of cardiotoxic doses of adriamycin on the function and morphology of epidermal nerves. Sensory neurogenic vasodilatation, plasma extravasation, and the neural CGRP release evoked by TRPV1 and TRPA1 agonists in vitro were examined by using laser Doppler flowmetry, the Evans blue technique, and ELISA, respectively. Carrageenan-induced hyperalgesia was assessed with the Hargreaves method. Immunohistochemistry was utilized to study cutaneous innervation. Adriamycin treatment resulted in profound reductions in the cutaneous neurogenic sensory vasodilatation and plasma extravasation evoked by the TRPV1 and TRPA1 agonists capsaicin and mustard oil, respectively. The in vitro capsaicin-, but not high potassium-evoked neural release of the major sensory neuropeptide, CGRP, was markedly attenuated after adriamycin treatment. Carrageenan-induced inflammatory hyperalgesia was largely abolished following the administration of adriamycin. Immunohistochemistry revealed a substantial loss of epidermal TRPV1-expressing nociceptive nerves and a marked thinning of the epidermis. These findings indicate impairments in the functions of TRPV1 and TRPA1 receptors expressed on cutaneous chemosensitive nociceptive nerves and the loss of epidermal axons following the administration of cardiotoxic doses of adriamycin. Monitoring of the cutaneous nociceptor function in the course of adriamycin therapy may well be of predictive value for early detection of the deterioration of cardiac nerves which confer protection against the deleterious effects of the drug. PMID:27342418

  1. Ozone-Oxidative Preconditioning Prevents Doxorubicin-induced Cardiotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Livan Delgado-Roche

    2014-08-01

    Full Text Available Objectives: Induced dilated cardiomyopathy is the main limitation of the anti-cancer drug doxorubicin, which causes oxidative stress and cardiomyocyte death. As ozone therapy can activate the antioxidant systems, this study aimed to investigate the therapeutic efficacy of ozone-oxidative preconditioning against doxorubicin-induced cardiotoxicity. Methods: The study was carried out from September 2013 to January 2014. Sprague-Dawley rats were randomly distributed in the following treatment groups: Group 1 were treated with 2 mg/kg intraperitoneal (i.p. of doxorubicin twice a week for 50 days; Group 2 were treated with 0.3 mg of ozone/oxygen mixture at 50 μg/ mL of ozone per 6 mL of oxygen by rectal insufflation and then treated with doxorubicin; Group 3 were treated as Group 2 but only with the oxygen, and Group 4 were treated with oxygen first, and then with sodium chloride i.p. as the control group. Results: The results showed that ozone therapy preserved left ventricle morphology which was accompanied by a reduction of serum pro-brain natriuretic peptide levels. The cardioprotective effects of ozoneoxidative preconditioning were associated with a significant increase (P <0.05 of antioxidant enzymes activities and a reduction of lipid and protein oxidation (P <0.05. Conclusion: Ozone-oxidative preconditioning prevents doxorubicin-induced dilated cardiomyopathy through an increase of antioxidant enzymes and a reduction of oxidised macromolecules. This establishes the background for future studies to determine if ozone therapy can be used as a complementary treatment for attenuating doxorubicin-induced cardiotoxicity in cancer patients.

  2. The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity

    Science.gov (United States)

    Lazzarini, Edoardo; Balbi, Carolina; Altieri, Paola; Pfeffer, Ulrich; Gambini, Elisa; Canepa, Marco; Varesio, Luigi; Bosco, Maria Carla; Coviello, Domenico; Pompilio, Giulio; Brunelli, Claudio; Cancedda, Ranieri; Ameri, Pietro; Bollini, Sveva

    2016-01-01

    The anthracycline doxorubicin (Dox) is widely used in oncology, but it may cause a cardiomyopathy with bleak prognosis that cannot be effectively prevented. The secretome of human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to significantly reduce ischemic cardiac damage. Here it is shown that, following hypoxic preconditioning, hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis of cardiomyocytes and cardiac progenitor cells, two major features of Dox cardiotoxicity. Mechanistic studies with mouse neonatal ventricular cardiomyocytes (mNVCM) reveal that hAFS-CM inhibition of Dox-elicited senescence and apoptosis is associated with decreased DNA damage, nuclear translocation of NF-kB, and upregulation of the NF-kB controlled genes, Il6 and Cxcl1, promoting mNVCM survival. Furthermore, hAFS-CM induces expression of the efflux transporter, Abcb1b, and Dox extrusion from mNVCM. The PI3K/Akt signaling cascade, upstream of NF-kB, is potently activated by hAFS-CM and pre-treatment with a PI3K inhibitor abrogates NF-kB accumulation into the nucleus, modulation of Il6, Cxcl1 and Abcb1b, and prevention of Dox-initiated senescence and apoptosis in response to hAFS-CM. These results support the concept that hAFS are a valuable source of cardioprotective factors and lay the foundations for the development of a stem cell-based paracrine treatment of chemotherapy-related cardiotoxicity. PMID:27444332

  3. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    International Nuclear Information System (INIS)

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dtmax of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  4. Peroxisome Proliferator-Activated Receptor-α Inhibition Protects Against Doxorubicin-Induced Cardiotoxicity in Mice.

    Science.gov (United States)

    Rahmatollahi, Mahdieh; Baram, Somayeh Mahmoodi; Rahimian, Reza; Saeedi Saravi, Seyed Soheil; Dehpour, Ahmad Reza

    2016-07-01

    Doxorubicin is an effective chemotherapeutic drug against a considerable number of malignancies. However, its toxic effects on myocardium are confirmed as major limit of utilization. PPAR-α is highly expressed in the heart, and its activation leads to an increased cardiac fatty acid oxidation and cardiomyocyte necrosis. This study was performed to adjust the hypothesis that PPAR-α receptor inhibition protects against doxorubicin-induced cardiac dysfunction in mice. Male Balb/c mice were used in this study. Left atria were isolated, and their contractility was measured in response to electrical field stimulation in a standard organ bath. PPAR-α activity was measured using specific PPAR-α antibody in an ELISA-based system coated with double-strand DNA containing PPAR-α response element sequence. Moreover, cardiac MDA and TNF-α levels were measured by ELISA method. Following incubation with doxorubicin (35 µM), a significant reduction in atrial contractility was observed (P < 0.001). Pretreatment of animals with a selective PPAR-α antagonist, GW6471, significantly improved doxorubicin-induced atrial dysfunction (P < 0.001). Furthermore, pretreatment of the mice with a non-selective cannabinoid agonist, WIN55212-2, significantly decreased PPAR-α activity in cardiac tissue, subsequently leading to significant improvement in doxorubicin-induced atrial dysfunction (P < 0.001). Also, GW6471 and WIN significantly reduced cardiac MDA and TNF-α levels compared with animals receiving doxorubicin (P < 0.001). The study showed that inhibition of PPAR-α is associated with protection against doxorubicin-induced cardiotoxicity in mice, and cannabinoids can potentiate the protection by PPAR-α blockade. Moreover, PPAR-α may be considered as a target to prevent cardiotoxicity induced by doxorubicin in patients undergoing chemotherapy. PMID:26082188

  5. Transient occult cardiotoxicity in children receiving continuous beta-agonist therapy

    Institute of Scientific and Technical Information of China (English)

    Christopher L Carroll; Melinda Coro; Allison Cowl; Kathleen A Sala; Craig M Schramm

    2014-01-01

    Background: Continuous beta-agonist therapy, typically in the form of inhaled albuterol, is the first line therapy for the treatment of acute and severe bronchospasm in children. Although this treatment is commonly used, concerns about cardiotoxicity have been raised. We aimed to investigate the cardiotoxic effects of continuous beta-agonist therapy in children. Methods: We conducted a retrospective review of children admitted to the intensive care unit (ICU) between May 2008 and April 2009, who were treated with continuous beta-agonist therapy (intravenous and nebulized). Results: Twenty of the 36 children treated with continuous albuterol had repeated serum troponin-T and lactate levels measured. Eleven patients (55%) were also treated with continuous intravenous terbutaline. Elevated levels of troponin-T levels were found in 25% of children, and elevated lactate levels were found in 60%. However, all returned to normal levels within 48 hours of ICU admission, despite continued beta-agonist therapy. No children experienced arrhythmias during therapy. There was no association between intravenous terbutaline use and elevated troponin-T [odds ratio (OR), 1.3; 95% CI, 0.2-10.3] or with elevated serum lactate (OR, 0.6; 95% CI, 0.1-3.7). There was also no association between elevated troponin-T or lactate and ICU or hospital length of stay. Conclusions: In this small study, a significant proportion of children had elevated serum troponin-T and lactate levels while receiving inhaled continuous beta-agonist therapy, irrespective of intravenous therapy. However, these abnormal values all returned to normal within 48 hours of ICU admission and were not associated with increased duration of hospitalization.

  6. Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Zhe; SONG Xiao-dong; XIN Ying; WANG Xiao-jian; YU Hui; BAI Yong-yi; LIU Jun-hao; ZHANG Chan-na; HUI Ru-tai

    2009-01-01

    Background The use of doxorubicin(DOX)is limited by its dose-dependent cardiotoxicity.Reactive oxygen species (ROSs)play an important role in the pathological process of DOX-induced cardiotoxicity.The aim of this study was to evaluate the protective effect of chrysoeriol,a flavone compound,against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.Methods We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay,Hoechst33258 staining and measurement of lactate dehydrogenase(LDH)release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells.To find out the mechanism of this protective effect,we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GPx).Furthermore,we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTI assay.Results The results of MTT assay,Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death.Chrysoeriol at a dose of 20 pg/ml notably reduced intracellular ROS,decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels.Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.

  7. Obravnava hematoloških bolnikov, zdravljenih s kardiotoksičnimi zdravili: Management of haematological pateints treated with cardiotoxic drugs:

    OpenAIRE

    Dolenc, Jure; Koželj, Mirta; Zver, Samo

    2008-01-01

    Background Recent advances in the treatment of malign haematological deseases with chemotherapy have led to significant improvement in prognosis and qualityof life of the pacients. The same drugs can lead to development of serious cardiac side effects, especially the syndrome of heart failure. Anthracycline drugs are best known for their cardiotoxicity, the role of otherdrugs is less well understood. Conclusions Predisposing factors to cardiotoxicity should be taken into consideration when de...

  8. Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

    International Nuclear Information System (INIS)

    Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca2+ flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation of

  9. A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology.

    Science.gov (United States)

    Spallarossa, Paolo; Maurea, Nicola; Cadeddu, Christian; Madonna, Rosalinda; Mele, Donato; Monte, Ines; Novo, Giuseppina; Pagliaro, Pasquale; Pepe, Alessia; Tocchetti, Carlo G; Zito, Concetta; Mercuro, Giuseppe

    2016-05-01

    Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment. This manuscript, which is specifically addressed to the cardiologist who has not accumulated much experience in the field of cancer therapy, focuses on several topics, that is old and new mechanisms of cardiac toxicity, late cardiac toxicity, the importance of overall risk assessment, the key role of a cardiology consult before starting cancer therapy, and the pros and cons of primary and secondary prevention programmes. PMID:27183529

  10. Evaluation of the Cardiotoxicity of Mitragynine and Its Analogues Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

    OpenAIRE

    Lu, Jun; Wei, Heming; Wu, Jianjun; Jamil, Mohd Fadzly Amar; Tan, Mei Lan; Adenan, Mohd Ilham; Wong, Philip; Shim, Winston

    2014-01-01

    Introduction Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other che...

  11. Biochemical and histopathological studies on the protective effect of propionyl-L-carnitine against cardiotoxicity in rats

    International Nuclear Information System (INIS)

    In many kinds of thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding tissue. it has been hypothesized that irradiation of whole body may be an additional risk factor for the development of early radiation -induced cardiotoxicity. Adriamycin (ADR)is a widely used anthacycline anticancer agent. the development of cumulative dose-related cardiotoxicity forms the major limitation of clinical ADR use combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy . However, the combination of ADR and irradiation (IRR) could precipitate the unexpected expression of congestive heart failure. oxidative lesions induced by IRR and ADR could represent one of the pathogenic factors of myocardial dysfunction . The aim of this study is to investigate whether changes in the plasma levels of plasma endothelin-1 (ET-1) total nitrate/nitrite NO (x) have a relationship with the development of ADR and or IRR -induced cardiotoxicity. Also, propionyl-l-carnitine (PLC), a natural short chain derivative of l-carntine, has been evaluated in this study as a potential protective agent against adr and/or IRR-indused cardiotoxicity using biochemical and histopathological approaches. This data obtained revealed that , whole body irradiation and ADR induced a statistically significant increase in plasma ET-1, NO(x) and NO(x) in cardiac tissues. combination of IRR and ADR induced significant increase in ET-1 and NO(x) compared to each group alone . Preadminstration of plc showed protective effect against the increase in ET-1 and NO (x) . Light microscopic exmination revealed myocardial degenerative changes, which were more frequently encounted as the duration of ADR administration was increased. also whole body γ -irradiation 2 gy induced myocardial capillary damage, interstitial oedema between muscle fibers, myolsis or necrosis and inflammatory cells

  12. Scientific validation of cardioprotective attribute by standardized extract of Bombyx mori against doxorubicin-induced cardiotoxicity in murine model

    OpenAIRE

    Khan, Masood S.; Mhaveer Singh, Mhaveer; Khan, Mohammad A.; Arya, D. S.; Ahmad, Sayeed

    2014-01-01

    Doxorubicin (DOX) is an excellent antineoplastic agent used for the treatment of hematological and solid malignancies. The aqueous extract of Bombyx mori (BMAE) contains amino acids and some flavonoids with obvious cardioprot ective effect. The aim of this study was to investigate the possible protective effect of BMAE against DOX-induced cardiotoxicity and its underlying mechanisms on murine model. The metabolic profiling of BMAE was carried out by Ultra Performance Liquid Chromatography-Mas...

  13. Effects of Lagenaria Sicessaria Fruit Juice on Lipid Profile and Glycoprotein Contents in Cardiotoxicity Induced by Isoproterenol in Rats

    OpenAIRE

    Upaganlawar, Aman; Balaraman, R

    2012-01-01

    This study investigated antihyperlipidemic effects of Lagenaria siceraria fruit juice (LSFJ) in isoproterenol (ISO)induced cardiotoxicity in rats. Rats treated with ISO (200 mg/kg, s.c.) showed a significant increase in the levels of triglycerides, cholesterol, and free fatty acids, in both serum and heart tissue. An increase in the levels of phospholipids, low-density lipoprotein, and very low-density lipoprotein-cholesterol, and decrease in high-density lipoprotein-cholesterol in serum and ...

  14. Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.

    Science.gov (United States)

    Clements, Mike; Millar, Val; Williams, Angela S; Kalinka, Sian

    2015-11-01

    More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form of functional assays to predict the potential for drug-induced ECG abnormalities in vivo. Cardiotoxicity can also be structural in nature, so a full and efficient assessment of cardiac liabilities for new chemical entities should account for both these phenomena. As well as providing a more appropriate nonclinical model for in vitro cardiotoxicity testing, human stem cell-derived cardiomyocytes offer an integrated system to study drug impact on cardiomyocyte structure as well as function. Employing human embryonic stem cell-derived cardiacmyocytes (hESC-CMs) on 3 assay platforms with complementary insights into cardiac biology (multielectrode array assay, electrophysiology; impedance assay, cell movement/beating; and high content analysis assay, subcellular structure) we profiled a panel of 13 drugs with well characterized cardiac liabilities (Amiodarone, Aspirin, Astemizole, Axitinib, AZT, Bepridil, Doxorubicin, E-4031, Mexiletine, Rosiglitazone, Sunitinib, Sibutramine, and Verapamil). Our data show good correlations with previous studies and reported clinical observations. Using multiparameter phenotypic profiling techniques we demonstrate the dynamic relationship that exists between functional and structural toxicity, and the benefits of this more holistic approach to risk assessment. We conclude by showing for the first time how the advent of transparent MEA plate technology enables functional and structural cardiotoxic responses to be recorded from the same cell population. This approach more directly links changes in morphology of the hESC-CMs with recorded electrophysiology signatures, offering even greater insight into the wide range of potential drug impacts on cardiac physiology, with a throughput that is more amenable to early drug discovery. PMID:26259608

  15. Human epidermal growth factor antagonists and cardiotoxicity-A short review of the problem and preventative measures.

    Science.gov (United States)

    Dias, A; Claudino, W; Sinha, R; Perez, C A; Jain, D

    2016-08-01

    The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer. Although trastuzumab is devoid of the classical toxicities associated with chemotherapy, one of the major concerns noted is the occurrence of symptomatic and asymptomatic cardiotoxicity (decline in left-ventricular-ejection-fraction (LVEF). Additionally, newer HER2 therapies such as Lapatinib, Pertuzumab and Ado-trastuzumab (TDM1) are either approved or are being evaluated in clinical trials for cancer therapy. Targeted therapies against HER2 have led to revolutionary strides in breast cancer research and treatment. With the concern of cardiotoxicity caused by these agents, new treatment strategies for preventing cardiac side effects need to be developed. In this review, we discuss the proposed mechanisms of HER 2 antagonist-induced cardiotoxicity and the ways to prevent it. PMID:27338847

  16. Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: A biochemical, electrocardiographic and histopathological study

    Directory of Open Access Journals (Sweden)

    A. H. M. Viswanatha Swamy

    2013-01-01

    Full Text Available Objectives: Cardioprotective activity of alcoholic extract of Saraca indica (SI bark was investigated against cyclophosphamide induced cardiotoxicity. Materials and Methods: Cardiotoxicity was induced in Wistar rats by administering cyclophosphamide (200 mg/kg, i.p. single injection on first day of experimental period. Saraca indica (200 and 400 mg/kg, p.o. was administered immediately after administration of cyclophosphamide on first day and daily for 10 days. The general observations and mortality were measured. Results: Cyclophosphamide administration significantly (p < 0.05 increased lipid peroxidation (LPO and decreased the levels of antioxidant markers such as reduced glutathione (GSH, superoxide dismutase (SOD and catalase (CAT. Cyclophosphamide elevated the levels of biomarker enzymes like creatine kinase (CK, creatine kinase isoenzyme MB (CK-MB, lactate dehydrogenase (LDH, aspartate transaminase (AST, alanine transaminase (ALT and alkaline phosphatase (ALP. Further, the cyclophosphamide treated rats showed changes in electrocardiogram (ECG along with increased levels of cholesterol and triglycerides. Treatment with Saraca indica significantly (p < 0.05 reversed the status of cardiac biomarkers, ECG, oxidative enzymes and lipid profile in cyclophosphamide induced cardiotoxicity. Potential cardioprotective effect of Saraca indica was supported by histopathological examination that reduced severity of cellular damage of the myocardium. Conclusion: The biochemical, ECG and histopathology reports support the cardioprotective effect of Saraca indica which could be attributed to antioxidant activity.

  17. High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

    Energy Technology Data Exchange (ETDEWEB)

    Chapalamadugu, Kalyan C.; Panguluri, Siva K. [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); Bennett, Eric S. [Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Kolliputi, Narasaiah [Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Tipparaju, Srinivas M., E-mail: stippara@health.usf.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States)

    2015-01-01

    Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD{sub 90}; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co

  18. High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

    International Nuclear Information System (INIS)

    Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD90; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co-regulated in

  19. Role of oxidative stress in cocaine-induced cardiotoxicity and cocaine-related death.

    Science.gov (United States)

    Cerretani, D; Fineschi, V; Bello, S; Riezzo, I; Turillazzi, E; Neri, M

    2012-01-01

    Cocaine-induced cardiovascular disorders such as hypertension, thrombosis, myocardial dysfunction, cardiac dysrhythmias and endocarditis have received widespread attention in the context of cocaine abuse. The number of sudden deaths from cardiac causes, including myocardial infarction, ventricular tachyarrhythmia or aortic dissection, is also increasing. This manuscript will highlight the recent employment of study about cocaine cardiotoxicity and oxidative stress. Evidence has revealed that cardiac oxidative stress is a prominent early event of cocaine administration, which severely compromises the cardiac antioxidant cellular system and causes cardiac antioxidant cellular system injuries. Oxidative damage such as peroxidation of membrane phospholipids and depletion of nonenzymatic antioxidants such as glutathione have been found in the myocardium of chronic cocaine-treated animals and in patients. The data indicate that cocaine administration compromised the heart's antioxidant defense system. About the mechanisms involved in the cellular damage, the evidence that cocaine causes apoptosis in the heart comes from in vivo study. In animals model after short-term and long term-cocaine administration, the investigators demonstrates the role of Reactive Oxygen Species as a trigger of cardiac injury induced by cocaine. Cocaine also increased infiltration of inflammatory cells in the heart, and apoptotic cells were predominantly found near inflammatory cells. The role of oxidative stress in cocaine-induced apoptosis in the heart is wide studied and documented. PMID:22856662

  20. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

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    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  1. Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs.

    Science.gov (United States)

    Mercurio, Valentina; Pirozzi, Flora; Lazzarini, Edoardo; Marone, Giancarlo; Rizzo, Paola; Agnetti, Giulio; Tocchetti, Carlo G; Ghigo, Alessandra; Ameri, Pietro

    2016-06-01

    Heart failure (HF) is a complication of oncological treatments that may have dramatic clinical impact. It may acutely worsen a patient's condition or it may present with delayed onset, even years after treatment, when cancer has been cured or is in stable remission. Several studies have addressed the mechanisms of cancer therapy-related HF and some have led to the definition of disease models that hold valid for other and more common types of HF. Here, we review these models of HF based on the cardiotoxicity of antineoplastic drugs and classify them in cardiomyocyte-intrinsic, paracrine, or potentially secondary to effects on cardiac progenitor cells. The first group includes HF resulting from the combination of oxidative stress, mitochondrial dysfunction, and activation of the DNA damage response, which is typically caused by anthracyclines, and HF resulting from deranged myocardial energetics, such as that triggered by anthracyclines and sunitinib. Blockade of the neuregulin-1/ErbB4/ErbB2, vascular endothelial growth factor/vascular endothelial growth factor receptor and platelet-derived growth factor /platelet-derived growth factor receptor pathways by trastuzumab, sorafenib and sunitinib is proposed as paradigm of cancer therapy-related HF associated with alterations of myocardial paracrine pathways. Finally, anthracyclines and trastuzumab are also presented as examples of antitumor agents that induce HF by affecting the cardiac progenitor cell population. PMID:27103426

  2. Possible Radio-Protective Efficiency of Bee-Pollen against Radiation Induced Cardiotoxicity in Male Rats

    International Nuclear Information System (INIS)

    The Present study was designed to evaluate the possible radio-protective effect of Bee-Pollen (B.P.) against radiation-induced cardiotoxicity. B.P. was orally administrated to rats in a concentration of 2 mg/ kg body wt/ day for 7 days before as well as during exposure to fractionated doses of gamma-radiation (1 Gy 3 times week for a period of 2 weeks to attain a cumulative dose of 6 Gy). The protective effect of B.P. was monitored by assessment of activities of lactate dehydrogenase (LDH), aspartate transaminase (AST) and creatin phosphatase (CPK) in serum and superoxide dismutase activity (SOD), glutathione peroxidase activity (GSHPX) and reduced glutathione (GSH) and concentrations of malonaldehyde (MDA) and nitric oxide (NO) were determined in heart tissues.In addition, certain metals (Fe, Cu, Zn and Ca) were also measured in serum, selenium (Se) was detected in heart tissues.Results revealed that when B.P. was given before as well as during irradiation, it ameliorated the increases in serum enzyme activities (LDH, AST and CPK), decreases in the cardiac antioxidants, an increase in MDA and NO concentrations and metals disturbances in irradiated rats. The present results demonstrated that B.P. has antioxidant properties and could exert radio-protective effect. These, might be related to its balanced nutritional antioxidant components

  3. Acute cardiotoxicity evaluation of the marine biotoxins OA, DTX-1 and YTX.

    Science.gov (United States)

    Ferreiro, Sara F; Carrera, Cristina; Vilariño, Natalia; Louzao, M Carmen; Santamarina, Germán; Cantalapiedra, Antonio G; Botana, Luis M

    2015-04-01

    Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA) and dynophysistoxins (DTXs) are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP). Yessotoxins (YTXs) are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene) channel activity and in vivo using electrocardiogram (ECG) recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term. PMID:25826053

  4. Acute Cardiotoxicity Evaluation of the Marine Biotoxins OA, DTX-1 and YTX

    Directory of Open Access Journals (Sweden)

    Sara F. Ferreiro

    2015-03-01

    Full Text Available Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA and dynophysistoxins (DTXs are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP. Yessotoxins (YTXs are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene channel activity and in vivo using electrocardiogram (ECG recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term.

  5. Protective effect of lagenaria siceraria against doxorubicin induced cardiotoxicity in wistar rats

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    Singh M. K

    2012-06-01

    Full Text Available In the present study it was aimed to evaluate the combined effect of simvastatin (SIM and hydro alcoholic seeds extract of Lagenaria siceraria (H.L.S.S.E. in doxorubicin (DOX induced cardio toxicity in Wister rats. DOX 10 mg/ kg i.p. single dose was given to cause cardiac damage and the levels of cardiac biomarker enzyme viz LDH, CK, CK-MB and total protein & antioxidants superoxide dismutase (SOD, catalase (CAT, glutathione (GSH and lipid peroxidation (LPO were observed and in the end of experiment histopathology was carried out for heart. SIM (15 mg/kg and (H.L.S.S.E. 200 & 400mg/kg were given in combination with DOX 10 mg/ kg i.p. single dose to rats at the 30th day of experiment and as a pretreatment for 29 days (H.L.S.S.E. 200 & 400mg/kg were given orally. Pretreatment with SIM and (H.L.S.S.E significantly (P<0.001 reduced the elevated cardiac toxicity biomarker enzyme level and raised the level of antioxidants viz CAT, GSH, SOD and decrease LPO in the extract treated groups as compared to the disease control group .In the histopathological studies H.L.S.S.E and SIM showed protection against myocardial toxicity induced by doxorubicin. The result obtained from the present study indicates that the pretreatment of SIM and H.L.S.S.E may significantly reduse the (DOX induced cardiotoxicity.

  6. Synthetic catecholamine triggers β1-adrenergic receptor activation and stimulates cardiotoxicity via oxidative stress mediated apoptotic cell death in rats: Abrogating action of thymol.

    Science.gov (United States)

    Meeran, M F Nagoor; Jagadeesh, G S; Selvaraj, P

    2016-05-01

    Nowadays, there are considerable interests in the studies which are more connected with the impact of natural antioxidants against the free radical mediated damage in biological systems. Cardiotoxicity is one of the lethal manifestations of cardiovascular diseases (CVDs) which have been associated with the incidence of apoptotic cell death due to oxidative stress. We evaluated the impact of thymol, a dietary monoterpene phenol on isoproterenol (ISO), a synthetic catecholamine and a β1-adrenergic receptor agonist in rats. Thymol (7.5 mg/kg body weight) was pre and co-treated into male albino Wistar rats daily for a period of 7 days. Induction of cardiotoxicity was done by the subcutaneous administration of ISO (100 mg/kg body weight) into rats on 6th and 7th day. Cardiotoxicity in rats was confirmed by the increased levels/activity of serum troponin-T and creatine kinase in the serum alongwith decreased activity of creatine kinase in the heart. ISO induced cardiotoxic rats also showed a significant increase in the concentrations of lipid peroxidation products and a significant decrease in the activities/levels of antioxidants in the myocardium whereas Reverse Transcription Polymerase Chain Reaction study revealed an increased expression of caspase-8, caspase-9 and Fas genes along with a decreased expression of Bcl-xL gene in the myocardium. Thymol pre and co-treated ISO induced cardiotoxic rats showed considerable protective effects on all the biochemical parameters studied. Histopathological and in vitro findings are found in line with our biochemical findings. Thus, the present study revealed that thymol counters ISO induced cardiotoxicity by inhibiting oxidative stress and apoptotic cell death in rats by virtue of its potent antioxidant property. PMID:26996544

  7. Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

    International Nuclear Information System (INIS)

    Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300 mg/m2), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3 mg/kg/week for 10 weeks); DEX (60 mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300 mg/m2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug

  8. Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

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    Zheng K

    2015-08-01

    Full Text Available Ke Zheng,1 Rui Li,2 Xiaolei Zhou,2 Ping Hu,2 Yaxin Zhang,2 Yunmei Huang,3 Zhuo Chen,2 Mingdong Huang2 1College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China; 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People’s Republic of China; 3Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Abstract: Doxorubicin (DOX is an effective chemotherapy drug used to treat different types of cancers. However, DOX has severe side effects, especially life-threatening cardiotoxicity. We herein report a new approach to reduce the toxicity of DOX by embedding DOX inside human serum albumin (HSA. HSA is further fused by a molecular biology technique with a tumor-targeting agent, amino-terminal fragment of urokinase (ATF. ATF binds with a high affinity to urokinase receptor, which is a cell-surface receptor overexpressed in many types of tumors. The as-prepared macromolecule complex (ATF–HSA:DOX was not as cytotoxic as free DOX to cells in vitro, and was mainly localized in cell cytosol in contrast to DOX that was localized in cell nuclei. However, in tumor-bearing mice, ATF–HSA:DOX was demonstrated to have an enhanced tumor-targeting and antitumor efficacy compared with free DOX. More importantly, histopathological examinations of the hearts from the mice treated with ATF–HSA:DOX showed a significantly reduced cardiotoxicity compared with hearts from mice treated with free DOX. These results demonstrate the feasibility of this approach in reducing the cardiotoxicity of DOX while strengthening its antitumor efficacy. Such a tumor-targeted albumin packaging strategy can also be applied to other antitumor drugs. Keywords: amino-terminal fragment of urokinase, urokinase receptor, drug carrier, human serum albumin, doxorubicin, cytotoxicity

  9. Inhibition of lipid peroxidation by IRFI 042, a vitamin E analogue, decreases monensin cardiotoxicity in chicks

    International Nuclear Information System (INIS)

    Monensin, a well-known ionophore antibiotic, may cause severe damage in myocardial cells. We investigated whether IRFI 042, a new analogue of vitamin E, may block lipid peroxidation in myocardial cells and in turn protect against monensin toxicity. Monensin toxicity was induced by repeated daily administration of the ionophore antibiotic (150 mg/kg/day for 7 days). Sham animals received by oral gavages only a saline solution and were used as controls. All animals were randomized to receive concomitantly by oral gavages IRFI 042 (20 mg/kg) or its vehicle. The experiment lasted 8 days. Survival rate, heart lipid peroxidation, studied by means of thiobarbituric acid-reactive substances (TBARs) levels, cardiac expression of endothelial nitric oxide (e-NOS) and histological analysis of the heart were performed. Monensin administration caused a decrease in survival rate. Mortality appeared following the second monensin injection and at day 7 caused a survival rate of 20%. Thereafter, no further mortality was observed. IRFI 042 administration improved survival rate. Injection of the ionophore antibiotic resulted in a marked cardiac lipid peroxidation and in a significant reduction in cardiac e-NOS message and protein expression. IRFI 042 decreased heart TBARs levels (Monensin + vehicle = 6.5 ± 0.8 nmol/mg; Monensin + IRFI 042 = 3.2 ± 1.1 nmol/mg; P < 0.001) and increased e-NOS message and protein expression. Histological analysis showed that IRFI 042 improved myocardial cells damage and enhanced the depressed e-NOS expression in chick heart samples following monensin administration. Our data suggest that IRFI 042 is a promising drug to reduce monensin cardio-toxicity in chicks

  10. Endosulfan-induced cardiotoxicity and free radical metabolism in rats: the protective effect of vitamin E

    International Nuclear Information System (INIS)

    Endosulfan is widely used in insect control and it is absorbed by both humans and animals through ingestion, inhalation and percutaneously. The aim of this work was to study antioxidant enzyme system which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and malondialdehyde (MDA), the end product of lipid peroxidation and ultrastructural changes that might occur in the heart tissue of adult male Wistar rats as a result of endosulfan intoxication. Vitamin E (200 mg/kg, twice a week), endosulfan (2 mg/kg, per day, once a day in corn oil) and vitamin E (200 mg/kg, twice a week)+endosulfan (2 mg/kg, per day, once a day in corn oil) combination were given to rats (n = 10/group) orally via gavage for 6 weeks. SOD, GPx, CAT activities and MDA level increased in the endosulfan-treated group heart tissue compared to control group (P < 0.01, P < 0.01, P < 0.05 and P < 0.01, respectively). SOD, GPx activities and MDA level decreased in the vitamin E + endosulfan-treated group compared to endosulfan-treated group (P < 0.05, P < 0.05 and P < 0.05, respectively). Decrease of CAT activity was not significant statistically in the vitamin E + endosulfan-treated group compared to endosulfan-treated group. CAT activity increased in the vitamin E + endosulfan treated group compared to control group (P < 0.05). Increase of SOD, GPx activities and MDA levels were not significant statistically in the vitamin E + endosulfan-treated group compared to control group. In electron microscopic investigations while cytoplasmic edema and swelling and vacuolization of mitochondria of myocardial cells in endosulfan-treated group was observing, only a weak swelling of mitochondria of myocardial cells in vitamin E + endosulfan-treated group was observed. We conclude that vitamin E significantly reduce endosulfan-induced cardiotoxicity in rats

  11. Protective role of antioxidant vitamin E and catechin on idarubicin-induced cardiotoxicity in rats

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    Kalender S.

    2002-01-01

    Full Text Available Idarubicin is an anthracycline antibiotic extensively used in acute leukemia. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of idarubicin. Vitamin E (200 IU kg-1 week-1, catechin (200 mg kg-1 week-1, idarubicin (5 mg kg-1 week-1, idarubicin + vitamin E (200 IU kg-1 week-1, and idarubicin + catechin (200 mg kg-1 week-1 combinations were given to male Sprague-Dawley rats weighing 210 to 230 g (N = 6/group. Idarubicin-treated animals exhibited a decrease in body and heart weight, a decrease in myocardial contractility, and changes in ECG parameters (P<0.01. Catechin + idarubicin- and vitamin E + idarubicin-treated groups exhibited similar alterations, but changes were attenuated in comparison to those in cardiac muscle of idarubicin-treated rats (P<0.05. Superoxide dismutase and catalase activity was reduced in the idarubicin-treated group (P<0.05. Glutathione peroxidase levels were decreased in the idarubicin-treated group (P<0.05 and reached maximum concentrations in the catechin- and catechin + idarubicin-treated groups compared to control (P<0.01. Malondialdehyde activity was decreased in the catechin + idarubicin-treated groups compared to control and increased in the other groups, reaching maximum concentrations in the vitamin E-treated group (P<0.01. In electron microscopy studies, swelling of the mitochondria and dilatation of the sarcoplasmic reticulum of myocytes were observed in the idarubicin-treated groups. In groups that were given idarubicin + vitamin E and idarubicin + catechin, the only morphological change was a weak dilatation of the sarcoplasmic reticulum. We conclude that catechin and vitamin E significantly reduce idarubicin-induced cardiotoxicity in rats.

  12. Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis

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    Mina Thabet Kelleni

    2015-01-01

    Full Text Available Doxorubicin (DOX is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05 cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.

  13. Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich's carcinoma.

    Science.gov (United States)

    Ali, Shimaa A; Zaitone, Sawsan A; Moustafa, Yasser M

    2015-08-01

    This study aimed to test whether boswellic acids add to the antitumor effects of doxorubicin against solid tumors of Ehrlich's ascites carcinoma (EAC) grown in mice, and to investigate the protective effects of boswellic acids against doxorubicin-induced cardiotoxicity. Sixty-four female Swiss albino mice bearing EAC solid tumors were distributed among 8 groups as follows: group 1, EAC control group; group 2, doxorubicin treatment group [mice were injected with doxorubicin (6 mg·(kg body mass)(-1)·week(-1)) for 3 weeks]; groups 3-5, these mice were treated with boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively; groups 6-8, these mice were treated with a combination of doxorubicin and boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively, for 3 weeks. The results indicated that boswellic acids synergized the antitumor activity of doxorubicin. Doxorubicin-treated mice showed elevated serum activities of lactate dehydrogenase and creatine kinase isoenzyme MB as well as cardiac malondialdehyde. Further, decreases in cardiac levels of reduced glutathione, superoxide dismutase, and catalase activities were observed. These effects were accompanied by an increase in cardiac expression of caspase 3. Thus, treatment with boswellic acids attenuated doxorubicin-evoked disturbances in the above-mentioned parameters, highlighting antioxidant and antiapoptotic activities. Therefore, boswellic acids could be potential candidates for ameliorating the cardiotoxicity of doxorubicin. PMID:26230640

  14. Effects of Lagenaria Sicessaria Fruit Juice on Lipid Profile and Glycoprotein Contents in Cardiotoxicity Induced by Isoproterenol in Rats

    Science.gov (United States)

    Upaganlawar, Aman; Balaraman, R.

    2012-01-01

    This study investigated antihyperlipidemic effects of Lagenaria siceraria fruit juice (LSFJ) in isoproterenol (ISO)induced cardiotoxicity in rats. Rats treated with ISO (200 mg/kg, s.c.) showed a significant increase in the levels of triglycerides, cholesterol, and free fatty acids, in both serum and heart tissue. An increase in the levels of phospholipids, low-density lipoprotein, and very low-density lipoprotein-cholesterol, and decrease in high-density lipoprotein-cholesterol in serum and phospholipid levels in the heart were observed. ISO intoxicated rats also showed a significant decrease in the activities of lecithin: cholesterol acyl transferase, whereas lipoprotein lipase was found to be increased. Administration of LSFJ (400 mg/kg, p.o.) for 30 consecutive days and challenged with ISO on day 29th and 30th significantly attenuated these alterations and restored the levels of serum and heart lipids along with lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the protective effect of LSFJ during ISO-induced cardiotoxicity in rats. PMID:22736897

  15. Total Flavonoids from Clinopodium chinense (Benth. O. Ktze Protect against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo

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    Rong Chang Chen

    2015-01-01

    Full Text Available Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. This study aims to investigate the protective effects of the total flavonoids from Clinopodium chinense (Benth. O. Ktze (TFCC against doxorubicin- (DOX- induced cardiotoxicity. Male rats were intraperitoneally injected with a single dose of DOX (3 mg/kg every 2 days for three injections. Heart samples were collected 2 weeks after the last DOX dose and then analyzed. DOX delayed body and heart growth and caused cardiac tissue injury, oxidative stress, apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. Similar experiments in H9C2 cardiomyocytes showed that doxorubicin reduced cell viability, increased ROS generation and DNA fragmentation, disrupted mitochondrial membrane potential, and induced apoptotic cell death. However, TFCC pretreatment suppressed all of these adverse effects of doxorubicin. Signal transduction studies indicated that TFCC suppressed DOX-induced overexpression of p53 and phosphorylation of JNK, p38, and ERK. Studies with LY294002 (a PI3K/AKT inhibitor demonstrated that the mechanism of TFCC-induced cardioprotection also involves activation of PI3K/AKT. These findings indicated the potential clinical application of TFCC in preventing DOX-induced cardiac oxidative stress.

  16. Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity: Potential role of tannins in cancer chemotherapy

    International Nuclear Information System (INIS)

    Doxorubicin, an anthracycline antibiotic, is widely used in the treatment of various solid tumors including breast cancer. However, its use is limited due to a variety of toxicities including cardiotoxicity. The present study aimed to evaluate the effect of tannic acid, a PARG/PARP inhibitor and an antioxidant, on doxorubicin-induced cardiotoxicity in H9c2 embryonic rat heart myoblasts and its anti-cancer activity in MDA-MB-231 human breast cancer cells as well as in DMBA-induced mammary tumor animals. Doxorubicin-induced cardiotoxicity was assessed by measurement of heart weight, plasma LDH level and histopathology. Bcl-2, Bax, PARP-1 and p53 expression were examined by western blotting. Our results show that tannic acid prevents activation of PARP-1, reduces Bax and increases Bcl-2 expression in H9c2 cells, thus, preventing doxorubicin-induced cell death. Further, it reduces the cell viability of MDA-MB-231 breast cancer cells, increases p53 expression in mammary tumors and shows maximum tumor volume reduction, suggesting that tannic acid potentiates the anti-cancer activity of doxorubicin. To the best of our knowledge, this is the first report which shows that tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity both in vitro (H9c2 and MDA-MB-231 cells) as well as in in vivo model of DMBA-induced mammary tumor animals.

  17. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F1 mouse model

    International Nuclear Information System (INIS)

    Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F1 mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F1 mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F1 mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F1 male mice.

  18. Scientific validation of cardioprotective attribute by standardized extract of Bombyx mori against doxorubicin-induced cardiotoxicity in murine model.

    Science.gov (United States)

    Khan, Masood S; Singh, Mhaveer; Khan, Mohammad A; Arya, D S; Ahmad, Sayeed

    2014-01-01

    Doxorubicin (DOX) is an excellent antineoplastic agent used for the treatment of hematological and solid malignancies. The aqueous extract of Bombyx mori (BMAE) contains amino acids and some flavonoids with obvious cardioprotective effect. The aim of this study was to investigate the possible protective effect of BMAE against DOX-induced cardiotoxicity and its underlying mechanisms on murine model. The metabolic profiling of BMAE was carried out by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and the amino acid profiling by HPLC method using fluorescence detector (HPLC-FLD). The biochemical parameter like caspase-3, tumor necrosis factor-alpha (TNF-α), interleukin -6 (IL-6), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA) were studied. Tissue damage was further evaluated by histopathological studies. The metabolic profiling of BMAE exhibited presence of quercetin 7-O-ß-D-glucoside, kaempferol 7-O-ß-D-glucopyranoside, coumaric acid glucoside, 2-hydroxy-nonadecanoic acid and 9,12-dihydroxy stearic acid as important constituents. The amino acid profile by HPLC-FLD showed presence of 17 amino acids. The BMAE showed prominent free radical scavenging activity when assessed by the H2O2 and super-oxide method. The results of present investigation showed protection against DOX-induced oxidative stress (lipid peroxidation), by reverting activities of apoptotic markers (caspase-3 and TNF-α), cardiac markers (CK-MB and LDH activities) as well as pro-inflammatory marker IL-6 followed by oral administration of BMAE. In addition, results of histopathology also supported well the above results. It was observed that BMAE protects DOX-induced cardiotoxicity by virtue of its antioxidants possibly by flavonoids and amino acids. PMID:26417320

  19. Cardioprotective Activity of Ethanolic Extract of Citrus grandis (L. Osbeck Peel on Doxorubicin and Cyclophosphamide Induced Cardiotoxicity in Albino Rats

    Directory of Open Access Journals (Sweden)

    Samir Baniya

    2015-07-01

    Full Text Available The present study was designed to evaluate the cardioprotective potential of Citrus grandis (L. Osbeck (CGO peel extract in rats. Citrus grandis (L. Osbeck peel extract was evaluated for protection against cyclophosphamide (200 mg/kg body wt., i.p. and doxorubicin (15 mg/kg body wt., i.p. induced cardiotoxicity in male albino rats. Biomarkers like lactate dehydrogenase (LDH, alanine aminotransaminase (ALT, aspartate aminotransaminase (AST, alkaline phosphatase (ALP, total cholesterol (TC, triglyceride (TG and creatinine kinase (CK-MB along with heart weight index and antioxidant enzymes was considered to determine the cardioprotective property. Histopathological study was also carried out on heart of experimental animals. The CGO peel extract was found to contain alkaloids, flavonoids, steroids and triterpenoids, saponins, phenolic compounds and tannin as chemical constituents. Cyclophosphamide (CYP and doxorubicin (DOX treated groups exhibited significant increase in LDH, ALT, AST, ALP, TC, TG and CK-MB level and decrease in catalase (CAT, superoxide dimutase (SOD when compared to control group. Pretreatment with different doses of CGO significantly reduced the serum biomarkers and increased the tissue antioxidant level when compared to DOX and CYP alone treated groups. Moreover, treatment with CGO also improved CYP induced changes in histopathology of heart which may be due to its antioxidant property. The Citrus grandis (L. Osbeck exerted protective effect against CYP and DOX induced cardiotoxicity in rats, which may be due its lipid lowering and antioxidant properties. These findings might be helpful to understand the beneficial effects of CGO extract against myocardial injury although further study is needed to confirm its mechanism.

  20. Cardioprotective effect of Vedic Guard against doxorubicin-induced cardiotoxicity in rats: A biochemical, electrocardiographic, and histopathological study

    Directory of Open Access Journals (Sweden)

    Basavaraj C Koti

    2013-01-01

    Full Text Available Background: Vedic Guard is a polyherbal formulation used in the treatment of various ailments, however, is not scientifically assessed for its effect on doxorubicin-induced cardiotoxicity. Objective: To find out the preventive role of Vedic Guard against doxorubicin-induced myocardial toxicity in rats. Materials and Methods: Cardiotoxicity was produced by doxorubicin (15 mg/kg for 2 weeks. Vedic Guard (270 mg/kg, orally was administered as pre-treatment for 2 weeks and then for 2 weeks alternated with doxorubicin (DXR. The general observations, mortality, histopathology, biomarker like lactate dehydrogenase (LDH, creatine phosphokinase (CPK, aspartate aminotransferase (AST, alanine transaminase (ALT, electrocardiographic (ECG parameters, antioxidants such as glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT were monitored after 3 weeks of last dose. Results: The repeated administration of DXR causes cardiomyopathy associated with an antioxidant deficit. Pre-treatment with Vedic Guard decreases serum enzyme viz LDH, CPK, AST, and ALT levels to that of normal values. Vedic Guard significantly protected the myocardium from the toxic effect of DXR, by increasing the levels of antioxidants such as GSH, SOD, and CAT and decreased the elevated level of malondialdehyde. The study shows significant alteration of ECG pattern in DXR administered rats. The characteristic findings were elevation of ST segment, reduction in P waves, QRS complex, and R-R interval. Vedic Guard showed a protective effect against DXR-induced altered ECG pattern. It also reduced the severity of cellular damage of the myocardium confirmed by histopathology. Conclusion: The results of the present study indicated c ardioprotective effect of Vedic Guard might be attributed to its antioxidant activity.

  1. Stem Cell Therapy and Breast Cancer Treatment: Review of Stem Cell Research and Potential Therapeutic Impact Against Cardiotoxicities Due to Breast Cancer Treatment

    OpenAIRE

    Sharp, Thomas E.; George, Jon C.

    2014-01-01

    A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually ...

  2. Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: Role of oxidative stress and apoptosis

    International Nuclear Information System (INIS)

    Doxorubicin (DXR) has been used in variety of human malignancies for decades. Despite its efficacy in cancer, clinical usage is limited because of its cardiotoxicity, which has been associated with oxidative stress and apoptosis. Carbon monoxide-releasing molecules (CORMs) have been shown to reduce the oxidative damage and apoptosis. The present study investigated the effects of CORM-2, a fast CO-releaser, against DXR-induced cardiotoxicity in mice using biochemical, histopathological and gene expression approaches. CORM-2 (3, 10 and 30 mg/kg/day) was administered intraperitoneally (i.p.) for 10 days and terminated the study on day 11. DXR (20 mg/kg, i.p.) was injected before 72 h of termination. Mice treated with DXR showed cardiotoxicity as evidenced by elevation of serum creatine kinase (CK) and lactate dehydrogenase (LDH), tissue malondialdehyde (MDA), caspase-3 and decrease the level of total antioxidant status (TAS) in heart tissues. Pre- and post-treatment with CORM-2 (30 mg/kg, i.p.) elicited significant improvement in CK, LDH, MDA, caspase-3 and TAS levels. Histopathological studies showed that cardiac damage with DXR has been reversed with CORM-2 + DXR treatment. There was dramatic decrease in hematological count in DXR-treated mice, which has been improved with CORM-2. Furthermore, there was also elevation of mRNA expression of heme oxygenase-1, hypoxia inducible factor-1 alpha, vascular endothelial growth factor and decrease in inducible-nitric oxide synthase expression upon treatment with CORM-2 that might be linked to cardioprotection. These data suggest that CORM-2 treatment provides cardioprotection against acute doxorubicin-induced cardiotoxicity in mice and this effect may be attributed to CORM-2-mediated antioxidant and anti-apoptotic properties.

  3. Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study

    International Nuclear Information System (INIS)

    Radiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry. BACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions

  4. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

    2013-04-15

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  5. Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.

    Science.gov (United States)

    Granados-Principal, Sergio; El-Azem, Nuri; Pamplona, Reinald; Ramirez-Tortosa, Cesar; Pulido-Moran, Mario; Vera-Ramirez, Laura; Quiles, Jose L; Sanchez-Rovira, Pedro; Naudí, Alba; Portero-Otin, Manuel; Perez-Lopez, Patricia; Ramirez-Tortosa, Mcarmen

    2014-07-01

    Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin-associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty-six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week), doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations. PMID:24727461

  6. Cardiotoxicity of acetogenins from Persea americana occurs through the mitochondrial permeability transition pore and caspase-dependent apoptosis pathways.

    Science.gov (United States)

    Silva-Platas, Christian; García, Noemí; Fernández-Sada, Evaristo; Dávila, Daniel; Hernández-Brenes, Carmen; Rodríguez, Dariana; García-Rivas, Gerardo

    2012-08-01

    Acetogenins are cell-membrane permeable, naturally occurring secondary metabolites of plants such as Annonaceae, Lauraceae and other related phylogenic families. They belong to the chemical derivatives of polyketides, which are synthesized from fatty acid precursors. Although acetogenins have displayed diverse biological activities, the anti-proliferative effect on human cancer cells has been widely reported. Acetogenins are inhibitors of complex I in the electron transport chain therefore they interrupt ATP synthesis in mitochondria. We tested a new acetogenins-enriched extract from the seed of Persea americana in order to investigate if any toxicity was induced on cardiac tissue and determine the involved mechanism. In isolated perfused heart we found that contractility was completely inhibited at an accumulative dose of 77 μg/ml. In isolated cardiomyocytes, the acetogenins-enriched extract induced apoptosis through the activation of the intrinsic pathway at 43 μg/ml. In isolated mitochondria, it inhibited complex I activity on NADH-linked respiration, as would be expected, but also induced permeability transition on succinate-linked respiration. Cyclosporine A, a known blocker of permeability transition, significantly prevented the permeability transition triggered by the acetogenins-enriched extract. In addition, our acetogenins-enriched extract inhibited ADP/ATP exchange, suggesting that an important element in phosphate or adenylate transport was affected. In this manner we suggest that acetogenins-enriched extract from Persea americana could directly modulate permeability transition, an entity not yet associated with the acetogenins' direct effects, resulting in cardiotoxicity. PMID:22733015

  7. High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters.

    Science.gov (United States)

    Emer, E; Yildiz, O; Seyrek, M; Demirkol, S; Topal, T; Kurt, B; Sayal, A

    2016-05-01

    The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats. PMID:26199281

  8. A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais? Is cardiolipin the target of local anesthetic cardiotoxicity?

    Directory of Open Access Journals (Sweden)

    XiaoFeng Shen

    2010-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os anestésicos locais são amplamente utilizados na prevenção ou na reversão de dor aguda e no tratamento de dor crônica. A reação de cardiotoxicidade induzida pelos anestésicos locais é um evento acidental sem terapia farmacológica, exceto a infusão de intralípides relatados recentemente cujo mecanismo de ação ainda não é bem compreendido. CONTEÚDO: A cardiolipina, um fosfolipídio aniônico, desempenha papel relevante na determinação de reação respiratória mitocondrial, metabolismo de ácidos graxos e apoptose celular. A disfunção do metabolismo energético mitocondrial é sugerida em associação com a cardiotoxicidade dos anestésicos locais, a partir de um estudo in vitro de que ela talvez se deva a fortes ligações eletrostáticas entre os anestésicos locais e a cardiolipina na membrana mitocondrial. Não há, contudo, evidência experimental. Portanto, levantamos a hipótese de que as interações anestésico-cardiolipina sejam o principal determinante associado à reação de cardiotoxicidade, o que pode ser estabelecido com a adoção de métodos teóricos e biológicos estruturais. Esse modelo de interação nos daria uma pista sobre o mecanismo da cardiotoxicidade dos anestésicos locais, visando a futuras pesquisas na área de desenvolvimento de fármacos de prevenção a esse evento na prática clínica. CONCLUSÕES: A interação entre a cardiolipina mitocondrial e os anestésicos locais pode ser a principal fonte de sua cardiotoxicidade, em função de seus efeitos sobre o metabolismo energético e o estado eletrostático.BACKGROUND AND OBJECTIVES: Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well

  9. Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

    2015-05-15

    Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

  10. Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

    International Nuclear Information System (INIS)

    Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

  11. General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid.

    OpenAIRE

    Ghibu, Steliana; Delemasure, Stéphanie; Richard, Carole; Guilland, Jean-Claude; Martin, Laurent; Gambert, Ségolène; Rochette, Luc; Vergely, Catherine

    2012-01-01

    To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) a...

  12. Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Jun Lu

    Full Text Available Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa, a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs.The rapid delayed rectifier potassium current (IKr, L-type Ca2+ current (ICa,L and action potential duration (APD were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90 (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.

  13. Protective effect of dexrazoxane on daunorubicin cardiotoxicity.%临床用药研究右丙亚胺对柔红霉素所致心脏毒性的防治作用

    Institute of Scientific and Technical Information of China (English)

    庞缨; 陈军初; 谢玮; 冯莹

    2011-01-01

    目的 探讨右丙亚胺对柔红霉素所致心脏毒性的防治作用.方法 观察10例急性非淋巴细胞白血病患者,在接受含柔红霉素化疗时合用右丙亚胺后心电图及左室射血分数(EF)的变化.并与未使用右丙亚胺的对照组12例作比较.结果 在柔红霉素方案化疗1个疗程后,右丙亚胺组与对照组心电图异常发生率分别为10.0%(1/10)和25.0%(3/12),左室EF下降超过10%的发生率分别为10%(1/10)和16.7%(2/12),两者差异均无统计学意义.3个疗程后,右丙亚胺组与对照组心电图异常发生率分别为20.0%(2/10)和50.0%(6/12),左室EF分数下降超过10%的发生率分别为20.0%(2/10)和41.7%(5/12)(P<0.01).对产生心脏毒性的8例患者,在其后再次接受含柔红霉素方案化疗时联合使用右丙亚胺,2个疗程结束后有5例患者异常心电图转为正常,4例患者EF分数得到恢复,无一例心脏损害加重.结论 右丙亚胺对柔红霉素所致心脏毒性的发生有一定的防护作用,并且对已经形成的损害有一定的修复作用.%Objective To investigate the protective effects of dexrazoxane on daunorubicin cardiotoxicity.Methods Patients with acute non - lymphoid leukemia were enrolled into chemotherapy group ( Group A, 12 cases ) and dexrazoxane combined chemotherapy group ( Group B, 10 cases ). ECG and evaluation of ejection fraction ( EF ) were carried out after each course of chemotherapy. Results After the 1st course of chemotherapy, the incidences of ECG abnormal were 25.0% ( 3/12 ) and 10. 0% ( 1/10 ) in the Group A and B, respectively. Meanwhile, incidences of EF reduced by more than 10% were 16.7% ( 2/12 ) and 10. 0% ( 1/10 ) in Group A and B, respectively. No significant difference was revealed between the two groups. After the 3rd course of chemotherapy, the incidences of abnormal ECG were 50. 0%( 6/12 ) and 20. 0% ( 2/10 ) in Group A and B, respectively. Meanwhile, the incidences of EF reduced by more than 10

  14. Observation on FDG myocardial uptake in patients of lymphoma undergoing treatment with Adriamycin: can (18F)FDG-PET be an early marker of chemotherapeutic cardiotoxicity

    International Nuclear Information System (INIS)

    Full text: Adriamycin is a commonly used chemotherapeutic agent in patients with cancer, having cardiotoxicity as its main side effect. This effect is through generation of free radicals and mitochondrial damage. Adriamycin produces hypoxia and decreases synthesis of ATP molecules by aerobic oxidation. To meet this energy synthesis-demand deficit, glycolysis is favored. Hence such 'injured' myocardial cells switch over to glucose as their main source of energy. Neuregulins are a family of growth factors which exert cytoprotection in Adriamycin treated myocytes. Increased glycolysis is one of the downregulatory signal in this pathway. (18F)FDG is concentrated in the myocardial cells via Glut receptors and acts as a marker of glucose metabolism. Based on the above facts, we decided to study the effects of adriamycin on glucose metabolism in myocardium in vivo, with the help of 18F-FDG PET. Aim: To observe (18F)FDG myocardial uptake in patients of lymphoma undergoing treatment with Adriamycin. Materials and Methods: A retrospective analysis was done from the data of (18F)FDG PET scan of lymphoma patients who have completed anthracycline chemotherapy and underwent the said scan for their routine evaluation. The cardiac processing was done separately and a polar map (Bulls eye) generated from the SA slices of the myocardial tracer activity of these patients. Mean SUV value was calculated for the above-mentioned map. This mean SUV calculated in both pre- and post-chemotherapy scans was compared and analysed. Results: 18 patients (16M and 2F with mean age: 32.66 ± 14.81 years) of lymphoma who underwent pre- and post-doxorubicin therapy formed part of the study. The mean dose of doxorubicin received was 227.7 ± 116.59 mg/M2 of BSA. Three different groups were identified among these cases, 1) Group A showing increase in cardiac FDG uptake in post doxorubicin PET scan. Mean dose of doxorubicin received was 256.25 mg/m2 of BSA. 2) Group B showing fall in myocardial FDG

  15. Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies

    International Nuclear Information System (INIS)

    The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m2. With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart congestive

  16. High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity

    DEFF Research Database (Denmark)

    Hansen, A; Kemp, K; Kemp, E;

    2001-01-01

    WF10 is a stabilized chlorite matrix with immunosuppressive effects. In vitro studies have demonstrated its ability to suppress T cells and delay or abolish antigen presentation. Hence, WF10 may prove useful to prolong graft survival after transplantation. In this study, we evaluated the use of...... high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population......, receiving high dose WF10 for 5 days, were compared with a matched control group. Ultrastructural examination of cardiac tissue as well as biochemical analysis of the cardiac enzymes troponin I, myoglobin and MB isoenzyme of creatine kinase showed no signs of damage. Thus, while prolonging graft survival...

  17. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Leslie C., E-mail: shark009@umn.edu [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Radin, M. Judith, E-mail: radin.1@osu.edu [Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210 (United States); Heller, Lois, E-mail: lheller@d.umn.edu [Department of Biomedical Sciences, University of Minnesota Medical School—Duluth, 1035 University Drive, Duluth, MN 55812-3031 (United States); Rogers, Lynette K., E-mail: Lynette.Rogers@nationwidechildrens.org [Center for Perinatal Research, The Research Institute at Nationwide Children' s Hospital, 700 Childrens Drive, Columbus, OH 43205 (United States); Tobias, Anthony [Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, St. Paul, MN 55108 (United States); Matise, Ilze, E-mail: imatise.vh@gmail.com [Veterinary Population Medicine Department, University of Minnesota, 1365 Gortner Ave, St Paul, MN (United States); Wang, Qi, E-mail: wangx890@umn.edu [Clinical and Translational Science Institute (CTSI), University of Minnesota, 717 Delaware St SE, Minneapolis, MN (United States); Apple, Fred S., E-mail: apple004@umn.edu [Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota, 701 Park Ave S, Minneapolis, MN USA (United States); McCune, Sylvia A., E-mail: sylvia.mccune@skybeam.com [Department of Integrative Physiology, University of Colorado at Boulder, 354 UCB, Clare Small 114, Boulder, CO 80309 (United States)

    2013-11-15

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

  18. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    International Nuclear Information System (INIS)

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

  19. Inhibition of gene expression of carnitine palmitoyltransferase I and heart fatty acid binding protein in cyclophosphamide and ifosfamide-induced acute cardiotoxic rat models.

    Science.gov (United States)

    Sayed-Ahmed, Mohamed M; Aldelemy, Meshan L; Al-Shabanah, Othman A; Hafez, Mohamed M; Al-Hosaini, Khaled A; Al-Harbi, Naif O; Al-Sharary, Shakir D; Al-Harbi, Mohamed M

    2014-09-01

    This study investigated whether cyclophosphamide (CP) and ifosfamide (IFO) therapy alters the expression of the key genes engaged in long-chain fatty acid (LCFA) oxidation outside rat heart mitochondria, and if so, whether these alterations should be viewed as a mechanism during CP- and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of the six treatment groups: Rats in group 1 (control) and group 2 (L-carnitine) were injected intraperitoneal (i.p.) with normal saline and L-carnitine (200 mg/kg/day), respectively, for 10 successive days. Animals in group 3 (CP group) were injected i.p. with normal saline for 5 days before and 5 days after a single dose of CP (200 mg/kg, i.p.). Rats in group 4 (IFO group) received normal saline for 5 successive days followed by IFO (50 mg/kg/day, i.p.) for 5 successive days. Rats in group 5 (CP-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5 days before and 5 days after a single dose of CP as group 3. Rats in group 6 (IFO-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5 days before and 5 days concomitant with IFO as group 4. Immediately, after the last dose of the treatment protocol, blood samples were withdrawn and animals were killed for biochemical, histopathological and gene expression studies. Treatment with CP and IFO significantly decreased expression of heart fatty acid binding protein (H-FABP) and carnitine palmitoyltransferase I (CPT I) genes in cardiac tissues. Moreover, CP but not IFO significantly increased acetyl-CoA carboxylase2 mRNA expression. Conversely, IFO but not CP significantly decreased mRNA expression of malonyl-CoA decarboxylase. Both CP and IFO significantly increased serum lactate dehydrogenase, creatine kinase isoenzyme MB and malonyl-CoA content and histopathological lesions in cardiac tissues. Interestingly, carnitine supplementation completely reversed all the biochemical, histopathological and

  20. Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-Sectional Study from the St. Jude Lifetime Cohort

    Science.gov (United States)

    Mulrooney, Daniel A.; Armstrong, Gregory T.; Huang, Sujuan; Ness, Kirsten K.; Ehrhardt, Matthew J.; Joshi, Vijaya M.; Plana, Juan Carlos; Soliman, Elsayed Z.; Green, Daniel M.; Srivastava, Deokumar; Santucci, Aimee; Krasin, Matthew J.; Robison, Leslie L.; Hudson, Melissa M.

    2016-01-01

    Background Studies of cardiac disease among adult survivors of childhood cancer have generally relied upon self-reported or registry-based data. Objective Systematically assess cardiac outcomes among childhood cancer survivors Design Cross-sectional Setting St. Jude Children's Research Hospital Patients 1,853 adult survivors of childhood cancer, ≥18 years old, and ≥10 years from treatment with cardiotoxic therapy for childhood cancer. Measurements History/physical examination, fasting metabolic and lipid panels, echocardiogram, electrocardiogram (ECG), 6-minute walk test (6MWT) all collected at baseline evaluation. Results Half (52.3%) of the survivors were male, median age 8.0 years (range: 0-24) at cancer diagnosis, 31.0 years (18-60) at evaluation. Cardiomyopathy was present in 7.4% (newly identified at the time of evaluation in 4.7%), coronary artery disease (CAD) in 3.8% (newly identified in 2.2%), valvular regurgitation/stenosis in 28.0% (newly identified in 24.8%), and conduction/rhythm abnormalities in 4.6% (newly identified in 1.4%). Nearly all (99.7%) were asymptomatic. The prevalences of cardiac conditions increased with age at evaluation, ranging from 3-24% among those 30-39 years to 10-37% among those ≥40 years. On multivariable analysis, anthracycline exposure ≥250 mg/m2 increased the odds of cardiomyopathy (odds ratio [OR] 2.7, 95% CI 1.1-6.9) compared to anthracycline unexposed survivors. Radiation to the heart increased the odds of cardiomyopathy (OR 1.9 95% CI 1.1-3.7) compared to radiation unexposed survivors. Radiation >1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. Limitations 61% participation rate of survivors exposed to cardiotoxic therapies, which were limited to anthracyclines and cardiac-directed radiation. A comparison group and longitudinal assessments are not available. Conclusions Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood

  1. Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine.

    Science.gov (United States)

    Li, Aizhu; Guo, Xuejun; Xie, Jiabin; Liu, Xinyu; Zhang, Zhenzhu; Li, Yubo; Zhang, Yanjun

    2016-05-10

    Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2mmol/L, 0.4mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis. A "supervised" Support Vector Machine (SVM) study was used to optimize and verify the reliability of these biomarkers. In these biomarkers, all biomarkers, including carnitine, acetylcarnitine, lysoPC(16:0), proline, glutamic acid, pyroglutamic acid, leucine, pantothenic acid, tryptophan, indoleacrylic acid and citric acid, revealed a downward trend with the increase of dosage. Moreover, pathway analysis showed that these metabolites were associated with amino acid metabolism, energy metabolism and sphingolipid metabolism, which contributes to a further understanding of the toxicity mechanism of Corex Periplocae and its clinical safety. Additionally, we demonstrate that an UPLC-Q-TOF/MS-based metabolomic approach is a powerful tool and provides a promising approach for assessing the toxicity of traditional Chinese medicine and drug safety screening. PMID:26924293

  2. Failure of intravenous lipid emulsion in treatment of cardiotoxicity caused by mixed overdose including dihydropyridine calcium channel blockers

    Directory of Open Access Journals (Sweden)

    Jović-Stošić Jasmina

    2016-01-01

    Full Text Available Introduction. Calcium channel blockers and beta-blockers are among the most frequently ingested cardiovascular drugs in self-poisoning causing significant mortality. Intravenous lipid emulsion (ILE is reported as a potentially novel antidote for treatment of acute poisoning caused by some of these drugs. Case report. We presented two cases of poisoning with these drugs. The case 1, a 24-year-old woman ingested amplodipine, metformin and gliclazide for self-poisoning. She presented with tachycardia and hypotension. Laboratory analyses revealed hyperglycaemia and metabolic acidosis. Despite the treatment which included fluid resuscitation, vasopressors, intravenous calcium, glucagon and ILE, circulatory shock occurred. The patient died 10 hours after admission due to cardiac arrest refractory to cardiopulmonary resuscitation. The case 2, a 41-year old man, was found in a coma with empty packages of nifedipine, metoprolol and diazepam tablets. On admission vital signs included Glasgow Coma Scale (GCS of 3, weak palpable pulses, undetectable blood pressure, and irregular breathing with oxygen saturation of 60%. An electrocardiography showed AV block (Mobitz II with ventricular rate of 44/min with progression to third degree of AV block. In attempt to increase heart rate and blood pressure the following agents were administered: atropine boluses, normal saline with dopamine, glucagon, calcium chloride and ILE. Temporary transvenous pacemaker was placed, electrical capture was recorded, but without improvement in haemodynamics. Three hours after admission cardiac arrest happened and cardiopulmonary resuscitation was unsuccessful. Conclusion. Intravenous lipid emulsion may be ineffective in acute poisonings with amlodipine, nifedipine or metoprolol.

  3. Novel self-emulsifying formulation of quercetin for improved in vivo antioxidant potential: implications for drug-induced cardiotoxicity and nephrotoxicity.

    Science.gov (United States)

    Jain, Sanyog; Jain, Amit K; Pohekar, Milind; Thanki, Kaushik

    2013-12-01

    Quercetin (QT) was formulated into a novel self-emulsifying drug delivery system (SEDDS) to improve its oral bioavailability and antioxidant potential compared to free drug. Capmul MCM was selected as the oily phase on the basis of optimum solubility of QT in oil. Tween 20 and ethanol were selected as surfactant and cosurfactant from a large pool of excipients, depending upon their spontaneous self-emulsifying ability with the selected oily phase. Pseudoternary-phase diagrams were constructed to identify the efficient self-emulsification regions in various dilution media, viz., water, pH 1.2, and pH 6.8. The ratio of 40:40:20 w/w, Capmul MCM:QT (19:1)/Tween 20/ethanol was optimized based on its ability to form a spontaneous submicrometer emulsion in simulated gastrointestinal fluids. DPPH scavenging assay showed comparable antioxidant activity of QT-SEDDS to free QT. QT-SEDDS was robust in terms of stability against short-term excursion of freeze/thaw cycles and accelerated stability for 6 months as per International Conference on Harmonisation guidelines. A fluorescent dye-loaded SEDDS formulation showed rapid internalization within 1h of incubation with Caco-2 cells as evident by confocal laser scanning microscopy. QT-SEDDS showed a significant increase in cellular uptake by 23.75-fold in comparison with free QT cultured with Caco-2 cells. The SEDDS demonstrated ~5-fold enhancement in oral bioavailability compared to free QT suspension. The in vitro-in vivo relation between in vitro Caco-2 cell uptake and in vivo pharmacokinetics of QT-SEDDS showed a correlation coefficient of ~0.9961, as evident from a Levy plot. Finally, QT-SEDDS showed a significantly higher in vivo antioxidant potential compared to free QT when evaluated as a function of ability to combat doxorubicin- and cyclosporin A-induced cardiotoxicity and nephrotoxicity, respectively. PMID:23792276

  4. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety. PMID:26441377

  5. Cardioprotective Activity of N′′,N′′′-Bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide Derivative against Doxorubicin Induced Cardiotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Salma Tabassum

    2014-01-01

    Full Text Available The present study was aimed at evaluating the cardioprotective effect of novel synthetic N′′,N′′′-bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide derivative, by estimating the various biomarkers like creatine kinase-myoglobin (CK-MB, lactate dehydrogenase (LDH, aspartate aminotransferase (AST, and triglycerides (TG in plasma and antioxidants like catalase, superoxide dismutase in heart tissue homogenate, and histopathological examination of heart tissues. The results showed the significant (P<0.05 dose dependent decrease in elevated cardiotoxic biomarkers CK-MB, LDH, AST, and TG levels. The histopathological studies of heart tissues showed mild degeneration of muscle bundles and less interstitial edematous changes. The results showed the significant (P<0.05 dose dependent increase in antioxidant enzymes catalase and superoxide dismutase in heart tissue homogenates. These observations enable us to conclude that N′′,N′′′-bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide has cardioprotective activity against doxorubicin induced cardiotoxicity.

  6. Systematic Review of Clozapine Cardiotoxicity.

    Science.gov (United States)

    Curto, Martina; Girardi, Nicoletta; Lionetto, Luana; Ciavarella, Giuseppino M; Ferracuti, Stefano; Baldessarini, Ross J

    2016-07-01

    Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse effects, including myocarditis and cardiomyopathy. Given their clinical importance, we systematically reviewed research on adverse cardiac effects of clozapine, aiming to improve estimates of their incidence, summarize features supporting their diagnosis, and evaluate proposed monitoring procedures. Incidence of early (≤2 months) myocarditis ranges from ECG changes, elevated indices of myocardial damage, cardiac MRI findings, and importantly, echocardiographic evidence of developing ventricular failure. Treatment involves stopping clozapine and empirical applications of steroids, diuretics, beta-blockers, and antiangiotensin agents. Mortality averages approximately 25 %. Safety of clozapine reuse remains uncertain. Systematic studies are needed to improve knowledge of the epidemiology, avoidance, early identification, and treatment of these adverse effects, with effective and practicable monitoring protocols. PMID:27222142

  7. Sorafenib in metastatic MTC – a case report and minireview of the literature

    Directory of Open Access Journals (Sweden)

    Mila Petrova

    2010-05-01

    Full Text Available Mila Petrova1, Zhasmina Mihaylova1, Albena Fakirova21Hematology and Oncology Department, 2Pathology Department, Medical Military Academy, Sofia, BulgariaAbstract: Medullary thyroid cancer (MTC is a rare and only surgically treatable disease with early development of metastases and bad prognosis. Due to the lack of efficient systemic treatment, new strategies and approaches are needed to better the patients’ outcome. One of the most promising treatment options is the use of tyrosine multikinase inhibitors, which appear to have some effect on the disease progression with tolerable toxicity. Most of them affect many key pathways in the cancer genesis and have proven their effect in different malignancies. We report a case of a young patient with metastatic MTC treated successfully for two months with sorafenib.Keywords: medullary thyroid cancer, tumor response, cardiotoxicity, TKIs

  8. Scleroderma in a Patient on Capecitabine: Is this a Variant of Hand-Foot Syndrome?

    Science.gov (United States)

    Agarwal, Archana; Hellinger, James; Park, Dorothy J; Volkmann, Elizabeth

    2016-01-01

    Drug-induced scleroderma is a rare adverse effect of some chemotherapeutic drugs, such as taxanes and bleomycin. Capecitabine, an oral fluoropyrimidine approved for the treatment of metastatic breast and colon cancer, commonly causes cutaneous side effects including the hand-and-foot syndrome (HFS). Scleroderma-like skin changes associated with HFS associated with capecitabine is rare. However, diffuse scleroderma has never before been reported. We report a case of capecitabine-induced diffuse/systemic scleroderma in an 86-year-old female treated with capecitabine for metastatic colorectal cancer. She developed progressive skin and visceral sclerosis involving the lungs. We discuss the association between chemotherapy and scleroderma. We believe this is the first case of diffuse/systemic capecitabine-induced scleroderma without the presence of HFS. Early diagnosis is essential as fibrosis might be prevented in early stages. The capecitabine should be discontinued as early as possible. PMID:27493845

  9. Preventive effects of Egyptian sweet marjoram (Origanum majorana L.) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats.

    Science.gov (United States)

    Ramadan, Gamal; El-Beih, Nadia M; Arafa, Nadia M S; Zahra, Mai M

    2013-06-01

    We made an attempt to evaluate/compare the cardioprotective activity of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) against isoproterenol (ISO)-induced myocardial infarcted rats (150 mg/kg body weight, twice at an interval of 24 h on days 29 and 30). The present study showed (probably for the first time) that both MLP and MLE (especially the high dose) significantly alleviated (P CPK), CPK-MB isoenzyme, lactate dehydrogenase and aminotransferase) in ISO-treated rats through reactivating non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant defence system and inhibiting the production of nitric oxide and lipid peroxidation in heart tissues. The modulatory effects of marjoram leaves shown in the present study were dose-dependent in most cases and much higher in MLE (4.3-20.3 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, this study may have a significant impact on myocardial infarcted patients. PMID:23054890

  10. Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies; Evaluacion de la cardiotoxicidad secundaria al empleo de adriamicina en pacientes con cancer de mama con estudios de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Garcia P, S

    2003-07-01

    The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m{sup 2}. With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart

  11. Ibogaine-associated cardiac arrest and death: case report and review of the literature.

    Science.gov (United States)

    Meisner, Jessica A; Wilcox, Susan R; Richards, Jeremy B

    2016-04-01

    A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine's clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

  12. A case of apical ballooning syndrome in a male with status asthmaticus; highlighting the role of B2 agonists in the pathophysiology of a reversible cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Farah F. Salahuddin

    2013-07-01

    Full Text Available Apical ballooning syndrome (ABS, also known as Takotsubo cardiomyopathy, was first reported by Dote and colleagues in Japanese literature in 1991 in a review of five cases. Case series have highlighted the association of severe psychological stressors as the major precipitating factors of this syndrome. Status Epilepticus and Sub-Arachnoid hemorrhage are also now established independent etiologies for this phenomenon in patients without coronary artery disease. We report a case of reversible apical ventricular dysfunction in a 50-year-old male presenting with status asthmaticus who quickly underwent intubation. Following this, he had ST elevations in precordial leads with mild cardiac enzyme leak. Subsequent cardiac catheterization revealed a left ventricular ejection fraction of 25–30% with apical aneurismal segment. No obstructive disease was observed. Three days later there was marked clinical improvement; the patient was extubated and repeat echocardiography revealed a remarkable return to normal ventricular size and systolic function. Our case demonstrates that excess use of beta-agonists may be a potential risk factor for ABS and raises the possibility of cathecholamine cardiotoxicity being mediated via beta-receptors. Furthermore, it also negates the propensity of apical ballooning so far reported only in women with respiratory distress without confounding emotional stressors.

  13. Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity

    NARCIS (Netherlands)

    Perik, P. J.; Rikhof, B.; de Jong, F. A.; Verweij, J.; Gietema, J. A.; van der Graaf, W. T. A.

    2008-01-01

    Background: Recently, case reports of patients treated with imatinib (imatinib mesylate; Gleevec (R); Glvec (R)) indicated that this tyrosine kinase inhibitor may induce cardiomyopathy. Consequently, careful cardiac monitoring was advocated for clinical studies. The purpose of this study was to pros

  14. Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity

    NARCIS (Netherlands)

    P.J. Perik; B. Rikhof; M.J.A. de Jonge (Maja); J. Verweij (Jaap); J.A. Gietema (Jourik); W.T.A. van der Graaf (Winette)

    2008-01-01

    textabstractBackground: Recently, case reports of patients treated with imatinib (imatinib mesylate; Gleevec®; Glivec®) indicated that this tyrosine kinase inhibitor may induce cardiomyopathy. Consequently, careful cardiac monitoring was advocated for clinical studies. The purpose of this study was

  15. Case law

    International Nuclear Information System (INIS)

    This section treats of the two following case laws: Slovak Republic: Further developments in cases related to the challenge by Greenpeace Slovakia to the Mochovce nuclear power plant; United States: Judgment of the Nuclear Regulatory Commission denying requests from petitioners to suspend final reactor licensing decisions pending the issuance of a final determination of reasonable assurance of permanent disposal of spent fuel

  16. Clinical cases

    International Nuclear Information System (INIS)

    This presentation is about clinical cases and the contribution of the PET - CT Fag application in the diagnosis and treatment of different types of cancer. The cases presented were: neck diseases, epidermoid carcinoma, liver damage and metastasize, lymphoma, thrombosis, colonic cancer and lung disease

  17. Case Studies

    International Nuclear Information System (INIS)

    Proven options available to Sri Lanka for large scale electricity generation in the future are coal-fired thermal, oil-fired thermal and Nuclear. Four case studies for groups participated are indicated. Case study for group 1 is comparison of the three options by taking into consideration the capital and recurrent expenditure involved. Environmental effects of the three options are also given. Case study for group 2 is economic comparison of three renewable energy based power generation system. Case study for group 3 is based on energy conservation, efficiency, improvement and demand management. Assuming that a continuous saving of 20 MW of demand from 1996 onwards is effective two projects are suggested to achieve this result. Case study for group 4 is a feasibility study for hydro power development of the Kukule Ganga (river) in Sri Lanka. Participants are required to evaluate one of the three optional development concepts which are technically feasible

  18. Case - Case-Law - Law

    DEFF Research Database (Denmark)

    Sadl, Urska

    2013-01-01

    Reasoning of the Court of Justice of the European Union – Constr uction of arguments in the case-law of the Court – Citation technique – The use of formulas to transform case-law into ‘law’ – ‘Formulaic style’ – European citizenship as a fundamental status – Ruiz Zambrano – Reasoning from...

  19. Barium cardiotoxicity: Relationship between ultrastructural damage and mechanical effects.

    Science.gov (United States)

    Delfino, G; Amerini, S; Mugelli, A

    1988-01-01

    The ultrastructural damage in guinea-pig ventricular strips caused by barium was analysed. At a concentration of 1 mmol/litre, barium chloride caused a dramatic increase in the developed tension associated with the onset of automaticity. The ultrastructural analysis demonstrated that barium caused notable and consistent alterations which affected most myocyte components. Various degenerative aspects were observed in mitochondria and in the contractile apparatus. Glycogen deposits were completely depleted. Preparations driven at 4 Hz (i.e. the rate of spontaneous firing of barium-treated preparations) showed moderate ultrastructural alterations, thus demonstrating that the increase in the rate of beating is not the only determinant of the observed damage. These results suggest that the myocardial toxicity of barium is due not only to the well-known modifications in membrane permeability, but possibly also to alterations in cell function. PMID:20702358

  20. Perflurooctanoic Acid Induces Developmental Cardiotoxicity in Chicken Embryos and Hatchlings

    Science.gov (United States)

    Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxi...

  1. Bleomycin cardiotoxicity during chemotherapy for an ovarian germ cell tumor

    OpenAIRE

    Didagelos, M; Boutis, A; Diamantopoulos, N; Sotiriadou, M; Fotiou, C

    2013-01-01

    Introduction: Platinum-based chemotherapeutic regimens, including BEP (bleomycin, etoposide, cisplatin) represent the standard of care, first line therapy in non-epithelial ovarian tumours. Cardiovascular toxicity is a rare adverse effect of bleomycin.

  2. Case law

    International Nuclear Information System (INIS)

    This section gathers the following case laws: 1 - Canada: Judicial review of Darlington new nuclear power plant project; Appeal decision upholding criminal convictions related to attempt to export nuclear-related dual-use items to Iran: Her Majesty the Queen V. Yadegari; 2 - European Commission: Greenland cases; 3 - France: Chernobyl accident - decision of dismissal of the Court of Appeal of Paris; 4 - Slovak Republic: Aarhus Convention compliance update; 5 - United States: Judgement of a US court of appeals upholding the NRC's dismissal of challenges to the renewal of the operating licence for Oyster Creek Nuclear Generating Station; reexamination of the project of high-level waste disposal site at Yucca Mountain

  3. Case work

    DEFF Research Database (Denmark)

    Shaw, Ian Frank

    2016-01-01

    Answers to the question just what is the ?case? partly defined the fields of sociology and social work in early 20th century Chicago. Drawing on the archives of the University of Chicago, I describe and appraise the way the ?case? figured in social work at Chicago and elsewhere. I ask the...... corresponding question of sociology. Finally, I briefly consider why not much came of social work and sociology ploughing similar territory in ways that served for a time to hallmark their identities. This analysis opens up ways of rethinking how social work and sociological research are distinctive to their...

  4. Cases Description

    DEFF Research Database (Denmark)

    Hansen, Jesper Rohr; Savini, Federico; Wallin, Sirkku;

    2013-01-01

    The JPI Urban Europe research project ‘APRILab’ focuses on planning dilemmas for the transformation of city areas in the urban fringe. In this Working Document we describe the case studies selected by the involved partners: - Aalto University, Finland: T3 in Espoo City - Aalborg University, Denmark...

  5. Case competitions

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram

    2009-01-01

    The paper presents and discusses a teaching project with case competitions for MA students of specialised translation at the Aarhus School of Business, Aarhus University. Drawing on a series of online questionnaires, the paper ascertains how the project was evaluated by the participating students...

  6. Case report

    DEFF Research Database (Denmark)

    Füchtbauer, Laila; Brusgaard, Klaus; Ledaal, Pål;

    2015-01-01

    ey Clinical Message Vitamin D-dependent rickets type 1 VDDR-1 is a recessive inherited disorder with impaired activation of vitamin D, caused by mutations in CYP27B1. We present long-time follow-up of a case with a novel mutation including high-resolution peripheral quantitative computed tomography...

  7. The Case for Case Reports

    Directory of Open Access Journals (Sweden)

    George R. Saade

    2011-09-01

    Full Text Available If you are reading a hard copy of this editorial, then you are holding in hand the first issue of the American Journal of Perinatology Reports, or AJP Reports as we like to refer to it. Welcome to AJP Reports and thank you for taking the time to peruse it. I hope you find many of the reports interesting and helpful. The editorial team and publisher are very pleased to be able to bring this journal to our readers. Judging by the journal title, the editorial team, and the layout you may have already guessed that this is a companion to the American Journal of Perinatology. We will continue to publish original articles and topical reviews in the American Journal of Perinatology, but all case reports or case series will be referred to AJP Reports. Some may question the need for more case reports. Our decision to start AJP Reports obviously indicates that we think that case reports can be useful. I can refer to several diseases, treatment complications, and procedures that were first brought to the attention of healthcare providers through case reports. The best example of the usefulness of case reports is probably in infectious diseases. In the early phases of an emerging infectious disease, the case report or case series are usually the first clues of a problem. HIV was first brought to the attention of the medical community by case reports.[1] [2] [3] In our own field, the first attempts at treatment of twin-to-twin transfusion syndrome (TTTS using laser coagulation were reported in a case series.[4] After additional reports about the use of laser in TTTS, a randomized trial was performed that cemented laser photocoagulation as a therapeutic modality for TTTS.[5] While case reports or series are not considered the highest form of evidence, they are frequently the first form of evidence and the nudge that starts the cascade of investigation that ultimately leads to high-level evidence. Therefore, their impact on clinical practice may be easily

  8. Case law

    International Nuclear Information System (INIS)

    This section of the Bulletin brings together the texts of the following case laws: Canada: - Judgment of the Federal Court of Canada sending back to a joint review panel for reconsideration the environmental assessment of a proposed new nuclear power plant in Ontario. France : - Conseil d'etat, 24 March 2014 (Request No. 358882); - Conseil d'etat, 24 March 2014 (Request No. 362001). Slovak Republic: - Further developments in cases related to the challenge by Greenpeace Slovakia to the Mochovce nuclear power plant; - Developments in relation to the disclosure of information concerning the Mochovce nuclear power plant. United States: - Initial Decision of the Atomic Safety and Licensing Board Ruling in Favour of Nuclear Innovation North America, LLC (NINA) Regarding Foreign Ownership, Control or Domination

  9. Case Report

    DEFF Research Database (Denmark)

    Bilgin-Freiert, Arzu; Fugleholm, Kåre; Poulsgaard, Lars

    2015-01-01

    We report a case of an intraneural ganglion cyst of the hypoglossal canal. The patient presented with unilateral hypoglossal nerve palsy, and magnetic resonance imaging showed a small lesion in the hypoglossal canal with no contrast enhancement and high signal on T2-weighted imaging. The lesion was...... assumed to be a cystic schwannoma of the hypoglossal nerve. Stereotactic irradiation was considered, but in accordance with the patient's wishes, surgical exploration was performed. This revealed that, rather than a schwannoma, the patient had an intraneural ganglion cyst, retrospectively contraindicating...... irradiation as an option. This case illustrates a very rare location of an intraneural ganglion cyst in the hypoglossal nerve. To our knowledge there are no previous reports of an intraneural ganglion cyst confined to the hypoglossal canal....

  10. Corruption case.

    Science.gov (United States)

    1999-07-23

    A Federal jury in Puerto Rico found three defendants guilty of participating in the theft of $2.2 million in Federal funds from the San Juan AIDS Institute. The key figure in the case is [name removed], a consultant to the institute. He was convicted of 12 counts of money laundering and faces up to 25 years in prison. Two other administrative officials were also convicted in the case. Four others have pleaded guilty, and three more await trial. Rep. Jose Granados Navado was among those implicated; he received $100,000 for his campaign for mayor of San Juan in 1988 from the institute=s medical director. U.S. Rep. Tom Coburn (R-Okla.) has called for an audit of all Ryan White CARE Act funds since this scandal was uncovered. PMID:11366596

  11. Case04

    DEFF Research Database (Denmark)

    Vestergaard, Flemming; Karlshøj, Jan; Hauch, Peter; Lambrecht, Jan; Mouritsen, Jan

    Casestudiets formål er at beskrive og måle en større entreprenørvirksomheds omkostninger og gevin-ster ved at anvende metoder og værktøjer, der er modelbaserede. Case 04 tager udgangspunkt i et konkret byggeprojekt, hvor BIM teknologien er anvendt på et for den danske entreprenørbranche rela...

  12. Case Corabelle

    OpenAIRE

    Hansen, Casper; Henriksen, Jesper; Loznica, Javor; Ragnarsson, Stefan; Hensing, Marcus

    2015-01-01

    This project explores the relation between organizational identity and online brands as formed through interaction and communication on online, social media through a case study of the cancelled music festival event Corabelle that was supposed to have been held in August of 2014. The investigation draws on the theories of Carlos Scolari and David A. Whetten to establish the relation between organizational identity and online brands, and the theories of Henry Jenkins and Jan H. Kietzmann in an...

  13. Bertoko case

    Directory of Open Access Journals (Sweden)

    AMAIA LAFUENTE RUIZ DE SABANDO

    2001-12-01

    Full Text Available Bertoko Gar, S.A. is a minibrewer firm established in 1999. It produces and sells a beer characterized by its local and home-produced character. Despite the fact that no other bottled beer brewers with the same characteristics exist in its home market, Bertoko competes in a market dominated by multinationals. Once it has set its aims, Bertoko is currently designing its marketing strategy and setting which are the actions to be taken for its near future (some of which are detailed in this case.

  14. Case law

    OpenAIRE

    OECD

    2012-01-01

    France Administrative Court of Appeal of Lyon, 19 June 2012, Judgements Nos. 12LY00233 and 12LY00290 regarding EDF’s permit to construct a waste conditioning and storage facility (ICEDA) in the town of Saint-Vulbas Germany Request for arbitration against Germany at the World Bank’s International Centre for the Settlement of Investment Disputes (ICSID) because of Germany’s legislation leading to the phase-out of nuclear energy India Cases related to the Kudankulam Nuclear Power Project (KKNPP)...

  15. Case Law

    International Nuclear Information System (INIS)

    This section treats of the following case laws sorted by country: 1 - Germany: Federal Administrative Court confirms the judgments of the Higher Administrative Court of the Land Hesse: The shutdown of nuclear power plant Biblis blocks A and B based on a 'moratorium' imposed by the Government was unlawful; List of lawsuits in the nuclear field. 2 - Slovak Republic: Further developments in cases related to the challenge by Greenpeace Slovakia to the Mochovce nuclear power plant; Developments in relation to the disclosure of information concerning the Mochovce nuclear power plant. 3 - United States: Judgment of the Nuclear Regulatory Commission resuming the licensing process for the Department of Energy's construction authorisation application for the Yucca Mountain high-level radioactive waste repository; Judgment of the Licensing Board in favour of Shaw AREVA MOX Services regarding the material control and accounting system at the proposed MOX Facility; Dismissal by US District Court Judge of lawsuit brought by US military personnel against Tokyo Electric Power Company (TEPCO) in connection with the Fukushima Daiichi nuclear power plant accident

  16. Case Law

    International Nuclear Information System (INIS)

    Different case law are presented in this part: By decision dated 17 july 2009, the Ontario Court of Appeal (Canada) has ruled on the scope of solicitor-client privilege and the protections that may be afforded to privileged investigations reports. The decision reaffirms the canadian court system view of the importance of the protection of solicitor-client privilege to the administration of justice; For United states here is a judgment of a U.S. court of Appeals on the design basis threat security rule (2009), this case concerns a challenge to the U.S. Nuclear regulatory commission (N.R.C.) revised design basis threat rule, which was adopted in 2007 (nuclear bulletin law no. 80). The petitioners public citizen, Inc., San Luis Obispo Mothers for Peace and the State of New York filed a lawsuit in the U.S. court of appeals for the Ninth circuit alleging that the N.R.C. acted arbitrarily and capriciously and in violation of law by refusing to include the treat of air attacks in its final revised design basis rule. On the 24. july 2009, a panel of three ninth circuit judges rules 2-1 that the N.R.C. acted reasonably in not including an air treat in its design basis rule. Secondly, judgment of a U.S. court of appeals on consideration of the environmental impact of terrorist attacks on nuclear facilities (2009), this case concerns the scope of the U.S. Nuclear regulatory commission environmental analysis during its review of applications to re-licence commercial nuclear power plants. New Jersey urged the N.R.C. to consider the environmental impact of an airborne terrorist attack on the power plant, arguing that such analysis was required by the national environmental policy act (N.E.P.A.). On 31. march 2009, a panel of three circuit judges declined to follow the ninth circuit opinion and affirmed NRC decision 3-0 ruling that NRC was not required to consider terrorism in its N.E.P.A. analysis because NRC re-licensing would not be a reasonably close cause of terrorism

  17. Case law

    International Nuclear Information System (INIS)

    Concerning the France, the judgement of the European Court of Human Rights on the Right to a fair Trial, in the litigation Collectif Stop Melox and Mox versus France (2007) and the decision of the Council of State Quashing a decree concerning a nuclear installation in Brennilis, for the want of public information and consultation (2007) are reported. For South Africa, the judgment of the Cape High Court in the case of Mc donald and others versus Minister of Minerals and Energy and others (2007) is reported. United Kingdom states the decision of the Wick Sheriff Court Fining UKAEA for plutonium exposure (2007). Concerning Usa the judgment of the US Court of Appeals on environment Analysis of the effects of terrorism (2006) and the vacatur of US Court of Federal Claims Decision regarding Price-Anderson Compensation of Costs in a private Tort Claim (2007) are reported. (N.C.)

  18. Case management.

    Science.gov (United States)

    Rosenstein, A H; Propotnik, T

    1997-03-01

    Providing cost-effective high quality healthcare services ranks as the number one concern for anyone involved with the healthcare delivery system. While quality of care should always be the number one priority, controlling healthcare costs receives most of the attention. With limited healthcare dollars and providers assuming more of the financial risk for services rendered, a whole assortment of cost-containment strategies are being introduced in an effort to maintain some semblance of financial viability. Healthcare providers can approach cost control from two different angles. On the fixed-cost operational overhead side, traditional cost-containment techniques have focused on downsizing, maximizing productivity, staffing redesign, improved purchasing contracts, standardization, inventory control, and other more individualized restructured service models. On the variable-cost clinical side, cost control has been approached by introducing a variety of cost-containment strategies designed to improve efficiency and effectiveness of provider performance. While many of these strategies, previously discussed in the Journal of Healthcare Resource Management have stressed the importance of education, guidelines, pathways, and other clinical "tools for improvement," the success of many of these tools resides in the ability to provide real-time intervention. Real-time intervention rather than the more passive retrospective variance analysis has the greatest potential for producing cost savings by actually making a recommendation that prevents the unwanted event from occurring. In many institutions, the case manager bears the responsibility for monitoring and managing these programs. This article describes various case management models currently used by different institutions. PMID:10166062

  19. Case law

    International Nuclear Information System (INIS)

    This section reports on 7 case laws from 4 countries: - France: Conseil d'Etat decision, 28 June 2013, refusing to suspend operation of the Fessenheim nuclear power plant; - Slovak Republic: New developments including the Supreme Court's judgment in a matter involving Greenpeace Slovakia's claims regarding the Mochovce nuclear power plant; New developments in the matter involving Greenpeace's demands for information under the Freedom of Information Act; - Switzerland: Judgment of the Federal Supreme Court in the matter of the Departement federal de l'environnement, des transports, de l'energie et de la communication (DETEC) against Ursula Balmer-Schafroth and others on consideration of admissibility of a request to withdraw the operating licence for the Muehleberg nuclear power plant; - United States: Judgment of the Court of Appeals for the District of Columbia Circuit granting petition for writ of mandamus ordering US Nuclear Regulatory Commission (NRC) to resume Yucca Mountain licensing; Judgment of the Court of Appeals for the Second Circuit invalidating two Vermont statutes as preempted by the Atomic Energy Act; Judgment of the NRC on transferring Shieldalloy site to New Jersey's jurisdiction

  20. Case law

    International Nuclear Information System (INIS)

    Five articles are tackled: in France, the judgement of the Court of Appeal of Limoges concerning the dumping of radioactive waste by Areva N.C.(2006). The Court of Appeal of Limoges ruled that Areva N.C. was not guilty of dumping radioactive waste, and neither had it infringed radiation protection regulations or general mining industry regulations. there was no proof of damage to fish fauna. In Sweden, judgement on Plans for the dismantling of Barsebaeck (2006). This court case resulted from a dispute between the operator and the Swedish government Swedish radiation Protection Institute. The Swedish Government wanted decommissioning to commence immediately whereas plant management at Barsebaeck had indicated its intention to wait until 2020, when the radiation dose to workers during decommissioning work would be lower. The court approved the plans to commence dismantling in 2020, when a repository for large reactor components will be ready at the national final repository for radioactive waste at the Forsmark plant. In United Kingdom, on October 2006, British Nuclear group Sellafield Ltd. (B.N.G.S.L.) was fined 500 000 pounds (G.B.P.) plus G.B.P. 68000 in costs in a case brought by the UK health and Safety Executive (H.S.E.) for failing to identify and stop an eight-month long leak of 83 400 litres of radioactive liquid at the Thermal Oxide reprocessing Plant (T.H.O.R.P.) at Sellafield in Cumbria. The fine was levied at Carlisle Crown Court after B.N.G.S.L. pleaded guilty, at an earlier hearing, to the three counts of breaching conditions attached to the Sellafield site licence, granted under the 1965 Nuclear Installations Act as amended. These conditions require the licensee to make and comply with written instructions; to ensure safety systems are in good working order; and to ensure radioactive material is contained and, if leaks occur, they are detected and reported. In Usa, in accordance with the Nuclear Waste Policy Act of 1982, as amended (N.W.P.A.) the US

  1. Case law

    International Nuclear Information System (INIS)

    This section treats of the following case laws: 1 - Canada: Decision of the Canadian Federal Court of Appeal overturning a decision to send back for reconsideration an environmental assessment of a proposed new nuclear power plant in Ontario; 2 - France: Council of State decision, 28 November 2014, Federation 'Reseau sortir du nucleaire' (Nuclear Phase-Out network) and others vs. Electricite de France (EDF), Request No. 367013 for the annulment of: - The resolution of the French Nuclear Safety Authority (ASN) dated 4 July 2011 specifying additional regulations for Electricite de France (EDF) designed to strengthen the reactor basemat of reactor No. 1 in the Fessenheim nuclear power plant, and - The resolution of ASN dated 19 December 2012 approving the start of work on reinforcing the reactor basemat in accordance with the dossier submitted by EDF; 3 - Germany: Judgment of the European Court of Justice on the nuclear fuel tax; 4 - India: Judgment of the High Court of Kerala in a public interest litigation challenging the constitutional validity of the Civil Liability for Nuclear Damage Act, 2010; 5 - Japan - District court decisions on lawsuits related to the restart of Sendai NPP and Takahama NPP; 6 - Poland: Decision of the Masovian Voivod concerning the legality of the resolution on holding a local referendum in the Commune of Rozan regarding a new radioactive waste repository; Certain provisions of the Regulation of the Minister of Health of 18 February 2011 on the conditions for safe use of ionising radiation for all types of medical exposure have been declared unconstitutional by a judgment pronounced by the Constitutional Tribunal; 7 - Slovak Republic: Developments in relation to the disclosure of information concerning the Mochovce nuclear power plant

  2. Indian common krait envenomation presenting as fulminant myocarditis and coma: a case report

    OpenAIRE

    Vijay Kumar Verma; Vijender Maurya; Rajesh Verma

    2014-01-01

    Fulminant myocarditis is an unusual manifestation of cardiotoxicity with severe elapid snake envenoming and is meagrely reported with snake bite due to Indian common krait. We report a 12-year-old boy who was admitted in complete locked-in state and hemodynamic instability after severe neurotoxic snake envenoming by Bungarus caeruleus (Indian common krait). His hospital course was complicated with recurrent episodes of sustained ventricular tachycardia requiring defibrillation; and cardiogeni...

  3. Case Study: Writing a Journal Case Study

    Science.gov (United States)

    Prud'homme-Genereux, Annie

    2016-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's issue describes incorporating a journal article into the classroom by first converting it into a case study.

  4. Case Study Teaching

    Science.gov (United States)

    Herreid, Clyde Freeman

    2011-01-01

    This chapter describes the history of case study teaching, types of cases, and experimental data supporting their effectiveness. It also describes a model for comparing the efficacy of the various case study methods. (Contains 1 figure.)

  5. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  6. CASING DRILLING TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Nediljka Gaurina-Međimurec

    2005-12-01

    Full Text Available Casing drilling is an alternative option to conventional drilling and uses standard oilfield casing instead of drillstring. This technology is one of the greatest developments in drilling operations. Casing drilling involves drilling and casing a well simultaneously. In casing driling process, downhole tools can be retrieved, through the casing on wire-line, meaning tool recovery or replacement of tools can take minutes versus hours under conventional methods. This process employs wireline-retrievable tools and a drill-lock assembly, permitting bit and BHA changes, coring, electrical logging and even directional or horizontal drilling. Once the casing point is reached, the casing is cemented in place without tripping pipe.

  7. Project management case studies

    CERN Document Server

    Kerzner, Harold R

    2013-01-01

    A new edition of the most popular book of project management case studies, expanded to include more than 100 cases plus a ""super case"" on the Iridium Project Case studies are an important part of project management education and training. This Fourth Edition of Harold Kerzner''s Project Management Case Studies features a number of new cases covering value measurement in project management. Also included is the well-received ""super case,"" which covers all aspects of project management and may be used as a capstone for a course. This new edition:Contains 100-plus case studies drawn from re

  8. Case Base Maintenance Approach.

    OpenAIRE

    Haouchine, Mohamed-Karim; Chebel-Morello, Brigitte; Zerhouni, Noureddine

    2007-01-01

    Case base Maintenance is an active Case Based Reasoning research area. The main stream focuses on the method for reducing the size of the case-base while maintaining case-base competence. This paper gives an overview of these works, and proposes a case deletion strategy based on competence criteria using a novel approach. The proposed method, even if inspired from existing literature, combines an algorithm with a Competence Metric (CM). A series of tests are conducted using two standards data...

  9. Case Based Reasoning: Case Representation Methodologies

    Directory of Open Access Journals (Sweden)

    Shaker H. El-Sappagh

    2015-11-01

    Full Text Available Case Based Reasoning (CBR is an important technique in artificial intelligence, which has been applied to various kinds of problems in a wide range of domains. Selecting case representation formalism is critical for the proper operation of the overall CBR system. In this paper, we survey and evaluate all of the existing case representation methodologies. Moreover, the case retrieval and future challenges for effective CBR are explained. Case representation methods are grouped in to knowledge-intensive approaches and traditional approaches. The first group overweight the second one. The first methods depend on ontology and enhance all CBR processes including case representation, retrieval, storage, and adaptation. By using a proposed set of qualitative metrics, the existing methods based on ontology for case representation are studied and evaluated in details. All these systems have limitations. No approach exceeds 53% of the specified metrics. The results of the survey explain the current limitations of CBR systems. It shows that ontology usage in case representation needs improvements to achieve semantic representation and semantic retrieval in CBR system.

  10. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  11. Xeroderma pigmentosum (case report

    Directory of Open Access Journals (Sweden)

    Dubey Arvind

    1990-01-01

    Full Text Available Xeroderma pigmentosum is a rare, hereditary and fatal disease of the skin. Ocular involvement is known to occur in 80% of cases. A case with typical cutaneous and ocular lesions is reported.

  12. PSS Case Book

    DEFF Research Database (Denmark)

    Neugebauer, Line Maria; Mougaard, Krestine; Andersen, Jakob Bejbro; McAloone, Tim C.; Bey, Niki; Hsuan, Juliana; Ahm, Thorkild

    The transformation process towards a PSS-oriented company is describes, through the presentation of the best practice cases. Each case describes motivations, challenges, business models and PSS offerings....

  13. FHEO Filed Cases

    Data.gov (United States)

    Department of Housing and Urban Development — The dataset is a list of all the Title VIII fair housing cases filed by FHEO from 1/1/2007 - 12/31/2012 including the case number, case name, filing date, state and...

  14. Defining a periodontitis case

    DEFF Research Database (Denmark)

    Baelum, Vibeke; Lopez, Rodrigo

    2012-01-01

    Aim The purpose of the present study was to assess the extent to which the three periodontitis case definition systems proposed by van der Velden, Tonetti & Claffey and Page & Eke identify the same cases in a population of never-treated adults with limited tradition for oral hygiene procedures...... concomitant presence of CAL and BOP at the site level. Results The case definitions by Tonetti & Claffey and by Page & Eke yielded similar results, which were also quite similar to the results of simply identifying a case of periodontitis as a person having at least one site showing both CAL ≥ 4 mm and BOP....... Conclusions The results indicate that it should be feasible for the periodontal community to reach an agreement over the distinction between a case and a non-case. The classification system proposed by van der Velden is better suited for providing clinicians with a clear image of the case....

  15. Trastuzumab-induced cardiomyopathy.

    Science.gov (United States)

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity. PMID:18514938

  16. Osteopoikilosis - Case report

    Directory of Open Access Journals (Sweden)

    Vilson Ruci

    2014-03-01

    Full Text Available Osteopoikilosis is a rare bone anomaly usually benign which may be confused with other severe primary diseases or dangerous metastatic bone lesions. We present one new case describing typical radiological findings with no clinical signs or other associations. No malignant transformation or other complications happened in the last ten years. Osteopoikilosis is found in most cases incidentally, and in most cases is not associated with other serious medical complications. Screening of family members may be considered.

  17. Borderline Cases and Definiteness

    OpenAIRE

    Vecsey, Zoltán

    2012-01-01

    Borderline cases of vague predicates are often characterized with the help of a definiteness operator. Although such operators can certainly contribute to the solution of the problem of vagueness, they may also generate unexpected consequences. Either borderlineness is identified implicitly with a well-defined range of cases, or borderline cases are seen as being definitely borderline. In this paper I argue that we can avoid these consequences by providing an asymmetric definition of borderli...

  18. Teaching Case: Enterprise Architecture Specification Case Study

    Science.gov (United States)

    Steenkamp, Annette Lerine; Alawdah, Amal; Almasri, Osama; Gai, Keke; Khattab, Nidal; Swaby, Carval; Abaas, Ramy

    2013-01-01

    A graduate course in enterprise architecture had a team project component in which a real-world business case, provided by an industry sponsor, formed the basis of the project charter and the architecture statement of work. The paper aims to share the team project experience on developing the architecture specifications based on the business case…

  19. Case-based reasoning

    CERN Document Server

    Kolodner, Janet

    1993-01-01

    Case-based reasoning is one of the fastest growing areas in the field of knowledge-based systems and this book, authored by a leader in the field, is the first comprehensive text on the subject. Case-based reasoning systems are systems that store information about situations in their memory. As new problems arise, similar situations are searched out to help solve these problems. Problems are understood and inferences are made by finding the closest cases in memory, comparing and contrasting the problem with those cases, making inferences based on those comparisons, and asking questions whe

  20. Commissioners' Monthly Case Activity Report

    Data.gov (United States)

    Occupational Safety and Health Review Commission — Total cases pending at the beginning of the month, total cases added to the docket during the month, total cases disposed of during the month, and total cases...

  1. Essential trichomegaly: case report

    Directory of Open Access Journals (Sweden)

    Julia Dutra Rossetto

    2013-02-01

    Full Text Available The present study reports two cases of symptomatic essential trichomegaly. Trichomegaly may develop in various diseases, including anorexia nervosa, hypothyroidism, pregnancy, pretibial myxedema, systemic lupus erythematosus, vernal keratoconjunctivitis, and uveitis. The exact incidence trichomegaly is unknown, and the condition remains sporadically reported. Two cases of symptomatic trichomegaly without any associated systemic disorder are presented in this paper.

  2. Centralizer for well casing

    International Nuclear Information System (INIS)

    This patent describes an improved centralizer for centering a well casing in a wellbore. It comprises: a first anchor adapted to fit around and be securely fixed to the casing, the first anchor being threaded on its external surface; a first collar adapted to fit around and be threadedly engaged by the first anchor; a second collar adapted to fit around and free to rotate and move axially with respect to the casing; a second anchor adapted to fit around and be securely fixed to the casing spaced from the first anchor and comprising a bearing surface for restraining axial movement of the second collar along the casing; and metallic straps extending between the first collar and the second collar, and being securely fixed to each

  3. Aortic dissection: case series

    Directory of Open Access Journals (Sweden)

    Bhavana Venkata Nagabhushana Rao

    2016-04-01

    Full Text Available Aortic dissection may not be attended by a physician in his lifetime, but he should possess all the clinical acumen to deal with as it is a catastrophic disease. Early and accurate diagnosis will save a life. Here we present three cases we faced in sequence over a period of two months. A case of extensive dissection arch to thoracic aorta, its display in detail. Second case eliciting ambiguity between coronary ischemia and aortic dissection. Management difficulties of such clinician situation are discussed. Third case, the fracture of a renal artery stent leading to severe hypertension, abdominal pain, and aortic dissection. Such case was not described in the literature to our knowledge. [Int J Res Med Sci 2016; 4(4.000: 1268-1271

  4. [Autoptically confirmed malpractice cases].

    Science.gov (United States)

    Madea, Burkhard

    2008-01-01

    Claims of lethal medical malpractice cases in penal law are mostly dealt with by experts in forensic medicine since in lethal cases the autopsy is crucial for determining the cause of death. Knowledge of the cause of death, in turn, is the necessary basis of an expert opinion on negligence and the causality between negligence and cause of death. Compared to civil lawsuits filed for malpractice and cases dealt with at the arbitration committees of the medical councils penal lawsuits with 1500 to 2000 cases per year are of minor importance. Our own retrospective multicentre study on lawsuits filed for lethal cases of medical malpractice (based on autopsy findings of 4450 cases) revealed an annual increase in autopsies due to medical negligence from 3 to 6 hundred. Hospital doctors are more frequently affected by medical malpractice claims than private-practice physicians. However, the rate of confirmed medical malpractice cases is much higher for doctors in private practice. Although surgeons are most frequently charged with medical malpractice the rate of confirmed medical malpractice cases is comparatively low in surgery. Medico-legal autopsies in cases of alleged medical malpractice are often ordered by the public prosecutor because the manner of death was classified as unnatural or undetermined. Therefore the often-heard reproach that doctors frequently make mistakes and do their very best to hide them is not true. Thus, it has to be recommended that in a case of unexpected death associated with medical treatment the doctor in his own interest should classify the manner of death as undetermined. PMID:19213446

  5. Some of the cases

    DEFF Research Database (Denmark)

    Eller, Nanna Hurwitz; Mogensen, Jørn Thykjær; Gyntelberg, Finn

    2014-01-01

    matched on age and gender. The cases had experienced significantly fewer incidents of violence and had less anxiety and flashback symptoms than the controls. The results suggest that the negative press coverage was the reason for the psychiatric symptoms rather than exposures at the workplace.......Some of the cases of acknowledged occupational psychiatric disorder in Denmark have been exposed to negative press coverage. Such individuals might have been exposed to violence to a lower extent than other with an acknowledged psychological work injury. We compared 25 cases with 35 controls...

  6. Case File: The Spazzoids

    Science.gov (United States)

    ... classroom activities. More Related Links Healthy Schools Case file: The Spazzzoids Recommend on Facebook Tweet Share Compartir ... your classroom activities. More Related Links Healthy Schools File Formats Help: How do I view different file ...

  7. Neurilemoma. A case report.

    Science.gov (United States)

    Caporusso, J; Cook, M; Bullard, B P; Harkless, L B

    1994-10-01

    In this article, a case report of a patient presenting with "burning pain in the ball of her right foot" is detailed. Topics discussed include the diagnosis, surgical excision, and histopathology. PMID:7812908

  8. Ovarian Cysts. Case Presentation

    International Nuclear Information System (INIS)

    We present the clinical case of a 50 days old girl, born with cystic ovaries, secondary to hormonal stimulation. The clinical diagnosis and management is described and a revision of the literature is made.

  9. USCIS My Case Status

    Data.gov (United States)

    Department of Homeland Security — USCIS provide a way for the public who applied for U.S. citizenship to check the status of their application online. To view the status of a case, the application...

  10. HYDROGEOLOGIC CASE STUDIES

    Science.gov (United States)

    Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

  11. Safety case plan 2008

    International Nuclear Information System (INIS)

    Following the guidelines set forth by the Ministry of Trade and Industry (now Ministry of Employment and Economy) Posiva is preparing to submit the construction license application for a spent fuel repository by the end of the year 2012. The long-term safety section supporting the license application is based on a safety case, which, according to the internationally adopted definition, is a compilation of the evidence, analyses and arguments that quantify and substantiate the safety and the level of expert confidence in the safety of the planned repository. In 2005, Posiva presented a plan to prepare such a safety case. The present report provides a revised plan of the safety case contents mentioned above. The update of the safety case plan takes into account the recommendations made by the Radiation and Nuclear Safety Authority (STUK) about improving the focus and further developing the plan. Accordingly, particular attention is given to the quality management of the safety case work, the management of uncertainties and the scenario methodology. The quality management is based on the ISO 9001:2000 standard process thinking enhanced with special features arising from STUK's YVL Guides. The safety case production process is divided into four main sub-processes. The conceptualisation and methodology sub-process defines the framework for the assessment. The critical data handling and modelling sub-process links Posiva's main technical and scientific activities to the production of the safety case. The assessment sub-process analyses the consequences of the evolution of the disposal system in various scenarios, classified either as part of the expected evolution or as disruptive scenarios. The compliance and confidence sub-process is responsible for final evaluation of compliance of the assessment results with the regulatory criteria and the overall confidence in the safety case. As in the previous safety case plan, the safety case will be based on several reports, but

  12. Leakage behind casing

    OpenAIRE

    Khandka, Rupak Kumar

    2007-01-01

    Achieving zonal isolation by cementing annulus space between casing and well bore is an important job in many oil wells. Gas leakage in the annulus has been recognised as a major completion problem in the oil well. A successful cement job results in complete zonal isolation on a permanent basis. To achieve these goals, various factors such as well security, casing centralization, effective mud removal, and gas migration must be considered in the design. The design of the cement must be such t...

  13. Pseudocide: A Case Report.

    Science.gov (United States)

    Coffey, M Justin; Ahmedani, Brian K

    2016-07-01

    The authors describe a case of "pseudocide" in which the patient appears to have feigned his own suicide. This case was identified as a result of a routine reconciliation of internally collected suicide data with government-collected mortality data. The authors discuss the evolution of the concept of pseudocide in the clinical literature and consider issues related to deceitful and factitious behaviors and suicide surveillance and measurement. PMID:27427845

  14. SIRENOMELIA: A CASE REPORT

    OpenAIRE

    Wankhede,, Mahendra; Shrivastava

    2016-01-01

    The incidence of Sirenomelia is thought to be about 1 in 65,000 live births (Oxford Medical database, Dysmorphology). In Sirenomelia, lower limbs are fused together. Common associated malformations include absent genitalia, imperforate anus, lumbosacral vertebral pelvic abnormalities and renal agenesis. Sirenomelia with craniorachischisis totalis (CT) is a rare fetal malformation, only six cases have been reported in English literature (1-5) and none yet from Asia. Our case is of ...

  15. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  16. Dysphagia aortica: Case report

    OpenAIRE

    Jovančević Ljiljana; Jović Rajko M.; Mitrović Slobodan M.

    2005-01-01

    Introduction Dysphagia aortica is a swallowing condition caused by external compression of the esophagus due to aortic aneurysm or atherosclerotic changes affecting the aorta. The case report on this rare cause of dysphagia should contribute to better diagnosis of dysphagia aortica and swallowing difficulties in general. Case report A 63-year-old male patient was hospitalized duo to a four month history of intermittent swallowing difficulties. Chest radiography showed a widened mediastinum an...

  17. Oral Myiasis : Case Report

    OpenAIRE

    Ramli, Roszalina; Abd Rahman, Roslan

    2002-01-01

    Myiasis occurs when living tissues of mammals are invaded by eggs or larvae of flies, mainly from the order of Diptera. Most of the previousty reported cases are in the tropics and they were usually associated with inadequate personal hygiene, sometimes with poor manual dexterity. This report describes two cases of oral myiasis in cerebral palsy patients in Seremban General Hospital, Malaysia. This article also discusses the therapeutic property of maggots and highlights the importance of ora...

  18. The case for Dounreay

    International Nuclear Information System (INIS)

    This document sets out to state the case for the Commercial Demonstration Fast Reactor and to explain the reasons why it should be situated at Dounreay, Caithness, Scotland. Headings are: the case for CDFR; why should the CDFR be sited in Caithness (Caithness before Dounreay; the social and economic significance of Dounreay; the Caithness economy today; Caithness - the need for jobs); the CDFR and Caithness; conclusions. (U.K.)

  19. a case report

    OpenAIRE

    Snoj, Marko; Kadivec, Maksimiljan; Zebič, Marta; Podobnik, Gašper; Škof, Erik

    2015-01-01

    Background Contralateral breast cancer (CLB) is the most common second primary breast cancer in patients diagnosed with breast cancer. The majority of patients harbouring CLB tumours develop the invasive disease. Almost all invasive carcinomas are believed to begin as ductal carcinoma in situ (DCIS) lesions. The sensitivity of MRI for DCIS is much higher than that of mammography. Case report We report the case of a woman who was treated with breast conserving therapy 10 years ago. At that tim...

  20. Dental autotransplant: case report

    OpenAIRE

    Nathália Martins Pacini; Dirceu Tavares Formiga Nery; Daniel Rey de Carvalho; Normeu Lima Junior; Alexandre Franco Miranda; Sérgio Bruzadelli Macedo

    2012-01-01

    Introduction: The autogenous transplantation or dental autotransplantation is defined as the replacement of an absent or impaired tooth by another transplanted one, usually the third molar. The tooth is transplanted to a prepared or existing tooth socket occupied by the lost tooth, in a same person. This technique is considered a viable method due to its high success rate when properly indicated combined with a relatively low cost. Objective and case report: To report a clinical case study co...

  1. Worst case selection

    International Nuclear Information System (INIS)

    For large safety related DOE facilities, re-evaluation of features to ensure the mitigation of natural phenomena hazards can be costly and require long schedules to implement. This is especially true for features which are numerous and diverse such as building steel structures, concrete structures, masonry/tile walls, tanks, equipment and their anchorages, penetrations to containment vessels, steel platforms, embedded plates, conduit, conduit supports, cable tray, cable tray supports, HVAC ductwork, duct supports, piping and pipe supports. To reduce the cost and time required for re-evaluation, worst cases can be selected from populations of civil features with similar attributes based on drawing reviews, field investigations and review of any available existing calculations. If worst cases then qualify by evaluation or testing, it is reasonable to accept an entire population of features as justified. In addition, when modifications are required for worst cases, further investigation to assess the remaining non-worst case population for the presence of critical attributes, and conditions that contribute to the need for modification of worst cases, can be performed. However to ensure valid results, the methodology and process must be systematic, logical, based on applicable design criteria, traceable, independently verifiable, and reproducible. This paper will offer approaches developed from experiences implementing worst case qualification programs for the upgrade of existing facilities

  2. Unusual Cases of Epidermoid cyst: Case Series

    Directory of Open Access Journals (Sweden)

    Lalita Yadav

    2013-09-01

    Full Text Available In the oro-facial region cystic lesions of different etiologies are encountered owing to the presence of the teeth in the jaw bones. A bewildering variety of developmental, odontogenic and non-odontogenic cysts are seen. Epidermoid cyst is a rare developmental cyst of the oro-facial region which results from entrapped epidermal elements without adnexal appendages. Dermoid and epidermoid cysts occur in oro-facial region with an incidence of 6.9-7% and represents less than 0.01% of all oral cavity cysts. Here we report two cases of epidermoid cysts occurring at unusual locations involving upper left maxillary region lateral to the nose and pinna of the ear.

  3. Indian common krait envenomation presenting as fulminant myocarditis and coma: a case report

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Verma

    2014-08-01

    Full Text Available Fulminant myocarditis is an unusual manifestation of cardiotoxicity with severe elapid snake envenoming and is meagrely reported with snake bite due to Indian common krait. We report a 12-year-old boy who was admitted in complete locked-in state and hemodynamic instability after severe neurotoxic snake envenoming by Bungarus caeruleus (Indian common krait. His hospital course was complicated with recurrent episodes of sustained ventricular tachycardia requiring defibrillation; and cardiogenic shock requiring inotropes, vasopressors and intraaortic balloon counterpulsation. Severe heart failure features secondary to fulminant toxic myocarditis persisted even after full neurological recovery requiring prolonged standard medical heart failure therapy. Patient subsequently achieved full clinical recovery and regained normal left ventricular systolic function. We also reviewed the literature on cardiac manifestations, possible mechanisms and treatment of patients with cardiotoxicity due to elapid snake bites. The importance of anticipating severe cardiovascular complications is highlighted to help formulate appropriate therapeutic strategy. [Int J Res Med Sci 2014; 2(4.000: 1713-1717

  4. MIDAS case studies

    Energy Technology Data Exchange (ETDEWEB)

    Brusger, E.C.; Farber, M.A.; Sharpe Hayes, M.M.

    1989-07-01

    This series of three case studies illustrates the validity and usefulness of MIDAS, a microcomputer-based tool for integrated resource planning under uncertainty. The first, at Union Electric, serves to test and validate the model and to illustrate its use for demand/supply option evaluation. Focusing on nuclear plant life extension, the Virginia Power case demonstrates the model's extensive detail, particularly in the production cost and financial areas, as well as its flexibility in addressing approximately 70 uncertainty scenarios. Puget Sound Power Light, the third case, used MIDAS for the preparation of its integrated resource plan. A 108-endpoint decision tree illustrates the full power of the decision analysis capability.

  5. Repairing leaks in casings

    Energy Technology Data Exchange (ETDEWEB)

    Harris, K.L.; Vinson, E.F.; Bour, D.L.; Ewert, D.P.; Ekstrand, B.B.

    1992-06-23

    This patent describes a method for repairing a hole in a casing disposed in a wellbore. It comprises locating the hole in the casing; isolating the hole by defining a space within the casing in communication with the hole; introducing into the space a volume of a slurry of hydraulic cement in water; permitting the slurry to penetrate into the hole from the space; and maintaining the slurry in the hole for a time sufficient to enable the slurry to form a rigid plug of cement in the hole; wherein the slurry is comprised of a mixture of water and the hydraulic cement in the ratio of from about 0.5 to about 5.0 pounds of water per pound of cement.

  6. BURKING: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Durga Prasad

    2014-08-01

    Full Text Available Homicide means causing death of a person by another person. This homicide may be lawful or unlawful. There are many ways of committing a homicide. Burking is one of the methods. The term ‘Burking’ is derived from notorious criminal ‘Burke’, who with his accomplice ‘Hare’, killed old people by a combination of smothering and traumatic asphyxia, and sold the bodies to the medical school in Edinburgh. We here presented a case of homicide by burking. AIM: To explain the term burking and to present a real case of homicide by burking, which we encountered. MATERIALS & METHODS: Various journal articles, textbooks of Forensic Medicine, FIR copy of the case, crime scene visit, photos, inquest report, post mortem examination, crime investigation information. CONCLUSION: Burking is a type of homicide by smothering with traumatic asphyxia. Though it is rare, it is not completely unseen

  7. Objectivist case study research

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Fachner, Jörg

    2016-01-01

    In order to comprehend the impact of music therapy or music therapy processes, a researcher might look for an approach where the topic under investigation can be understood within a broader context. This calls for a rich inclusion of data and consequently a limited number of participants and may be...... achieved through the use of objectivist case study research. The strength of the case study design is that it allows for uncovering or suggesting causal relationships in real-life settings through an intensive and rich collection of data. According to Hilliard (1993), the opposite applies for extensive...... designs, in which a small amount of data is gathered on a large number of subjects. With the richness of data, the intensive design is ―the primary pragmatic reason for engaging in single-case or small N research‖ (p. 374) and for working from an idiographic rather than a nomothetic perspective....

  8. Craniosynostoses. A case presentation.

    Directory of Open Access Journals (Sweden)

    Barbara Aleida García Hernández

    2008-12-01

    Full Text Available A case of a three-month female infant who was born in an ectopic and institutional delivery is described. His parents are healthy and came to the consultation office due to an enlargement in the posterior part of the head. Precocious Hyperostosis due to synostoses of the sagittal and diastasis suture of the lambdoidal suture was confirmed in the radiography. It was decide to put the patient under surgical treatment after assessing the case with a neurosurgeon. An early diagnosis and treatment of this non frequent disease are of great importance because it does not permit a presentation of neurological sequelae.

  9. Two cases of tetanus?

    Science.gov (United States)

    Horn, Janneke; Vroom, Margreeth B; Tijssen, Marina A J; Schultz, Marcus J

    2006-01-01

    Tetanus is a rare infectious disease in Western countries that leads to diagnostic difficulties. Several diseases may mimic tetanus, and diagnostic considerations can at times be difficult, especially in critically ill patients, who need prompt treatment. Two patients are presented who were diagnosed with and treated for tetanus. However, the course of these patients' diseases strongly suggested that the diagnoses were incorrect. The article includes reflections on these 2 difficult diagnostic cases. These 2 cases illustrate the importance of proposing alternative diagnoses in suspected tetanus in Western countries. This may prevent loss of valuable time and prevent a delay of possibly effective therapy. PMID:17121213

  10. Asiakkuuksienhallinta : case Yritys X

    OpenAIRE

    Könönen, Maarit

    2013-01-01

    Tämä opinnäytetyö käsittelee asiakkuudenhallintaa ja sen kehittämistä. Tutkimuk-sen tavoitteena oli selkiyttää mitä asiakkuudenhallinta case yrityksessä tarkoittaa ja millaisia toimenpiteitä yrityksessä tulisi tehdä asiakkuuksienhallinnan kehittä-miseksi. Samalla kartoitettiin, millaista informaatiota asiakkuudenhallinnassa tarvitaan johtamisen ja päätöksenteon tueksi, ja mihin asiakastietoa kootaan. Tutkimuskysymykseksi muotoutui, mitä asiakkuuksienhallinta case-yrityksessä tulisi olla ja mi...

  11. Tinea incognito: Case series

    Directory of Open Access Journals (Sweden)

    Mikail Yılmaz

    2015-09-01

    Full Text Available Tinea incognito is a dermatophytic infection which has lost its typical clinical appearance because of inappropriate use of topical or systemic corticosteroids. The clinical manifestations of tinea incognito can mimic many dermatoses such as eczema, psoriasis, allergic contact dermatitis, rosacea, seborrheic dermatitis and atopic dermatitis. The diagnosis of tinea incognito is confirmed by direct KOH (potassium hydroxide examination ( native preparation, making the fungal cultures from the lesion and histopathological examination in some cases. Systemic antifungal therapy is recommended in the treatment of tinea incognito. Herein, 10 cases of tinea incognito which mimicking various dermatoses were diagnosed and treated in our clinic in 2014 is presented.

  12. Pseudoxanthoma elasticum. Case presentation

    Directory of Open Access Journals (Sweden)

    Graciela Caridad Cabrera Acea

    2009-05-01

    Full Text Available The case of a female patient of 23 years of age is presented. The patient attended to the dermatology consultation in her health area for skin lesions in the neck area, of 10 years of evolution with new lesions after three years in different parts of her body (armpits, periumbilical, vaginal and rectal regions. These lesions present an aspect similar to orange skin, surrounded by yellow papules. the diagnosis was pseudoxanthoma elasticum after the clinical and histopathological analysis, and the perimetry. We present this case since this is an infrequent disease and for the importance of an early diagnosis of skin lesions in a systemic disease.

  13. Melioidosis: a case report.

    Science.gov (United States)

    Barman, Purabi; Sidhwa, Harish; Shirkhande, Pinak A

    2011-04-01

    Burkhloderia pseudomallei has recently gained importance as an emerging pathogen in India. It causes various clinical manifestations like pneumoniae, septicaemia, arthritis, abscess etc. Cases have been reported from Southeast Asia mainly Thailand, Malaysia, Vietnam, etc. In India, few cases have been reported mainly from the southern part of the country. Patient was a 65-year-old male and presented with fever 1 month back, cough and breathlessness for same period, swelling on both ankles from 7 days. B. pseudomallei was isolated from endotracheal secretions, blood cultures, leg wound. He was successfully treated with Imipenem and Doxycycline and put on maintenance therapy now, and is currently doing well. PMID:21731307

  14. Melioidosis: A case report

    Directory of Open Access Journals (Sweden)

    Purabi Barman

    2011-01-01

    Full Text Available Burkhloderia pseudomallei has recently gained importance as an emerging pathogen in India. It causes various clinical manifestations like pneumoniae, septicaemia, arthritis, abscess etc. Cases have been reported from Southeast Asia mainly Thailand, Malaysia, Vietnam, etc. In India, few cases have been reported mainly from the southern part of the country. Patient was a 65-year-old male and presented with fever 1 month back, cough and breathlessness for same period, swelling on both ankles from 7 days. B. pseudomallei was isolated from endotracheal secretions, blood cultures, leg wound. He was successfully treated with Imipenem and Doxycycline and put on maintenance therapy now, and is currently doing well.

  15. Hematologic case: Fanconi anemia

    OpenAIRE

    Nascimento, P.; Costa, E; Porto, B.; Barbot, J.

    2010-01-01

    The authors present the case of a child with complex congenital heart defect, bilateral malformation of the thumbs, hearing loss, failure to thrive and delayed psychomotor development, oriented to the hematology consultation at the age of 9 years for the presence of thrombocytopenia and macrocytosis.

  16. Aglossia: A case report

    OpenAIRE

    Kumar Prashant; Chaubey K

    2007-01-01

    A female child of 4 years with congenital absence of tongue has been described. This anomaly is usually associated with other congenital defects particularly limb and other cranio-facial defects. But in this case, the child enjoys the normal life, the unusual absence of tongue; she used to go to school play around with her friends and had a comparable I.Q.

  17. Apert Syndrome. Case Report

    Directory of Open Access Journals (Sweden)

    Ninecta Pérez Breña

    2010-08-01

    Full Text Available The case of a white female aged 7 is evaluated in the Primary Care Service of the Barrio Adentro medical mission in Nueva Esparta state, Republic of Venezuela. After a clinical and radiological evaluation she is diagnosed with a genetic syndrome known as Apert Syndrome.

  18. Whipple's disease: a case

    International Nuclear Information System (INIS)

    Whipple's disease, or intestinal lipodystrophy, is an uncommon systemic pathology which generally involves small bowel, but occasionally presents at an extra intestinal site. The clinical onset usually consists of the classical triad of diarrhea, arthralgias and fever, and the definitive diagnosis is based on the histological study. We present a case diagnosed by computed tomography (CT) and confirmed by intestinal biopsy. (Author)

  19. Nesidioblastosis: a case study.

    Science.gov (United States)

    Starbuck, A L

    1997-09-01

    Hypoglycemia is a common problem among neonates. Transient in nature, it usually resolves with an increase in glucose intake. However, as clinicians, we must recognize that prolonged hypoglycemia may be caused by increased insulin production. Nesidioblastosis is one cause of persistent hyperinsulinism of the newborn. This case study reviews fetal physiology, neonatal presentation, and treatment. PMID:9325879

  20. Querying Safety Cases

    Science.gov (United States)

    Denney, Ewen W.; Naylor, Dwight; Pai, Ganesh

    2014-01-01

    Querying a safety case to show how the various stakeholders' concerns about system safety are addressed has been put forth as one of the benefits of argument-based assurance (in a recent study by the Health Foundation, UK, which reviewed the use of safety cases in safety-critical industries). However, neither the literature nor current practice offer much guidance on querying mechanisms appropriate for, or available within, a safety case paradigm. This paper presents a preliminary approach that uses a formal basis for querying safety cases, specifically Goal Structuring Notation (GSN) argument structures. Our approach semantically enriches GSN arguments with domain-specific metadata that the query language leverages, along with its inherent structure, to produce views. We have implemented the approach in our toolset AdvoCATE, and illustrate it by application to a fragment of the safety argument for an Unmanned Aircraft System (UAS) being developed at NASA Ames. We also discuss the potential practical utility of our query mechanism within the context of the existing framework for UAS safety assurance.

  1. : Case studies: France

    OpenAIRE

    Bonerandi, Emmanuelle; Santamaria, Frédéric

    2005-01-01

    Case studies on territorial governance : urban region of Lyon (France) and the "Pays" policy (France) in the framework of the ESPON 2.3.2 project Études de cas sur la gouvernance territoriale : région urbaine de Lyon et politique des pays

  2. An unexpected tetanus case.

    Science.gov (United States)

    Ergonul, Onder; Egeli, Demet; Kahyaoglu, Bulent; Bahar, Mois; Etienne, Mill; Bleck, Thomas

    2016-06-01

    1 million cases of tetanus are estimated to occur worldwide each year, with more than 200 000 deaths. Tetanus is a life-threatening but preventable disease caused by a toxin produced by Clostridium tetani-a Gram-positive bacillus found in high concentrations in soil and animal excrement. Tetanus is almost completely preventable by active immunisation, but very rarely unexpected cases can occur in individuals who have been previously vaccinated. We report a case of generalised tetanus in a 22-year-old woman that arose despite the protective antitoxin antibody in her serum. The patient received all her vaccinations in the USA; her last vaccination was 6 years ago. The case was unusual because the patient had received all standard vaccinations, had no defined port of entry at disease onset, and had symptoms lasting for 6 months. Tetanus can present with unusual clinical forms; therefore, the diagnosis and management of this rare but difficult disease should be updated. In this Grand Round, we review the clinical features, epidemiology, treatment, and prognosis of C tetani infections. PMID:27301930

  3. Intercultural Communicative Case Study

    Institute of Scientific and Technical Information of China (English)

    吴冬梅

    2009-01-01

    The essay is mainly about the author's comprehension of cultural differences and intercultural communication after reading the book Communication Between Cultures.In addition,the author also analyses three cases with the theories and approaches mentioned in Communication Between Cultures.

  4. Test Case Generation Based on Use case and Sequence Diagram

    OpenAIRE

    Santosh Kumar Swain; Durga Prasad Mohapatra; Rajib Mall

    2010-01-01

    We present a comprehensive test case generation technique from UML models. We use the features in UML 2.0 sequence diagram including conditions, iterations, asynchronous messages and concurrent components. In our approach, test cases are derived from analysis artifacts such as use cases, their corresponding sequence diagrams and constraints specified across all these artifacts. We construct Use case Dependency Graph (UDG) from use case diagram and Concurrent Control Flow Graph (CCFG) from cor...

  5. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    OpenAIRE

    T. Scott Devera; Prusator, Dawn K.; Joshi, Sunil K.; Ballard, Jimmy D.; Lang, Mark L.

    2015-01-01

    Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefo...

  6. Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations

    OpenAIRE

    Corrias, A.; Jie, X.; Romero, L.; Bishop, M. J.; Bernabeu, M.; Pueyo, E.; Rodriguez, B.

    2010-01-01

    In this paper, we illustrate how advanced computational modelling and simulation can be used to investigate drug-induced effects on cardiac electrophysiology and on specific biomarkers of pro-arrhythmic risk. To do so, we first perform a thorough literature review of proposed arrhythmic risk biomarkers from the ionic to the electrocardiogram levels. The review highlights the variety of proposed biomarkers, the complexity of the mechanisms of drug-induced pro-arrhythmia and the existence of si...

  7. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: role of echocardiography.

    Science.gov (United States)

    Zito, Concetta; Longobardo, Luca; Cadeddu, Christian; Monte, Ines; Novo, Giuseppina; Dell'Oglio, Sonia; Pepe, Alessia; Madonna, Rosalinda; Tocchetti, Carlo G; Mele, Donato

    2016-05-01

    The evaluation by cardiovascular imaging of chemotherapy patients became a central topic in the last several years. The use of drugs for the treatment of cancers increased, and new molecules and protocols were developed to improve outcomes in these patients. Although, these novel approaches also produced a progressive increase in side effects, particularly myocardial dysfunction. Imaging of the heart was highly accurate in the early diagnosis of cancer therapeutics related-cardiac dysfunction. Echocardiography is the first-line method to assess ventricular function alterations, and it is required to satisfy the need for an early, easy and accurate diagnosis to stratify the risk of heart failure and manage treatments. A careful monitoring of cardiac function during the course of therapy should prevent the onset of severe heart impairment. This review provides an overview of the most important findings of the role of echocardiography in the management of chemotherapy-treated patients to create a clear and complete description of the efficacy of conventional measurements, the importance of comprehensive heart evaluations, the additional role of new echocardiographic techniques, the utility of integrated studies using other imaging tools and the positions of the most important international societies on this topic. PMID:27183524

  8. [Correction of cardiotoxic effect of chronic alcoholic intoxication by GABA-ergic compounds].

    Science.gov (United States)

    Perfilova, V N; Tiurenkov, I N; Lebedeva, S A

    2007-01-01

    Toxic effect of 50% ethanol solution (8 g/kg) on the heart appeared as diminishment of contractile properties of the myocardium. Structural GABA-analogues - citrocard (50 mg/kg), phenibut (50 mg/kg) and pyracetam (200 mg/kg) prevented injurious action of alcohol. This was evidenced by higher indices of contraction and relaxation velocity, and left ventricular pressure in intervention groups of animals compared with controls during functional tests with volume and maximal isometric load. PMID:18260875

  9. Cardioprotective effect of royal jelly on paclitaxel-induced cardio-toxicity in rats

    Directory of Open Access Journals (Sweden)

    Hassan Malekinejad

    2016-02-01

    Full Text Available Objective(s:Paclitaxel is a potent chemotherapy agent with severe side effects, including allergic reactions, cardiovascular problems, complete hair loss, joint and muscle pain, which may limit its use and lower its efficiency. The cardioprotective effect of royal jelly was investigated on paclitaxel-induced damages. Materials and Methods:Adult male Wistar rats were divided into control and test groups (n=8. The test group was assigned into five subgroups; 4 groups, along with paclitaxel administration (7.5 mg/kg BW, weekly, received various doses of royal jelly (50, 100, and 150 mg/kg BW for 28 consecutive days. The last group received only royal jelly at 100 mg/kg. In addition to oxidative and nitrosative stress biomarkers, the creatine kinase (CK-BM level was also determined. To show the cardioprotective effect of royal jelly on paclitaxel-induced damages, histopathological examinations were conducted. Results:Royal jelly lowered the paclitaxel-elevated malondialdehyde and nitric oxide levels in the heart. Royal jelly could also remarkably reduce the paclitaxel-induced cardiac biomarker of creatine kinase (CK-BM level and pathological injuries such as diffused edema, hemorrhage, congestion, hyaline exudates, and necrosis. Moreover, royal jelly administration in a dose-dependent manner resulted in a significant (P

  10. Cardiotoxicity screening: a review of rapid-throughput in vitro approaches.

    Science.gov (United States)

    Li, Xichun; Zhang, Rui; Zhao, Bin; Lossin, Christoph; Cao, Zhengyu

    2016-08-01

    Cardiac toxicity represents one of the leading causes of drug failure along different stages of drug development. Multiple very successful pharmaceuticals had to be pulled from the market or labeled with strict usage warnings due to adverse cardiac effects. In order to protect clinical trial participants and patients, the International Conference on Harmonization published guidelines to recommend that all new drugs to be tested preclinically for hERG (Kv11.1) channel sensitivity before submitting for regulatory reviews. However, extensive studies have demonstrated that measurement of hERG activity has limitations due to the multiple molecular targets of drug compound through which it may mitigate or abolish a potential arrhythmia, and therefore, a model measuring multiple ion channel effects is likely to be more predictive. Several phenotypic rapid-throughput methods have been developed to predict the potential cardiac toxic compounds in the early stages of drug development using embryonic stem cells- or human induced pluripotent stem cell-derived cardiomyocytes. These rapid-throughput methods include microelectrode array-based field potential assay, impedance-based or Ca(2+) dynamics-based cardiomyocytes contractility assays. This review aims to discuss advantages and limitations of these phenotypic assays for cardiac toxicity assessment. PMID:26676948

  11. p21WAF1/Cip1/Sdi1 knockout mice respond to doxorubicin with reduced cardiotoxicity

    International Nuclear Information System (INIS)

    Doxorubicin (Dox) is an antineoplastic agent that can cause cardiomyopathy in humans and experimental animals. As an inducer of reactive oxygen species and a DNA damaging agent, Dox causes elevated expression of p21WAF1/Cip1/Sdi1 (p21) gene. Elevated levels of p21 mRNA and p21 protein have been detected in the myocardium of mice following Dox treatment. With chronic treatment of Dox, wild type (WT) animals develop cardiomyopathy evidenced by elongated nuclei, mitochondrial swelling, myofilamental disarray, reduced cardiac output, reduced ejection fraction, reduced left ventricular contractility, and elevated expression of ANF gene. In contrast, p21 knockout (p21KO) mice did not show significant changes in the same parameters in response to Dox treatment. In an effort to understand the mechanism of the resistance against Dox induced cardiomyopathy, we measured levels of antioxidant enzymes and found that p21KO mice did not contain elevated basal or inducible levels of glutathione peroxidase and catalase. Measurements of 6 circulating cytokines indicated elevation of IL-6, IL-12, IFNγ and TNFα in Dox treated WT mice but not p21KO mice. Dox induced elevation of IL-6 mRNA was detected in the myocardium of WT mice but not p21KO mice. While the mechanism of the resistance against Dox induced cardiomyopathy remains unclear, lack of inflammatory response may contribute to the observed cardiac protection in p21KO mice. -- Highlights: ► Doxorubicin induces p21 elevation in the myocardium. ► Doxorubicin causes dilated cardiomyopathy in wild type mice. ► p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. ► Lack of inflammatory response correlates with the resistance in p21 knockout mice.

  12. VENTRICULAR LATE POTENTIALS - ANOTHER EXPRESSION OF CARDIOTOXICITY OF CYTOSTATIC DRUGS IN CHILDREN

    NARCIS (Netherlands)

    TAMMINGA, RYJ; BINKBOELKENS, MTE; KIEVIT, J

    1992-01-01

    With the aim of finding a sensitive method to detect early anthracycline-induced myocardial damage ultimately resulting in cardiomyopathy, we studied the occurrence of ventricular late potentials, using a signal averaged electrocardiogram, in 68 children with cancer during or after chemotherapy. Ten

  13. Cardiotoxicity study of the aqueous extract of corn silk in rats

    Directory of Open Access Journals (Sweden)

    Adeolu Adedapo

    2016-03-01

    Full Text Available In the ear of corn there are silky strands which run its length and these strands are known as corn silks. Folk remedies show that the corn silks have been used as an oral antidiabetic agent in China for many years and as herbal tea in other world nations for the amelioration of urinary tract infection. The extract is being assessed for safety in this study using histopathological changes, as well as an electrocardiogram (ECG. Graded doses (200, 400 and 800 mg/kg of aqueous CS extract were administered to rats for seven days. The fourth group which served as control received 3 ml/kg dose of distilled water. On the eighth day, ECG was evaluated in ketamine/xylazine-induced anaesthesia in rats to determine changes in the heart rate, P-wave duration, P-R interval, R-amplitude, QRS duration, QT interval and QTc. Hearts from the experimental animals were collected for histopathological changes. The results showed that there was a significant change in the heart rate (groups B and C, P-wave duration (group D, QT interval (groups B, C and D and QTc (groups B, C and D when compared to the control group. Histology also indicated that sections of the heart showed fatty infiltration of inflamed heart and areas of moderate inflammation of the atrium and ventricle. It could therefore be concluded from this study that though folklore indicated that corn silk (CS is of high medicinal value, one must be careful in using this product as medicinal agent especially in patients with compromised heart conditions.

  14. Indication of doxorubicin cardiotoxicity by impairment of pIPPA I 131 utilization

    International Nuclear Information System (INIS)

    The present study was designed to evaluate if doxorubicin (D) can impair myocardial fatty acid utilization. To this end we studied the myocardial utilization of pIPPA I 131 in untreated (Co, n=6) and D (20 mg/kg intraperitoneal) treated rats. D was given 24 h (24 D, n=6) and 48 hours (48 D, n=6) before tracer administration. One min after i.v. pIPPA I 131 (50 μCi) injection, the hearts were rapidly removed, frozen in liquid nitrogen, weighed, and counted. Following lipid extraction of homogenized heart extracts 131 I radioactivity distribution was analyzed by thin-layer chromatographity (TLC). In additional rat experiments, high energy phosphates (12 rats/group) and carnitine (20 rats/group) were determined enzymatically in heart extracts. The mean pIPPA uptake in rat heart (%dose/g) was 2.49 in Co, 1.74 in 24 D, and 2.36 in 48 D rats. Usually five peaks were separated by TLC, that with a mean Rf value of 0.92 corresponding to pIPPA I 131, the remaining four representing catabolites of pIPPA metabolism. The mean relative amount of unmetabolized pIPPA I 131 as compared to the sum of pIPPA I 131 catabolites was less in Co than in 24 D or 48 D rats (P<0.05) (anti x: 46.5% vs 72.4% vs 59.4%, respectively). The mean carnitine content of H extracts was higher in Co (0.55 μM/g) than in D treated rats (24 D, 0.42 μM/g; 48 D, 0.46 μM/g) (P<0.05). The total amount of higher energy phosphates was not different between the groups. However the mean ATP/AMP ratio was higher in Co (35.9) than in 24 D (22.3) or 48 D (27.1) rats (P<0.05). We conclude that D therapy is accompanied by a partial reversible impairment in myocardial pIPPA utilization, possibly mediated by carnitine deficiency. Thus, pIPPA I 131 might be useful in patients on D therapy to evaluate eventual D-induced effects on myocardial fatty acid utilization. (orig.)

  15. The influence of diclofenac and ketoprofen on the cardiotoxicity in rats

    OpenAIRE

    Boris Milijasevic

    2010-01-01

    Introduction. Diclofenac and ketoprofen are drugs from the group of Non steroidal anti-inflammatory drugs with good therapeutical effect and with a great consumption. New literature data show increased frequency of acute myocardial infarction with use of these drugs, especially diclofenac, but after use of ketoprofen risk is significantly lower.The aim of study was to investigate influence of diclofenac and ketoprofen on rat myocardial sensitivity to adrenaline, verapamil and lidocaine, as al...

  16. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

    OpenAIRE

    Sayed-Ahmed, Mohamed M; Darweesh, Amal Q.; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with ...

  17. The Protective Effects of Silymarin against Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity in Rats

    OpenAIRE

    Momir Mikov; Saša Vukmirović; Jovanka Kolarović; Velibor Vasović; Aleksandar Rašković; Nebojša Stilinović

    2011-01-01

    Silymarin is a complex of five major compounds, and silibinin is the most biologically active component of the complex. The aim of this study was to investigate, evaluate and confirm the potential cardioprotective and hepatoprotective effects of administration of silymarin, rich in silibinin, at a dose of 60 mg/kg orally for a time-span of 12 days on doxorubicin induced toxicity in male Wistar rats. The in vivo model was used to explore whether silymarin could prevent damage of liver and hear...

  18. The Protective Effects of Silymarin against Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Momir Mikov

    2011-10-01

    Full Text Available Silymarin is a complex of five major compounds, and silibinin is the most biologically active component of the complex. The aim of this study was to investigate, evaluate and confirm the potential cardioprotective and hepatoprotective effects of administration of silymarin, rich in silibinin, at a dose of 60 mg/kg orally for a time-span of 12 days on doxorubicin induced toxicity in male Wistar rats. The in vivo model was used to explore whether silymarin could prevent damage of liver and heart tissue induced by doxorubicin administered every other day at dose of 1.66 mg/kg intraperitoneally for twelve days. In the study the change of body weight, ECG changes, biochemical parameters of oxidative stress, serum activity of alanine and aspartate transaminase, lactate dehydrogenase, creatine kinase and histological preparations of heart and liver samples of treated animals were examined. According to physiological, pharmacological, microscopic and biochemical results, we confirmed that at the examined dose, silymarin exhibits a protective influence on the heart and liver tissue against toxicity induced by doxorubicin.

  19. Pro1170 Ala polymorphism in HER2-neu is associated with risk of trastuzumab cardiotoxicity

    OpenAIRE

    Stanton, Sasha E; Ward, Maureen M.; Christos, Paul; Sanford, Rachel; Lam, Christina; Cobham, Marta V; Donovan, Diana; Scheff, Ronald J; Cigler, Tessa; Moore, Anne; Vahdat, Linda T.; Lane, Maureen E.; Chuang, Ellen

    2015-01-01

    Background Variations in single nucleotide polymorphisms (SNPs) have been associated with enhanced drug efficacy and toxicity in cancer therapy. SNP variations in the ErbB2 gene have been identified that alter the protein sequence of the HER2-neu protein, but how these polymorphisms affect prognosis and response to HER2 targeted therapy is unknown. We examined eleven ErbB2 SNPs that alter the HER2-neu amino acid sequence to determine whether any of these particular polymorphisms were associat...

  20. Cardiotoxic effects of venoms from Chironex fleckeri and Chiropsalmus sp. on an invertebrate model

    Directory of Open Access Journals (Sweden)

    T. Carrette

    2006-04-01

    Full Text Available Extracted venoms from two species of cubozoan, Chironex fleckeri (C. fleckeriand Chiropsalmus sp., were injected into the freshwater crayfish Cherax quadricarinatus (C. quadricarinatus. By means of a Vascular Doppler, the cardiac parameters heart rate and contraction amplitude were recorded, with the theoretical total heart output calculated from these two recordings. Cherax quadricarinatus reflects prey items utilized by these two species in the wild and so comparisons of venom action on this animal have greater ecological relevance than those of previous mammalian models used. While the results of this study reflect previous research showing that the overall potency of C. fleckeri venom is greater than that of Chiropsalmus sp. venom, the action of the venoms on the heart muscle is found to be different. Chironex fleckeri,which has the most potent venom out of these two species, is actually less effective in reducing cardiac activity than Chiropsalmus sp., which may be a direct reflection of the variation in primary prey utilized by each species.

  1. Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

    OpenAIRE

    Brindha, E.; Rajasekapandiyan, M.

    2015-01-01

    This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50...

  2. Acute Cardiotoxicity Evaluation of the Marine Biotoxins OA, DTX-1 and YTX

    OpenAIRE

    Sara F. Ferreiro; Cristina Carrera; Natalia Vilariño; M. Carmen Louzao; Germán Santamarina; Cantalapiedra, Antonio G.; Botana, Luis M.

    2015-01-01

    Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA) and dynophysistoxins (DTXs) are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP). Yessotoxins (YTXs) are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from sever...

  3. Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

    Science.gov (United States)

    The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

  4. Odontoameloblastoma: A case report

    Directory of Open Access Journals (Sweden)

    Amita Negi

    2015-01-01

    Full Text Available Odontoameloblastoma (OA is an extremely rare odontogenic tumor that contains an ameloblastomatous component together with odontoma-like elements. Till date, very few cases have fulfilled the criteria of the current World Health Organization classification of odontogenic tumors. It is characterized by slow, progressively growing lesion with growth pattern similar to solid multi-cystic ameloblastoma. The majority of the tumors are associated with unerupted teeth and commonly seen in males. It is usually asymptomatic and may occur in either maxilla or mandible, but shows a slight predilection for mandible. As this tumor is extremely rare, there exists controversy regarding its treatment. Here, we present a case of OA in 17-year-old female patient resembling a fibro-osseous lesion and a brief review of the related literature.

  5. Odontoameloblastoma: A case report.

    Science.gov (United States)

    Negi, Amita; Puri, Abhiney; Nangia, Rajat; Sachdeva, Alisha

    2015-01-01

    Odontoameloblastoma (OA) is an extremely rare odontogenic tumor that contains an ameloblastomatous component together with odontoma-like elements. Till date, very few cases have fulfilled the criteria of the current World Health Organization classification of odontogenic tumors. It is characterized by slow, progressively growing lesion with growth pattern similar to solid multi-cystic ameloblastoma. The majority of the tumors are associated with unerupted teeth and commonly seen in males. It is usually asymptomatic and may occur in either maxilla or mandible, but shows a slight predilection for mandible. As this tumor is extremely rare, there exists controversy regarding its treatment. Here, we present a case of OA in 17-year-old female patient resembling a fibro-osseous lesion and a brief review of the related literature. PMID:26604505

  6. Company cases Denmark

    DEFF Research Database (Denmark)

    Tølle, Martin; Pedersen, Jørgen Lindgaard

    2005-01-01

    The Danish part of the publication describes two Danish cases with foreign companies taking over Danish companies. The first case is from software industry where Datacentralen (DC) was taken over by American company Computer Sciences Corporation (CSC) in 1986. DC delivered IT - solutions for...... - solitions. CSC wanted to buy DC to penetrate the Nordic market. Some effects can be mentioned: Employment in CSC - DK is in 2003 1,700 persons or 2,600 including other companies bought up recently. In innovation positive effects can be registered from contacts with CSC - International. Not only from access...... - Laboratoriet, Benzon - Pharma and Pharma - Medica during years 1988 - 1991.Nycomed wants to establish itself as a company on European level.After a decade with different owners, fusions and splitting ups a construction in which head quarter and R&D move to Denmark close to Copenhagen. The importance of that...

  7. [Pharyngeal tuberculosis: Case report].

    Science.gov (United States)

    Spini, Roxana Gabriela; Bordino, Lucas; Cohen, Daniela; Martins, Andrea; Ramírez, Zaida; González, Norma E

    2015-08-01

    Pharyngeal tuberculosis is a rare extrapulmonary manifestation. In Argentina, the number of cases of tuberculosis reported in children under 19 years in 2012 was 1752. Only 12.15% had extrapulmonary manifestation. A case of a 17 year old girl with pharyngeal tuberculosis is reported. The patient presented intermittent fever and swallowing pain for 6 months, without response to conventional antibiotic treatment. Chest X-ray showedbilateral micronodular infiltrate, so hospitalization was decided to study and treat. The sputum examination for acid-fast resistant bacilli was positive and treatment with four antituberculous drugs was started, with good evolution and disappearance of symptoms. Diagnostic confirmation with the isolation of Mycobacterium tuberculosis in sputum culture was obtained. The main symptoms of pharyngeal tuberculosis are sore throat and difficulty in swallowing of long evolution. It is important to consider tuberculosis as differential diagnosis in patients with chronic pharyngitis unresponsive to conventional treatment. PMID:26172025

  8. Executable Use Cases

    DEFF Research Database (Denmark)

    Jørgensen, Jens Bæk; Bossen, Claus

    2004-01-01

    that eventually and inevitably emerges during system implementation; and spur communication between users and system developers. Iterative prototyping is a feasible starting point to pursue these goals. But EUCs encompass both iterative prototyping and explicit environment descriptions in terms of...... workflow modeling. This article describes a case study in which developers used EUCs to prototype an electronic patient record system for hospitals in Aarhus, Denmark....

  9. Dealing with RSPCA cases

    OpenAIRE

    Mason, Jane; Blackwood, I.

    2010-01-01

    The Animal Welfare Sub-Unit of the NSW Department of Industry and Investment, in association with some members of the Extensive Livestock Industry and Development (ELID) sheep and beef team, have been developing procedures and training to help District Livestock Officers (DLOs) deal with RSPCA cases involving failure to provide animals with food. These procedures are being developed to ensure evidence collected will withstand a courtroom cross-examination. The resources developed will be exte...

  10. Case record analysis

    OpenAIRE

    Whitaker, Simon

    2009-01-01

    It is argued that the determinates of low frequency (less than once an hour) challenging behavior are likely to be more complex than those of high frequency behavior involving setting events that may not be present when the behavior occurs. The analysis of case records is then examined as a method of identifying possible setting events to low frequency behaviours. It is suggested that time series analysis, correlational analysis and time lag sequential analysis may all be useful methods in th...

  11. The Quinlan case revisited.

    Science.gov (United States)

    Frader, Joel

    1996-01-01

    ... The point is that although physicians and hospitals (and their legal counsel) certainly feared in the 1970s and still fear prosecution and civil liability (and perhaps to an unreasonable degree), neither the complex psychosocial and economic nor the equally complex philosophical questions surrounding stopping artificial life support were settled at the time of the Quinlan case, and they are still not settled today. Perhaps our legal history does not need to be revised all that much. PMID:11644806

  12. Two cases with dysferlinopathy

    Directory of Open Access Journals (Sweden)

    Gaye Eryaşar

    2011-03-01

    Full Text Available Dysferlinopathy includes a rare spectrum of muscle disease characterized by two main phenotypes: Miyoshi myopathy(MM and Limb Girdle muscular dystrophy(LGMD 2B and results from a mutation of the gene that codes dysferline protein (DYSF gene, 2p13. In this report, we present 2 cases with dysferlinopathy whose diagnosis were confirmed by clinical and muscle biopsy findings.

  13. NECROTIZING SIALOMETAPLASIA. CASE REPORT

    OpenAIRE

    A.I. Navazo Eguía; F. García Vicario; E. Suárez Muñiz; M.C. Gutiérrez Ortega

    2010-01-01

    Introduction: Necrotizing sialometaplasia (NSM) is a benign lesion affecting the salivary glands mainly in the hard palate. It presents as an ulcer with irregular borders, slightly elevated and necrotic The differential diagnosis should include malignant neoplasms. Case Report: A 26-year-old woman sought medical advice for a painful 2 cm ulceration of the hard palate. She is carrying pierced tongue. The patient had a history of cigarette smoking, chronic anxiety disorder and bulimia,. Analyti...

  14. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  15. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Cystic fibrosis is a autosomal recessive genetic disease. Among caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  16. Rotordynamic Stability Case Studies

    OpenAIRE

    Choudhury Pranabesh

    2004-01-01

    In this article case studies are presented involving rotordynamic instability of modern high-speed turbomachinery relating the field data to analytical methods. The studies include oil seal related field problems, instability caused by aerodynamic cross-coupling in high-pressure, high-speed compressors, and hydrodynamic bearing instability resulting in subsynchronous vibration of a high-speed turbocharger. It has been shown that the analytical tools not only help in problem diagnostics, bu...

  17. Corporate Governance. Case Studies

    OpenAIRE

    Manuel, Eduardo

    2007-01-01

    This paper pretends to do a theoretical approach of Corporate Governance, having as support some case studies about companies like Coca-Cola, Nokia, Microsoft, and Amazon.com. The methodology adopted for this work is based in information from these companies available in their websites and annual reports. I concluded that both companies show the corporate governance components according to their core business and their environmental business.

  18. Case study - Czechoslovakia

    International Nuclear Information System (INIS)

    In the lecture Case Study - Czechoslovakia with the sub-title 'Unified System of Personnel Preparation for Nuclear Programme in Czechoslovakia' the actual status and the current experience of NPP personnel training and preparation in Czechoslovakia are introduced. The above mentioned training system is presented and demonstrated by the story of a proxy person who is going to become shift engineer in a nuclear power plant in Czechoslovakia. (orig./HP)

  19. Cystic fibrosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui [Gachon Medical School, Inchon (Korea, Republic of)

    2002-12-01

    Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis.

  20. Phagophobia: a case report

    OpenAIRE

    Suraweera, Chathurie; Hanwella, Raveen; de Silva, Varuni

    2014-01-01

    Background Phagophobia is a rare disorder and the literature is sparse. There is no specific treatment described for this life threatening condition. Case presentation The patient is a 25-year-old Sri Lankan female with recurrent difficulty in swallowing. Following her initial episode which lasted one year, she presented to us with inability to swallow for one week. She was dependent on liquids and semisolids. The medical team confidently excluded an organic cause. She had difficulty swallowi...

  1. Otocephaly: a case report

    OpenAIRE

    Anshu Sharma; Amrutha K. V.; Joseph Abraham; Mahesh Sharma

    2016-01-01

    A case of otocephaly was reported in 26+/-4 week's female fetus during routine fetal autopsy at GMCH, Chandigarh, India. Mother was 25 years old, second gravid. The first child is one year old normal male baby. Present pregnancy resulted in spontaneous abortion. Antenatal history, past history, family history and medical history of mother was not suggestive of any ethiological factor responsible for the defect. The external examination showed 2 vessels in umbilical cord. There was anteroposte...

  2. Four cases of pneumomediastinum

    OpenAIRE

    Aujayeb, Avinash; Miller, Jonathan; Weatherhead, Mark; Cooper, David

    2015-01-01

    Pneumomediastinum or mediastinal emphysema is defined as the presence of air in the mediastinum, the central compartment of the thoracic cavity that contains the heart and its vessels, the oesophagus, trachea, vagus and phrenic nerves, and thymus, among other organs. There are no concrete epidemiological data but case series point to an approximate incidence of one in 7000 to one to 45 000 hospital admissions [1–3], with a predilection for young males [2].

  3. Case Studies - Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2010-10-15

    Dr. Alan Waxman, a professor of obstetrics and gynecology at the University of New Mexico and chair of the American College of Obstetricians and Gynecologists (ACOG) committee for the underserved, talks about several case studies for cervical cancer screening and management.  Created: 10/15/2010 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  4. Prague Case Study Report

    Czech Academy of Sciences Publication Activity Database

    Kostelecký, Tomáš; Patočková, Věra; Illner, Michal; Vobecká, Jana; Čermák, Daniel

    Aarau: Centre for Democracy Studies Aarau (ZDA), 2014 - (Widmer, C.; Kübler, D.), s. 131-177 ISBN 978-3-9524228-2-3 R&D Projects: GA AV ČR IAA700280802 Institutional support: RVO:68378025 Keywords : urban neighbourhods * regeneration * Prague Subject RIV: AD - Politology ; Political Sciences http://www.zdaarau.ch/dokumente/en/ZDA_Working-Papers/No3_RUN_case-studies_2014.pdf

  5. Automated Test Case Generation

    CERN Document Server

    CERN. Geneva

    2015-01-01

    I would like to present the concept of automated test case generation. I work on it as part of my PhD and I think it would be interesting also for other people. It is also the topic of a workshop paper that I am introducing in Paris. (abstract below) Please note that the talk itself would be more general and not about the specifics of my PhD, but about the broad field of Automated Test Case Generation. I would introduce the main approaches (combinatorial testing, symbolic execution, adaptive random testing) and their advantages and problems. (oracle problem, combinatorial explosion, ...) Abstract of the paper: Over the last decade code-based test case generation techniques such as combinatorial testing or dynamic symbolic execution have seen growing research popularity. Most algorithms and tool implementations are based on finding assignments for input parameter values in order to maximise the execution branch coverage. Only few of them consider dependencies from outside the Code Under Test’s scope such...

  6. A Case Report

    Science.gov (United States)

    Choy, Bonnie Nga Kwan; Ng, Alex Lap Ki; Shum, Jennifer Wei Huen; Fan, Michelle Ching Yim; Lai, Jimmy Shiu Ming

    2016-01-01

    Abstract Chlorpromazine is known to cause ocular pigmentary deposits. However, delayed presentation after cessation of chlorpromazine has not been reported. There are also no reports on whether newer generation of anti-psychotic agents contribute to ocular toxicity. We describe a case of ocular toxicity related to anti-psychotic agents. To the best of our knowledge, this is the first reported case of anterior segment pigmentary deposits associated with olanzapine use, 2 years after the cessation of chlorpromazine. We report a case of ocular toxicity in a patient with history of chlorpromazine usage of 100 mg per day for 13 years and subsequently switched to olanzapine 5 mg for 2 years. There were no signs of ocular toxicity while the patient was on chlorpromazine. However, when the patient switched to olanzapine, she developed the ocular side effect as described for chlorpromazine-induced ocular toxicity, with pigmentary depositions on both corneas and the anterior lens surface and decrease in vision. Olanzapine, a newer anti-psychotic agent, may play a role in the ocular pigmentary deposition, either directly causing pigmentary deposition itself or accentuating the effect of chlorpromazine as the 2 drugs act on the same receptors, although further studies are required to support this hypothesis. As patients with psychiatric conditions may not voluntarily complain of visual symptoms, ocular screening could be considered in these patients receiving chronic anti-psychotic treatment, so that any ocular toxicity could be diagnosed in a timely manner. PMID:27082594

  7. Nonketotic hyperglycinemia case series

    Directory of Open Access Journals (Sweden)

    Mehtab Iqbal

    2015-01-01

    Full Text Available To present three cases who presented with neonatal hiccups and who were later diagnosed with nonketotic hyperglycinemia (NKH. Case series. We present three babies who presented in neonatal life with hiccups who later were diagnosed with NKH. Two babies presented on the 2nd day of life with hypotonia, poor feeding, and abnormal movements including jitteriness, hiccups, and twitching. The third baby only had transient hiccups lasting for a couple of days in the 1st week of life but later presented at 3 months of age with poor feeding, drowsiness, and jerky movements. All three cases needed extensive investigations before reaching the diagnosis including metabolic screen, lumbar puncture, electroencephalography, and computed tomography/magnetic resonance imaging. The first two babies needed intubation on their 2nd day of life because of apneas in whom later, the care was withdrawn after reaching the diagnosis of NKH because of poor prognosis. The third baby was discharged home on oral dextromethorphan and ketogenic diet. We discuss the importance of early recognition of symptoms (frequent hiccups and investigation needed to reach the diagnosis early as it helps in making decision to either carry on treatment or withdraw care because of poor prognosis. It also helps in genetic counseling and prenatal diagnosis can be offered at the subsequent pregnancy.

  8. TFTR coil case design

    International Nuclear Information System (INIS)

    The TFTR (TOKAMAK Fusion Test Reactor) TF (Toroidal Field) coil cases are highly loaded structures designed within severe constraints. Foremost among these are basic machine geometry, material characteristics of both the case and the copper/epoxy matrix it supports, and overall cost. Scoping and parametric studies have been performed continuously since conceptual design. The progression of design decisions including coil shape, support locations and their stiffnesses, material selection, and element sizing are described. The significant variables are identified for each of the studies. The current coil case design is presented in detail along with aspects of the design still under consideration. Questions that remain involve the effects of limitations placed upon the coil materials (copper, epoxy) themselves. Resolution of these questions is to be accomplished by development tests of coil elements similar to those in the current design. Two alternate designs have been held in reserve pending completion of the development tests. Each is briefly described as to its basic configuration, potential for improvement, and its effect on the overall device

  9. Oral lymphangioma: case report

    Directory of Open Access Journals (Sweden)

    Marcelo Gadelha Vasconcelos

    2011-07-01

    Full Text Available Introduction: Lymphangioma is a change of lymphatic vessels that frequently affects the head and neck region. Its occurrence at oral cavity is rare and it is most commonly identified at the anterior two-thirds of the tongue. At this location, it is clinically characterized as transparent and generally grouped vesicles, which can be red or purple. The deep lesions appear as nodular masses of variable color and superficial texture. It can be classified according to the size of vessels into three types: capillary, cavernous, and cystic lymphangioma. Several types of treatment have been suggested; and the most commonly used treatments are: surgical excision, application of carbon dioxide laser, cryotherapy using liquid nitrogen, and sclerosing agents. Objective and case report: To describe a case of oral lymphangioma diagnosed in a 17-year-old female patient. The lesion was presented as multiple vesicles of soft consistency with thin epithelial lining and color ranging from translucent to yellow-reddish, involving the soft palate and the left retromolar region. Incisional biopsy confirmed the hypothesis of cavernous lymphangioma. Patient was followed-up for one year without signs of lesion relapse. Conclusion: Through this clinical case report and literature review, this study emphasizes the relevance of the clinical and histopathological features that should be considered to confirm the clinical hypothesis and indicate the proper therapeutic for oral lymphangiomas.

  10. RSG Deployment Case Testing Results

    Energy Technology Data Exchange (ETDEWEB)

    Owsley, Stanley L.; Dodson, Michael G.; Hatchell, Brian K.; Seim, Thomas A.; Alexander, David L.; Hawthorne, Woodrow T.

    2005-09-01

    The RSG deployment case design is centered on taking the RSG system and producing a transport case that houses the RSG in a safe and controlled manner for transport. The transport case was driven by two conflicting constraints, first that the case be as light as possible, and second that it meet a stringent list of Military Specified requirements. The design team worked to extract every bit of weight from the design while striving to meet the rigorous Mil-Spec constraints. In the end compromises were made primarily on the specification side to control the overall weight of the transport case. This report outlines the case testing results.

  11. Xeroderma pigmentosum. Case presentation.

    Directory of Open Access Journals (Sweden)

    Damaris Díaz Leonard

    2008-08-01

    Full Text Available Twelve years old patient (YGS, female, white, of rural origin; with history of facial and truncal bullae since the age of eight months when exposed to the sun light. It was first diagnosed as solar dermatitis. At the age of 6 it was assessed as xeroderma pigmentosum. This diagnosis was confirmed at the age of 10 by the histopathology department and reassessed by the National Reference Centre. For the infrequency of this disease, a bibliographic revision was carried out to make a report for this case presentation.

  12. Pulmonary lymphangioleiomyomatosis: case reports

    International Nuclear Information System (INIS)

    We reviewed the radiologic, physiologic, and pathologic features of biopsy-proved pulmonary lymphangioleiomyomatosis (LAM) in 2 patients. Chest radiographs showed diffuse increased interstitial lung markings with normal or slightly increased lung volume. The prominent computed tomographic (CT) feature was thin-walled cysts throughout the lungs. Pulmonary function test showed a mixed obstructive and restrictive pattern in one and a mainly restrictive pattern in another, which was somewhat different from that of the reported cases. Proliferation of smooth muscle cells in the lymphatics, alveolar septae, vessels, and bronchioles was the pathologic finding

  13. Gallbladder torsion. Case report

    DEFF Research Database (Denmark)

    Brasso, K; Rasmussen, O V

    1991-01-01

    Gallbladder torsion is a rare surgical emergency occurring primarily in elderly women. The anatomical background is a variation in the attachment of the gallbladder to the inferior margin of the liver. Increasing life span will probably lead to an increasing number of cases, and gallbladder torsion...... must be kept in mind in patients with sudden onset of pain in the upper right quadrant, nausea, vomiting, and a palpable mass. None of the laboratory routines or non-invasive examinations enables one to make the right preoperative diagnosis. Treatment is cholecystectomy. Promptly treated, the prognosis...

  14. A case of standardization?

    DEFF Research Database (Denmark)

    Rod, Morten Hulvej; Høybye, Mette Terp

    2015-01-01

    Guidelines are increasingly used in an effort to standardize and systematize health practices at the local level and to promote evidence-based practice. The implementation of guidelines frequently faces problems, however, and standardization processes may in general have other outcomes than...... describe this process as a case of epistemic standardization....... the ones envisioned by the makers of standards. In 2012, the Danish National Health Authorities introduced a set of health promotion guidelines that were meant to guide the decision making and priority setting of Denmark's 98 local governments. The guidelines provided recommendations for health promotion...

  15. Tuloverotus: Case Koirahalli

    OpenAIRE

    Urpilainen, Milla; Björklund, Sari-Anne

    2014-01-01

    Opinnäytetyössä käsiteltiin Suomen tuloverojärjestelmää vuonna 2014 ja 2015 yritysverotuksen näkökulmasta. Case yrityksenä oli suunnittelutasolla oleva Koirahalli-projekti, jolle tässä tutkielmassa haettiin verotuksellisesti kannattavinta yritysmuotoa. Opinnäytetyössä otettiin huomioon sekä yrityksen verotus että yrittäjän verotus. Verolainsäädäntö muuttuu vuosittain. Vuoden 2014 alussa tuli voimaan merkittäviä lakimuutoksia, jotka koskivat yritysverotuksen osalta esimerkiksi yhteisövero...

  16. Case Management Directors

    OpenAIRE

    Bankston-White, Cheri; Birmingham, Jackie

    2015-01-01

    Purpose and Objectives: Case management directors are in a dynamic position to affect the transition of care for patients across the continuum, work with all levels of providers, and support the financial well-being of a hospital. Most importantly, they can drive good patient outcomes. Although the position is critical on many different levels, there is little to help guide a new director in attending to all the “moving parts” of such a complex role. The purpose of this two-part article is to...

  17. Spinal Neurocysticercosis: Case Report

    International Nuclear Information System (INIS)

    Neurocysticercosis (NCC) is the most frequent parasitic illness of the central nervous system caused by the larval form of Taenia solium and its considered to be endemic in Latin America. Its diagnosis is based on imaging findings and epidemiological data; although its diagnosis can be made through the detection of specific IgG antibodies, these tests have limited availability in our environment. Central nervous system involvement is generally observed in the brain parenchyma, and less commonly in the ventricular system and subarachnoid space; only infrequently is reported to involve the structures within the spinal canal, in this article we review a case of a patient with spinal cysticercal involvement.

  18. Neurocysticercosis. Case report.

    Directory of Open Access Journals (Sweden)

    Gilberto Serrano Ocaña

    2009-05-01

    Full Text Available A female patient (15 years, from Eastern Cape, South Africa, was admitted in the hospital on July 13th, 2007 with general tonic-clonic convulsions. There was not history of epilepsy or fever convulsions and the patient denied alcohol, cigar or drugs consumption. The physical examination showed postictal confusion, without neurological deficit, neck rigidity or peripheral edema. Computer axial tomography was definitive for neurocysticercosis disgnosis. Since it is a serious health problem for the area the patient lives in, we decided to publish the case.

  19. Oral Myiasis: Case report

    Directory of Open Access Journals (Sweden)

    S Jimson

    2013-01-01

    Full Text Available Oral myiasis is a rare disease caused by larvae of dipteran flies. Houseflies are strongly suspected of transmitting at least 65 diseases to humans, including typhoid fever, dysentery and cholera. Flies regurgitate and excrete wherever they come to rest and thereby mechanically are the root cause for disease organisms. A case of oral myiasis caused by Chrysomya bezziana in the maxillary anterior region in a 40-year-old patient is presented. Manual removal of maggots, and surgical debridement of wound was done followed by broad-spectrum anti-parasitic medications. A note on the identification of the larva and histopathology of the tissue is also highlighted here.

  20. [Otic myiasis. Case report].

    Science.gov (United States)

    González Poggioli, Nicolás; Vázquez Barro, Juan Carlos

    2009-01-01

    Otic myiasis is rare in developed countries and is related to environmental conditions and poor hygiene. We present the case of a 65-year-old woman with pain and tinnitus in the left ear lasting for one week. Physical examination in the emergency room showed numerous dipteran larvae totally occupying the external auditory canal. After the diagnosis of otic myiasis, the larvae were removed and the patient was discharged after 24 hours of medical observation. The diagnosis of otic myiasis is by means of direct visualization of the larvae in the ear cavities and treatment includes the removal of larvae from the ear. Prognosis is generally good. PMID:19558911

  1. Lumbar stenosis: clinical case

    Directory of Open Access Journals (Sweden)

    Pedro Sá

    2014-08-01

    Full Text Available Lumbar stenosis is an increasingly common pathological condition that is becoming more frequent with increasing mean life expectancy, with high costs for society. It has many causes, among which degenerative, neoplastic and traumatic causes stand out. Most of the patients respond well to conservative therapy. Surgical treatment is reserved for patients who present symptoms after implementation of conservative measures. Here, a case of severe stenosis of the lumbar spine at several levels, in a female patient with pathological and surgical antecedents in the lumbar spine, is presented. The patient underwent two different decompression techniques within the same operation.

  2. Chinese court case fiction

    DEFF Research Database (Denmark)

    Hansen, Kim Toft

    2011-01-01

    breathed the breath of life into it? The usual answer is that crime fiction, in fact, was invented by Poe, but another counter-view is that China – at that point – had had a long narrative tradition for stories about crime and detection. The socalled gongan genre – court case fiction – was probably...... sinological sources introducing a revised introduction of crime fiction on the world’s literary scene. So to answer Doyle’s question about crime fiction before Poe: Crime fiction may have been in China....

  3. NOx trade. Case studies

    International Nuclear Information System (INIS)

    Some of the questions with respect to the trade of nitrogen oxides that businesses in the Netherlands have to deal with are dealt with: should a business buy or sell rights for NOx emission; which measures must be taken to reduce NOx emission; how much must be invested; and how to deal with uncertainties with regard to prices. Simulations were carried out with the MOSES model to find the answers to those questions. Results of some case studies are presented, focusing on the chemical sector in the Netherlands. Finally, the financial (dis)advantages of NOx trade and the related uncertainties for a single enterprise are discussed

  4. Neuromyelitis Optica. Case Report

    Directory of Open Access Journals (Sweden)

    Patricia Quintero Cusguen

    2009-04-01

    Full Text Available Neuromyelitis Optica, also known as Devic’sSyndrome, is a disease which combines opticneuritis and transverse myelitis. Some years ago it was considered as a form of multiple sclerosis.Actually, it is consider as a different disease, onthe basis of the clinical, imaging, serology andimmunopatholoy profile.A case of 29 years old female patient is reported,based on her clinical findings which beganin the fifth postpartum month, with progressivelower limb paresis, associated with bilateralvision loss.This paper attempts giving a synoptic overviewof this uncommon immune mediateddemyelinating condition; it summarises themost important epidemiological parameters andpresents the diagnostic and therapeutic possibilitiesavailable today.

  5. Teaching Pharmacology by Case Study.

    Science.gov (United States)

    Jordan, Sue

    1997-01-01

    Using pharmacology case studies with nursing students encourages theory-practice links and infuses real-life content. Cases provide rich qualitative data for evaluating curriculum. However, they are not a substitute for evidence-based practice. (SK)

  6. Pseudohypoaldosteronism: Case Report

    Directory of Open Access Journals (Sweden)

    Kazım Küçüktaşçı

    2009-12-01

    Full Text Available Introduction: Pseudohypoaldosteronism is a disease which occurs as a result of peripheral resistance to aldosterone and is characterised by salt wasting. Case Report: Hyponatremia, hyperkalemia, metabolic acidosis, high renin and aldosterone levels were determined in the patient admitted with decrease in sucking and getting sleepy during breast-feeding. The case was diagnosed as systemic form of pseudohypoaldosteronism. His treatment was continued with oral salt. Conclusion: Pseudohypoaldosteronism has three types as primary, secondary and Gordon syndrome. Primary form is due to epithelial sodium channel and mineralocorticoid receptor gene mutation, whilst secondary form is frequently caused by urinary malformation and urinary tract infections. In Gordon syndrome, plasma aldosterone level is usuallly normal, and plasma renin activity is depressed, there is an adequate response to mineralocorticoids. Probability of secondary pseudohypoaldosteronism was investigated at the same time because of the urinary infection present in our subject. The patient was accepted as systemic form of primary pseudohypoaldosteronism because of positive sweat test result and prolonged salt necessity. (Journal of Current Pediatrics 2009; 7: 151-3

  7. [Pneumobilia. A case report].

    Science.gov (United States)

    Reinoso Reyes, Joaquín; de Echeverría Robles, Lila Cruz; Reinoso Toledo, Joaquín G

    2005-01-01

    Pneumobilia, gas within the biliary tract, is due to an abnormal connection between the gastrointestinal tract and the biliary tract and is considered a serious pathology usually requiring surgical intervention. Most cases of pneumobilia are related to gallstone disease, and spontaneous biliary-enteric fistula is reported to be the most common cause of pneumobilia. Another well-documented cause of pneumobilia is a surgically created anastomosis between the biliary tract and the bowel, the Whipple procedure, and choledocho-jejunostomy, endoscopic retrograde cholangiopancreatography with papillosphincterotomy or surgical transduodenal sphincteroplasty. Transient incompetence of the sphincter of Oddi, gas-forming infections, and trauma have also been reported to cause pneumobilia. We present the case of a 74-year-old woman with asymptomatic cholelithiasis, pneumobilia and cholecystoduodenal fistula treated with cholecystectomy, fistula closure with Graham patch, Stamm-Kader gastrostomy and needle catheter jejunostomy. On the first postoperative day she developed a biliary duodenal fistula that required nutritional support with parenteral, enteral nutrition and octreotide acetate with fistula closure 2 weeks later. We review the etiology, surgical treatment and economic burden. Laparoscopic cholecysto-fistulectomy by skilled laparoscopic surgeons can be adopted as a first-choice treatment for cholecystoduodenal fistula to reduce morbility risks and costs. PMID:15998480

  8. Scleroderma: a case report

    Directory of Open Access Journals (Sweden)

    Prachi Sankhe

    2015-06-01

    Full Text Available Scleroderma is systemic multi organ autoimmune disorder characterized by hardening of skin. Also known as systemic sclerosis. Estimated annual incidences of approximately 19 cases per million persons. The limited skin disease has a 10-year survival rate of 71%, whereas those with diffuse skin disease have a 10-year survival rate of just 21%. Risk is higher in women than men and peak in individuals aged 30-50 years. It has no definitive treatment. It may be limited or diffuse depending upon manifestations of symptoms or signs affecting internal organs especially lungs, heart, or kidney. We report a case of scleroderma with pulmonary hypertension and interstitial lung disease in our hospital who presented with tightening of skin, joint pain, dysphagia, and breathlessness. On examination skin appeared dark, shiny, and tight, with loss of hair, paraesthesia and digital ulceration. Patient also has history of Raynauds phenomenon. On investigation, Scl-70 and ANA (antinuclear antibodies by enzyme immunoassay came positive. HRCT thorax was suggestive of interstitial fibrosis and PFT revealed moderate restriction. On 2D echocardiography, mild pulmonary hypertension was present while barium swallow showed motility disorder involving oesophagus. On view of extensive systemic involvement like skin, respiratory system, gastrointestinal system and heart, we would like to present this rare disorder. [Int J Res Med Sci 2015; 3(3.000: 802-804

  9. SIRENOMELIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Wankhede

    2016-02-01

    Full Text Available The incidence of Sirenomelia is thought to be about 1 in 65,000 live births (Oxford Medical database, Dysmorphology. In Sirenomelia, lower limbs are fused together. Common associated malformations include absent genitalia, imperforate anus, lumbosacral vertebral pelvic abnormalities and renal agenesis. Sirenomelia with craniorachischisis totalis (CT is a rare fetal malformation, only six cases have been reported in English literature (1-5 and none yet from Asia. Our case is of a 26 weeks fetus born to a 20-year-old primi mother and 24-year-old father. It was a lower category Hindu couple. Mother was anemic and was undergoing treatment for anemia. On USG examination of mother showed a single line fetus of 26 weeks placental calcification, marked oligohydramnios. The fetus weighs 250 grams of unidentifiable sex on external examination. There is absence of pubis, definite buttocks and single fused lower limb ending in a bifid foot with 5 toes. X-rays show no skeletal abnormality or absence of bones. Study of internal structures will be discussed later on.

  10. Vertebral Angiosarcoma. Case Study.

    Science.gov (United States)

    Guzik, Grzegorz

    2015-01-01

    Bone angiosarcomas, especially vertebral angiosarcomas, are very rare. There are no studies based on large clinical samples in the literature, and only a few single case reports can be found. The symptoms of the disease are not specific. It is usually detected incidentally or at a late stage when pathological vertebral fractures or neurological complications occur. Diagnostic imaging and history help to recognize the tumour behind the symptoms, but do not allow accurate clinical diagnosis. The basis for a diagnosis is the histopathological examination supported by immunohistochemistry (IHC) assays. The case of a 26-year-old woman with an angiosarcoma involving the eighth thoracic vertebra we report reflects diagnostic problems adversely affecting the efficacy and accuracy of treatment offered to patients. The patient underwent three surgeries of the spine, including two biopsies. A needle biopsy did not provide sufficient information for the diagnosis. An open excisional biopsy, which at the same time temporarily reduced neurological deficits in the patient, was the only chance to obtain an accurate diagnosis. The third surgery was posterior decompression of the spinal cord due to the rapidly escalating paraparesis. It was not until 8 weeks later that the final diagnosis was established. At that time, the patient could not be qualified for any supplementary treatment. The patient died in hospital 6 months after the onset of disease. PMID:26468177

  11. Dysphagia aortica: Case report

    Directory of Open Access Journals (Sweden)

    Jovančević Ljiljana

    2005-01-01

    Full Text Available Introduction Dysphagia aortica is a swallowing condition caused by external compression of the esophagus due to aortic aneurysm or atherosclerotic changes affecting the aorta. The case report on this rare cause of dysphagia should contribute to better diagnosis of dysphagia aortica and swallowing difficulties in general. Case report A 63-year-old male patient was hospitalized duo to a four month history of intermittent swallowing difficulties. Chest radiography showed a widened mediastinum and an enlarged aortic arch. Rigid esophagus endoscopy was done in general endotracheal anesthesia. At 28 cm from the upper incisors, a difficulty in passing the endoscope appeared, revealing an external compression as a probable cause, since the whole esophagus had no intraluminal pathological changes. Contrast esophagography revealed an aortic aneurysm. The esophagus had a normal lumen width, wall tension and elasticity, and smooth contours. After cardiovascular examination and magnetic resonance imaging, a giant aneurysm of the aortic arch was diagnosed. Discussion Patients with dysphagia aortica as well as patients with any other swallowing difficulties should be managed by multidisciplinary "dysphagia team". The team should include an otorhinolaryngologist, neurologist, radiologist, gastroenterologist, surgeon, dietitian, speech and language therapist and specially trained nurses. Conclusion Aneurysm of the thoracic aorta is a very rare cause of dysphagia. Mild to moderate symptoms can be in great disproportion with the severe condition which causes them.

  12. Case of spontaneous ventriculocisternostomy

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru (Hiroshima Univ. (Japan). School of Medicine); Kuwabara, Satoshi

    1983-05-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH/sub 2/O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy.

  13. Otocephaly: a case report

    Directory of Open Access Journals (Sweden)

    Anshu Sharma

    2016-04-01

    Full Text Available A case of otocephaly was reported in 26+/-4 week's female fetus during routine fetal autopsy at GMCH, Chandigarh, India. Mother was 25 years old, second gravid. The first child is one year old normal male baby. Present pregnancy resulted in spontaneous abortion. Antenatal history, past history, family history and medical history of mother was not suggestive of any ethiological factor responsible for the defect. The external examination showed 2 vessels in umbilical cord. There was anteroposterior lengthening of skull, mouth was in the form of a proboscis with a small opening in the centre, the right ear was absent. The left pinna was low placed and had small tags. On internal examination oral cavity was found small with hypoplastic mandible, tongue was absent (aglossia, thoracic cavity was small, left lung was absent, right lung had only single lobe, heart dilated with normal position of major vessels, In abdominal cavity gut was opening in a dilated cloaca like chamber. X-ray examination revealed small hypoplastic mandible and maxilla. Otocephaly is a rare lethal syndrome of microstomia, agnatia and ear anomalies. Other anomalies associated are holoprosenxcephaly, skeletal, genitourinary, cardiovascular system, endocrine gland hypoplasia etc. The differential diagnosis includes Treacher Collins syndrome, Goldenhar syndrome and Mobius syndrome. The etiology, incidence, causative factors of this case will be discussed in light of available literature. [Int J Res Med Sci 2016; 4(4.000: 1286-1289

  14. Coinfection: A Case Report

    Directory of Open Access Journals (Sweden)

    Huldah I. Nwokeukwu

    2013-01-01

    Full Text Available Background. Tuberculosis is a major public health problem, and its control has been facing a lot of challenges with emergence of HIV. The occurrence of multidrug-resistant strain has also propounded the problem especially in children where diagnosis is difficult to make. Multidrug-resistant tuberculosis (MDR-TB is in vitro resistant to isoniazid (H and rifampicin (R. Paediatric multi-drug resistant tuberculosis with HIV coinfection is rare, and there is no documented report from Nigeria. Objective. To report a case of paediatric MDR-TB in Nigeria about it. Methods. The case note of the patient was retrieved, and relevant data were extracted and summarized. Results. A 9-year-old female HIV-positive pupil with a year history of recurrent cough, 3 months history of recurrent fever, and generalized weight loss was diagnosed and treated for tuberculosis but failed after retreatment. She was later diagnosed with MDR-TB and is presently on DOT-Plus regimen. Conclusion. Paediatric MDR-TB with HIV co-infection is rare. Early diagnosis and treatment is important to prevent spread of the disease. The use of Isoniazid preventive therapy is recommended for children who come in contact with patients with active tuberculosis and also for HIV patients without active tuberculosis.

  15. Test Case Generation Based on Use case and Sequence Diagram

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Swain

    2010-07-01

    Full Text Available We present a comprehensive test case generation technique from UML models. We use the features in UML 2.0 sequence diagram including conditions, iterations, asynchronous messages and concurrent components. In our approach, test cases are derived from analysis artifacts such as use cases, their corresponding sequence diagrams and constraints specified across all these artifacts. We construct Use case Dependency Graph (UDG from use case diagram and Concurrent Control Flow Graph (CCFG from corresponding sequence diagrams for test sequence generation. We focus testing on sequences of messages among objects of use case scenarios. Our testing strategy derives test cases using full predicate coverage criteria. Our proposed test case generation technique can be used for integration and system testing accommodating the object message and condition information associated with the use case scenarios. The test cases thus generated are suitable for detecting synchronization and dependency of use cases and messages, object interaction and operational faults. Finally, we have made an analysis and comparison of our approach with existing approaches, which are based on other coverage criterion through an example.

  16. The Panalba Role Playing Case

    OpenAIRE

    JS Armstrong

    2004-01-01

    The Panalba Role Playing Case was designed to get participants to examine their behavior in a situation where their role can lead them to act in a socially irresponsible manner. A description of the case is provided along with instructions to the administrator. Much research has been done on this case, allowing subjects to compare their behavior with that of previous subjects.

  17. A case of unilateral dysmenorrhea

    Directory of Open Access Journals (Sweden)

    Tulon Borah

    2010-01-01

    Full Text Available Unilateral dysmenorrhea in an adolescent may be associated with uterine malformation. Relevant investigations in suspected cases and timely intervention can prevent future complications in such cases. Here, we present a case of unicornuate uterus with rudimentary horn in an adolescent complaining of unilateral dysmenorrhea.

  18. A case of unilateral dysmenorrhea

    OpenAIRE

    Tulon Borah; Ananya Das; Subrat Panda; Santa Singh

    2010-01-01

    Unilateral dysmenorrhea in an adolescent may be associated with uterine malformation. Relevant investigations in suspected cases and timely intervention can prevent future complications in such cases. Here, we present a case of unicornuate uterus with rudimentary horn in an adolescent complaining of unilateral dysmenorrhea.

  19. Natural Learning Case Study Archives

    Science.gov (United States)

    Lawler, Robert W.

    2015-01-01

    Natural Learning Case Study Archives (NLCSA) is a research facility for those interested in using case study analysis to deepen their understanding of common sense knowledge and natural learning (how the mind interacts with everyday experiences to develop common sense knowledge). The database comprises three case study corpora based on experiences…

  20. Measles (Rubeola) Cases and Outbreaks

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Measles Cases and Outbreaks Language: English Español (Spanish) Recommend ... ol: Casos y brotes de sarampión Number of measles cases by year since 2010 Year Cases 2010 ...

  1. Symptomatic 5-fluorouracil-induced sinus bradycardia.

    Science.gov (United States)

    Lee, A D; McKay, M J

    2011-07-01

    5-Fluorouracil (5-FU) is a commonly used anti-neoplastic agent. 5-FU has been not uncommonly associated with cardiotoxicity, although the many potentially causative mechanisms are yet to be established. Here, we present the case of a 61-year-old gemstone miner who developed symptomatic sinus bradycardia while receiving a continuous 5-FU infusion combined with radiotherapy for locally advanced rectal cancer. This dysrhythmia is an unusual type of 5-FU toxicity, our case being the second described. We review the actions of 5-FU and the various proposed mechanisms of its cardiotoxic effects. PMID:21762335

  2. Peritoneal lymphomatosis: case report

    International Nuclear Information System (INIS)

    Peritoneal lymphomatosis is a rare manifestation of high grade lymphomas. Although it is difficult to differentiate peritoneal lymphomatosis from other peritoneal diseases such as peritoneal carcinomatosis and leiomyomatosis clinically and radiologically, it should be included in differential diagnosis because the disease is curable with chemotherapy. Consequently, radiologic diagnosis plays a very important role in the detection of this disease. We experienced two cases of peritoneal lymphomatosis with primary gastrointestinal lymphomas in the distal ileum. The two patients were 25 and 50-year-old males. Abdominal CT, ultrasound and barium study were performed on both patients. Both patients had non-Hodgkin's lymphoma confirmed with open or sonographically guided biopsies. Although radiologic appearances overlapped, characteristic findings of long-segmental circumscribed annular mass, aneurysmal luminal dilatation, small to moderate amount of ascites without septation or loculation, diffuse involvement of mesentery, omentum and peritoneum, and enlarged lymph nodes were helpful in narrowing the range of possible diagnoses

  3. The Case of CUL

    DEFF Research Database (Denmark)

    Lauridsen, Ole; Jensen, Torben K.; Jørgensen, Bente Mosgaard;

    career levels. These courses comprise: (i) supervision and mentoring, educational ICT, teaching in the multicultural/multilingual classroom (for associate and full professors); (ii) planning/developing courses; teaching techniques (for assistant professors); (iii) teaching techniques (for graduate......The Case of CUL (Centre for Teaching and Learning), School of Business and Social Sciences, Aarhus University, Denmark: Dilemmas in Large Scale Educational Development Ole Lauridsen, Torben Jensen, Maja Hjerrild, Bente Jørgensen, Aarhus University. Abstract When developmental work within the area...... of HE pedagogy goes from small scale to large scale, it changes character and new challenges arise. The session invites directors of developmental units and all interested educational developers to discuss dilemmas of such a transition and exchange experiences with the aim of ameliorating the work of...

  4. The case for cryonics.

    Science.gov (United States)

    Moen, Ole Martin

    2015-08-01

    Cryonics is the low temperature preservation of people who can no longer be sustained by contemporary medicine in the hope that future medicine will make it possible to revive them and restore their health. A speculative practice at the outer edge of science, cryonics is often viewed with suspicion. In this paper I defend two theses. I first argue that there is a small, yet non-negligible, chance that cryonics is technically feasible. I make the case for this by reference to what we know about death and cryobiology, and what we can expect of future nanorobotics. I further argue that insofar as the alternatives to cryonics are burial or cremation, and thus certain, irreversible death, even small chances for success can be sufficient to make opting for cryonics a rational choice. Finally, I reply to five objections. PMID:25717141

  5. Buschke Scleredema, case report

    Directory of Open Access Journals (Sweden)

    R. De Pasquale

    2011-09-01

    Full Text Available Buschke Scleredema is a rare connective tissue disorder of unknown aetiology, characterized by thickening of the dermis whose characteristics may mainly to mime systemic sclerosis, eosinophilic fasciitis and cutaneous amyloidosis. Scleredema may be associated with a history of an antecedent febrile illness, diabetes mellitus, or blood dyscrasia. Scleredema can be classified into three clinical groups; each has a different history, course, and prognosis. Each one of these share reduction in chest articular movements and limitation of limbs movements. The skin histology is characterised by thickened dermis and increased spaces between large collagen bundles due to increased deposition of mucopolysaccharide in the dermis. Differential diagnosis can be made considering the typical clinical features and the histologic peculiarity. No therapy has been found effective. The autors describe a case of Buschke Scleredema successfully treated by steroids and colchicines. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment.

  6. TETANUS: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sreelatha

    2014-09-01

    Full Text Available Clostridium tetani is the causative agent of Tetanus. The aim was to detect the presence of Clostridium tetani in a case of suspected Tetanus in a 40 year old male who had history of handling a a thorn injury in the agricultural field 15 days ago. The patient presented with spasm of all the limb muscles and Lockjaw of 2 days duration together with history of convulsions for the last 3 days. Bits of tissue were collected from the necrotic depth of the wound abscess and were analyzed. Clostridium tetani was isolated. A diagnosis of Tetanus was made and the concerned authority was immediately notified. The patient was successfully treated with complete recovery. An early diagnosis of TETANUS is significant because it can help the clinician in early management and prevention of development of terminal respiratory failure and death

  7. TACE Case Presentations

    Directory of Open Access Journals (Sweden)

    Mahyar Mohammadifard

    2010-05-01

    Full Text Available Gold standard treatment of hepatocellular carci-noma is surgical resection but more than 80% of patients with HCC are unresectable at the time of diagnosis, and due to poor local circumstances or the patient's general condition, the prognosis is poor. "nBecause HCC tumors are fed exclusively by the he-patic artery, successful TACE leads to tumor necrosis. The liver parenchyma is rarely damaged because it is fed by the portal vein. Injection of an emulsion of iodized oil and cytostatic agents into the hepatic artery leads to selective deposition of the emulsion in the tumor. Compared with intravenous administration of cytostatic material, TACE reduces the maximum plasma concentration and increases the average concentration of cytostatic agents in the tumor, especially when the cytostatic material is combined with gelatin powder particles. "nFor example, concentration of an emulsion of cisplatin in iodized oil 4-9 weeks after intraarterial administration is 42 times greater in the tumor than in the parenchyma."nTwo cases of HCC are presented which were treated successfully with TACE 20 months ago."nIn the first patient after one session of TACE, tumor markers fell down into normal range and MDCT showed complete necrosis and cystic changes in the mass without residual or recurrent tumor until this time. "nIn the next case tumor markers showed no significant decrease after the first session of TACE and MDCT showed residual tumor which was fed by an accessory arterial branch from SMA. This branch was treated in another session. Two months later, tumor markers fell down and MDCT showed no tumor activity. "nThese patients have been symptom free after the mentioned interventions.

  8. Delusional Parasitosis : Series Of 25 Cases

    Directory of Open Access Journals (Sweden)

    Bhatia M S

    1996-01-01

    Full Text Available A series 25 cases of delusional parasitosis is being reported. There were three cases below 45 years, 12 cases between 46-45 years and 11 cases above 55 years of age, 64% cases were females. A majority of cases (92% had insidious onset. The duration of symptoms in all the cases (except one was 6 months or more. 13 cases presented with infestation with insects over body and 10 cases with insects crawling over scalp. There were three cases each with diabetes mellitus and leprosy. Three cased had dementia, 2 cases had depression and one case presented with trichotillomania. Pimozide was used in22 cases, amitriptyline in 2 cases and fluoxetine in one. 14 cases (52% showed complete remission while receiving drug, 8 cases showed partial improvement and 3 cases did not respond.

  9. The case for the case report: refine to save.

    LENUS (Irish Health Repository)

    Lennon, P

    2012-01-31

    INTRODUCTION: The case report is the cornerstone of both medical teaching and writing. However, during recent years the value of the case report has been questioned, so much so that it has been abandoned by many journals. The aim of this study was to assess case reports published by the Irish Journal of Medical Science (IJMS) and to examine ways to preserve this type of article. METHODS: A review of all single-patient case reports published in the IJMS in 2008 and 2009. RESULTS: Forty-eight cases were published from nine countries. The range of authors was 2-11, length 525-1,787 words and number of references 4-24. All cases contained abstracts. CONCLUSION: Stricter guidelines with regards to a shorter more focused article should help to preserve this form of publication.

  10. Dilated cardiomyopathy following trastuzumab chemotherapy

    Directory of Open Access Journals (Sweden)

    Saurabh Karmakar

    2012-01-01

    Cardiotoxicity manifesting as dilated cardiomyopathy is a rarely reported adverse effect of trastuzumab. We hereby report a case of dilated cardiomyopathy, which occurred following trastuzumab chemotherapy in a 32-year-old female. The patient responded to discontinuation of trastuzumab and standard medical treatment. Extensive search of Indian literature revealed no reported case of dilated cardiomyopathy occurring due to trastuzumab.

  11. An unusual case of suprascapular nerve neuropathy: a case report

    OpenAIRE

    Kyriakides Theodoros; Christodoulou Loizos; Economides Charalambos P; Soteriades Elpidoforos S

    2011-01-01

    Abstract Introduction Suprascapular nerve neuropathy constitutes an unusual cause of shoulder weakness, with the most common etiology being nerve compression from a ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling case of a man with suprascapular nerve neuropathy that may have been associated with an appendectomy. The case was attributed to nerve injury as the most likely cause that may have occurred during improper post-operative patient mobilization. Case pres...

  12. FMCT verification: Case studies

    International Nuclear Information System (INIS)

    Full text: How to manage the trade-off between the need for transparency and the concern about the disclosure of sensitive information would be a key issue during the negotiations of FMCT verification provision. This paper will explore the general concerns on FMCT verification; and demonstrate what verification measures might be applied to those reprocessing and enrichment plants. A primary goal of an FMCT will be to have the five declared nuclear weapon states and the three that operate unsafeguarded nuclear facilities become parties. One focus in negotiating the FMCT will be verification. Appropriate verification measures should be applied in each case. Most importantly, FMCT verification would focus, in the first instance, on these states' fissile material production facilities. After the FMCT enters into force, all these facilities should be declared. Some would continue operating to produce civil nuclear power or to produce fissile material for non- explosive military uses. The verification measures necessary for these operating facilities would be essentially IAEA safeguards, as currently being applied to non-nuclear weapon states under the NPT. However, some production facilities would be declared and shut down. Thus, one important task of the FMCT verifications will be to confirm the status of these closed facilities. As case studies, this paper will focus on the verification of those shutdown facilities. The FMCT verification system for former military facilities would have to differ in some ways from traditional IAEA safeguards. For example, there could be concerns about the potential loss of sensitive information at these facilities or at collocated facilities. Eventually, some safeguards measures such as environmental sampling might be seen as too intrusive. Thus, effective but less intrusive verification measures may be needed. Some sensitive nuclear facilities would be subject for the first time to international inspections, which could raise concerns

  13. Cryptococcosis in captive cheetah (Acinonyx jubatus : two cases : case report

    Directory of Open Access Journals (Sweden)

    L.A. Bolton

    1999-07-01

    Full Text Available Cryptococcus neoformans is a yeast-like organism associated with pulmonary, meningoencephalitic, or systemic disease. This case report documents 2 cases of cryptococcosis with central nervous system involvement in captive cheetah (Acinonyx jubatus. In both cases the predominant post mortal lesions were pulmonary cryptococcomas and extensive meningoencephalomyelitis. Both cheetahs tested negative for feline immunodeficiency virus and feline leukaemia virus. The organism isolated in Case 2 was classified as Cryptococcus neoformans var. gattii, which is mainly associated with disease in immunocompetent hosts.

  14. 5-FU-induced cardiac toxicity - an underestimated problem in radiooncology?

    International Nuclear Information System (INIS)

    5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeutic agent for combined chemoradiotherapy. The purpose of this study was to present the clinical course of three patients who developed severe cardiac toxicity by 5-FU and to give a review of the literature on the cardiotoxic potential of 5-FU. Cardiotoxicity is a rare, but relevant side effect of fluoropyrimidines. It comprehends a wide spectrum of side effects, from electrocardiogram changes (69% of cardiac events) to myocardial infarction (22%) and cardiogenic shock (1%). In this case series three patients with cardiotoxic events during chemoradiotherapy including 5-FU, the reaction's characteristics and their influence on further therapy are described. Two of the patients could not be treated with 5-FU any more because they had developed a myocardial ischemia, which was most likely caused by fluorouracil. Another patient, who complained about typical angina pectoris during 5-FU-infusion and had a new left anterior hemiblock, was reexposed with prophylactic administration of nitrendipine. Cardiotoxicity caused by 5-FU is an underestimated problem in radiooncology. Especially patients without history of cardiac disease are often treated as out-patients and therefore without cardiac monitoring. Consequently asymptomatic and symptomatic cardiac events may be overlooked. The benefit of prophylactic agents remains unclear, so close cardiac monitoring is the most established method to prevent manifest cardiotoxic events

  15. Melorheostosis: A case report

    Directory of Open Access Journals (Sweden)

    Bruno Pereira Alpoim

    2013-06-01

    Full Text Available Melorheostosis is a rare disease (0.9/million habitants, characterized by linear hyperostosis along the cortex bone. It can affect any bone, being more frequent in long bones. The lesions tend to be segmental and unilateral. The etiology remains unknown although several theories proposed over the past year (vascular, inflammatory processes, embryonic defects or genetic. Show no significant difference between sexes or heredity. Clinical manifestations are mainly pain, deformity and joint stiffness. The diagnosis is obtained by combining the clinical findings with imaging studies (mainly radiography with typical image in "candle wax". There is no definitive or specific treatment, being always palliative. We describe a case of a patient of twenty-four years, followed in Orthopedic consultation since age eight, with a deformity of the right side of the body. X-rays showed hyperostosis of the bones of the limbs in the right side of the body (image in "candle wax". The patient is in physical therapy program and has a positive response to analgesia with ibuprofen.

  16. NECROTIZING SIALOMETAPLASIA. CASE REPORT

    Directory of Open Access Journals (Sweden)

    A.I. Navazo Eguía

    2010-01-01

    Full Text Available Introduction: Necrotizing sialometaplasia (NSM is a benign lesion affecting the salivary glands mainly in the hard palate. It presents as an ulcer with irregular borders, slightly elevated and necrotic The differential diagnosis should include malignant neoplasms. Case Report: A 26-year-old woman sought medical advice for a painful 2 cm ulceration of the hard palate. She is carrying pierced tongue. The patient had a history of cigarette smoking, chronic anxiety disorder and bulimia,. Analytical normal (including HIV and syphilis serology. Histopathology: accessory gland with squamous metaplasia, pseudoepitheliomatous hyperplasia and conservation lobulararchitecture. She had an important improvement with total resolution of the lesion in 4 months Discussion: The NSM is a necrotizing inflammatory process. It presents as an ulcer located in the posterior hard palate or the junction between the hard and soft palate. This situation has been associated with local ischemia as surgical trauma, thromboangiitis obliterans, dentures, alcohol, snuff, cocaine, and certain malignancies such as lymphomas, rhabdomyosarcoma or Warthin tumor. Currently associated withbulimia, it being necessary suspected in young women. It is important to rule out neoplasms and infectious processes (tuberculosis or syphilis. Also consider subacute necrotizing sialadenitis, nonspecific acute inflammatory process of unknown cause, with focal necrosis without hyperplasia or ductal metaplasia pseudoepitheliomatous. Treatment is symptomatic and usually resolves in 2-3 months. Conclusion: The NSM is a benign lesion which may mimic neoplasia. The trend is toward resolution. It must be recognized to avoid unnecessary surgery.

  17. Pseudoachondroplasia: A case report

    Directory of Open Access Journals (Sweden)

    Radlović Vladimir

    2013-01-01

    Full Text Available Introduction. Pseudoachondroplasia (PSACH is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. Case Outline. A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm,

  18. Case of administrative dispute

    Directory of Open Access Journals (Sweden)

    Xhemazie Ibraimi

    2015-11-01

    Full Text Available The activity of administrative bodies includes big numbers of various acts and actions, through which the will of public administration is formed. The will of public administration bodies, expressed in administrative individual and normative acts, in administrative contracts and real acts, finds its reflection in the Constitution, laws and other provisions of legal character. All this activity is not inerrant and therefore, it is not uncontrollable. The supervision of executive activity is subject to political control of administrative acts through authorities designated for this purpose, as well as internal control and the judicial control. The institution of judicial control of administrative acts and actions appears as very important and widely treated in the legal doctrine. The protection of constitutional and legal rights of private persons is accomplished by subjecting administrative activity both to internal administrative control, as well as to the judicial control in accordance with legal provisions. The judicial control of administrative acts represents a constitutional guarantee for citizens to protect their rights through public and fair trial by an independent and impartial court. In this way, the Constitution empowers the common administrative court that invalidates an action or administrative act, but not all administrative acts may be subject to administrative dispute, with the exception of cases against which the administrative conflict cannot be carried out (negative enumeration.

  19. The LMFBR safety case

    International Nuclear Information System (INIS)

    The main objective of this report is to review the present status of the safety case for the liquid metal cooled fast reactor (FBR). A particular emphasis is placed on activities in Europe where the FBR has been progressively developed for many years during which time systems have passed from small experimental plants to the 1200 MWe SPX-1. The FBR has been found to be an easily controlled plant with low impact on the environment and low dose rates to operational personnel. Aspects of reactor design and associated R and D that are required for FBRs to be licensed and the progress made to meet these requirements are described. Fault conditions in the credible range can be dealt with safely, the FBR having several advantageous characteristics which assist safety. Also measures are foreseen to mitigate potential consequences of more severe but improbable accidents. This study sponsored by the Commission of the European Communities was carried out by Colenco Ltd in vlose collaboration with the Safety Working Group (SWG) which is a subgroup of the CEC Fast Reactor Coordinating Committee (FRCC)

  20. Multiple myeloma: 45 cases

    International Nuclear Information System (INIS)

    We evaluated 45 cases of multiple myelomas retrospectively confirmed in Severance Hospital from the period of 1983-1989. In order to assess the radiologic features of the multiple myeloma and to assist in possible early diagnosis and treatment. The result were as follows: 1. IgG(41%) was the most common immunoglobulin type secreted followed by light chain(36%). IgA(19%) and IgD(2%). Two percent of the patients had non-secretory type. 89% of patients were in their stage III of the disease. 2. Among the 45 patients, 96% had abnormal plain radiographic findings with average number of 4.5 lesions. Common sites were the spine, rib, skull, pelvis, and humerus in descending orders. The findings were localized or diffuse osteolytic bone destruction(85%). osteoporosis(49%), pathologic fracture and endosteal scalloping(55%). Osteoporosis was more prominent in stage III than stage II. 3. Both plain X-ray and radioisotope study was available for comparison in 28 patients. Concordance between the two studies were 44%, lesions detected only on plain X-ray film were 51%, and lesions detected only on the radioisotope were 5%. The plain radiography was able to detect only 54% of bone lesions confirmed by bone marrow biopsy. With the above results, accurate evaluation of bone lesions in multiple myeloma may be difficult with radiologic studies only. But familiarity with these radiologic findings of the this disease entity is necessary for early suspicion of the disease, thus for early diagnosis and treatment

  1. The case for iron

    International Nuclear Information System (INIS)

    Excess major nutrients occur in offshore areas ranging from the tropical equatorial Pacific to the polar Antarctic. In spite of the great ecological differences in these environments, the authors believe they share a common trait: iron deficiency. Here they present the case of iron; they point out that all of these areas are far from Fe-rich terrestrial sources and that atmospheric dust loads in these regions are among the lowest in the world. The authors summarize experiments performed in three nutrient-rich areas: The Gulf of Alaska, the Ross Sea, and the equatorial Pacific. In general, populations without added Fe doubled at rates 11-40% of the expected maxima at various temperatures. The additions of nanomole quantities of Fe increased these doubling rates by factors of 2-3. In spite of the lack of Fe, tightly coupled phytoplankton/zooplankton communities seem to inhabit these major nutrient-rich areas. Since Fe is required for the synthesis of chlorophyll and nitrate reductase, little chlorophyll is found and NH3 is the favored N source. Normal rate values of specific productivity indicate that these populations are healthy, but limited by the insufficient Fe supply. When Fe becomes available either artificially in bottle experiments or in the environment as Fe-rich land masses are approached, diatoms quickly bloom, chlorophyll levels increase, and nutrient stocks are rapidly depleted. These combined results indicate that Fe availability is the primary factor controlling phytoplankton production in nutrient-rich areas of the open sea

  2. Arthrogryposis - case report

    Directory of Open Access Journals (Sweden)

    Mariana CEVEI

    2008-05-01

    Full Text Available Arthrogryposis is a congenital disorder characterized by multiple joint contractures found throughout the body at birth. We present the case of a 3.5 year-old girl with multiple congenital defects: arthrogryposis involving bilateral hip, knee and ankle joints, together with sacral agenesis and with lumbar dysmorphism, anorectal agenesis, hydronephrosis of the left kidney as the result from reflux, right kidney hypoplasia, renal fusion and heart anomalies: tetralogy of Fallot. Immediately after birth, in several steps, colostomy, left ureterocystoneostomy and suprapubic cystostomy were performed. Later in infancy corrective surgery for the heart defect was required. At the age of 2 years, surgery for the equinovarus deformities and for left genu flexum was performed. Medical rehabilitation tries to maximize independent function. The main goals were increasing the muscle tonus of upper-limbs, increase the rate of motion of the joints, establishment of stability for ambulation, learning different schemes of movement according to her needs, obtaining of a functional independency. The therapies were successful, after 10 weeks an improvement of the moving capacity and of the transfer in orthostatism with minimal external assistance, with the obvious increasing of the patient's satisfaction, were noticed.

  3. Termination: A Case Study.

    Science.gov (United States)

    Friedberg, Ahron L

    2015-12-01

    In this article I posit and examine certain criteria and qualities for ending an analysis. The case study describes the end phase of a four-year psychoanalysis in which the patient's decision to move to another area forced the end of his analysis. We continued to explore and work through his core neurotic conflicts that included issues of competitive rivalry, dominance and submission, control, and anxiety about birth and death. A shift in the transference from me as a negative father to me as a supportive but competitive older brother was also examined in the context of ending treatment as well as other aspects of the transference. In addition, we analyzed the meaning of his ending treatment based on an extra-analytic circumstance. In discussing this phase of treatment, the definition and history of the term "termination" and its connotations are reviewed. Various criteria for completing an analysis are examined, and technical observations about this phase of treatment are investigated. It was found that while a significant shift in the transference occurred in this phase of the patient's analysis, conflicts related to the transference were not "resolved" in the classical sense. Terminating treatment was considered as a practical matter in which the patient's autonomy and sense of choice were respected and analyzed. PMID:26583444

  4. Pressurized waterproof case electronic device

    KAUST Repository

    Berumen, Michael L.

    2013-01-31

    A pressurized waterproof case for an electronic device is particularly adapted for fluid-tight containment and operation of a touch-screen electronic device or the like therein at some appreciable water depth. In one example, the case may be formed as an enclosure having an open top panel or face covered by a flexible, transparent membrane or the like for the operation of the touchscreen device within the case. A pressurizing system is provided for the case to pressurize the case and the electronic device therein to slightly greater than ambient in order to prevent the external water pressure from bearing against the transparent membrane and pressing it against the touch screen, thereby precluding operation of the touch screen device within the case. The pressurizing system may include a small gas cartridge or may be provided from an external source.

  5. A report on case reports

    Directory of Open Access Journals (Sweden)

    Gopikrishna Velayutham

    2010-01-01

    Full Text Available Case reports are defined as the scientific documentation of a single clinical observation and have a time-honored and rich tradition in medicine and scientific publication. This article discusses the role and relevance of case reports in the current evidence-based medical literature. It also seeks to help and guide authors to understand how to prepare a reasonable and well-written case report and how they may anticipate concerns that peer reviewers may express when scrutinizing their manuscript. An overview of the Journal of Conservative Dentistry′s review process of a manuscript submission is provided for the benefit of future authors. It is important to be able to read a case report critically and to use the information they contain appropriately. This article also discusses the factors to consider in evaluating individual case reports, and discusses a practical conceptual scheme for evaluating the potential value and educational content of a case report.

  6. Membranous Dysmenorrhea: A Case Series

    Directory of Open Access Journals (Sweden)

    Hatim A. Omar

    2007-01-01

    Full Text Available The purpose was to illustrate the variability of hormonal contraception of patients that presented with membranous dysmenorrheal. A case analysis chart review was completed on six patients referred to a Pediatric Gynecologist in an academic setting. In each case the patient underwent a thorough pelvic and bimanual exam. Following the initial presentation, each patient continued to be followed on a regular visits. Cases: Two were using the transdermal contraceptive patch and oral contraceptive, but following the expulsion of decidual cast, they were both placed on depot medroxyprogesterone acetate (DMPA without further complications. Three of the six cases were on DMPA prior to the similar occurrence of membranous dysmenorrheal and following this incident, continued on DMPA without further problems. The final case was on the transdermal patch prior to decidual cast expulsion and remained on this form of hormonal contraception without further complications. These cases indicate that membranous dysmenorrheal is not limited to the use of DMPA.

  7. A report on case reports

    OpenAIRE

    Gopikrishna Velayutham

    2010-01-01

    Case reports are defined as the scientific documentation of a single clinical observation and have a time-honored and rich tradition in medicine and scientific publication. This article discusses the role and relevance of case reports in the current evidence-based medical literature. It also seeks to help and guide authors to understand how to prepare a reasonable and well-written case report and how they may anticipate concerns that peer reviewers may express when scrutinizing their manuscri...

  8. Intrahepatic splenosis: a case report

    International Nuclear Information System (INIS)

    Splenosis is heterotopic autotransplantation and seeding of splenic tissue. In the literature, only a few cases of splenosis involving the liver and the radiologic characteristics of these lesions have been reported. We report a case of intrahepatic splenosis diagnosed by ultrasound, computed tomography, magnetic resonance imaging and scintigraphic features. To our knowledge, our patient is the first case diagnosed only by radiologic and radionuclide examination without any intervention. (orig.)

  9. Non-ferromagnetic overburden casing

    Energy Technology Data Exchange (ETDEWEB)

    Vinegar, Harold J. (Bellaire, TX); Harris, Christopher Kelvin (Houston, TX); Mason, Stanley Leroy (Allen, TX)

    2010-09-14

    Systems, methods, and heaters for treating a subsurface formation are described herein. At least one system for electrically insulating an overburden portion of a heater wellbore is described. The system may include a heater wellbore located in a subsurface formation and an electrically insulating casing located in the overburden portion of the heater wellbore. The casing may include at least one non-ferromagnetic material such that ferromagnetic effects are inhibited in the casing.

  10. Marketing communication plan. Case: EKOenergy.

    OpenAIRE

    Jäkälä, Elina

    2016-01-01

    This project-based thesis has an objective of creating a marketing communication plan for a non-profit organisation. The marketing communication plan targets other non-profit organisa-tions that the case organisation wants to cooperate with. This thesis will introduce theory about marketing communication, give information about the case organisation’s target audience and present the actual marketing communication plan. Since the case organisation and its target audience are all non-profit...

  11. Dioctophymiasis: A Rare Case Report.

    Science.gov (United States)

    Chauhan, Sapna; Kaval, Sunil; Tewari, Swati

    2016-02-01

    Dioctophyma renale commonly known as "giant kidney worm' is found in the kidney of carnivorous mammals. Human infestation is rare, but results in destruction of the kidneys. Very few cases have been reported worldwide. We are here reporting a case of Dioctophymiasis in a 35-year-old male patient who presented with retention of urine and subsequent passage of worm and blood in urine. The worm was confirmed as Dioctophyma renale based on its morphology and clinical presentation. This is a very rare case report and to best of our knowledge only two cases have been reported from India. PMID:27042466

  12. Theory Testing Using Case Studies

    DEFF Research Database (Denmark)

    Møller, Ann-Kristina Løkke; Dissing Sørensen, Pernille

    2014-01-01

    The appropriateness of case studies as a tool for theory testing is still a controversial issue, and discussions about the weaknesses of such research designs have previously taken precedence over those about its strengths. The purpose of the paper is to examine and revive the approach of theory...... testing using case studies, including the associated research goal, analysis, and generalisability. We argue that research designs for theory testing using case studies differ from theorybuilding case study research designs because different research projects serve different purposes and follow different...

  13. Statute law or case law?

    OpenAIRE

    Anderlini, Luca; Felli, Leonardo; RIBONI, Alessandro

    2008-01-01

    In a Case Law regime Courts have more flexibility than in a Statute Law regime. Since Statutes are inevitably incomplete, this confers an advantage to the Statute Law regime over the Case Law one. However, all Courts rule ex-post, after most economic decisions are already taken. Therefore, the advantage of flexibility for Case Law is unavoidably paired with the potential for time-inconsistency. Under Case Law, Courts may be tempted to behave myopically and neglect ex-ante welfare because, ex-...

  14. Urachal endometrioma: a case report.

    LENUS (Irish Health Repository)

    Browne, Katherine M

    2009-01-01

    INTRODUCTION: We discuss a rare presentation of an unusual case of endometrioma. CASE PRESENTATION: A 40-year-old Caucasian woman presented with subacute abdominal pain and a suprapubic mass. A final diagnosis was made after the mass was resected and histopathology confirmed an endometrioma originating from an urachal remnant. Select imaging studies and histopathology are presented in this case report. CONCLUSION: While endometriomata are well known to arise from abdominal scars, the condition described in this case report is a rare example of an endometrioma arising from the urachus. A review of the pathological complications of the urachus is also included.

  15. Case Study: Case Studies and the Flipped Classroom

    Science.gov (United States)

    Herreid, Clyde Freeman; Schiller, Nancy A.

    2013-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's issue discusses the positive and negative aspects of the "flipped classroom." In the flipped classroom model, what is normally done in class and what is normally done as…

  16. Goiania incident case study

    International Nuclear Information System (INIS)

    The reasons for wanting to document this case study and present the findings are simple. According to USDOE technical risk assessments (and our own initial work on the Hanford socioeconomic study), the likelihood of a major accident involving exposure to radioactive materials in the process of site characterization, construction, operation, and closure of a high-level waste repository is extremely remote. Most would agree, however, that there is a relatively high probability that a minor accident involving radiological contamination will occur sometime during the lifetime of the repository -- for example, during transport, at an MRS site or at the permanent site itself during repacking and deposition. Thus, one of the major concerns of the Yucca Mountain Socioeconomic Study is the potential impact of a relatively minor radiation-related accident. A large number of potential impact of a relatively minor radiation-related accident. A large number of potential accident scenarios have been under consideration (such as a transportation or other surface accident which results in a significant decline in tourism, the number of conventions, or the selection of Nevada as a retirement residence). The results of the work in Goiania make it clear, however, that such a significant shift in established social patterns and trends is not likely to occur as a direct outcome of a single nuclear-related accident (even, perhaps, a relatively major one), but rather, are likely to occur as a result of the enduring social interpretations of such an accident -- that is, as a result of the process of understanding, communicating, and socially sustaining a particular set of associations with respect to the initial incident

  17. BOUVERET'S SYNDROME (CASE PRESENTATION

    Directory of Open Access Journals (Sweden)

    Dipak

    2014-01-01

    Full Text Available Bouveret's syndrome is defined as gastric outlet obstruction caused by duodenal impaction of a large gallstone which passes into the duodenal bulb through a cholecystogastric or cholecystoduodenal fistula. We describe a case of Bouv eret's Syndrome in an middle aged patient that was successfully treated with resection of distal part of stomach and 1 st part of duodenum by laparotomy. We will also review the literature on this uncommon condition. Biliary enteric fistula is as such a rar e complication and comparatively rare cause of intestinal obstruction. And even if becomes so; generally it lodges in the terminal ileum and rarely in duodenum. Obstructing proximal part of duodenum or distal part of stomach is a curiosity and i.e. Bouvere t’s syndrome. Generally patient presents with nausea, vomiting, haematemesis, abdominal distention or epigastric pain. G.I. bleeding, obstructive jaundice, pancreatitis or duodenal or gastric perforation are rare complications. The treatment is purely surg ical – either enterolithotomy or gastrotomy with associated cholecystectomy with repair of fistula or enterolithotomy with or without second stage cholecystectomy. It is worth to mention here that so far histological findings of Bouveret’s syndrome are no t described in the literature. Even though findings are not that much specific; but presence of foci of abscesses, dense mixed inflammatory exudates in all the coats of distal part of stomach, 1 st part of duodenum and gall bladder along with formation of l ymphoid follicles with prominent germinal centers in muscle coat are definitely mentionable and we feel these may give clue. On gross examination the thickness of stomach wall and duodenal wall are increased and there is narrowing of lumen. If there is sto ne in gall bladder; it may also show thickened out wall due to presence of chronic cholelithiasis with cholecystitis.

  18. Case Studies on Sustainable Buildings

    OpenAIRE

    Hui, Sam CM

    2005-01-01

    This web site is developed with the aim to promote sustainable design and planning of buildings. A knowledge base of case studies and resources has been established to illustrate the sustainable design strategies and features in realistic building projects all over the world. The database of case studies can be searched by project names, locations, design strategies and design features.

  19. CASE-BASED CONCEPTUAL DESIGN

    Institute of Scientific and Technical Information of China (English)

    Ling Weiqing; Yan Junwei; Wang Jian; Xie Youbai

    2004-01-01

    The current method of case-based design (CBD) can be well practiced for configuration design in which design experience knowledge is involved.However, since the design case is confined to a certain application domain, it is difficult for CBD to be applied to conceptual design process that develops concepts to meet design specifications.Firstly, a function factor description space is erected to provide an exhibition room for all functions of design cases.Next, the approach for identifying the space state of function factor in description space is proposed, including the determination of the similarities between function factors of design case.And then a general object-oriented representation for design case is presented by bringing the class of function and in-out flow into the current case representation.Finally, a living example for electro-pet design that illustrates the implementation of the method for case-based conceptual design based on distributed design case repositories is described.

  20. Three Community College Case Studies

    Science.gov (United States)

    Wojtysiak, Joseph; Sutton, William J., II; Wright, Tommy; Brantley, Linda

    2011-01-01

    This article presents three case studies that focus on specific projects that are underway or have been completed. In the first case study, Joseph Wojtysiak and William J. Sutton, II discuss the Green Center of Central Pennsylvania, which is designed to serve as the state's preeminent source for education, training and public information about…

  1. The Economic Case for Education

    Science.gov (United States)

    Woessmann, Ludger

    2016-01-01

    The case for education can be made from many perspectives. This paper makes the case for education based on economic outcomes. Surveying the most recent empirical evidence, it shows the crucial role of education for individual and societal prosperity. Education is a leading determinant of economic growth, employment, and earnings in modern…

  2. The Big Read: Case Studies

    Science.gov (United States)

    National Endowment for the Arts, 2009

    2009-01-01

    The Big Read evaluation included a series of 35 case studies designed to gather more in-depth information on the program's implementation and impact. The case studies gave readers a valuable first-hand look at The Big Read in context. Both formal and informal interviews, focus groups, attendance at a wide range of events--all showed how…

  3. A case of etizolam dependence.

    Science.gov (United States)

    Gupta, Sumit; Garg, Bhavuk

    2014-01-01

    Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine. PMID:25538342

  4. A case of etizolam dependence

    OpenAIRE

    Sumit Gupta; Bhavuk Garg

    2014-01-01

    Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine.

  5. Iatrogenic psoas abscess. Case report

    DEFF Research Database (Denmark)

    Bernstein, Inge Thomsen; Hansen, B J

    1991-01-01

    A case of iatrogenic pneumococcus psoas abscess is reported. The etiology was probably repeated local anaesthetic blockades in the lumbogluteal structures because of lumbago.......A case of iatrogenic pneumococcus psoas abscess is reported. The etiology was probably repeated local anaesthetic blockades in the lumbogluteal structures because of lumbago....

  6. Customs Modernization Initiatives : Case Studies

    OpenAIRE

    De Wulf, Luc; José B. Sokol

    2004-01-01

    This volume presents case studies of customs modernization initiatives in eight developing countries: Bolivia, Ghana, Morocco, Mozambique, Peru, the Philippines, Turkey, and Uganda. The purpose of these case studies was to obtain a firsthand view of how these countries undertook customs reforms and to assess their success. The overall lessons learned from these studies are presented in cha...

  7. Joint Case Development with Wharton

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      February 18,2005marked an agreement between Wharton School of the University of Pennsylvania and the China Europe International Business School (CEIBS).Together,Wharton's Snider Entrepreneurial Research Centre (SEC) and CEIBS' Centre of Entrepreneurship and Case Development Centre will work together creating a series of cases to be used in each institution's entrepreneurship courses.……

  8. Joint Case Development with Wharton

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ February 18,2005marked an agreement between Wharton School of the University of Pennsylvania and the China Europe International Business School (CEIBS).Together,Wharton's Snider Entrepreneurial Research Centre (SEC) and CEIBS' Centre of Entrepreneurship and Case Development Centre will work together creating a series of cases to be used in each institution's entrepreneurship courses.

  9. Joubert Syndrome: A Case Report

    OpenAIRE

    Türdoğan-Sözüer, Dilşad; Suyugül, Zuhal; Yüksel, Adnan; Cenani, Asım; Yalçın, Erdinç

    1994-01-01

    Joubert syndrome is associated with hypotonia developmental delay cerebellar vermis hypoplasia abnormal breathing and abnormal eye movements Cases should be classified into two groups: those with retinal distrophy and those without We determined bilateral pallor optic disc without retinal dystrophy in our case that has psychomotor retardation hypotonia vermis hypoplasia and abnormal eye movements Key words: Joubert Syndrome Vermis Hypoplasia Abnormal Eye Movements

  10. Use cases versus task descriptions

    DEFF Research Database (Denmark)

    Lauesen, Søren; Kuhail, Mohammad Amin

    2011-01-01

    without specifying a dialog. [Contribution] It turned out that the traditional use cases covered the customer's needs poorly in areas where improvement was important but diffi-cult. Use cases also restricted the solution space severely. Tasks didn't have these problems and allowed an easy comparison...

  11. Two energy system analysis - cases

    DEFF Research Database (Denmark)

    Lund, Henrik; Antonoff, Jayson; Andersen, Anders N.

    2004-01-01

    The chapter presents tow cases of energy system analysis, illustrating the types of tools and methodologies presently being used for these studies in Denamrk and elsewhere.......The chapter presents tow cases of energy system analysis, illustrating the types of tools and methodologies presently being used for these studies in Denamrk and elsewhere....

  12. Case Studies in Science Ethics

    Science.gov (United States)

    Williams, Karen

    2010-03-01

    Everyone in science should have ethics education training. I have seen graduate students taken advantage of by their mentors. Many of us have seen misconduct...but what should we do about it? Young scientists are often unaware of the rules in science and make mistakes because of their ignorance of the rules in that particular field of study. Then there are an increasing number of cases in the news of overt cases of misrepresentation in science. All are welcome to attend this discussion of case studies. A case study on topics such as: how to treat data properly, how our values in science affect our work, who gets authorship on scientific papers, who is first author on a paper, what you should do if you uncover misconduct or plagiarism in your university, and we will discuss the scientist's role in society. This will be a painless, non-confrontational small group, then large group discussion of each case

  13. Theory testing using case studies

    DEFF Research Database (Denmark)

    Dissing Sørensen, Pernille; Løkke Nielsen, Ann-Kristina

    Case studies may have different research goals. One such goal is the testing of small-scale and middle-range theories. Theory testing refers to the critical examination, observation, and evaluation of the 'why' and 'how' of a specified phenomenon in a particular setting. In this paper, we focus on...... the strengths of theory-testing case studies. We specify research paths associated with theory testing in case studies and present a coherent argument for the logic of theoretical development and refinement using case studies. We emphasize different uses of rival explanations and their implications...... for research design. Finally, we discuss the epistemological logic, i.e., the value to larger research programmes, of such studies and, following Lakatos, conclude that the value of theory-testing case studies lies beyond naïve falsification and in their contribution to developing research programmes...

  14. MyCases-a portable application for radiologic case collections.

    Science.gov (United States)

    Kammerer, Ferdinand Josef; Janka, Rolf; Kramer, Manuel; Hammon, Matthias; Uder, Michael; Schlechtweg, Philipp Martin

    2014-10-01

    Radiologists come across interesting patient cases almost every day. This work proposes a novel case database server for quick and easy storage of such cases including whole image series, patient data, and annotations. Cases can be added to the database by saving DICOM images into a predefined directory on the local network. The application automatically extracts patient and study data from the DICOM header and saves it in the database while images are stored as anonymized JPEG files. Users can mark their cases as private or public (visible to all users). Different data fields for annotations and categorization of a case are available. The user frontend also provides several retrieval mechanisms allowing for browsing the cases and performing different kinds of search queries. The stored series can be scrolled interactively in the form of scrollable image stacks. The project is realized as a web-based application using a portable web and database server software package (XAMPP). This makes the system very lightweight and easy to run on almost any desktop computer, even from a USB flash drive, without the need for deeper IT knowledge and administrative rights. PMID:24788304

  15. CaseWorld™: Interactive, media rich, multidisciplinary case based learning.

    Science.gov (United States)

    Gillham, David; Tucker, Katie; Parker, Steve; Wright, Victoria; Kargillis, Christina

    2015-11-01

    Nurse educators are challenged to keep up with highly specialised clinical practice, emerging research evidence, regulation requirements and rapidly changing information technology while teaching very large numbers of diverse students in a resource constrained environment. This complex setting provides the context for the CaseWorld project, which aims to simulate those aspects of clinical practice that can be represented by e-learning. This paper describes the development, implementation and evaluation of CaseWorld, a simulated learning environment that supports case based learning. CaseWorld provides nursing students with the opportunity to view unfolding authentic cases presented in a rich multimedia context. The first round of comprehensive summative evaluation of CaseWorld is discussed in the context of earlier formative evaluation, reference group input and strategies for integration of CaseWorld with subject content. This discussion highlights the unique approach taken in this project that involved simultaneous prototype development and large scale implementation, thereby necessitating strong emphasis on staff development, uptake and engagement. The lessons learned provide an interesting basis for further discussion of broad content sharing across disciplines and universities, and the contribution that local innovations can make to global education advancement. PMID:26522447

  16. Lunar drill footplate and casing

    Science.gov (United States)

    Maassen, Erik C.; Hendrix, Thomas H.; Morrison, Eddie W.; Phillips, Rodrick B.; Le, Vu Quang; Works, Bruce A.

    1989-01-01

    To prevent hole collapse during lunar drilling operations, a casing has been devised of a graphite reinforced polyimide composite which will be able to withstand the lunar environment. Additionally, this casing will be inserted into the ground in segments two meters long which will penetrate the regolith simultaneously with the auger. The vertical action of the mobile platform will provide a downward force to the casing string through a special adaptor, giving the casing the needed impetus to sink the anticipated depth of ten meters. Casing segments will be connected with a simple snap arrangement. Excess casing will be cut off by a cylindrical cutting tool which will also transport the excess casing away from the hole. A footplate will be incorporated to grasp the auger rod string during rod segment additions or removals. The footplate grasping mechanism will consist of a set of vice-like arms, one end of each bearing threaded to a common power screw. The power screw will be threaded such that one end's thread pitch opposes that of the other end. The weight of the auger and rod string will be transmitted through the arms to the power screw and absorbed by a set of three ball bearing assemblies. The power screw will be driven by a one-half horsepower brushless motor actuated by radio control. The footplate will rest on four short legs and be anchored with pins that are an integral part of each leg.

  17. Hemicrania continua. The first Spanish case: a case report.

    Science.gov (United States)

    Pareja, J A; Palomo, T; Gorriti, M A; Pareja, J; Espejo, J; Morón, B; Trigo, M

    1990-06-01

    The case of a patient suffering from strictly unilateral continuous headache, absolutely responsive to indomethacin is reported. This is the first Hemicrania continua case to be documented in Spain. The tyramine test resulted in anisocoria with the smaller pupil on the symptomatic side. A second tyramine test after one week on 75 mg indomethacin per day failed to produce anisocoria. Treatment was reduced to 25 mg indomethacin per day, and this dose was sufficient to control the headache completely. PMID:2245459

  18. Task descriptions versus use cases

    DEFF Research Database (Denmark)

    Lauesen, Søren; Kuhail, Mohammad Amin

    2011-01-01

    Use cases are widely used as a substantial part of requirements, also when little programming is expected (COTS-based systems, Commercial-Off-The-Shelf). Are use cases effective as requirements? To answer this question, we invited professionals and researchers to specify requirements for the same...... project: Acquire a new system to support a hotline. Among the 15 replies, eight used traditional use cases that specified a dialog between user and system. Seven used a related technique, task description, which specified the customer’s needs without specifying a dialog. It also allowed the analyst to...

  19. Emphysematous cystitis: 3 cases report

    International Nuclear Information System (INIS)

    Emphysematous cystitis is a rare condition characterized by gas collection in the wall and lumen of the bladder. We experienced three cases of emphysematous cystitis. All patients were female; one was associated with a long term history of diabetes mellitus and another with urinary indwelling catheter. All of the cases were easily diagnosed on plain radiograph and CT scan, and were successfully treated with antibiotic therapy. In one of the cases, however, associated abscess due to perivesical extension of inflammation was treated by combined external drainage

  20. Case-yrityksen hinnoittelun kannattavuus

    OpenAIRE

    Huhtasalo, Jenna

    2015-01-01

    Opinnäytetyön aiheena oli selvittää siivousalalla toimivan Case-yrityksen hinnoittelun kannattavuutta. Opinnäytetyön tarkoituksena oli perehtyä Case-yrityksen hinnoittelemiin sopimuksiin, sekä niihin kohdistuviin kustannuksiin. Tarkoituksena oli myös kehittää Excel-pohjaan laskukaava kannattavien sopimushintojen laskemiseen. Opinnäytetyön tavoitteena oli selvittää Case-yrityksen palvelukohteiden hinnoittelun kannattavuus kustannuslaskennan, sekä hinnoittelu- ja kannattavuuslaskelmien avulla. ...

  1. A case of inflammatory ascites

    Directory of Open Access Journals (Sweden)

    Marco Biolato

    2008-03-01

    Full Text Available Even ascites appears mainly as sign of portal hypertension in patiens with liver cirrhosis, in some case depends on a different lying condition such as right congestive heart failure, peritoneal carcinomatosis or tuberculosis. In these cases, paracentesis represents the key tool for diagnosis. We report a case of cardiac ascites in a 71-years-old woman who developed in four-month an abdominal distension. Preliminary exams showed exudative ascites related to portal hypertension, a pelvic mass with caseous apparence, and inflammatory status ad an elevation of CA-125. Successive evaluation exluded peritoneal carcinomatosis or tuberculosis, underlyng a tricuspidal regurgitation. The literature on ascites has also been reviewed.

  2. Congenital mesoblastic nephroma: case report

    OpenAIRE

    POLAT, Mesut; Arisoy, Resul; Erdoğdu, Emre; ANGIN, A.Doğukan; TUĞRUL, Ahmet Semih

    2014-01-01

    Aim: Aim of the report is discuss the case who was prenatally diagnosed as congenital mesoblastic nephroma and  postnatal managenent. Case: We reported a case of 27 year old gravida 3, parity 1, abortion 1 referred to our clinic with the diagnosis of preterm labour and polihydramniosis at 34. gestational week. The ultrasonografic examination of the patient, with no antenatal follow up before, revealed a fetal biometry of 33 weeks and polyhydramniosis. A 63x66 mm solid mass with reguler border...

  3. TEACHING ECONOMICS – THE CASE METHOD

    OpenAIRE

    DANIELA POPESCU

    2014-01-01

    One of the most efficient approaches in teaching Economics is the Case Method. The Case Method combines two elements: the case itself and the discussion of that case. A teaching case is a rich narrative in which individuals or groups of individuals have to make a decision or solve a problem. A teaching case is not a case study of the type used in academic research, as it provides information, but neither analysis nor conclusions. During the classroom discussions, the students perf...

  4. Typhoid spine - A case report

    Directory of Open Access Journals (Sweden)

    Rajesh P

    2004-01-01

    Full Text Available A case of Salmonella typhi isolated from L4-L5 spine is reported here. The causative organism was not suspected preoperatively. The patient responded favourably to surgical drainage and appropriate antibiotic therapy.

  5. Teaching astronomy with case studies

    Science.gov (United States)

    Slater, Timothy F.

    2015-11-01

    Breaking the students into small, collaborative learning groups to solve a meaningful task together is one of the most successful and fully evaluated teaching techniques implemented over the last century. Although there are many ways to accomplish small group learning, a long-standing and consistently successful collaborative class activity is to use the case study teaching strategy. The use of case studies is common in medical schools and law schools, but not so common in the teaching of astronomy. Case studies create meaningful conversations among students and with the professor by focusing on life-like dilemmas to be solved. Case study tasks ask audience members to synthesize several ideas or evaluate scenarios that have not been explicitly presented to them in the lecture or in available readings.

  6. Case and Administrative Support Tools

    Data.gov (United States)

    U.S. Environmental Protection Agency — Case and Administrative Support Tools (CAST) is the secure portion of the Office of General Counsel (OGC) Dashboard business process automation tool used to help...

  7. Nasopharyngeal Case-Control Study

    Science.gov (United States)

    A case-control study conducted in Taiwan between 1991-1994 among approximately 1,000 individuals to examine the role of viral, environmental, and genetic factors associated with the development of nasopharyngeal carcinoma

  8. Degree distribution in discrete case

    International Nuclear Information System (INIS)

    Vertex degree of many network models and real-life networks is limited to non-negative integer. By means of measure and integral, the relation of the degree distribution and the cumulative degree distribution in discrete case is analyzed. The degree distribution, obtained by the differential of its cumulative, is only suitable for continuous case or discrete case with constant degree change. When degree change is not a constant but proportional to degree itself, power-law degree distribution and its cumulative have the same exponent and the mean value is finite for power-law exponent greater than 1. -- Highlights: → Degree change is the crux for using the cumulative degree distribution method. → It suits for discrete case with constant degree change. → If degree change is proportional to degree, power-law degree distribution and its cumulative have the same exponent. → In addition, the mean value is finite for power-law exponent greater than 1.

  9. Postherpetic neuralgia: two clinical cases

    Directory of Open Access Journals (Sweden)

    Daniel Serrano

    2014-03-01

    Full Text Available Postherpetic neuralgia (PHN is the most common complication of Herpes Zoster, characterized by the presence of neuropathic-type pain limited to a dermatomic area after outbreak of Herpes Zoster (commonly known as shingles, usually a month after the appearance of vesicles on the skin . The aim of this report is to present two cases of PHN and their responses to different treatments. The first case presented intolerance to amitriptyline and a good clinical response to gabapentin at a dose of 900 mg/day. The second case showed intolerance to capsaicin but responded well to the combination of pregabalin and topical lidocaine. Gabapentin, pregabalin and lidocaine are effective for the treatment of postherpetic neuralgia. All these recommendations are consistent with those treatments used by the family physicians in the two cases study presented.

  10. HYDROGEOLOGIC CASE STUDIES (CHICAGO, IL)

    Science.gov (United States)

    Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

  11. HYDROGEOLOGIC CASE STUDIES (DENVER PRESENTATION)

    Science.gov (United States)

    Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

  12. Hydrogeologic Case Studies (Seattle, WA)

    Science.gov (United States)

    Hydrogeology is the foundation of subsurface site characterization for evaluations of monitored natural attenuation (MNA). Three case studies are presented. Examples of the potentially detrimental effects of drilling additives on ground-water samples from monitoring wells are d...

  13. Intraocular coenurosis: a case report.

    OpenAIRE

    Ibechukwu, B. I.; Onwukeme, K. E.

    1991-01-01

    A case of intraocular coenurosis was clinically diagnosed and treated with praziquantel. The drug destroyed the coenurus, but vision was lost through toxic endophthalmitis and retinal detachment. There were no systemic side effects.

  14. One case of intraosseous ganglion

    International Nuclear Information System (INIS)

    Intraosseous ganglion is a rare disease and identified as a cystic lesion on plain radiograph. One case of intraosseous ganglion is examined by plain radiography and computed tomography and findings are analyzed.

  15. One case of intraosseous ganglion

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sun Seob; Shim, Hyung Jin; Lee, Yong Chul [Chung Ang University College of Medicine, Seoul (Korea, Republic of)

    1983-09-15

    Intraosseous ganglion is a rare disease and identified as a cystic lesion on plain radiograph. One case of intraosseous ganglion is examined by plain radiography and computed tomography and findings are analyzed.

  16. Genetic Algorithms for Case Adaptation

    International Nuclear Information System (INIS)

    Case based reasoning (CBR) paradigm has been widely used to provide computer support for recalling and adapting known cases to novel situations. Case adaptation algorithms generally rely on knowledge based and heuristics in order to change the past solutions to solve new problems. However, case adaptation has always been a difficult process to engineers within (CBR) cycle. Its difficulties can be referred to its domain dependency; and computational cost. In an effort to solve this problem, this research explores a general-purpose method that applying a genetic algorithm (GA) to CBR adaptation. Therefore, it can decrease the computational complexity of the search space in the problems having a great dependency on their domain knowledge. The proposed model can be used to perform a variety of design tasks on a broad set of application domains. However, it has been implemented for the tablet formulation as a domain of application. The proposed system has improved the performance of the CBR design systems

  17. Sebaceous horn: An interesting case

    Directory of Open Access Journals (Sweden)

    Saraf Sanjay

    2007-01-01

    Full Text Available Sebaceous horn or cutaneous horn of the nose is a rare clinical entity. A case of a giant sebaceous horn of the nose presenting in an elderly male, which was successfully excised and reconstructed is reported.

  18. Secondary middle turbinate: case report

    Energy Technology Data Exchange (ETDEWEB)

    Aburjeli, Bruna de Oliveira Melim; Avila, Ana Flavia Assis de; Diniz, Renata Lopes Furletti Caldeira; Motta, Emilia Guerra Pinto Coelho; Ribeiro, Marcelo Almeida; Moreira, Wanderval, E-mail: bruninha86@hotmail.com [Radiology and Imaging Diagnosis, Hospital Mater Dei, Belo Horizonte, MG (Brazil)

    2012-11-15

    Secondary middle turbinate is an anatomical variant rarely observed in the nasal cavity, firstly described by Khanobthamchai et al. as a bone structure originating from the lateral nasal wall and covered by soft tissue. In most cases reported in the literature, this variant is bilateral, occurring without associated complications. In the present report, the authors describe the case of patient of their institution with such anatomical variation. (author)

  19. Sternocleidomastoid syndrome: a case study

    OpenAIRE

    Missaghi, Babak

    2004-01-01

    This article presents a case study of a patient diagnosed with dysfunction of the sternocleidomastoid (SCM) muscle, a condition which can result in head and face pain, nausea, dizziness, coryza, and lacrimation. In this particular case, the SCM muscle had developed tightness and weakness with presence of multiple trigger points within both heads. A combination of passive and active treatments were utilized to successfully treat this condition.

  20. WOMB STONE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sankareswari

    2014-11-01

    Full Text Available We report a case of calcified fibroid in a 34 year old reproductive female, persisting for more than nine years, with secondary infertility, without symptoms. Final diagnosis of calcified fibroid was made through radio-diagnosis. When the whole of the tumour is converted into a calcified mass, it is called ‘womb stone’. [1] A calcified fibroid in reproductive age group is very rare. Hence we are presenting this case.

  1. SUBCUTANEOUS PHYCOMYCOSIS: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Thilak Sundararaj, Meera Govindaraju, Brindha Thangaraj

    2015-01-01

    Full Text Available Subcutaneous Phycomycosis is a rare tropical Mycoses characterized by the development of a chronic, firm swelling of the subcutaneous tissue. Infection caused by Basidiobolus species commonly affects young children. In this article we present a case of Subcutaneous Phycomycosis which presented as a diffuse swelling in the posterior aspect of the knee. Early diagnosis and treatment with Itraconazole caused complete clearance of the lesion. We highlight the merits of accurate diagnosis and early therapeutic intervention in this rare case.

  2. Intestinal actinomycosis: a case report

    International Nuclear Information System (INIS)

    Intestinal actinomycosis: a case report. The authors describe a case of intestinal actinomycosis, which was manisfestated by abdominal mass and suggested, clinical and radiologically, a bowel carcinoma. They discuss the pathogenesis, and the clinical and radiological manisfestations of this disease, and its differential diagnosis. This is an infrequent disease which must be considered whenever suggestive clinical aspects are associated with a radiological ''malignant pattern'' of a bowel lesion. (author)

  3. Implant periapical lesion. Case report

    OpenAIRE

    Gregory Venetis, Fotis Iordanidis, Paraskevi Giovani, Lambros Zouloumis

    2011-01-01

    Ιmplant periapical lesion (IPL) is probably not a uniform entity in all cases presented in the literature. Asseptic bone necrosis may be a cause for some of the IPLs, whilst the presence of microorganisms is not always detectable with conventional methods. A case of IPL in a male patient who underwent an extraction of 12 tooth and an immediate implantation at this site is presented. Eight months postoperatively, an IPL was revealed on radiologic examination. After surgical exploration, the IP...

  4. A case of etizolam dependence

    Directory of Open Access Journals (Sweden)

    Sumit Gupta

    2014-01-01

    Full Text Available Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine.

  5. Acute Echinococcosis: a Case Report

    OpenAIRE

    Di Comite, Gabriele; Dognini, Giuseppina; Gaiera, Giovanni; Ieri, Rossella; Praderio, Luisa

    2000-01-01

    We report the case of a 69-year-old man with acute pulmonary echinococcosis. A computed tomographic scan of the thorax revealed the presence of multiple nodules in both lungs, and laboratory tests showed eosinophilia and the presence of antibodies against Echinococcus granulosus. Therapy with albendazole led to resolution of the pulmonary nodules and a normalization of the white cell count. To our knowledge this is the first described case of acute echinococcosis, as the diagnosis of this dis...

  6. A Case of Hepatopulmonary Syndrome

    Science.gov (United States)

    Sindhuja, R.; Natarajan, M.; Rajamurugan, P.S. Arul; Palanikumar, B.

    2016-01-01

    We report the case of a 52-year-old female, a known case of Chronic Liver Disease with portal hypertension. She presented with dyspnoea, platypnoea, melena, cyanosis, clubbing and orthodeoxia. She had oesophageal varices and splenomegaly indicating portal hypertension. Her arterial blood gas revealed hypoxaemia and orthodeoxia. From this clinical background and investigation, a diagnosis of hepatopulmonary syndrome was made. Patient was managed conservatively as she was not willing for liver transplantation.

  7. Meteorological Test Reference Case - Copenhagen

    DEFF Research Database (Denmark)

    Kragh, Mikkel Kristian

    1997-01-01

    The report describes a case study. Actual weather data is converted into input for hygrothermal calculations. A survey of the literature on calculation of driving rain is reported and a ‘driving rain potential’ is generated on the basis of hourly meteorological data for selected years. The study is...... focusing on the significance of the driving rain parameters and comparing the case study data to the contents of the commonly used Danish Design Reference Year....

  8. A case of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Maria Alice Monti

    2009-09-01

    Full Text Available As the expected survival improves for patients with cystic fibrosis (CF, there is a growing population of adults with this disease. We describe a case of a 33-year-old woman with CF presenting with recurrent pancreatitis, malnutrition, borderline sweat test and respiratory diseases. The case report underlines the importance of diagnosis and management of CF in adults, and the important role played by the Family Physician in developing an adult care program.

  9. Infantile Scurvy: Two Case Reports

    OpenAIRE

    Leila Ghedira Besbes; Samir Haddad; Chebil Ben Meriem; Mondher Golli; Mohamed-fadhel Najjar; Mohamed-Néji Guediche

    2010-01-01

    Background. Ascorbic acid (vitamin C) is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. SCURVY, a disease of dietary ascorbic acid deficiency, is uncommon today. It still exists in high risk groups including economically disadvantaged populations with poor nutrition. The incidence of SCURVY in the pediatric population is very low. Cases Report. Here we report two cases of SCURVY revealed by subperiosteal hematoma in children with cerebral palsy...

  10. Bladder Schwannoma - A Case Presentation

    OpenAIRE

    Mosier, Andrew D.; Leitman, David A.; Keylock, Joren; Nguyen, David; Grant, David

    2012-01-01

    Bladder schwannomas are exceedingly rare, benign or malignant, nerve sheath tumors that are most often discovered in patients with a known diagnosis of Neurofibromatosis type 1 (NF1). A few sporadic case reports of bladder schwannoma have been published in urologic, obstetric/gynecologic, and pathologic journals. However, this is the first case report in the radiologic literature where computed tomography imaging and radiology-specific descriptions are discussed. Furthermore, the patient pres...

  11. Cephalic Tetanus: A Case Report

    OpenAIRE

    F. L. Bukar; Atuanya, C. I.; Abdulhafiz, U.; M A Alhaji

    2011-01-01

    A case report of cephalic tetanus in a 2-year-old girl who was not immunized against tetanus following suppurative otitis media (SOM) is presented. This case is reported because of the rarity of cephalic tetanus associated with high mortality, to highlight the risk of cephalic tetanus as sequelae of SOM and the need for proper aural care and prompt treatment of SOM. Primary immunization of all eligible children as well as booster vaccination at appropriate time as an effective management stra...

  12. Intrapulmonary teratoma: a case report

    OpenAIRE

    Farahnak MR; Mirrokni SM

    2010-01-01

    "nBackground: Teratomas are tumors consisting of tissues derived from more than one germ cell line. Teratomas arise, most commonly in anterior mediastinum. Intrapulmonary Teratoma are among the rarest tumors encountered in pathology, in other words they are exceedingly uncommon, with only less than 100 cases documented by 1939. "n "nCase presentation: We describe a 19-year-old woman with a short history of retrosternal chest pain and non-productive cough due to a benign intrapu...

  13. A HARD CHOICE (CASE STUDY)

    OpenAIRE

    KRAVCHENKO NATALIYA A.; KUZNETSOVA SVETLANA A.

    2014-01-01

    The case describes the problems of strategic choice: a small company successfully working in the engineering market (automation of technological processes) in the electric power industry has to make a decision on its further development in a changing external environment and increased competition. The case was carried out to be used in training programs of different levels within the courses “Strategic Management”, “Innovation Management”, “Strategic Analysis Methods”, “Change Management” whe...

  14. [Simultaneous bilateral pneumothorax. Case report].

    Science.gov (United States)

    Paolini, A; Caminiti, F; Tosato, F; Ruggieri, M; Paolini, G; Carnevale, L; Corsini, F; Marano, S; Monsellato, I

    2001-04-01

    A case report of a 44 year-old white man admitted to the surgical unit for a bilateral simultaneous pneumothorax is presented. The pneumothorax occurred on day one after a surgical operation for discal hernia; in the past the patient already presented a right spontaneous pneumothorax at 32 years of age and a left pneumothorax at 37 years of age, both treated with a pleural drainage. A thoracic drain was bilaterally positioned with a good result only in the right side. The persistence of the left pneumothorax induced the authors to perform a postero-lateral thoracotomy bullae excision and pleurectomy with a good postoperative course. After a few months a new right pneumothorax occurred and the patient was treated with a right postero-lateral thoracotomy, bullae resection and pleurectomy. On the basis of the case reported, the authors consider the different opportunities in the treatment of spontaneous pneumothorax in relation to the present knowledges and technologies. Surgical procedure is to be preferred in case of persistence of pneumothorax despite a pleural drain and in case of pneumothorax in high risk subjects. Even if thoracoscopy seems to give better results regarding postoperative pain, it is not always possible with such a method to perform a careful pleurectomy neither to obtain it in all cases (above all in secondary pneumothorax). Every case must then be carefully studied to choose the best treatment at present available. PMID:11353349

  15. How to write a neurology case report.

    Science.gov (United States)

    Rison, Richard A

    2016-01-01

    Neurology case reports have a long history of transmitting important medical information across many generations for the improvement of patient care. Case reports contribute much to the physician's knowledge base from which treatment hypotheses and ideas form. Elements of a modern case report, as presented in the CARE (CAse REport) guidelines, include the abstract, introduction, case presentation, discussion, conclusion, patient's perspective, and consent statement. The sections are described here, as well as the application of CARE guidelines to a published neuromuscular case report. Writing case reports offer an ideal opportunity for neurologists to publish interesting case findings and carry on the tradition of neurologic case reporting. PMID:27048575

  16. A clinical study of effects on the human heart in the radiation and/or chemotherapy

    International Nuclear Information System (INIS)

    Two hundred and ninety four cases of carcinoma of the esophagus, lung, breast, malignant lymphoma and mediastinum were treated with radiation and/or chemotherapy from June 1976 to September 1981 at Tokyo Women's Medical College. Cardiotoxicity was estimated on the examination of Clinical symptoms, ECG changes, and chest x-p findings. The results were as follows: 1) Occurrence rate of Cardiotoxicity was 6.1% of all cases. 2) In the relation between cardiotoxicity and total dose, combination therapy was more toxic than radiation alone treatment. 3) They were found mostly at the period of between one and two months after irradiation in all cases. The appearance of cardiotoxicity was early in the patients with combination therapy. 4) The changes of cardiac shadow on plain chest x-p were more common in the combination therapy groups. Lung fibrosis was also occurred at the same time. 5) The ECG changes were occurred 10.5% in all cases and characteristic changes were (a) a variety of nonspecific ST-T wave abnormalities: 27.2%, (b) abnormalities of cardiac rhythm including supraventricular tachyarrhythmias and premature contractions: 23.8%, (c) sinus tachycardia: 20.4%. 6) Chief complaint of clinical symptoms were palpitation, discomfortness of chest and chest pain. (author)

  17. Clinical study of effects on the human heart in the radiation and/or chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Saito, R. (Tokyo Women' s Medical Coll. (Japan))

    1982-02-01

    Two hundred and ninety four cases of carcinoma of the esophagus, lung, breast, malignant lymphoma and mediastinum were treated with radiation and/or chemotherapy from June 1976 to September 1981 at Tokyo Women's Medical College. Cardiotoxicity was estimated on the examination of Clinical symptoms, ECG changes, and chest x-p findings. The results were as follows: 1) Occurrence rate of Cardiotoxicity was 6.1% of all cases. 2) In the relation between cardiotoxicity and total dose, combination therapy was more toxic than radiation alone treatment. 3) They were found mostly at the period of between one and two months after irradiation in all cases. The appearance of cardiotoxicity was early in the patients with combination therapy. 4) The changes of cardiac shadow on plain chest x-p were more common in the combination therapy groups. Lung fibrosis was also occurred at the same time. 5) The ECG changes were occurred 10.5% in all cases and characteristic changes were (a) a variety of nonspecific ST-T wave abnormalities: 27.2%, (b) abnormalities of cardiac rhythm including supraventricular tachyarrhythmias and premature contractions: 23.8%, (c) sinus tachycardia: 20.4%. 6) Chief complaint of clinical symptoms were palpitation, discomfortness of chest and chest pain.

  18. Collodion Baby - a Case Report

    Directory of Open Access Journals (Sweden)

    Stojanović Vesna

    2014-12-01

    Full Text Available Colloidon baby describes a highly characteristic clinical entity in newborns encased in a yellowish translucent membrane resembling collodion. In most cases the condition either precedes the development of one of a variety of ichthyoses, the commonest of which are lamellar ichthyosis and non-bullous ichthyosiform erythroderma, or occasionally represents an initial phase of other ichthyoses such as ichthyosis vulgaris. In at least 10% of all cases of collodion baby, the condition is followed by a mild ichthyosis of lamellar type, so mild as to be considered more or less normal, so-called self-healing collodion baby or ‘lamellar ichthyosis of the newborn’. In this report we present a rare case of collodion baby in whom, after collodion membrane peeled-off, the skin retained normal appearance.

  19. Glucagonoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    García Bernardo Carmen M

    2011-08-01

    Full Text Available Abstract Introduction Glucagonoma syndrome is a rare paraneoplastic phenomenon, with an estimated incidence of one in 20 million, characterized by necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, steatorrhea, diarrhea, venous thrombosis and neuropsychiatric disturbances in the setting of a glucagon-producing alpha-cell tumor of the pancreas. Necrolytic migratory erythema is the presenting manifestation in the majority of cases, so its early suspicion and correct diagnosis is a key factor in the management of the patient. Case presentation We present the case of a 70-year-old Caucasian woman with glucagonoma syndrome due to an alpha-cell tumor located in the tail of the pancreas, successfully treated with surgical resection. Conclusion Clinicians should be aware of the unusual initial manifestations of glucagonoma. Early diagnosis allows complete surgical resection of the neoplasm and provides the only chance of a cure.

  20. Costello Syndrome. A case report

    Directory of Open Access Journals (Sweden)

    Yadelis Maldonado Martínez

    2014-06-01

    Full Text Available Costello syndrome is an extremely rare multisystem congenital disorder; only about 250 cases have been described in the literature. Its inheritance pattern is considered to be autosomal dominant, although most cases are sporadic, suggesting de novo dominant mutations. The case of a 7-year-old patient from the Frank País municipality in Holguín with clinical manifestations consistent with Costello syndrome is presented. The clinical study and description of his physical characteristics were performed, detecting as main distinctive features: storage disease-like phenotype, failure to thrive, congenital heart disease, coarse facies, mental retardation and humorous personality. Early diagnosis allows early stimulation and intervention, active screening for tumor lesions, as well as provision of genetic counselling to patients.

  1. [Primary reading epilepsy. 11 cases].

    Science.gov (United States)

    Vercelletto, P; Cler, J M; Friol, M

    1985-01-01

    Eleven cases of primary reading epilepsy are reported. They confirm Bickford's description. These patients were otherwise normal. A family history of seizures was present in 6 cases. The first seizure occurred between 12 and 25 years. After a variable period of reading all patients developed a tightness and jerking in throat and jaw muscles. In 4 cases, occasionally, speaking could cause jaw or throat jerks. Whilst reading out loud or silently (exclusively in reading aloud in 1 patient) bilateral discharges were recorded in EEG, sometimes on the left hemisphere. The mechanisms are discussed. Seizures in primary reading epilepsy are facilitated by saccadic eye movements, impulse language muscles and mental concentration. The role of higher integrating systems of language is emphasized. Therapy is discussed. PMID:4048729

  2. The Schneeberg lung cancer cases

    International Nuclear Information System (INIS)

    47 cases of ''Schneeberg lung cancer'' are reported which received financial compensation in West Germany after 1945 after being officially acknowledged as occupational disease. With two exceptions, all patients had been occupied in the Saxonian and Bohemian uranium mines (or their extensions after World War II). The geotechnical fundamentals, industrial hygiene measures taken, the radiobiological situation and its effects are presented. Most patients had small-cell carcinomas or epitheliomas. Accompanying silicosis, usually in a mild form, was found in 35 cases. The mean exposure time was 10.3 years (in 11 cases, less than five years), the mean latency time 22 years (minimum: 8 years). The mean age at the time of death was 58.2 years, i.e. 10 years less than in a normal control group. (orig.)

  3. Testicular calculus: A rare case

    Directory of Open Access Journals (Sweden)

    Volkan Sen

    2015-06-01

    Full Text Available ABSTRACTBackground:Testicular calculus is an extremely rare case with unknown etiology and pathogenesis. To our knowledge, here we report the third case of testicular calculus. A 31-year-old man was admitted to our clinic with painful solid mass in left testis. After diagnostic work-up for a possible testicular tumour, he underwent inguinal orchiectomy and histopathologic examination showed a testicular calculus.Case hypothesis:Solid testicular lesions in young adults generally correspond to testicular cancer. Differential diagnosis should be done carefully.Future implications:In young adults with painful and solid testicular mass with hyperechogenic appearance on scrotal ultrasonography, testicular calculus must be kept in mind in differential diagnosis. Further reports on this topic may let us do more clear recommendations about the etiology and treatment of this rare disease.

  4. An unusual case of phospholipidosis.

    Science.gov (United States)

    Elleder, M; Jirásek, A; Smíd, F; Harzer, K; Schlegerová, D

    1978-04-17

    We present the results of a structural, histochemical and lipid-chromatographic study of tissues obtained at postmortem from an unusual case of phospholipidosis. A previous biopsy of the appendix and liver (Elleder et al., 1975a) had revealed a predominance of phosphoglyceride storage, principally of lysobisphosphatidic acid (LBPA) postmortem material showed that this lipid was stored exclusively in central neurons. In the spleen and the lymph node, however, sphingomyelin (SP) was shown, histochemically and chromatographically, to be the main lipid stored. Total sphingomyelinase (SPase) activity in the appendix was reduced to about 50% of normal. Neuroaxonal dystrophy (NAD) and a conspicuous discrepancy between the degree of distension of some neurons and their lipid content deserve special mention. The case is contrasted with classical sphingomyelinosis; the complexity of the Niemann-Pick group of diseases is discussed as an indication of the difficulties of classification of any atypical case. PMID:150105

  5. A complicated case of pachydermoperiostosis with spondyloarthritides: a case report

    OpenAIRE

    Zhang, Qing; Shen, Min; Yang, Bo; Yu, Keyi

    2013-01-01

    Introduction Pachydermoperiostosis is a rare, hereditary disease commonly presenting with digital clubbing, pachydermia and periosteal hypertrophy. Therapeutic options for pachydermoperiostosis are few because of the unknown pathogenesis. Here, we report the complicated case of a patient with pachydermoperiostosis combined with spondyloarthritides, who was refractory to steroids and tumor necrosis factor alpha antagonists. We treated this patient with zoledronic acid and performed an arthrosc...

  6. eCompetence Case Studies

    DEFF Research Database (Denmark)

    Jensen, Helle Bækkelund

    2006-01-01

    In this paper we present some details of the processes undertaken in the European eCompetence Initiative. We present two illustrative and representative case studies. The research aims to identify and understand patterns of individual and organisational eCompetence approaches.......In this paper we present some details of the processes undertaken in the European eCompetence Initiative. We present two illustrative and representative case studies. The research aims to identify and understand patterns of individual and organisational eCompetence approaches....

  7. Two cases of emphysematous pyelonephritis

    International Nuclear Information System (INIS)

    Emphysematous pyelonephritis is rare but frequently fatal complication of renal parenchymal infection, most commonly occurs in diabetic patients and is often associated with urinary obstruction, prior urological abnormality or infection. From 1898 to 1984, about 50 cases of emphysematous pyelonephritis have been reported universally. The diagnosis of emphysemaous pyelonephritis can be made only roentgenographically. In the last 2 years, we have had two cases of emphysematous pyelonephritis at our hospital. It is our purpose to report two patients who have survived with a brief review of the previous literature

  8. Two cases of sacral agenesis

    International Nuclear Information System (INIS)

    Sacral agenesis is a central component in the spectrum of anomalies comprising the caudal regression syndrome. Sacral agenesis occurs more frequently in an infant born to mother of diabetes, rubella infection in first trimester than normal mothers. In a patient of sacral agenesis, it is important to recognize the neurologic deficit, neurogenic bladder dysfunction and other congenital anomalies. A case of partial sacral agenesis of 10 years old girl and another case of complete total agenesis associated with multiple anomalies in autopsied newborn are reported.

  9. Odontoameloblastoma: Report of two cases

    Directory of Open Access Journals (Sweden)

    Mosca Rodrigo

    2009-01-01

    Full Text Available Odontoameloblastoma (OA is a very rare mixed odontogenic neoplasm, characterized by the simultaneous occurrence of an ameloblastoma and a compound or complex odontoma in the same tumor mass. To date, less than 50 cases of OA and/or ameloblastic odontoma have been reported in the English dental literature. This neoplasm was called ameloblastic odontoma. The term OA was included in the 1971 WHO classification. In this study, we present two cases of OA, which we hope will contribute to the awareness and knowledge of surgeons regarding the existence of this odontogenic tumor so that patients having it may be treated and followed-up properly.

  10. Erupted odontoma: a case report.

    Science.gov (United States)

    Raval, Nilesh; Mehta, Dhaval; Vachhrajani, Kanan; Nimavat, Abhishek

    2014-07-01

    Odontomas are nonaggressive, hamartomatous developmental malformations or lesions of odontogenic origin, which consist of enamel, dentin, cementum and pulpal tissue 'Erupted odontoma' is a term used to specifically denote odontomas, which are exposed into the oral cavity. These are rare entities with only 25-30 cases being reported so far in the dental literature. Here, we present a rare case of an erupted odontoma in an adolescent patient who came with a complaint of bad aesthetics due to the presence of multiple small teeth like structures in the upper front teeth region. PMID:25177649

  11. A case of drug abuse

    Directory of Open Access Journals (Sweden)

    Matteo Pacini

    2008-09-01

    Full Text Available Methadone maintenance is one of the well-known harm reduction strategies for public health intervention in heroin addiction. The significance of methadone treatment in preventing needle sharing, which in turn reduces the risk of HIV and HCV transmission among injectors, has been demonstrated. Methadone maintenance is also considered gathering site where heroin addicts can effectively acquire knowledge on harm reduction and drug rehabilitation. We report a case of a 34-years-old patient with a history of heroin abuse. Therapy with methadone was essential for an adequate management of the case. The article describe difficulties and complexities of heroin abuse management and the therapeutic role of methadone.

  12. Case Report on Anorexia Nervosa

    OpenAIRE

    Preeti Srinivasa; Chandrashekar, M; Nikitha Harish; Gowda, Mahesh R.; Sumit Durgoji

    2015-01-01

    Anorexia nervosa is an eating disorder characterized by excessive restriction on food intake and irrational fear of gaining weight, often accompanied by a distorted body self-perception. It is clinically diagnosed more frequently in females, with type and severity varying with each case. The current report is a case of a 25-year-old female, married for 5 years, educated up to 10 th standard, a homemaker, hailing from an upper social class Hindu (Marvadi) family, living with husband′s family i...

  13. Postinfectious encephalitis (21 cases appended)

    Institute of Scientific and Technical Information of China (English)

    丰宏林; 孙伟; 王文秋; 王德生

    2003-01-01

    Objective To report 21 cases of postinfectious encephatitis according to ICD-NA, postinfectious/parainfectious encephalitis is an independent disease.Methods Using the uniform criteria provided by The Council of State and Territorial Epidemiologists (CSTE) and Centers for Disease Control and Prevention (CDC), we diagnosed postinfectious encephalitis among patients admitted to The First Hospital of Harbin Medical University and analyzed the characteristics of these cases. Results All the patients had histories of preceding infection, and most of them suffered from mental and conscious disorders. Adrenocortical hormone was effective.Conclusions Postinfectious encephalitis is an independent disease. According to this article, about 10% patients with encephalitis admitted to our hospital are postinfectious.

  14. A case of abdominal trauma

    OpenAIRE

    Stephens, Georgina C.; Claydon, Matthew H.

    2015-01-01

    Multiple injuries resulting from the use of nail guns have been described in the literature; however, to date there has been no report of a nail gun injury to the abdomen. We describe the case of a 30-year-old male tradesperson who suffered a penetrating nail gun injury to the epigastrium, resulting in multiple injuries to the bowel and an inferior vena caval injury with massive haemorrhage. This case demonstrates the wide range of injuries capable of being inflicted by a single penetrating i...

  15. Dioctophymiasis: A Rare Case Report

    OpenAIRE

    Chauhan, Sapna; Kaval, Sunil; Tewari, Swati

    2016-01-01

    Dioctophyma renale commonly known as “giant kidney worm’ is found in the kidney of carnivorous mammals. Human infestation is rare, but results in destruction of the kidneys. Very few cases have been reported worldwide. We are here reporting a case of Dioctophymiasis in a 35-year-old male patient who presented with retention of urine and subsequent passage of worm and blood in urine. The worm was confirmed as Dioctophyma renale based on its morphology and clinical presentation. This is a very ...

  16. Malaria and stroke: case report

    Directory of Open Access Journals (Sweden)

    LEOPOLDINO JOSÉ FÁBIO SANTOS

    1999-01-01

    Full Text Available Malaria is a parasitic disease with high prevalence in several regions of the world. Infestation by Plasmodium faciparum can, in some cases, affect the central nervous system producing encephalitis resulting in death or neurological sequelae. The mechanisms involved in the pathophysiology of the cerebral lesion are not totally clear and there are currently two theories (mechanical and humoral concerning this. We report a case of malaria with an atypical evolution, with a stroke lesion in the territory of the middle cerebral artery, with no association with encephalitis. We conclude that the mechanical theory is the one applicable to this patient.

  17. Two cases of sacral agenesis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J. Y.; Bae, Y. K.; Hahm, C. K.; Kang, S. R. [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Sacral agenesis is a central component in the spectrum of anomalies comprising the caudal regression syndrome. Sacral agenesis occurs more frequently in an infant born to mother of diabetes, rubella infection in first trimester than normal mothers. In a patient of sacral agenesis, it is important to recognize the neurologic deficit, neurogenic bladder dysfunction and other congenital anomalies. A case of partial sacral agenesis of 10 years old girl and another case of complete total agenesis associated with multiple anomalies in autopsied newborn are reported.

  18. Intrapericardial Hemangioma: A Case Report

    OpenAIRE

    Gupta, Nalini

    2013-01-01

    Hemangiomas of the pericardium are very rare primary pericardial tumours. Very few cases of pericardial hemangioma have been reported in the literature till date. We are reporting a case of a 40 years old male who presented with the complaints of chest discomfort and palpitation on exertion, of 3 months duration. ECHO and Colour Doppler ECHO which were done, revealed a large heterogeneous mass which measured 7.6 × 7.1cms, which was possibly attached to the roof and the anterior surface of the...

  19. A Challenging Penetrating Trauma Case.

    Science.gov (United States)

    Snoek, Seetal; Butson, Benjamin; Wittenberg, Mark

    2016-01-01

    We present the prehospital management of a 23-year-old Australian Aboriginal man with an isolated knife stab wound to the posterior right chest. The lead author attended to the prehospital management of this young man during tenure as a registrar in retrieval medicine for CareFlight Medical Services (CMS) in North Queensland, Australia. The case is noteworthy because it involved a combination of a life-threatening injury with a superimposed iatrogenic injury. The case will be of interest to physicians and clinicians in prehospital medicine as well as those in low-volume emergency departments or facilities in which major trauma may present infrequently. PMID:27021676

  20. Microfibrillar cardiomyopathy: A rare case

    Directory of Open Access Journals (Sweden)

    Narender Kumar

    2011-01-01

    Full Text Available Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM. The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.

  1. Nonspecific Hyperamylasemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Julio Cesar Wiederkehr

    2013-01-01

    Full Text Available Context The elevation of serum amylase and lipase are generally associated with pancreatic diseases. However they can be associated with different pathologies unrelated with amylase and lipase. Case report This paper aims to report a case of a patient diagnosed with nonspecific hyperamylasemia and warn of this possibility in the differentiation of hyperamylasemia. Conclusion The correct diagnosis of silent hyperamylasemia is important in order to determine whether there is the risk of pancreatic disease or if we are just ahead of a benign hyperenzymemia.

  2. Infantile Scurvy: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Leila Ghedira Besbes

    2010-01-01

    Full Text Available Background. Ascorbic acid (vitamin C is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. SCURVY, a disease of dietary ascorbic acid deficiency, is uncommon today. It still exists in high risk groups including economically disadvantaged populations with poor nutrition. The incidence of SCURVY in the pediatric population is very low. Cases Report. Here we report two cases of SCURVY revealed by subperiosteal hematoma in children with cerebral palsy and developmental delay. Conclusion. SCURVY is extremely rare in children. Musculoskeletal manifestations are prominent in pediatric SCURVY. Multiple subperiosteal hematomas are an important indicator for diagnosis.

  3. Cardiac leiomyosarcoma, a case report

    DEFF Research Database (Denmark)

    Andersen, Rikke; Kristensen, Bjarne W; Gill, Sabine

    2013-01-01

    In this case report we present the history of a patient admitted with recurrent pulmonary edema. Transesophageal chocardiography showed a tumour in the left atrium, occluding the ostium of the mitral valve and mimicking intermittent mitral stenosis. Cardiac surgery followed by pathological...... examination revealed that the tumour was a leiomyosarcoma. Images from the echocardiography as well as the pathological findings are shown and discussed. The present case report illustrates that atrial tumors comprise also sarcomas, suggesting the use of careful, rapid diagnostic procedures and treatment to...

  4. Case-based medical informatics

    Directory of Open Access Journals (Sweden)

    Arocha José F

    2004-11-01

    Full Text Available Abstract Background The "applied" nature distinguishes applied sciences from theoretical sciences. To emphasize this distinction, we begin with a general, meta-level overview of the scientific endeavor. We introduce the knowledge spectrum and four interconnected modalities of knowledge. In addition to the traditional differentiation between implicit and explicit knowledge we outline the concepts of general and individual knowledge. We connect general knowledge with the "frame problem," a fundamental issue of artificial intelligence, and individual knowledge with another important paradigm of artificial intelligence, case-based reasoning, a method of individual knowledge processing that aims at solving new problems based on the solutions to similar past problems. We outline the fundamental differences between Medical Informatics and theoretical sciences and propose that Medical Informatics research should advance individual knowledge processing (case-based reasoning and that natural language processing research is an important step towards this goal that may have ethical implications for patient-centered health medicine. Discussion We focus on fundamental aspects of decision-making, which connect human expertise with individual knowledge processing. We continue with a knowledge spectrum perspective on biomedical knowledge and conclude that case-based reasoning is the paradigm that can advance towards personalized healthcare and that can enable the education of patients and providers. We center the discussion on formal methods of knowledge representation around the frame problem. We propose a context-dependent view on the notion of "meaning" and advocate the need for case-based reasoning research and natural language processing. In the context of memory based knowledge processing, pattern recognition, comparison and analogy-making, we conclude that while humans seem to naturally support the case-based reasoning paradigm (memory of past experiences

  5. Delleman (Oculocerebrocutaneous Syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Tomás Ortiz-Basso

    2014-01-01

    Full Text Available Delleman syndrome is an unusual entity, characterized by ocular cysts or microphthalmia, focal dermal anomalies and cerebral malformations. In the following article, we carry out a review of the disease and we present the case of a patient with microphthalmos and palpebral coloboma. As we could not put orbital expanders at an early stage, we performed reconstructive surgery.

  6. [A case of thoracic actinomycosis].

    Science.gov (United States)

    Denisova, O A; Cherniavskaia, G M; Beloborodova, É I; Topol'nitskiĭ, E B; Iakimenko, Iu V; Chernogoriuk, G É; Beloborodova, E V; Strezh, Iu A; Vil'danova, L R

    2014-01-01

    A case of thoracic actinomycosis manifest as round shadow in the lung is described. Diagnosis was based on the presence of actinomycetes in a transthoracic lung biopsy sample. Treatment for 3 months resulted in recovery. No relapse was documented during 1 year follow-up period. PMID:25265662

  7. Graphite oral tattoo: case report.

    Science.gov (United States)

    Moraes, Renata Mendonça; Gouvêa Lima, Gabriela de Morais; Guilhermino, Marinaldo; Vieira, Mayana Soares; Carvalho, Yasmin Rodarte; Anbinder, Ana Lia

    2015-10-01

    Pigmented oral lesions compose a large number of pathological entities, including exogenous pigmentat oral tattoos, such as amalgam and graphite tattoos. We report a rare case of a graphite tattoo on the palate of a 62-year-old patient with a history of pencil injury, compare it with amalgam tattoos, and determine the prevalence of oral tattoos in our Oral Pathology Service. We also compare the clinical and histological findings of grafite and amalgam tattoos. Oral tattoos affect women more frequently in the region of the alveolar ridge. Graphite tattoos occur in younger patients when compared with the amalgam type. Histologically, amalgam lesions represent impregnation of the reticular fibers of vessels and nerves with silver, whereas in cases of graphite tattoos, this impregnation is not observed, but it is common to observe a granulomatous inflammatory response, less evident in cases of amalgam tattoos. Both types of lesions require no treatment, but in some cases a biopsy may be done to rule out melanocytic lesions. PMID:26632800

  8. Supernumerary breast. A case Presentation

    Directory of Open Access Journals (Sweden)

    Juan Miguel Guerra Cabrera

    2010-07-01

    Full Text Available Congenital malformations of the breast appear in 10 % of the population. The existence of mammary tissue at any line of the breast is classified according to Kajava’s categories into eight classes which differ one from the other in the presence or absence of the areola of the breast, nipple and glandular tissue. This report presents a case of a puerpera who had delivered her child seven days before her attendance to hospital. She presented with discharge from her both axillae. On physical examination, a supernumerary nipple with milky secretion out from it was found in her right axilla and secretion throughout the contralateral axilla through the skin pores, with absence of nipple and areola in that axillary region. The echographic study revealed the presence of bilateral ectopic mammary tissue. This case belongs to Kajava’s class IV classification in the left axilla and a variery of Type I in the right axilla. In facing a mammary malformation, a conservative attitude seems to be the most appropriate although esthetics requires surgery. To keep into account the presence of supernumerary breasts will be a need for the prevention of breast cancer. This case has been presented due to all these reasons and the unusual features of this case.

  9. LAUGHING SEIZURES: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Deb K

    2015-12-01

    Full Text Available BACKGROUND Normal laughter is a human behavioral response to pleasant feeling, whereas pathological laughter is disproportionate to the emotional context. Hypothalamic hamartoma usually presented with laughing seizures. We are presenting a case of laughing seizure with hypothalamic hamartoma detected on MR Imaging in a 21 years female.

  10. Pancardiac tuberculosis - a case report.

    Science.gov (United States)

    Lad, Shilpa K; Amonkar, Gayathri

    2016-01-01

    Tuberculous involvement of the heart though not common has been reported in literature. Pericardium is commonly involved followed by the myocardium. Endocardial involvement is rare. We would like to report a case of a 14-year-old female with florid and extensive involvement of all the layers of the heart by tuberculosis. PMID:26507144

  11. In Case of Pesticide Emergency

    Science.gov (United States)

    ... Twitter Google+ Pinterest Contact Us In Case of Pesticide Emergency If someone has swallowed or inhaled a pesticide or gotten it in the eye or on ... for help with first aid information. The National Pesticide Information Center (NPIC) (1-800-858-7378) also ...

  12. Three cases of engaged research

    DEFF Research Database (Denmark)

    Hansen, Louise Ejgod

    2015-01-01

    The article is a case study of three different applied research projects analyzing and discussing the relationship between practice and research. The three projects are all arts projects occupied with participation in different forms: Theatre Talk is an audience development project conducted at...

  13. LICHEN STRIATUS – CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Caius Solovan

    2013-07-01

    Full Text Available Lichen striatus is an acquired linear inflammatory dermatosis, not frequently reported, with a peculiar clinical aspect, most often described in adults, with a poor response to treatment. We described 4 cases of lichen striatus diagnosed over an 8-month period of time.

  14. Parietal intraparenchymal Schwannoma: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Hwan; Chung, Tae Woong; Yoon, Woong; Jeong, Gwang Woo; Kang, Heoung Keun [Chonnam National University Hospital, Kwangju (Korea, Republic of)

    2008-10-15

    We report a case of an intraparenchymal schwannoma of the left parietal lobe. A 51-year-old woman was admitted to our hospital with complaints of intermittent headaches. Computed tomography and magnetic resonance images revealed a 1.3 cm sized intra-axial homogeneous enhancing mass in the left parietal lobe. The lesion was pathologically confirmed to be a schwannoma.

  15. Parietal intraparenchymal Schwannoma: case report

    International Nuclear Information System (INIS)

    We report a case of an intraparenchymal schwannoma of the left parietal lobe. A 51-year-old woman was admitted to our hospital with complaints of intermittent headaches. Computed tomography and magnetic resonance images revealed a 1.3 cm sized intra-axial homogeneous enhancing mass in the left parietal lobe. The lesion was pathologically confirmed to be a schwannoma

  16. CHRONIC PANNICULITIS-case report

    Directory of Open Access Journals (Sweden)

    I. Drljević,

    2005-08-01

    Full Text Available The case shows chronic panniculitis in a thirty-year-old female patient without general symptoms. The disease is very rare and its etiology is unknown. Clinical picture is characterized by subcutaneous, erythematous nodules on lower legs, sometimes occuring on the trunk. The diagnosis was based on anamnesis, clinical and laboratory findings,and dermatopathology.

  17. Gorlin syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Abbas Darjani

    2016-01-01

    Full Text Available Gorlin syndrome is a rare autosomal dominant disorder which characterize by multi-organ abnormities such as odontogenic keratocysts in the jaw, skeletal abnormities and multiple basal cell carcinoma etc. We report a case of this syndrome in a young man with palmar pits, multiple facial BCC, clacifications of the falx cerebri and bifid rib.

  18. Poland's syndrome (A case report)

    OpenAIRE

    Calpur, Osman U.; Aktas, Seref

    2004-01-01

    Poland s syndrome is a rare disease characterized by congenital aplasia of the pectoralis major muscle associated with ipsilateral hand deformities (mosr often synbrachydactylia). In this paper we presented a case of Poland s syndrome with a short review of contemporary literature.

  19. Hematologic case: Idiopathic thrombocytopenic purpura

    OpenAIRE

    São Simão, T.; Salgado, M.; Costa, E.; Barbot, J.

    2012-01-01

    The immune thrombocytopenic purpura (ITP) is a controversial disease. The generality of the literature argues that a historical objective clinical examination and a blood count with careful observation of the peripheral blood smear is sufficient for diagnosis. Some cases contradict this belief.

  20. [Progressive extrinsic ophthalmoplegia; case report].

    Science.gov (United States)

    Nóbrega, J A; Erwenne, C M; Vilanova, L C; Lima, J G

    1979-12-01

    A case of progressive ophtalmoplegia and ptosis affecting a 12 year old boy is reported. A miopatic pattern was detected by the electromyography, the cerebrospinal fluid showed an increase of the protein content and retinal pigmentary degeneration was detected. This findings call the attention for a more widespread degenerative disorders affecting not only the muscular sistem but other organs as well. PMID:533389

  1. Radiological case: idiopathic pulmonary hemosiderosis

    OpenAIRE

    Nascimento , J.; Morais, L; Macedo, F.

    2012-01-01

    ABSTRACT We present a case of a four year-old child with a second episode of iron deficiency anaemia. Following fever, cough and hemoptysis a chest X-ray and chest CT were performed. Bilateral and patchy areas of ground glass and consolidation were noted in the setting of intrapulmonary hemorrhage. The final diagnosis was idiopathic pulmonary hemosiderosis.

  2. RETT'S SYNDROME : A CASE REPORT

    OpenAIRE

    Gupta, Vinay

    2001-01-01

    Rett's syndrome is a rare condition affecting only the girl child. It presents as a pervasive developmental disorder with a remarkable behavioural phenotype. The cause for this remains unknown but genetic factors and brain dysfunction have been implicated. This case report emphasises the importance of being aware of rare yet significant disorders of interest to neuro-developmental psychiatrists.

  3. Lithium nephropathy: a case report

    Directory of Open Access Journals (Sweden)

    Raphael Reis Pereira-Silva

    2014-01-01

    Full Text Available Although widely used in the management of bipolar disorder, lithium may cause adverse kidney effects. The importance of the present study is to report the case of a 59-year-old woman who was under regular treatment with lithium for bipolar disorder and whose imaging studies demonstrated the presence of multiple renal microcysts, suggesting lithium nephropathy as main diagnostic hypothesis.

  4. CERVICAL SYNOVIAL CYST: CASE REPORT

    OpenAIRE

    Found, Ernest; Bewyer, Dennis

    2011-01-01

    A 47-year-old female school teacher with a six-week history of left-sided scapular and arm pain is presented. We report her evaluation and treatment Although lumbar degenerative synovial cysts have been reported over 200 times in the literature,6 cervical synovial cysts are much more rare. This case reports a cervicothoracic junction degenerative synovial cyst presenting as radiculopathy.

  5. Business Case for Enterprise Mashups

    OpenAIRE

    Kramer, Simone; Hoyer, Volker; Peukert, Hans; Fuchsloch, Andrea; Kowalkiewicz, Marek

    2010-01-01

    Despite the importance of a business case for supporting an investment decision, no statistics are available which evaluate the real value of enterprise mashups. The present SAP Research White Paper closes this gap and calculates the costs and benefits of enterprise mashups by means of a real-world scenario.

  6. A Melioidosis Case in Arizona

    Centers for Disease Control (CDC) Podcasts

    2011-10-03

    David Blaney, Medical Officer, Bacterial Special Pathogens Branch, discusses an unusual melioidosis case in Arizona.  Created: 10/3/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 10/5/2011.

  7. Bone cryptococcosis: a case report

    International Nuclear Information System (INIS)

    Cryptococcus neoformans is a rare cause of osteomyelitis that can be associated with high rates of morbidity and mortality. We present a case in a patient with idiopathic CD4+T lymphocytopenia, reviewing the pathogenesis and the radiographic findings. (Author) 6 refs

  8. Arteriovenous Malformation: A Case Report

    International Nuclear Information System (INIS)

    The present case illustrates an arteriovenous malformation of the cheek in a 25-year-old male. The clinical presentation, radiographic findings, differential diagnosis, treatment and histopathologic description are presented. Diagnosis of the lesion was confirmed by angiography, and the lesion was treated by angiographically controlled vascular embolization followed by complete surgical excision.

  9. The reflexive case study method

    DEFF Research Database (Denmark)

    Rittenhofer, Iris

    2015-01-01

    This paper extends the international business research on small to medium-sized enterprises (SME) at the nexus of globalization. Based on a conceptual synthesis across disciplines and theoretical perspectives, it offers management research a reflexive method for case study research of postnational...

  10. An unusual case of angiosarcoma.

    Science.gov (United States)

    Lowdell, C P; Cary, N; Burdge, A; Howard, N; Makey, A R

    1988-10-01

    A case of angiosarcoma arising in an arm affected by chronic lymphoedema and treated initially by intraarterial cytotoxic perfusion chemotherapy and radiotherapy is described. The patient is still alive twenty years after presentation. This represents the longest reported survival for this condition. PMID:3181449

  11. Three Cases of Reinfection Syphilis

    Institute of Scientific and Technical Information of China (English)

    刘胜欣

    2001-01-01

    These three cases of reinfection syphilis all had complete medical histories, clinical symptoms, and laboratory records of prior primary or secondary syphilis infection. The author held that the main reason for reinfection was failure of diagnosis and treatment of sex partners.

  12. Primary intracranial leiomyoma: case report

    International Nuclear Information System (INIS)

    We present a case of intracranial parenchymal leiomyoma in a 20-year-old woman with a chief complaint of numbness and a painful sensation over the right limbs for several years. CT and MRI revealed an intensely enhancing calcified mass. The patient was well, without recurrence, 2 years after surgery. (orig.)

  13. "Tarantula keratitis": a case report.

    LENUS (Irish Health Repository)

    McAnena, L

    2013-09-01

    A case of an 11-year-old boy presenting with a two-week history of a red, irritated right eye after handling a Chilean Rose Tarantula at an exotic pet exhibition. Examination revealed innumerable microscopic hairs embedded at all levels of the cornea. He was commenced on steroid drops with subjective and objective improvement at follow up.

  14. Kenya Groundwater Governance Case Study

    OpenAIRE

    Mumma, Albert; Lane, Michael; Kairu, Edward; Tuinhof, Albert; Hirji, Rafik

    2011-01-01

    This report presents a case study on groundwater governance in Kenya. The objectives of the study were to: (a) describe groundwater resource and socioeconomic settings for four selected aquifers; (b) describe governance arrangements for groundwater management in Kenya; and (c) identify the relevance of these arrangements for planning and implementing climate change mitigation measures. The ...

  15. Dengue encephalitis -a case report

    Institute of Scientific and Technical Information of China (English)

    P.C.Bhattacharyya; Jagdish Prasad Agarwal

    2009-01-01

    Encephalitis is an uncommon manifestation of dengue fever.Here we present a 4 years old female child from Northeast Region of India who suffered from dengue encephalitis.To our knowledge,this is probably the first diagnosed case of dengue fever from this region.

  16. Fetal Amelia: A Case Report

    OpenAIRE

    Mohammed Abdul-Latif; Asfhaq Ahmed; Shahila Tanzeem; Nihal Al Riyami

    2012-01-01

     Congenital limb defects are rare fetal anomalies with a birth prevalence of 0.55 per 1,000. Amelia is an extremely rare birth defect marked by the complete absence of one or more limbs. We report a case of fetal amelia, ultrasound findings, manifestations and the fetal outcome.

  17. Tailgut cyst. A case report.

    Science.gov (United States)

    Deltour, D; Veys, E

    2011-01-01

    Tailgut cysts, also called retro-rectal cystic hamartomas or mucin-secreting cysts, are uncommon vestigial masses. They can become complicated with infection or neoplastic degeneration. Surgery is the only treatment. We report here a case of a tailgut cyst in a 60-year-old female, that was discovered 10 years ago but not investigated. PMID:21780528

  18. The Case for Nudge Analytics

    Science.gov (United States)

    Carmean, Colleen; Mizzi, Philip

    2010-01-01

    Developed as a concept in the science of choice, subtle interactions--or "nudges"--can influence people's actions without infringing on their freedom of choice. This article makes the case that not only can the wealth of digital data in higher education nudge students to better achievement and persistence but also that the knowledge embedded in…

  19. Case report on anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Preeti Srinivasa

    2015-01-01

    Full Text Available Anorexia nervosa is an eating disorder characterized by excessive restriction on food intake and irrational fear of gaining weight, often accompanied by a distorted body self-perception. It is clinically diagnosed more frequently in females, with type and severity varying with each case. The current report is a case of a 25-year-old female, married for 5 years, educated up to 10 th standard, a homemaker, hailing from an upper social class Hindu (Marvadi family, living with husband′s family in Urban Bangalore; presented to our tertiary care centre with complaints of gradual loss of weight, recurrent episodes of vomiting, from a period of two years, menstrual irregularities from 1 year and amenorrhea since 6 months, with a probable precipitating factor being husband′s critical comment on her weight. Diagnosis of atypical anorexia nervosa was made, with the body mass index (BMI being 15.6. A multidisciplinary therapeutic approach was employed to facilitate remission. Through this case report the authors call for the attention of general practitioners and other medical practitioners to be aware of the symptomatology of eating disorders as most patients would overtly express somatic conditions similar to the reported case so as to facilitate early psychiatric intervention.

  20. Tuberculous Osteopathy: A Case Report

    Directory of Open Access Journals (Sweden)

    M. MAZAHER

    1971-07-01

    Full Text Available A rare case of tuberculosis of many bones (skull, ribs and pubis is described. There was also paravertebral cold abscess with fistulisation opened to groin region; no lesions were seen in lungs, urinary or gastrointestinal tracts. The response to medical treatment was favourable.