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Sample records for capecitabine-induced cardiotoxicity case

  1. Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Shahmarvand, Nahid; Vistisen, Kirsten

    2016-01-01

    OBJECTIVES: Case reports of capecitabine cardiotoxicity resemble those seen with intravenous 5-fluorouracil (5-FU) with chest pain as the predominant manifestation, but few studies of capecitabine cardiotoxicity are available. We aimed to determine the incidence of symptomatic cardiotoxicity from.......020) were risk factors of cardiotoxicity. CONCLUSIONS: The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (≈5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity....

  2. Capecitabine-induced lichenoid drug eruption: a case report.

    Science.gov (United States)

    Gehlhausen, Jeff R; Strausburg, Matthew B; Aouthmany, Mouhammad; Katona, Terrence M; Turner, Matthew J

    2017-02-15

    Capecitabine is a 5-fluorouracil basedchemotherapeutic drug widely used in the treatmentof solid tumors, especially colorectal and breast. Someof the most common side effects of capecitabine arecutaneous in nature, including hand-foot syndrome(palmar-plantar erythrodysesthesia). Several reports inthe literature link capecitabine use with photosensitivelichenoid eruptions. Herein, we present a case ofcapecitabine-induced lichenoid eruption in an elderlyfemale with metastatic breast cancer and discuss ourfindings in relationship to previously reported cases ofthis and other capecitabine-induced skin pathologies.

  3. Capecitabine-Induced Coronary Vasospasm

    Directory of Open Access Journals (Sweden)

    Danish Henry

    2016-10-01

    Full Text Available Capecitabine, an oral prodrug of 5-fluorouracil (5-FU, is approved for early-stage and advanced colorectal cancer and metastatic breast cancer. Cardiotoxicity of 5-FU is well described in the literature. However, cardiac adverse effects of capecitabine are poorly described. We report a case of coronary vasospasm induced by capecitabine. A 41-year-old female with metastatic breast cancer presented with chest pain 3 days after starting capecitabine. The chest pain was relieved by rest and exacerbated by exertion. Her physical examination was unremarkable except for a rapid heart rate of 100 bpm. Electrocardiogram test showed no acute ischemic changes. Troponin tests were negative. CT angiography of the chest was negative for acute pulmonary embolism. An echocardiogram showed a left ventricular ejection fraction of 60% without any wall motion abnormalities. The chest pain resolved with aspirin and analgesic use. She was discharged following an inconclusive cardiac workup. Further use of capecitabine was discontinued.

  4. Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity.

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    Mohebali, Donya; Matos, Jason; Chang, James Ducksoon

    2017-02-01

    Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity.

  5. [Herbs and cardiotoxic effects].

    Science.gov (United States)

    Maffè, Stefano; Paffoni, Paola; Laura Colombo, Maria; Davanzo, Franca; Dellavesa, Pierfranco; Cucchi, Lorenzo; Zenone, Franco; Paino, Anna Maria; Franchetti Pardo, Nicolò; Bergamasco, Luca; Signorotti, Fabiana; Parravicini, Umberto

    2013-06-01

    Accidental or deliberate ingestion of poisonous herbs has become an increasingly common phenomenon over the last years. From existing literature data and case reports from emergency room visits or poison control centers, an overview is presented of the potential cardiotoxic manifestations following intoxication by wild herbal plants of the territory. The effects of the consumption of cardiac glycoside-containing plants (e.g., digitalis) are discussed along with tachyarrhythmias induced by Aconitum napellus L., Atropa belladonna L., Mandragora officinarum L. or Ephedra distachya L. herbs, and hypertensive crises associated with licorice abuse. For each plant, a brief historical and botanical background is provided, focusing on pathophysiology of intoxication and cardiotoxic effects on the basis of the most recent literature. Finally, medical management of intoxication, from both a general and cardiological viewpoint, is reviewed.

  6. Cardiotoxicity of verapamil in renal failure: a case report and review of the literature

    OpenAIRE

    Jadhav, Praveen P; Bohra, Suresh

    2009-01-01

    We present a case of a 76-year-old diabetic patient on verapamil with undiagnosed renal failure presenting with collapse and severe life threatening bradyarrhythmias. She responded well to inotropic support and calcium supplementation.

  7. Arsenic cardiotoxicity: An overview.

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    Alamolhodaei, Nafiseh Sadat; Shirani, Kobra; Karimi, Gholamreza

    2015-11-01

    Arsenic, a naturally ubiquitous element, is found in foods and environment. Cardiac dysfunction is one of the major causes of morbidity and mortality in the world. Arsenic exposure is associated with various cardiopathologic effects including ischemia, arrhythmia and heart failure. Possible mechanisms of arsenic cardiotoxicity include oxidative stress, DNA fragmentation, apoptosis and functional changes of ion channels. Several evidences have shown that mitochondrial disruption, caspase activation, MAPK signaling and p53 are the pathways for arsenic induced apoptosis. Arsenic trioxide is an effective and potent antitumor agent used in patients with acute promyelocytic leukemia and produces dramatic remissions. As2O3 administration has major limitations such as T wave changes, QT prolongation and sudden death in humans. In this review, we discuss the underlying pathobiology of arsenic cardiotoxicity and provide information about cardiac health effects associated with some medicinal plants in arsenic toxicity.

  8. 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

  9. 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.

  10. The cardiotoxicity and long-term efficacy of different doses of epirubicin in the adjuvant treatment of breast cancer patients:A case control study

    Institute of Scientific and Technical Information of China (English)

    Yang Liu; Zhenyu You; Xiaohui Su; Bona Liu; Xuefei Liu

    2014-01-01

    Objective: The aim of the study was to observe the cardiac toxicity caused by diferent doses of epirubicin in the adjuvant treatment of breast cancer and to evaluate the long-term eficacy.Methods:The 180 cases of breast cancer patients received epirubicin based adjuvant chemotherapy. The patients were randomly assigned to high-dosage group (90 mg/m2), medium-dosage group (70 mg/m2) and low-dosage group (50 mg/m2), the primary endpoint was cardiac toxicity. The secondary outcomes were the 5-year overal survival (OS) and 5-year disease-free survival (DFS).Results: During chemo-therapy, the clinical symptoms such as palpitation, dyspnea and paroxysmal nocturnal dyspnea occurred in 6 patients with the high-dosage group, 4 patients with the medium-dosage group and 3 patients with the low-dosage group. The number of patients who had changed in electrocardiogram (ECG) was 7, 5 and 4 in three groups, respectively. The echocardiographic showed each group had only one case with LVEF 0.05). In the three groups, the 5-year DFS rates were 73.3% (44/60) in high-dose group, 53.3% (32/60) in medium-dose group and 41.6% (25/60) in low dose group. The 5-year OS rates were 85.0% (51/60), 68.3% (41/60) and 58.3% (35/60) in three groups, respectively. The diferences were statisticaly significant (P < 0.05).Conclusion: The high-dose epirubicin in adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin and fluorouracil) regimen could improve the 5-year OS rate and 5-year DFS rate on patients of breast cancer. The cardiotoxicity was mild-moderate and wel tolerated.

  11. Cardiotoxicity | Division of Cancer Prevention

    Science.gov (United States)

    Damage to the heart (cardiotoxicity), or blood vessels (cardiovascular toxicity) can occur during or after cancer treatment. As treatments have improved, more patients are surviving longer after a diagnosis of cancer than at any time in the past. See the article, Treating Cancer without Harming the Heart. |

  12. Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics

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    Khavandi, A; Walker, P R

    2007-01-01

    A man presented with recurrent syncope, weakness and fatigue. His ECG showed marked QRS widening and he had gross hyponatraemia and hypokalaemia. His medications included bendroflumethiazide (long term) and flecainide (started 2 months previously). This presentation was consistent with flacainide cardiotoxicity exacerbated by electrolyte disturbance. The syncopal episodes probably represented life‐threatening arrhythmias. The ECG and symptoms resolved completely once the electrolytes were corrected. Increased cardiotoxicity with hypokalaemia is documented, but not widely recognised. Hyponatraemia‐induced flecainide cardiotoxicity has not been documented. The clinical effects of flecainide are due to use‐dependent block of sodium channels. There are reports that support the use of hypertonic sodium salts to reverse flecainide toxicity via antagonism at the receptor. By this rationale, hyponatraemia would lead to Flecainide toxicity. Flecainide has been shown to reduce salt absorption in animal bowel. It is possible that in combination with bendroflumethiazide it acted synergistically to produce profound electrolyte disturbance. Flecainide cardiotoxicity has a significant mortality and can present non‐specifically. Thus, early recognition is essential. This case demonstrates the importance of strict electrolyte control in patients who are on flecainide. We would discourage concomitant use of flecainide and bendroflumethiazide. PMID:17452686

  13. Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics.

    Science.gov (United States)

    Khavandi, A; Walker, P R

    2007-05-01

    A man presented with recurrent syncope, weakness and fatigue. His ECG showed marked QRS widening and he had gross hyponatraemia and hypokalaemia. His medications included bendroflumethiazide (long term) and flecainide (started 2 months previously). This presentation was consistent with flacainide cardiotoxicity exacerbated by electrolyte disturbance. The syncopal episodes probably represented life-threatening arrhythmias. The ECG and symptoms resolved completely once the electrolytes were corrected. Increased cardiotoxicity with hypokalaemia is documented, but not widely recognised. Hyponatraemia-induced flecainide cardiotoxicity has not been documented. The clinical effects of flecainide are due to use-dependent block of sodium channels. There are reports that support the use of hypertonic sodium salts to reverse flecainide toxicity via antagonism at the receptor. By this rationale, hyponatraemia would lead to Flecainide toxicity. Flecainide has been shown to reduce salt absorption in animal bowel. It is possible that in combination with bendroflumethiazide it acted synergistically to produce profound electrolyte disturbance. Flecainide cardiotoxicity has a significant mortality and can present non-specifically. Thus, early recognition is essential. This case demonstrates the importance of strict electrolyte control in patients who are on flecainide. We would discourage concomitant use of flecainide and bendroflumethiazide.

  14. Therapeutic and recreational methadone cardiotoxicity.

    Science.gov (United States)

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2016-04-01

    Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression.

  15. Study of the cardiotoxic potential of pharmaceutical compounds in chick myocardial myocyte reaggregate cultures.

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    Seaman, C W; Toseland, C D; Maile, P A; Francis, I; White, D J

    1994-08-01

    Cardiotoxicity produced by doxorubicin in vivo is considered to be due to a direct effect on the myocardium and this is also a major component with toxicity of isoprenaline and digoxin. In the case of the cardiotoxicity produced at high doses by the antihypertensives hydralazine and pinacidil, an indirect mechanism operating by way of their exaggerated pharmacological effects is believed to be responsible. These compounds were examined for their cardiotoxic potential in vitro using chick myocardial myocyte reaggregate (MMR) cultures; allylamine HCl was used as a positive control. Cultures were incubated for up to 24 hr with each compound; parameters analysed were: spontaneous beating activity (SBA), lactate dehydrogenase (LDH) leakage and microscopic evidence of cytotoxicity. Allylamine, doxorubicin, digoxin and to a lesser extent isoprenaline were highly toxic to MMR cultures, as demonstrated by their effects on SBA, LDH leakage and morphology. Hydralazine showed very mild cytotoxicity at the highest concentrations with no LDH leakage; pinacidil was not cytotoxic but showed a dose-related inhibition of SBA. These results confirm the direct toxic action of doxorubicin and digoxin on myocardial cells and indicate that this is also an important mechanism in vivo for isoprenaline. The lack of any significant toxicity with hydralazine and pinacidil accords with an indirect mechanism based on their pharmacology.

  16. Pathophysiology of persistent doxorubicin cardiotoxicity : metabolic landscaping of the epigenome

    OpenAIRE

    Ferreira, André

    2015-01-01

    FERREIRA, André - Pathophysiology of persistent doxorubicin cardiotoxicity : metabolic landscaping of the epigenome. Coimbra : [s.n.], 2015. Dissertação de Mestrado em Biologia Molecular Doxorubicin (DOX), a potent and broad-spectrum antineoplastic agent, causes a cumulative dose-dependent cardiomyopathy of late-onset that may ultimately lead to congestive heart failure. The mechanisms responsible for the delayed nature of DOX cardiotoxicity remain poorly understood. Since DOX ind...

  17. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management.

    Science.gov (United States)

    Barry, Elly; Alvarez, Jorge A; Scully, Rebecca E; Miller, Tracie L; Lipshultz, Steven E

    2007-06-01

    Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

  18. Sudden Cardiac Death of a Body Packer Due to Cocaine Cardiotoxicity

    OpenAIRE

    Parthasarathi Pramanik; Raghvendra Kumar Vidua

    2016-01-01

    This article presents a case of sudden cardiac death due to the effects of cocaine concealed in the body of a male drug smuggler in his 40s, a so-called body packer. A total of 57 body packets filled with cocaine powder were discovered in his body cavities. The detailed autopsy examination, including histopathology and toxicology findings, is discussed with the aim of describing the mechanism of cocaine intoxication in the body packer and an analysis of cocaine-induced cardiotoxicity and sudd...

  19. Newest echocardiographic techniques for the detection of cardiotoxicity and heart failure during chemotherapy.

    Science.gov (United States)

    Sawaya, Heloisa; Plana, Juan Carlos; Scherrer-Crosbie, Marielle

    2011-07-01

    Chemotherapy-induced cardiotoxicity has become a significant public health issue. Left ventricular ejection fraction is routinely used to monitor cardiotoxicity but fails to detect subtle alterations in cardiac function. Improvements in the measurement of left ventricular ejection fraction, physical or pharmacologic stressors, and novel cardiac functional indices may be useful in the detection of cardiotoxicity. The improvements in the detection and therapy of cancer have led to the emergence of chemotherapy-induced cardiotoxicity. New echocardiographic techniques may be useful in the detection of patients undergoing chemotherapy treatments who could benefit from alternative cancer treatments, therefore decreasing the incidence of cardiotoxicity.

  20. 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.

  1. Effect of disulfiram on ketamine-induced cardiotoxicity in rats.

    Science.gov (United States)

    Cetin, Nihal; Suleyman, Bahadir; Altuner, Durdu; Kuyrukluyildiz, Ufuk; Ozcicek, Fatih; Coskun, Resit; Kurt, Nazahat; Suleyman, Halis

    2015-01-01

    It is known that ketamine increases the production of catecholamines, causing oxidative damage to the heart. Suppression of the production of catecholamines by disulfiram, a drug with antioxidant properties, indicates that disulfiram may decrease ketamine-induced cardiotoxicity. The objective of the present study was to investigate the effect of disulfiram on ketamine-induced cardiotoxicity in rats. Disulfiram was administered by oral gavage in doses of 25 mg/kg to rats in the DK-25 group and 50 mg/kg to rats in the DK-50 group. Distilled water was applied in the ketamine control (KC) and healthy (HG) rat groups. At one hour after drug administration and subsequently at ten-minute intervals, a 60 mg/kg dose of ketamine was intraperitoneally injected in the rats in all groups other than HG, and anesthesia was maintained for three hours. Disulfiram prevented both increase in the levels of parameters indicating oxidative and myocardial damage and decrease of antioxidant levels in the heart tissue with ketamine in a dose-dependent manner. Disulfiram better prevented occurrence of cardiotoxicity with ketamine in the 50 mg/kg dose than in the 25 mg/kg dose. It is concluded that disulfiram may usefully be applied in clinical practice in the prevention of cardiotoxicity as observed during anesthesia with ketamine.

  2. Nuclear imaging in detection and monitoring of cardiotoxicity.

    Science.gov (United States)

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

    2014-07-28

    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 monitoring of 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.

  3. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

    DEFF Research Database (Denmark)

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

    2014-01-01

    Evolving evidence of cardiotoxicity in cancer patients treated with 5-fluorouracil (5-FU) has been reported. We report two different clinical manifestations of asymptomatic 5-FU-associated cardiotoxicity in patients operated for colorectal cancer and treated with adjuvant chemotherapy of 5-FU...... (bolus-injection and continuous infusion for 46 hours), folinic acid and oxaliplatin (FOLFOX). For a research study evaluating cardiac events during 5-FU treatment, Holter monitoring, electrocardiogram (ECG) and echocardiography were done and cardiac markers monitored before and during the first...... 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 the Holter...

  4. 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.

  5. 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.

  6. Hyperbaric Oxygen Preconditioning Provides Preliminary Protection Against Doxorubicin Cardiotoxicity

    Science.gov (United States)

    Tezcan, Orhan; Karahan, Oguz; Alan, Mustafa; Ekinci, Cenap; Yavuz, Celal; Demirtas, Sinan; Ekinci, Aysun; Caliskan, Ahmet

    2017-01-01

    Background Doxorubicin (DOX) is generally recognized to have important cardiotoxic side effects. Studies are contradictory about the interaction between hyperbaric oxygen (HBO2) therapy and doxorubicin-induced cardiomyotoxicity. Recent data suggests that HBO2 therapy can lead to preconditioning of myocardium while generating oxidative stress. Herein we have investigated the effect of HBO2 therapy in a DOX-induced cardiomyocyte injury animal model. Methods Twenty-one rats were divided into three equal groups as follows: 1) Group 1 is a control group (without any intervention), used for evaluating the basal cardiac structures and determining the normal value of cardiacs and serum oxidative markers; 2) Group 2 is the doxorubicin group (single dose i.p. 20 mg/kg doxorubicin) for detecting the cardiotoxic and systemic effects of doxorubicin; 3) Group 3 is the doxorubicin and HBO2 group (100% oxygen at 2.5 atmospheric for 90 minutes, daily), for evaluating the effect of HBO2 in doxorubicin induced cardiotoxicity. At the end of the protocols, the hearts were harvested and blood samples (2 ml) were obtained. Results The doxorubicin treated animals (Group 2) had increased oxidative stress markers (both cardiac and serum) and severe cardiac injury as compared to the basal findings in the control group. Nevertheless, the highest cardiac oxidative stress index was detected in Group 3 (control vs. Group 3, p = 0.01). However, histological examination revealed that cardiac structures were well preserved in Group 3 when compared with Group 2. Conclusions Our results suggest that HBO2 preconditioning appears to be protective in the doxorubicin-induced cardiotoxicity model. Future studies are required to better elucidate the basis of this preconditioning effect of HBO2. PMID:28344418

  7. Cardiotoxicity of antineoplasic agents: onset, risk factors and clinical manifestation

    Directory of Open Access Journals (Sweden)

    Maria L. Rădulescu

    2011-11-01

    Full Text Available The continuously growing incidence of the neoplasic disease, estimated to be in 2020 themain cause of death in developed countries, has imposed an increasing research to discover newclasses of antineoplasic agents, which alone or in combination with classical chemotherapy agents,may turn cancer into a curable disease for the most of the patients. All these drugs affect the heart inrelation to the presence of risk factors: physiological (age, sex, race, general (malaise, pre-existingchronic diseases, pre-existing cardiovascular affections, previous mediastinal radiation therapy,association with other cardiotoxic substances, as well as in relation to factors related to medication(high daily dose, high cumulative dose, short interval between administrations, bolus injection. Themechanism that produces cardiotoxicity is incompletely elucidated, it appears to be plurifactorial, theproduction of oxygen free radicals being the main cause of morphological alterations. Anthracyclinescardiotoxicity is better known, with its two forms (acute/subacute and late or chronic or even thedelayed cardiotoxicity form in survivors of childhood cancers. There are also presented some cardiacdamage modalities after treatment with alkylating agents, antimetabolites, taxanes, monoclonalantibodies (trastuzumab.

  8. Cancer genetics and the cardiotoxicity of the therapeutics.

    Science.gov (United States)

    Lal, Hind; Kolaja, Kyle L; Force, Thomas

    2013-01-22

    Cancer genomics has focused on the discovery of mutations and chromosomal structural rearrangements that either increase susceptibility to cancer or support the cancer phenotype. Protein kinases are the most frequently mutated genes in the cancer genome, making them attractive therapeutic targets for drug design. However, the use of some of the kinase inhibitors (KIs) has been associated with toxicities to the heart and vasculature, including acute coronary syndromes and heart failure. Herein we discuss the genetic basis of cancer, focusing on mutations in the kinase genome (kinome) that lead to tumorigenesis. This will allow an understanding of the real and potential power of modern cancer therapeutics. The underlying mechanisms that drive the cardiotoxicity of the KIs are also examined. The preclinical models for predicting cardiotoxicity, including induced pluripotent stem cells and zebrafish, are reviewed, with the hope of eventually being able to identify problematic agents before their use in patients. Finally, the use of biomarkers in the clinic is discussed, and newer strategies (i.e., metabolomics and enhanced imaging strategies) that may allow earlier and more accurate detection of cardiotoxicity are reviewed.

  9. Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

    Directory of Open Access Journals (Sweden)

    Pardo Moira

    2007-01-01

    Full Text Available Abstract Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation.

  10. Erdosteine prevents doxorubicin-induced cardiotoxicity in rats.

    Science.gov (United States)

    Yagmurca, Murat; Fadillioglu, Ersin; Erdogan, Hasan; Ucar, Muharrem; Sogut, Sadik; Irmak, M Kemal

    2003-10-01

    The clinical use of doxorubicin (Dxr) is limited by its cardiotoxic effects which are mediated by oxygen radicals. The purpose of this study was to investigate in vivo protective effects of erdosteine, an antioxidant agent because of its secondary active metabolites in vivo, against the cardiotoxicity induced by Dxr in rats. Three groups of male Sprague-Dawley rats (60 days old) were used. Group 1 was untreated group used as control; the other groups were treated with Dxr (single i.p. dosage of 20 mg kg(-1) b.wt.) or Dxr plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. Erdosteine or oral saline treatment was done starting 2 days before Dxr for 12 days. The analyses were done at the 10th day of Dxr treatment. The protein carbonyl content, the activities of myeloperoxidase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) as well as heart rate and blood pressures were significantly increased in Dxr group in comparison with the other groups. However, pulse pressure was decreased in Dxr group. The body and heart weights were decreased in both Dxr administered groups in comparison with control group. Disorganization of myocardial histology, picnotic nuclei, edema, and increase in collagen content around vessels were seen in the slides of Dxr group, whereas normal myocardial microscopy was preserved in Dxr plus erdosteine group. Collectively, these in vivo hemodynamic, enzymatic and morphologic studies provide an evidence for a possible prevention of cardiac toxicity in Dxr-treated patients.

  11. The virtual heart as a platform for screening drug cardiotoxicity.

    Science.gov (United States)

    Yuan, Yongfeng; Bai, Xiangyun; Luo, Cunjin; Wang, Kuanquan; Zhang, Henggui

    2015-12-01

    To predict the safety of a drug at an early stage in its development is a major challenge as there is a lack of in vitro heart models that correlate data from preclinical toxicity screening assays with clinical results. A biophysically detailed computer model of the heart, the virtual heart, provides a powerful tool for simulating drug-ion channel interactions and cardiac functions during normal and disease conditions and, therefore, provides a powerful platform for drug cardiotoxicity screening. In this article, we first review recent progress in the development of theory on drug-ion channel interactions and mathematical modelling. Then we propose a family of biomarkers that can quantitatively characterize the actions of a drug on the electrical activity of the heart at multi-physical scales including cellular and tissue levels. We also conducted some simulations to demonstrate the application of the virtual heart to assess the pro-arrhythmic effects of cisapride and amiodarone. Using the model we investigated the mechanisms responsible for the differences between the two drugs on pro-arrhythmogenesis, even though both prolong the QT interval of ECGs. Several challenges for further development of a virtual heart as a platform for screening drug cardiotoxicity are discussed.

  12. The virtual heart as a platform for screening drug cardiotoxicity

    Science.gov (United States)

    Yuan, Yongfeng; Bai, Xiangyun; Luo, Cunjin; Wang, Kuanquan

    2015-01-01

    To predict the safety of a drug at an early stage in its development is a major challenge as there is a lack of in vitro heart models that correlate data from preclinical toxicity screening assays with clinical results. A biophysically detailed computer model of the heart, the virtual heart, provides a powerful tool for simulating drug–ion channel interactions and cardiac functions during normal and disease conditions and, therefore, provides a powerful platform for drug cardiotoxicity screening. In this article, we first review recent progress in the development of theory on drug–ion channel interactions and mathematical modelling. Then we propose a family of biomarkers that can quantitatively characterize the actions of a drug on the electrical activity of the heart at multi‐physical scales including cellular and tissue levels. We also conducted some simulations to demonstrate the application of the virtual heart to assess the pro‐arrhythmic effects of cisapride and amiodarone. Using the model we investigated the mechanisms responsible for the differences between the two drugs on pro‐arrhythmogenesis, even though both prolong the QT interval of ECGs. Several challenges for further development of a virtual heart as a platform for screening drug cardiotoxicity are discussed. Linked Articles This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23 PMID:25363597

  13. 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.

  14. [Anthracycline-induced cardiotoxicity: report of fatal cases].

    Science.gov (United States)

    Vargas-Neri, Jessica Liliana; Castelán-Martínez, Osvaldo Daniel; de Jesús Estrada-Loza, María; Betanzos-Cabrera, Yadira; Rivas-Ruiz, Rodolfo

    2016-01-01

    Introducción: las antraciclinas son fármacos eficaces en el tratamiento de pacientes pediátricos con cáncer. Sin embargo, la cardiotoxicidad inducida por antraciclinas (CIA) es una reacción adversa grave que afecta la sobrevida de niños y jóvenes. Casos clínicos: el caso 1 estuvo constituido por una paciente de nueve años con linfoma de Hodgkin estadio IV con 12 ciclos de quimioterapia con epirrubicina y una dosis acumulada de 576 mg/m2. Después del último ciclo de quimioterapia, la paciente ingresó con respuesta inflamatoria sistémica, astenia y adinamia. El ecocardiograma reportó una FEVI de 22 %, FA de 11 % e insuficiencia mitral moderada. La paciente falleció dos días después con diagnóstico de cardiomiopatía dilatada secundaria a antraciclinas. El caso 2 fue el de una paciente de 15 años con linfoma no Hodgkin tipo Burkitt estadio IV, con dos ciclos de quimioterapia con epirrubicina y una dosis acumulada de 90 mg/m2. Después del último ciclo, la paciente presentó diversos focos infecciosos. El ecocardiograma reportó una FEVI de 49 %, una FA de 20 % y dilatación del ventrículo izquierdo con aplanamiento septal. La paciente falleció 13 días después del diagnóstico de cardiomiopatía dilatada por antraciclinas. Conclusión: la CIA es un problema en los pacientes pediátricos que reciben antraciclinas. El monitoreo durante y después de la quimioterapia es indispensable para detectar el inicio del daño cardiaco a fin de brindar una intervención oportuna que evite la evolución a una insuficiencia cardiaca.

  15. 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 studies...... demonstrated 5-FU-induced: hemorrhagic infarction, interstitial fibrosis and inflammatory reaction in the myocardium; damage of the arterial endothelium followed by platelet aggregation; increased myocardial energy metabolism and depletion of high energy phosphate compounds; increased superoxide anion levels...

  16. 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 follow...... 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....

  17. A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

    Science.gov (United States)

    Brette, Fabien; Shiels, Holly A.; Galli, Gina L. J.; Cros, Caroline; Incardona, John P.; Scholz, Nathaniel L.; Block, Barbara A.

    2017-01-01

    The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.

  18. 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.

  19. Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies.

    Science.gov (United States)

    El-Awady, El-Sayed E; Moustafa, Yasser M; Abo-Elmatty, Dina M; Radwan, Asmaa

    2011-01-10

    Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of cisplatin as an anti-tumoral drug. Our study was conducted to evaluate the protective potential of acetyl-l-carnitine, DL-α-lipoic acid and silymarin against cisplatin-induced myocardial injury. Eighty male albino rats were divided into eight groups. The first four groups were treated with normal saline, acetyl-l-carnitine (500mg/kg, i.p.), DL-α-lipoic acid (100mg/kg, p.o.) and silymarin (100mg/kg, p.o.) respectively, for 10 successive days. The remaining groups were treated with the same doses of normal saline, acetyl-l-carnitine, DL-α-lipoic acid and silymarin, respectively, for 5 successive days before and after a single dose of cisplatin (10mg/kg, i.p.). Serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and plasma cardiac troponin I (cTnI) concentration were estimated. Malondialdehyde (MDA), reduced glutathione (GSH) contents, superoxide dismutase activity (SOD) and protein content in cardiac tissues were measured. Moreover, integrity of both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) was also examined. Cisplatin-treated rats experienced a significant elevation of serum activities of LDH, CK, CK-MB and cTnI plasma concentration. These effects were accompanied by a significant increase in MDA level. On the other hand, a significant decrease in GSH content, SOD activity and total protein content was observed. In addition, both mtDNA and nDNA were heavily damaged. However, acetyl-l-carnitine, DL-α-lipoic acid and silymarin significantly attenuated the cisplatin-evoked disturbances in the above-mentioned parameters. In conclusion, the former drugs were proven to be potential candidates to ameliorate cisplatin-induced cardiotoxicity.

  20. 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

  1. Right Ventricular Dysfunction in Patients Experiencing Cardiotoxicity during Breast Cancer Therapy

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    Anna Calleja

    2015-01-01

    Full Text Available Background. Right ventricular (RV dysfunction during cancer therapy related cardiotoxicity and its prognostic implications have not been examined. Aim. We sought to determine the incidence and prognostic value of RV dysfunction at time of LV defined cardiotoxicity. Methods. We retrospectively identified 30 HER2+ female patients with breast cancer treated with trastuzumab (± anthracycline who developed cardiotoxicity and had a diagnostic quality transthoracic echocardiography. LV ejection fraction (LVEF, RV fractional area change (RV FAC, and peak systolic longitudinal strain (for both LV and RV were measured on echocardiograms at the time of cardiotoxicity and during follow-up. Thirty age balanced precancer therapy and HER2+ breast cancer patients were used as controls. Results. In the 30 patients with cardiotoxicity (mean ± SD age 54 ± 12 years RV FAC was significantly lower (42 ± 7 versus 47 ± 6%, P=0.01 compared to controls. RV dysfunction defined by global longitudinal strain (GLS < −20.3% was seen in 40% (n=12. During follow-up in 16 out of 30 patients (23 ± 15 months, there was persistent LV dysfunction (EF < 55% in 69% (n=11. Concomitant RV dysfunction at the time of LV cardiotoxicity was associated with reduced recovery of LVEF during follow-up although this was not statistically significant. Conclusion. RV dysfunction at the time of LV cardiotoxicity is frequent in patients with breast cancer receiving trastuzumab therapy. Despite appropriate management, LV dysfunction persisted in the majority at follow-up. The prognostic value of RV dysfunction at the time of cardiotoxicity warrants further investigation.

  2. [Selective toxicity of cytostatic agents: studies on the cardiotoxicity of doxorubicin, its pathogenesis and contraindications].

    Science.gov (United States)

    Lenzhofer, R

    1983-01-01

    In the past few years the medical treatment of malignant diseases has steadily increased in scope and importance. However, the tumor regimens described in the textbooks still are rather schematic recommendations, which are inadequately tailored to the needs of the individual case. Current tumor therapy is based on the results of the statistical analysis using empirical data collected in randomized trials. While patients can today be given a statistical value which expresses their computed chance of a cure versus that of a defined population, there is still no generally valid method which could serve as a rational basis for individualized counselling. But cytostatic chemotherapy has yet another major shortcoming: the collective assessment of toxicity, which is related to one of the basic properties of cytostatic drugs, i.e. their extremely low therapeutic index. Many of the side effects of cytostatics may cause severe irreversible, at times even fatal, organ dysfunction. Consequently, the definition of the therapeutic risks involved on the basis of an objective identification of potential organ toxicity is a major challenge. "Surgery without a knife", as K.H. Spitzy has called chemotherapy, should be subjected to objective criteria for its indications and contraindications so that patients can truly benefit from what are become increasingly aggressive measures. The principle of weighing the benefits desired in the individual case against the potential risks involved in a specific treatment, which Paul Ehrlich postulated for antibacterial chemotherapy, should also be applied to cytostatic chemotherapy with a view to facilitating the decision for or against therapy in borderline cases. The present contribution which is designed to shed light on the cardiotoxicity of doxorubicin should be interpreted in light of this situation. Pathogenetic aspects and animal experiments on drug-induced lipid peroxidation will be discussed and clinical trials on both acute and chronic

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

    OpenAIRE

    Monica Lamberti; Giancarlo Giovane; Garzillo, Elpidio M.; Franca Avino; Antonia Feola; Stefania Porto; Vincenzo Tombolini; Marina Di Domenico

    2014-01-01

    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 cardiotoxic...

  4. 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

  5. Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: What is missing?

    Science.gov (United States)

    Magdy, Tarek; Burmeister, Brian T; Burridge, Paul W

    2016-12-01

    The cardiotoxicity of certain chemotherapeutic agents is now well-established, and has led to the development of the field of cardio-oncology, increased cardiac screening of cancer patients, and limitation of patients' maximum cumulative chemotherapeutic dose. The effect of chemotherapeutic regimes on the heart largely involves cardiomyocyte death, leading to cardiomyopathy and heart failure, or the induction of arrhythmias. Of these cardiotoxic drugs, those resulting in clinical cardiotoxicity can range from 8 to 26% for doxorubicin, 7-28% for trastuzumab, or 5-30% for paclitaxel. For tyrosine kinase inhibitors, QT prolongation and arrhythmia, ischemia and hypertension have been reported in 2-35% of patients. Furthermore, newly introduced chemotherapeutic agents are commonly used as part of changed combinational regimens with significantly increased incidence of cardiotoxicity. It is widely believed that the mechanism of action of these drugs is often independent of their cardiotoxicity, and the basis for why these drugs specifically affect the heart has yet to be established. The genetic rationale for why certain patients experience cardiotoxicity whilst other patients can tolerate high chemotherapy doses has proven highly illusive. This has led to significant genomic efforts using targeted and genome-wide association studies (GWAS) to divine the pharmacogenomic cause of this predilection. With the advent of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), the putative risk and protective role of single nucleotide polymorphisms (SNPs) can now be validated in a human model. Here we review the state of the art knowledge of the genetic predilection to chemotherapy-induced cardiotoxicity and discuss the future for establishing and validating the role of the genome in this disease.

  6. Protective effect of silymarin against chemical-induced cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Bibi Marjan Razavi

    2016-09-01

    Full Text Available Cardiac disorders remain one of the most important causes of death in the world. Oxidative stress has been suggested as one of the molecular mechanisms involved in drug-induced cardiac toxicity. Recently, several natural products have been utilized in different studies with the aim to protect the progression of oxidative stress-induced cardiac disorders. There is a large body of evidence that administration of antioxidants may be useful in ameliorating cardiac toxicity. Silymarin, a polyphenolic flavonoid has been shown to have utility in several cardiovascular disorders. In this review, various studies in scientific databases regarding the preventive effects of silymarin against cardiotoxicity induced by chemicals were introduced. Although there are many studies representing the valuable effects of silymarin in different diseases, the number of researches relating to the possible cardiac protective effects of silymarin against drugs induced toxicity is rather limited. Results of these studies show that silymarin has a broad spectrum of cardiac protective activity against toxicity induced by some chemicals including metals, environmental pollutants, oxidative agents and anticancer drugs. Further studies are needed to establish the utility of silymarin in protection against cardiac toxicity.

  7. Cardiotoxicity of Senna occidentalis in sheep (Ovis aries

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    D.I.S. Lopes

    2016-02-01

    Full Text Available 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.

  8. Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin

    Institute of Scientific and Technical Information of China (English)

    Ling-jie XU; Liang JIN; Hong PAN; Ao-zhen ZHANG; Gang WEI; Ping-ping LI; Wei-yue LU

    2006-01-01

    Aim: To investigate the effects of deferiprone on doxorubicin-induced cardiotoxicity and determine its protection on cardiac contractility in vivo at tissue level. Methods: Spontaneously-beating isolated atria from rats were pretreated with deferiprone for 10 min at 1.2 mmol/L or 0.3 mmol/L, respectively before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min. Contractility (dF/dt) was assessed every 10 min during the incubation. After that, the tissues around the sinuatrial nodes were fixed for ultrastructural study; succinate dehydrogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD) activity, as well as malondialdehyde (MDA) level of the atria were assayed. Results: Treatment with DOX alone resulted in a 49.34% reduction of the contractility, mitochondria swelling, disruption of mitochondrial crista and decreased electron density of the matrices. Conversely, with the presence of deferiprone, the negative inotropic effect and lesions in the cardiac mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity increased by 12.97%-12.11%, the MDA level decreased by 29.12%-39.82% and succinate dehydrogenase (SDH) activity was ameliorated by 25.15%-34.76%. Conclusion : Deferiprone can efficiently preserve cardiac contractility. Moreover, the results of this study indicate that deferiprone is able to protect mitochondrial function and structure form damage induced by DOX. This cardiac protective potential of deferiprone could be due to its defense capability against oxidative damage.

  9. Comparative Investigation of Protective Effects of Metyrosine and Metoprolol Against Ketamine Cardiotoxicity in Rats.

    Science.gov (United States)

    Ahiskalioglu, Ali; Ince, Ilker; Aksoy, Mehmet; Ahiskalioglu, Elif Oral; Comez, Mehmet; Dostbil, Aysenur; Celik, Mine; Alp, Hamit Hakan; Coskun, Resit; Taghizadehghalehjoughi, Ali; Suleyman, Bahadir

    2015-10-01

    This study investigated the effect of metyrosine against ketamine-induced cardiotoxicity in rats and compared the results with the effect of metoprolol. In this study, rats were divided into groups A, B and C. In group A, we investigated the effects of a single dose of metyrosine (150 mg/kg) and metoprolol (20 mg/kg) on single dose ketamine (60 mg/kg)-induced cardiotoxicity. In group B, we investigated the effect of metyrosine and metoprolol, which were given together with ketamine for 30 days. In group C, we investigated the effect of metyrosine and metoprolol given 15 days before ketamine and 30 days together with ketamine on ketamine cardiotoxicity. By the end of this process, we evaluated the effects of the levels of oxidant-antioxidant parameters such as MDA, MPO, 8-OHGua, tGSH, and SOD in addition to CK-MB and TP I on cardiotoxicity in rat heart tissue. The experimental results show that metyrosine prevented ketamine cardiotoxicity in groups A, B and C and metoprolol prevented it in only group C.

  10. Sodium Thiosulfate Versus Hydroxocobalamin in the Treatment of Acute, Severe Cyanide Induced Cardiotoxicity in a Swine (Sus Scrofa) Model

    Science.gov (United States)

    2011-09-22

    IUIVIJ:lt:M Sodium thiosulfate versus hydroxocoba~amin in the treatment of acute, severe cyanide induced cardiotoxicity in a swine (Sus Scrofa )model on...treatment of acute, severe cyanide induced cardiotoxicity in a swine (Sus Scrofa ) model .. 4. Principal Investigator (PI): ’ ~ I ’ ·, .. Name Rank Date

  11. 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.

  12. Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

    Institute of Scientific and Technical Information of China (English)

    Amie; J; Dirks-Naylor; Samir; A; Kouzi; Sendra; Yang; Ngan; TK; Tran; Joseph; D; Bero; Raean; Mabolo; Diep; T; Phan; Stephanie; D; Whitt; Heather; N; Taylor

    2014-01-01

    Doxorubicin(Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.

  13. 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.

  14. Oral Glutamine Protects against Acute Doxorubicin-Induced Cardiotoxicity of Tumor-Bearing Rats

    NARCIS (Netherlands)

    Todorova, Valentina K.; Kaufmann, Yihong; Hennings, Leah; Klimberg, V. Suzanne

    2010-01-01

    Doxorubicin (DOX), a widely used anticancer drug, has a dose-dependent cardiotoxicity, attributed mainly to free radical formation. The cardiomyocyte oxidative stress occurs rapidly after DOX treatment, resulting in harmful modifications to proteins, lipids, and DNA. Previous data showed that oral L

  15. Drug-related cardiotoxicity for the treatment of haematological malignancies in elderly.

    Science.gov (United States)

    Malato, Alessandra; Saccullo, Giorgia; Fazio, Giovanni; Vergara, Beatrice; Raso, Simona; Guarneri, Giovanni Paolo; Russo, Antonio; Abbadessa, Vincenzo; Siragusa, Sergio

    2010-01-01

    Several publications have focused on the cardiotoxicity of specific classes of hematological therapeutic agents such as antracyclines and cyclofosfamide. Cardiotoxicity of cancer chemotherapeutics is a problem for patients of all ages, but it increases with age. Toxicity can also develop months after the last chemotherapy dose, and late reactions can be seen years later when they present as new-onset cardiomyopathy. No data are available about the cardiotoxicity of non-chemotherapy agents currently used as preferred therapy for hematological malignancy in elderly. In this review we have provided a summary of the cardiovascular toxic effects produced by different drugs and therapeutic agents. Early identification of patients who are at risk for cardiotoxicity should be a primary goal for hematologists in the development of personalized antineoplastic therapeutic strategies or interventions. Thus, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is a high priority. Although targeted therapies such as imatinib and anti-CD20 antibody such rituximab are considered less toxic and better tolerated by patients compared with classic chemotherapy drugs, certain cardiological complications can be very serious and as these agents have been in use for a limited period of time.

  16. BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxity

    DEFF Research Database (Denmark)

    Vogelsang, T.W.; Jensen, R.J.; Hesse, B.;

    2007-01-01

    BACKGROUND: Cardiotoxity is a side-effect of cancer treatment with anthracycline that is currently monitored by measuring the left ventricular ejection fraction (LVEF) by gated equilibrium radionuclide ventriculography (RNV). We hypothesized that BNP measurements could replace, at least in part...

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

    Science.gov (United States)

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

    2014-11-01

    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 statistically measurable neurotoxicity as measured using mouse sciatic nerve compound action potential. Cucurbituril myotoxicity was measured by nerve-muscle force of contraction through chemical and electrical stimulation. Motor2 was found to display no myotoxicity, whereas both CB[6] and CB[7] showed myotoxic activity via a presynaptic effect. Finally, cardiotoxicity, which was measured by changes in the rate and force of right and left atria contraction, was observed for all three cucurbiturils. Free cisplatin displays neuro-, myo- and cardiotoxic activity, consistent with the side-effects seen in the clinic. Whilst CB[7] had no effect on the level of cisplatin's neurotoxic activity, drug encapsulation within the macrocycle had a marked reduction in both the drug's myo- and cardiotoxic activity. Overall the results are consistent with the relative lack of toxicity displayed by these macrocycles in whole animal acute systemic toxicity studies and indicate continued potential of cucurbiturils as drug delivery vehicles for the reduction of the side effects associated with platinum-based chemotherapy.

  18. 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

  19. Cardiotoxic effects of cocaine and anabolic-androgenic steroids in the athlete.

    Science.gov (United States)

    Welder, A A; Melchert, R B

    1993-04-01

    Cocaine and anabolic-androgenic steroid abuse have become major drug problems in the United States. Cocaine has been designated as "the drug of greatest national health concern" while as many as 1 million Americans have used or are currently using anabolic-androgenic steroids to promote athletic performance and/or improve physical appearance. Unfavorable cardiovascular events have been linked to both cocaine and anabolic-androgenic steroid abuse in healthy, physically active individuals. Deaths of several United States athletes in 1986 focused attention on the life-threatening cardiovascular consequences of cocaine abuse. Reports of myocardial injury with anabolic-androgenic steroid abuse are anecdotal. Nevertheless, case reports have illustrated the alarming cardiotoxic potential of these steroids in athletes. Anabolic-androgenic steroids were correlated to myocardial infarction in weight lifters and cardiomyopathy in a former professional football player. From the total emergency room episodes where cocaine was mentioned in 1990, approximately 66% of these episodes occurred in young individuals 18-29 years of age. Over 500,000 of the individuals currently taking anabolic-androgenic steroids for nonmedical purposes are high-school children. Because cocaine and anabolic-androgenic steroids are used improperly, more focus needs to be paid to the toxic mechanisms of their adverse effects. Therefore, the purpose of this review is to discuss mechanisms whereby exercise and/or exercise training may alter the cardiovascular responses to these drugs. Furthermore, we would like to illustrate that contrary to the popular belief, acute and chronic abuse of cocaine and anabolic-androgenic steroids have a negative impact on exercise performance.

  20. 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.

  1. Increasing membrane interactions of local anaesthetics as hypothetic mechanism for their cardiotoxicity enhanced by myocardial ischaemia.

    Science.gov (United States)

    Tsuchiya, Hironori; Mizogami, Maki; Shigemi, Kenji

    2012-11-01

    While myocardial ischaemia enhances the cardiotoxicity of local anaesthetics, the pharmacological background remains unclear. Cardiolipin (CL) localized in mitochondrial membranes is possibly the site of cardiotoxic action of local anaesthetics and peroxynitrite is produced by cardiac ischaemia and reperfusion. We verified the hypothetic mechanism that local anaesthetics may interact with CL-containing biomembranes to change the membrane biophysical property and their membrane interactions may be increased by peroxynitrite. Biomimetic membranes were prepared with different phospholipids and cholesterol of varying compositions. The membrane preparations were reacted with peroxynitrite of pathologically relevant concentrations and local anaesthetics (bupivacaine and lidocaine) of a cardiotoxic concentration separately or in combination. Changes in membrane fluidity were determined by measuring fluorescence polarization. Peroxynitrite decreased the fluidity of biomimetic membranes at 0.1-10 μM with the relative potency being CL>1-stearoyl-2-arachidonoylphosphatidylcholine>1,2-dipalmitoylphosphatidylcholine-constituting membranes, indicating the lipid peroxidation-induced membrane rigidification determined by the unsaturation degree of membrane lipids. When treated with 0.1-10 μM peroxynitrite, biomimetic membranes were more rigid with elevating the CL content from 0% to 30 mol%, suggesting that CL is a primary target of peroxynitrite. Bupivacaine and lidocaine fluidized at 200 μM biomimetic membranes containing 10 mol% CL and their effects were increased by pre-treating the membranes with 0.1 and 1 μM peroxynitrite. Cardiotoxic bupivacaine and lidocaine increasingly interact with CL-containing mitochondria model membranes which are relatively rigidified by peroxynitrite. Such an increasing membrane interaction may be, at least in part, responsible for the local anaesthetic cardiotoxicity enhanced by myocardial ischaemia.

  2. Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer

    NARCIS (Netherlands)

    Cheuka, Daniel K. L.; Sieswerda, Elske; van Dalen, Elvira C.; Postma, Aleida; Kremer, Leontien C. M.

    2016-01-01

    Background Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not kno

  3. 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

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

    OpenAIRE

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

  5. Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: To mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B could protect against doxorubicin (Dox-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity. METHODOLOGY: Rat was given intragastrically either vehicle or Sch B (50 mg/kg two hours prior to i.p. Dox (2.5 mg/kg weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo. PRINCIPAL FINDINGS: Pretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group. CONCLUSION: Sch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.

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

    Directory of Open Access Journals (Sweden)

    Shreesh Ojha

    2016-01-01

    Full Text Available 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.

  7. Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Jing Sun

    Full Text Available Doxorubicin (Dox is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. Isorhamnetin is a nature antioxidant with obvious cardiac protective effect. The aim of this study is going to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p. administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity. Daily pretreatment with isorhamnetin (5 mg/kg, i.p. for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. A further mechanism study indicated that isorhamnetin pretreatment can counteract Dox-induced oxidative stress and suppress the activation of mitochondrion apoptotic pathway and mitogen-activated protein kinase pathway. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox.

  8. Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro.

    Science.gov (United States)

    Sun, Jing; Sun, Guibo; Meng, Xiangbao; Wang, Hongwei; Luo, Yun; Qin, Meng; Ma, Bo; Wang, Min; Cai, Dayong; Guo, Peng; Sun, Xiaobo

    2013-01-01

    Doxorubicin (Dox) is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. Isorhamnetin is a nature antioxidant with obvious cardiac protective effect. The aim of this study is going to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p.) administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity. Daily pretreatment with isorhamnetin (5 mg/kg, i.p.) for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. A further mechanism study indicated that isorhamnetin pretreatment can counteract Dox-induced oxidative stress and suppress the activation of mitochondrion apoptotic pathway and mitogen-activated protein kinase pathway. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox.

  9. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology.

    Science.gov (United States)

    Pepe, Alessia; Pizzino, Fausto; Gargiulo, Paola; Perrone-Filardi, Pasquale; Cadeddu, Christian; Mele, Donato; Monte, Ines; Novo, Giuseppina; Zito, Concetta; Di Bella, Gianluca

    2016-05-01

    Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.

  10. Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway.

    Science.gov (United States)

    Su, Suwen; Li, Qian; Liu, Yi; Xiong, Chen; Li, Junxia; Zhang, Rong; Niu, Yujie; Zhao, Lijuan; Wang, Yongli; Guo, Huicai

    2014-01-13

    Oxidative stress caused by doxorubicin (DOX) is believed to be a major underlying molecular mechanism of DOX-induced cardiotoxicity. Sesamin (Ses), an active component extracted from sesame seeds, exhibits antioxidative and anti-inflammatory effects. In the present study, possible protective mechanisms of Ses on DOX-induced cardiotoxicity were investigated in rats and cultured H9C2 cells. We demonstrated that Ses exhibits a significant protective effect on cardiac tissue in animal and cell models of DOX-induced cardiac injury. Moreover, Ses can ameliorate DOX-induced oxidative stress and mitochondrial damage. Further studies suggested that Ses is able to up-regulate the protein expression of Mn-SOD in normal rats and to restore the decreased expression of Mn-SOD in DOX-induced cardiac injury rats. Exposure to Ses or DOX alone slightly increased the protein expression of Sirt1; however, a more remarkable increase in Sirt1 protein level was detected in the Ses+DOX group. Treatment with a pan-sirtuin inhibitor (nicotinamide) or a Sirt1-specific inhibitor (EX-527) partially antagonised the effect of Ses on DOX-induced mitochondrial damage and completely abolished the effect of Ses on Mn-SOD expression. These findings indicate that the protective mechanisms of Ses on DOX-induced cardiotoxicity are involved in the alleviation of oxidative stress injury and Mn-SOD dysfunction, partially via the activation of Sirt1.

  11. Potential Therapeutic Strategies for Hypertension-Exacerbated Cardiotoxicity of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Robin K. Kuriakose

    2016-01-01

    Full Text Available Despite their recognized cardiotoxic effects, anthracyclines remain an essential component in many anticancer regimens due to their superior antitumor efficacy. Epidemiologic data revealed that about one-third of cancer patients have hypertension, which is the most common comorbidity in cancer registries. The purpose of this review is to assess whether anthracycline chemotherapy exacerbates cardiotoxicity in patients with hypertension. A link between hypertension comorbidity and anthracycline-induced cardiotoxicity (AIC was first suggested in 1979. Subsequent preclinical and clinical studies have supported the notion that hypertension is a major risk factor for AIC, along with the cumulative anthracycline dosage. There are several common or overlapping pathological mechanisms in AIC and hypertension, such as oxidative stress. Current evidence supports the utility of cardioprotective modalities as adjunct treatment prior to and during anthracycline chemotherapy. Several promising cardioprotective approaches against AIC pathologies include dexrazoxane, early hypertension management, and dietary supplementation of nitrate with beetroot juice or other medicinal botanical derivatives (e.g., visnagin and Danshen, which have both antihypertensive and anti-AIC properties. Future research is warranted to further elucidate the mechanisms of hypertension and AIC comorbidity and to conduct well-controlled clinical trials for identifying effective clinical strategies to improve long-term prognoses in this subgroup of cancer patients.

  12. Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin.

    Science.gov (United States)

    Hao, Gang; Yu, Yunli; Gu, Bingren; Xing, Yiwen; Xue, Man

    2015-01-01

    1. The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin. 2. Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats. 3. Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin. 4. Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart. 5. These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.

  13. Potential effects of pomegranate on lipid peroxidation and pro-inflammatory changes in daunorubicin-induced cardiotoxicity in rats

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    Hayder M Al-Kuraishy

    2016-01-01

    Full Text Available 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 12 th 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 < 0.01, it induced lipid peroxidation during cardiotoxicity that reflected through an elevation in the serum MDA significantly P < 0.01, moreover, daunorubicin induces pro-inflammatory changes in cardiotoxicity; it raises the IL-17 serum level significantly P < 0.01 as compared with control. 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 < 0.01 as compared with daunorubicin-treated group. Conclusions: Pomegranate demonstrated significant cardioprotection in daunorubicin-induced cardiotoxicity through reduction of oxidative stress, lipid peroxidation, pro-inflammatory, and cardiac injury biomarkers.

  14. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor...... efficacy was found to be significantly higher (~1.76- and ~4.5-fold) for the combination as compared to Dox-LCNPs (per oral) and Adriamycin (i.v.) respectively. Notably, level of residual tumor burden was insignificant (P>0.05) after 30days in case of combination and LipoDox® (i.v.). Interestingly......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

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

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    Yubo Li

    2016-01-01

    Full Text Available 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.

  16. The protective effect of erdosteine against cyclosporine A-induced cardiotoxicity in rats.

    Science.gov (United States)

    Selcoki, Yusuf; Uz, Ebru; Bayrak, Reyhan; Sahin, Semsettin; Kaya, Arif; Uz, Burak; Karanfil, Aydin; Ozkara, Adem; Akcay, Ali

    2007-09-24

    Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection and in the treatment of autoimmune diseases. However, CsA generates reactive oxygen species, which causes nephrotoxicity, hepatotoxicity and cardiotoxicity. The use of antioxidants reduces the adverse effects of CsA. The aim of this study is to determine the protective effects of erdosteine on CsA-induced heart injury through tissue oxidant/antioxidant parameters and light microscopic evaluation in rats. CsA cardiotoxicity was induced by administrating an oral dose of 15mg/kg CsA daily for 21 days. The rats were divided into four groups: control group (n=4), CsA administrated group (15mg/kg, n=5), CsA+erdosteine administrated group (10mg/kg day orally erdosteine, n=4) and only erdosteine administrated group (10mg/kg day orally n=5). CsA treated rats showed increase in the number of infiltrated cells and disorganization of myocardial fibers with interstitial fibrosis. The number of infiltrated cells, disorganization of myocardial fibers and interstitial fibrosis was diminished in the hearts of CsA-treated rats given erdosteine. The malondialdehyde, the protein carbonyl content and nitric oxide levels were increased in the cyclosporine A group in comparison with the control and CsA plus erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in CsA plus erdosteine group than CsA group. However, the CAT, GSH-Px and SOD activities were significantly lower in CsA group than in control group and erdosteine group. These results suggest that erdosteine has protective effect against CsA-induced cardiotoxicity.

  17. ALDH2 attenuates Dox-induced cardiotoxicity by inhibiting cardiac apoptosis and oxidative stress.

    Science.gov (United States)

    Gao, Yawen; Xu, Yan; Hua, Songwen; Zhou, Shenghua; Wang, Kangkai

    2015-01-01

    The anthracycline chemotherapy drug doxorubicin (DOX) is cardiotoxic. This study aimed to explore the effect of acetaldehyde dehydrogenase 2 (ALDH2), a detoxifying protein, on DOX-induced cardiotoxicity and unveil the underlying mechanisms. BALB/c mice were randomly divided in four groups: control group (no treatment), DOX group (DOX administration for myocardial damage induction), DOX + Daidzin group (DOX administration + Daidzin, an ALDH2 antagonist) and DOX + Alda-1 group (DOX administration + Alda-1, an ALDH2 agonist). Then, survival, haemodynamic parameters, expression of pro- and anti-apoptosis markers, reactive oxygen species (ROS) and 4-Hydroxynonenal (4-HNE) levels, expression and localization of NADPH oxidase 2 (NOX2) and its cytoplasmic subunit p47(PHOX), and ALDH2 expression and activity were assessed. Mortality rates of 0, 35, 5, and 70% were obtained in the control, DOX, DOX + Alda-1, and DOX + Daidzin groups, respectively, at the ninth weekend. Compared with control animals, DOX treatment resulted in significantly reduced left ventricular systolic pressure (LVSP) and ± dp/dt, and overtly increased left ventricular end-diastolic pressure (LVEDP); increased Bax expression and caspase-3/7 activity, and reduced Bcl-2 expression in the myocardium; increased ROS (about 2 fold) and 4-HNE adduct (3 fold) levels in the myocardium; increased NOX2 protein expression and membrane translocation of P47(PHOX). These effects were aggravated in the DOX + Daidzin group, DOX + Alda-1 treated animals showed partial or complete alleviation. Finally, Daidzin further reduced the DOX-repressed ALDH2 activity, which was partially rescued by Alda-1. These results indicated that ALDH2 attenuates DOX-induced cardiotoxicity by inhibiting oxidative stress, NOX2 expression and activity, and reducing myocardial apoptosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Lücker, Petra B.; Zandstra, Peter W. [University of Toronto, 160 College Street, Office 1116, Toronto, Ontario M5S 3E1 (Canada); Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Wickham, Thomas J., E-mail: twickham@merrimackpharma.com [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States)

    2012-07-01

    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

  19. Mechanisms of Fatal Cardiotoxicity following High-Dose Cyclophosphamide Therapy and a Method for Its Prevention.

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    Takuro Nishikawa

    Full Text Available Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY. We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9. Cytotoxicity was then evaluated by 3-(4,5-dimethyl-2-thiazolyl¬2,5-diphenyl¬2H-tetrazolium bromide (MTT assay, lactate dehydrogenase release, production of reactive oxygen species (ROS, and incidence of apoptosis. We also investigated how the myocardial cellular effects of CYS9 were modified by acrolein scavenger N-acetylcysteine (NAC, antioxidant isorhamnetin (ISO, and CYP inhibitor β-ionone (BIO. Quantifying CY and CY metabolites by means of liquid chromatography coupled with electrospray tandem mass spectrometry, we assayed culture supernatants of CYS9 with and without candidate cardioprotectant agents. Assay results for MTT showed that treatment with CY (125-500 μM did not induce cytotoxicity. CYS9, however, exhibited myocardial cytotoxicity when CY concentration was 250 μM or more. After 250 μM of CY was metabolized in S9 mix for 2 h, the concentration of CY was 73.6 ± 8.0 μM, 4-hydroxy-cyclophosphamide (HCY 17.6 ± 4.3, o-carboxyethyl-phosphoramide (CEPM 26.6 ± 5.3 μM, and acrolein 26.7 ± 2.5 μM. Inhibition of CYS9-induced cytotoxicity occurred with NAC, ISO, and BIO. When treated with ISO or BIO, metabolism of CY was significantly inhibited. Pre-treatment with NAC, however, did not inhibit the metabolism of CY: compared to control samples, we observed no difference in HCY, a significant increase of CEPM, and a significant decrease of acrolein. Furthermore, NAC pre-treatment did not affect intracellular amounts of ROS produced by CYS9. Since acrolein seems to be heavily implicated in the onset of cardiotoxicity, any competitive metabolic processing of CY that reduces its transformation to acrolein

  20. Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials

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    Verrill Mark

    2010-06-01

    Full Text Available Abstract Background We conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian cancer, lymphoma, myeloma or sarcoma. Methods Randomized controlled trials were sought using comprehensive searches of electronic databases in June 2008. Reference lists of retrieved articles were also scanned for additional articles. Outcomes investigated were early or late clinical and sub-clinical cardiotoxicity. Trial quality was assessed, and data were pooled through meta-analysis where appropriate. Results Fifty-five published RCTs were included; the majority were on women with advanced breast cancer. A significantly greater risk of clinical cardiotoxicity was found with anthracycline compared with non-anthracycline regimens (OR 5.43 95% confidence interval: 2.34, 12.62, anthracycline versus mitoxantrone (OR 2.88 95% confidence interval: 1.29, 6.44, and bolus versus continuous anthracycline infusions (OR 4.13 95% confidence interval: 1.75, 9.72. Risk of clinical cardiotoxicity was significantly lower with epirubicin versus doxorubicin (OR 0.39 95% confidence interval: 0.20, 0.78, liposomal versus non-liposomal doxorubicin (OR 0.18 95% confidence interval: 0.08, 0.38 and with a concomitant cardioprotective agent (OR 0.21 95% confidence interval: 0.13, 0.33. No statistical heterogeneity was found for these pooled analyses. A similar pattern of results were found for subclinical cardiotoxicity; with risk significantly greater with anthracycline containing regimens and bolus administration; and significantly lower risk with epirubicin, liposomal doxorubicin versus doxorubicin but not epirubicin, and with concomitant use of a cardioprotective agent. Low to moderate statistical heterogeneity was found for two of the five pooled analyses, perhaps due to the different criteria used for reduction in Left Ventricular Ejection Fraction. Meta-analyses of any

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

    Science.gov (United States)

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

    2015-06-25

    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.

  2. ROLE OF COXSACKIEVIRUS AND ADENOVIRUS RECEPTOR ( CAR)IN CARDIOTOXICITY INFECTED BY COXSACKIEVIRUS B3

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wu; ZHOU Ai-qing; Fu Li-jun; LIANG Ying; TANG Ning

    2005-01-01

    Objective To explore the role of coxsackievirus and adenovirus receptor(CAR)in cardiotoxicity infected by coxsackievirus B3. Methods A toxic cellular model was established in vitro by adding myocarditic coxsackievirus B3(CVB3m)into the culture of neonatal mouse cardiomyocytes.48 h later, the cardiomyocytes were divided into control, CVB3m, and CAR antibody+CVB3m groups. CVB3m-mediated myocytopathic effect of above three groups was observed after further culturing for 48h. At the same time,the cardiomyocytes'viability of above three groups was assessed by MTT assay. Results The degree of cytopathic effect(CPE)of CAR antibody+CVB3m group was significantly lower than CVB3m group (P<0.01)and there was a significant increase in cell viability in CAR antibody+CVB3m group compared with CVB3m group(P<0.01). No significant difference was found between CAR antibody+CVB3m group and control group. Conclusion CAR antibody possesses a protective effect on CVB3m infected cardiomyoctyes, which indicates that CAR may play an important role in mediating cardiotoxicity infected by CVB3m.

  3. The Protective Role of Resveratrol against Arsenic Trioxide-Induced Cardiotoxicity

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    Weiqian Zhang

    2013-01-01

    Full Text Available Arsenic trioxide (As2O3 shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL. Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3 in heart via nuclear factor erythroid 2-related factor 2 (Nrf2 and heme oxygenase-1 (HO-1 is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3 on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3 might provide a novel therapeutic strategy for APL.

  4. Protective Effect of Silymarin against Acrolein-Induced Cardiotoxicity in Mice

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    Elahe Taghiabadi

    2012-01-01

    Full Text Available Reactive α,β-unsaturated aldehydes such as acrolein (ACR are major components of environmental pollutants and have been implicated in the neurodegenerative and cardiac diseases. In this study, the protective effect of silymarin (SN against cardiotoxicity induced by ACR in mice was evaluated. Studies were performed on seven groups of six animals each, including vehicle-control (normal saline + 0.5% w/v methylcellulose, ACR (7.5 mg/kg/day, gavage for 3 weeks, SN (25, 50 and 100 mg/kg/day, i.p. plus ACR, vitamin E (Vit E, 100 IU/kg, i.p. plus ACR, and SN (100 mg/kg, i.p. groups. Mice received SN 7 days before ACR and daily thereafter throughout the study. Pretreatment with SN attenuated ACR-induced increased levels of malondialdehyde (MDA, serum cardiac troponin I (cTnI, and creatine kinase-MB (CK-MB, as well as histopathological changes in cardiac tissues. Moreover, SN improved glutathione (GSH content, superoxide dismutase (SOD, and catalase (CAT activities in heart of ACR-treated mice. Western blot analysis showed that SN pretreatment inhibited apoptosis provoked by ACR through decreasing Bax/Bcl-2 ratio, cytosolic cytochrome c content, and cleaved caspase-3 level in heart. In conclusion, SN may have protective effects against cardiotoxicity of ACR by reducing lipid peroxidation, renewing the activities of antioxidant enzymes, and preventing apoptosis.

  5. Cardiotoxic drugs Herceptin and doxorubicin inhibit cardiac microvascular endothelial cell barrier formation resulting in increased drug permeability

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    Emma L. Wilkinson

    2016-10-01

    Full Text Available Cardiotoxicity induced by anti-cancer therapeutics is a severe, and potentially fatal, adverse reaction of the heart in response to certain drugs. Current in vitro approaches to assess cardiotoxicity have focused on analysing cardiomyocytes. More recently it has become apparent that non-cardiomyocyte cells of the heart can potentially contribute to cardiotoxicity. Herceptin and doxorubicin are known to induce cardiotoxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested by analysing tight junction formation and zona occludens-1 (ZO-1 levels, revealing that Herceptin and doxorubicin are able to induce barrier perturbment and decrease barrier function in human cardiac microvascular endothelial cells (HCMECs leading to increased permeability. Herceptin treatment had no effect on the tight junction barrier function in human dermal and human brain microvascular endothelial cells. HCMECs showed detectable levels of HER2 compared with the other endothelial cells suggesting that Herceptin binding to HER2 in these cells may interfere with tight junction formation. Our data suggests that doxorubicin and Herceptin can affect tight junction formation in the cardiac microvasculature leading to increased drug permeability and adverse effects on the cardiac myocytes.

  6. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells.

    Science.gov (United States)

    Liu, Mi-Hua; Lin, Xiao-Long; Yuan, Cong; He, Jun; Tan, Tian-Ping; Wu, Shao-Jian; Yu, Shan; Chen, Li; Liu, Jun; Tian, Wei; Chen, Yu-Dan; Fu, Hong-Yun; Li, Jian; Zhang, Yuan

    2016-01-01

    Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX‑induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX‑induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX‑induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N‑acetyl‑L‑cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX‑induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-γ-lyase were examined by western blotting.

  7. S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers.

    Directory of Open Access Journals (Sweden)

    Ufuk Eryilmaz

    Full Text Available This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment, T (n = 8, one time ip treatment with 10 mg/kg trastuzumab and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days. The activities of oxidative stress parameters Malondialdehyde (MDA, Superoxide dismutase (SOD, Catalase (CAT and Glutathione (GSH were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%, which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.

  8. 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

  9. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model.

    Science.gov (United States)

    Sirenko, Oksana; Grimm, Fabian A; Ryan, Kristen R; Iwata, Yasuhiro; Chiu, Weihsueh A; Parham, Frederick; Wignall, Jessica A; Anson, Blake; Cromwell, Evan F; Behl, Mamta; Rusyn, Ivan; Tice, Raymond R

    2017-03-01

    An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30min or 24h and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca(2+) flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of the tested chemicals exhibited effects on cardiomyocyte beating after 30min of exposure. In contrast, after 24h, effects on cell beating without concomitant cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes visualized using the Toxicological Prioritization Index (ToxPi) showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential at high exposure levels to alter cardiomyocyte function, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes.

  10. Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients

    Science.gov (United States)

    Oliveira-Carvalho Vagner, Rigaud; Ferreira, Ludmila R.P; Ayub-Ferreira, Silvia M; Ávila, Mônica S; Brandão, Sara M.G; Cruz, Fátima D; Santos, Marília H.H; Cruz, Cecilia B.B.V; Alves, Marco S.L; Issa, Victor S; Guimarães, Guilherme V; Cunha-Neto, Edécio; Bocchi, Edimar A

    2017-01-01

    Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from “Carvedilol Effect on Chemotherapy-induced Cardiotoxicity” (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients. PMID:28052002

  11. 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

  12. 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

  13. Prevention and treatment of doxorubicin-induced cardiotoxicity by dexrazoxane and schisandrin B in rabbits.

    Science.gov (United States)

    Che, Feifei; Liu, Yu; Xu, Caigang

    2011-12-01

    The cost of dexrazoxane, a drug used to provide protection from doxorubicin-induced cardiotoxicity, limits its use in low-income countries. We aimed to see whether schisandrin B, an inexpensive drug, could provide protection equivalent to that provided by dexrazoxane. New Zealand white rabbits were randomly divided into groups and treated with saline, doxorubicin, doxorubicin + dexrazoxane, or doxorubicin + schisandrin B. Doxorubicin-induced damage and the protective effects were studied by recording the echocardiographic parameters and serum levels of superoxide dismutase, malondialdehyde, cardiac troponin I, and brain natriuretic peptide and observing the histology and degree of apoptosis. Schisandrin B had dose-dependent effects in decreasing the magnitude of doxorubicin-induced indicators of cardiomyopathy to a degree that approximated the decrease produced by dexrazoxane treatment. Schisandrin B might be a useful, low-cost alternative drug for this application.

  14. [Prevention against and treatment of doxorubicin-induced acute cardiotoxicity by dexrazoxane and schisandrin B].

    Science.gov (United States)

    Hu, Kai-Yong; Yang, Yong; He, Li-Hua; Wang, Duo-Wei; Jia, Zhi-Rong; Li, Shu-Ran; Tian, Wei; Mao, Jie; Li, Xian-Jing; Zhang, Wei

    2014-07-01

    In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.

  15. Cardiotoxic effects of venom fractions from the Australian box jellyfish Chironex fleckeri on human myocardiocytes.

    Science.gov (United States)

    Saggiomo, Silvia L A; Seymour, Jamie E

    2012-09-01

    An investigation into the cardiotoxic effects in human cardiomyocytes of different fractions (as produced from an FPLC) of the venom from Chironex fleckeri showed that whole venom caused cardiac cell death in minutes, measured as cell detachment using xCELLigence technology. However, only one fraction of the venom was responsible for this effect. When all extracted venoms were recombined a similar result was seen for the toxic fraction, however these effects were slower than unfractionated venom alone even though the concentrations were similar. The difference in the results between fractioned and unfractionated venom may have been caused by compounds remaining in the FPLC column, which may interact with the toxic fraction to cause rapid cell detachment or death.

  16. Cardio-Oncology: An Update on Cardiotoxicity of Cancer-Related Treatment.

    Science.gov (United States)

    Lenneman, Carrie G; Sawyer, Douglas B

    2016-03-18

    Through the success of basic and disease-specific research, cancer survivors are one of the largest growing subsets of individuals accessing the healthcare system. Interestingly, cardiovascular disease is the second leading cause of morbidity and mortality in cancer survivors after recurrent malignancy. This recognition has helped stimulate a collaboration between oncology and cardiology practitioners and researchers, and the portmanteau cardio-oncology (also known as onco-cardiology) can now be found in many medical centers. This collaboration promises new insights into how cancer therapies impact cardiovascular homeostasis and long-term effects on cancer survivors. In this review, we will discuss the most recent views on the cardiotoxicity related to various classes of chemotherapy agents and radiation. We will also discuss broadly the current strategies for treating and preventing cardiovascular effects of cancer therapy.

  17. 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

    that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities......BACKGROUND: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly......, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines. Results and recommendations: Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment...

  18. Detection of adriamycin cardiotoxicity with indium-111 labeled antimyosin monoclonal antibody imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takehiko; Matsumori, Akira; Tamaki, Nagara; Morishima, Shigeru; Watanabe, Yuji; Yonekura, Yoshiharu; Endo, Keigo; Konishi, Junji; Kawai, Chuichi (Kyoto Univ. (Japan). Faculty of Medicine)

    1991-04-01

    Myocardial imaging with indium-111 labeled antimyosin monoclonal antibody (antimyosin imaging) has been reported to be useful in the noninvasive detection of myocardial cell necrosis in dilated cardiomyopathy as well as in myocardial infarction and myocarditis. We used antimyosin imaging to detect myocardial damage in 2 patients with malignant lymphoma in whom adriamycin cardiotoxicity was suspected. Patients were injected with 74 MBq of indium-111 labeled antimyosin (Fab. fraction). Forty-eight hours later, planar imaging and single-photon emission computed tomography were performed using a gamma camera with a medium energy general purpose collimator. Antimyosin imaging demonstrated diffuse myocardial uptake not only in one patient with congestive heart failure but also in another patient at the early stage without congestive heart failure. Antimyosin imaging may be a sensitive method for noninvasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease. (author).

  19. 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.

  20. Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

    Science.gov (United States)

    Varghese, Mathews V; Abhilash, M; Paul, M V Sauganth; Alex, Manju; Nair, R Harikumaran

    2017-04-01

    Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.

  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. Development of a CART Model to Predict the Synthesis of Cardiotoxic Daunorubicinol in Heart Tissue Samples From Donors With and Without Down Syndrome.

    Science.gov (United States)

    Hoefer, Carrie C; Blair, Rachael Hageman; Blanco, Javier G

    2016-06-01

    Daunorubicin (DAUN) and doxorubicin (DOX) are used to treat a variety of cancers. The use of DAUN and DOX is hampered by the development of cardiotoxicity. Clinical evidence suggests that patients with leukemia and Down syndrome are at increased risk for anthracycline-related cardiotoxicity. Carbonyl reductases and aldo-keto reductases (AKRs) catalyze the reduction of DAUN and DOX into cardiotoxic C-13 alcohol metabolites. Anthracyclines also exert cardiotoxicity by triggering mitochondrial dysfunction. In recent studies, a collection of heart samples from donors with and without Down syndrome was used to investigate determinants for anthracycline-related cardiotoxicity including cardiac daunorubicin reductase activity (DA), carbonyl reductase/AKRs protein expression, mitochondrial DNA content (mtDNA), and AKR7A2 DNA methylation status. In this study, the available demographic, biochemical, genetic, and epigenetic data were integrated through classification and regression trees analysis with the aim of pinpointing the most relevant variables for the synthesis of cardiotoxic daunorubicinol (i.e., DA). Seventeen variables were considered as potential predictors. Leave-one-out-cross-validation was performed for model selection and to estimate the generalization error. The classification and regression trees analysis model and variable importance measures suggest that cardiac mtDNA content, mtDNA(4977) deletion frequency, and AKR7A2 protein content are the most important variables in determining DA.

  3. Dietary phytoestrogens present in soy dramatically increase cardiotoxicity in male mice receiving a chemotherapeutic tyrosine kinase inhibitor.

    Science.gov (United States)

    Harvey, Pamela Ann; Leinwand, Leslie Anne

    2015-01-05

    Use of soy supplements to inhibit cancer cell growth is increasing among patients due to the perception that phytoestrogens in soy inhibit carcinogenesis via induction of apoptosis. Genistein, the most prevalent phytoestrogen in soy, is a potent endocrine disruptor and tyrosine kinase inhibitor (TKI) that causes apoptosis in many cells types. Chemotherapeutic TKIs limit cancer cell growth via the same mechanisms. However, TKIs such as Sunitinib cause cardiotoxicity in a significant number of patients. Molecular interactions between Sunitinib and dietary TKIs like genistein have not been examined in cardiomyocytes. Significant lethality occurred in mice treated with Sunitinib and fed a phytoestrogen-supplemented diet. Isolated cardiomyocytes co-treated with genistein and Sunitinib exhibited additive inhibition of signaling molecules important for normal cardiac function and increased apoptosis compared with Sunitinib alone. Thus, dietary soy supplementation should be avoided during administration of Sunitinib due to exacerbated cardiotoxicity, despite evidence for positive effects in cancer.

  4. Study of the cardiotoxicity of Venenum Bufonis in rats using an 1H NMR-based metabolomics approach.

    Directory of Open Access Journals (Sweden)

    Ge Dong

    Full Text Available Venenum Bufonis, a well-known traditional Chinese medicine, has been widely used in Asia and has gained popularity in Western countries over the last decade. Venenum Bufonis has obvious side effects that have been observed in clinical settings, but few studies have reported on its cardiotoxicity. In this work, the cardiotoxicity of Venenum Bufonis was investigated using a 11H NMR-based metabolomics approach. The 1H NMR profiles of the serum, myocardial extracts and liver extracts of specific-pathogen-free rats showed that Venenum Bufonis produced significant metabolic perturbations dose-dependently with a distinct time effect, peaking at 2 hr after dosing and attenuating gradually. Clinical chemistry, electrocardiographic recordings, and histopathological evaluation provided additional evidence of Venenum Bufonis-induced cardiac damage that complemented and supported the metabolomics findings. The combined results demonstrated that oxidative stress, mitochondrial dysfunction, and energy metabolism perturbations were associated with the cardiac damage that results from Venenum Bufonis.

  5. Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals.

    Science.gov (United States)

    Hussein, Asmma; Ahmed, Amany A E; Shouman, Samia A; Sharawy, Sabry

    2012-06-01

    Cisplatin is a potent chemotherapeutic agent with a wide range of activities. Nephrotoxicity and cardiotoxicity represent it's major complication upon clinical use. The present study was carried out to evaluate the possible protective effect of DL-α-lipoic acid (LA) against cisplatin-induced nephrotoxicity and cardiotoxicity. Different groups of rats (n = 10) were administered either saline (control), cisplatin (10 mg/kg, i.p.), LA (100 mg/kg, i.p.) or their combination (LA 30 min prior to cisplatin administration). Twenty-four hours later all animals were decapitated and sera were used for estimation of activities of urea (BUN), creatinine (Cr), lactate dehydrogenase (LDH), and creatine kinase (CK). Homogenates of the kidney and heart were used for estimation of oxidative stress markers (reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO)). Additionally, caspase-3 activities and DNA-fragmentation were investigated in renal tissues. The results showed that cisplatin produced significant elevation in serum activities of LDH, CK, BUN, and Cr and also induced significant elevation in the oxidative stress makers (MDA and NO) accompanied by significant reduction in GSH and SOD in both kidney and heart. The integrity of DNA was heavily damaged and caspase-3 was activated in renal tissues. The results emphasized nephrotoxicty and cardiotoxicity of cisplatin. On the other hand, prior administration of LA significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters and protected both kidney and heart tissues. The histopathological examination emphasized the obtained results. In conclusion, LA is suggested to be a potential candidate to ameliorate cisplatin-induced nephrotoxicity and cardiotoxicity without altering the antitumor efficacy of cisplatin.

  6. High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device.

    Science.gov (United States)

    Kim, Min Jung; Lee, Su Chul; Pal, Sukdeb; Han, Eunyoung; Song, Joon Myong

    2011-01-07

    Drug-induced cardiotoxicity or cytotoxicity followed by cell death in cardiac muscle is one of the major concerns in drug development. Herein, we report a high-content quantitative multicolor single cell imaging tool for automatic screening of drug-induced cardiotoxicity in an intact cell. A tunable multicolor imaging system coupled with a miniaturized sample platform was destined to elucidate drug-induced cardiotoxicity via simultaneous quantitative monitoring of intracellular sodium ion concentration, potassium ion channel permeability and apoptosis/necrosis in H9c2(2-1) cell line. Cells were treated with cisapride (a human ether-à-go-go-related gene (hERG) channel blocker), digoxin (Na(+)/K(+)-pump blocker), camptothecin (anticancer agent) and a newly synthesized anti-cancer drug candidate (SH-03). Decrease in potassium channel permeability in cisapride-treated cells indicated that it can also inhibit the trafficking of the hERG channel. Digoxin treatment resulted in an increase of intracellular [Na(+)]. However, it did not affect potassium channel permeability. Camptothecin and SH-03 did not show any cytotoxic effect at normal use (≤300 nM and 10 μM, respectively). This result clearly indicates the potential of SH-03 as a new anticancer drug candidate. The developed method was also used to correlate the cell death pathway with alterations in intracellular [Na(+)]. The developed protocol can directly depict and quantitate targeted cellular responses, subsequently enabling an automated, easy to operate tool that is applicable to drug-induced cytotoxicity monitoring with special reference to next generation drug discovery screening. This multicolor imaging based system has great potential as a complementary system to the conventional patch clamp technique and flow cytometric measurement for the screening of drug cardiotoxicity.

  7. QT dispersion and prognostication of the outcome in acute cardiotoxicities: A comparison with SAPS II and APACHE II scoring systems.

    Science.gov (United States)

    Hassanian-Moghaddam, Hossein; Amiri, Hassan; Zamani, Nasim; Rahimi, Mitra; Shadnia, Shahin; Taherkhani, Maryam

    2014-06-01

    We aimed to evaluate the efficacy of QT dispersion (QTD) in determining the outcome of the patients poisoned by cardiotoxic medications and toxins. Patients who referred to our emergency department (ED) due to acute toxicity with any cardiotoxic medication or toxin and were admitted to medical toxicology intensive care unit (MTICU) were enrolled into the study. A questionnaire containing the demographic characteristics, vital signs, laboratory tests, electrocardiographic (ECG) parameters of the first ECG taken on MTICU or ED admission, simplified acute physiology score (SAPS), and acute physiology and chronic health evaluation (APACHE) score was filled for every single patient. QTD was manually calculated. The patients were divided into two groups of survivors and non-survivors and compared. Although QTD was not significantly different between the survivors and non-survivors (P = 0.8), SAPS II and APACHE II score were so. SAPS and APACHE had the highest sensitivity and specificity in determining the patients' mortality, respectively. SAPS had the highest sensitivity, and QTD had the highest specificity in predicting the later development of the complications. SAPS II and APACHE II scoring systems are the best systems for prognostication of death in patients with acute cardiotoxic medication-induced poisonings. QTD can be successfully used for the prediction of complications.

  8. 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

  9. [Myocardial infarction and anabolic steroid use. A case report].

    Science.gov (United States)

    Godon, P; Bonnefoy, E; Guérard, S; Munet, M; Velon, S; Brion, R; Touboul, P

    2000-07-01

    The potential cardiotoxicity of anabolic steroids is not well known. The authors report the case of a young man who was a top class body builder and who developed severe ischaemic cardiomyopathy presenting with an inferior wall myocardial infarction. The clinical history revealed prolonged and intensive usage of two types of anabolic steroids to be the only risk factor. This cardiotoxicity may be related to several physiopathological mechanisms: accelerated atherogenesis by lipid changes, increased platelet aggregation, coronary spasm or a direct toxic effect on the myocytes. The apparent scarcity of the reported clinical details in the literature is probably an underestimation of the consequences of this usage.

  10. Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice

    Science.gov (United States)

    Ibrahim, Abdelaziz E.; Abdel-Daim, Mohamed Mohamed

    2015-01-01

    Objective Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Materials and Methods Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. Results TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Conclusion Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity. PMID:25870843

  11. [Hypofractionated adjuvant radiotherapy for breast cancer: no signs of increased risk of cardiotoxicity].

    Science.gov (United States)

    Aleman, Berthe M P; van Leeuwen, Floor E

    2015-01-01

    Adjuvant radiotherapy is frequently used in women with breast cancer to improve both local control of the tumour and overall survival. Hypofractionated regimens are increasingly being used as they involve fewer treatment sessions and, in terms of tumour control, the effects of conventionally fractionated and hypofractionated radiotherapy seem to be comparable. However, there is concern regarding increased cardiotoxicity following hypofractionated radiotherapy treatment to the left side. In order to determine if cardiac mortality increases with hypofractionation relative to conventional fractionation, a Canadian research group performed a retrospective analysis in 5334 women with breast cancer treated between 1990-1998 with postoperative radiotherapy to the breast/chest wall only. At 15-year follow-up the authors concluded that cardiac mortality was not statistically different among patients with left-sided breast cancer whether treated with hypofractionated or conventionally fractionated whole breast/chest wall irradiation. This commentary discusses the data presented in the paper, puts them into perspective and describes the clinical implications.

  12. 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.

  13. Cardiotoxicity in rabbits after a low-level exposure to diazinon, propoxur, and chlorpyrifos.

    Science.gov (United States)

    Zafiropoulos, A; Tsarouhas, K; Tsitsimpikou, C; Fragkiadaki, P; Germanakis, I; Tsardi, M; Maravgakis, G; Goutzourelas, N; Vasilaki, F; Kouretas, D; Hayes, Aw; Tsatsakis, Am

    2014-12-01

    Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.

  14. Analysis of Cardiotoxicity from rh-Endostatin Therapy Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Jing Qin; Penghai Zhang; Xinyu Qian; Aimin Li; Rongcheng Luo; Dingli Xu

    2008-01-01

    OBJECTIVE To evaluate the cardotoxicity from recombinant human endostatin (rh-endostatin) combined with chemotherapy.METHODS A total of 12 cancer patients treated with rh-endostatin combined with chemotherapy were selected, and their clinical data collected. Their symptoms, including cardiopalmus,chest distress, dyspnea and changes in their electrocardiogram (ECG), myocardium enzymogram and left ventricular ejection fraction (LVEF), were observed during the drug treatment. These indicators were used for early diagnosis of cardiotoxicity.RESULTS Compared with a pre-therapeutic value, there was a significant increase in the CK-MB value at one week after startingthe treatment as well as at the end of treatment (P<0.05). There was a significant change in the ECG at the end of treatment,compared to a pre-therapeutic condition (P < 0.05), but there was no significant difference when comparing the pre- and post-therapeutic LVEF values.CONCLUSION It was recognized that mild cardiac adverse reactions exist in the regimen of recombinant human endostatin combined with chemotherapy. This therapy caused definite injury to the cardiac muscle, but cardiac functions were not obviously changed. CK-MB and ECG may be used as indicators for early monitoring cardiac toxicity. Vigilance against cardiac adverse reactions should be heightened during a course of rh-endostatin combined with chemotherapy.

  15. Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Toblli

    2014-01-01

    Full Text Available Since anthracycline-induced cardiotoxicity (AIC, a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM modulates the influence of iron deficiency anaemia (IDA and doxorubicin (3–5 mg per kg body weight [BW] on oxidative/nitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW, either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase, nitrosative stress (inducible nitric oxide synthase and nitrotyrosine, inflammation (tumour necrosis factor-alpha and interleukin-6, and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC.

  16. Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Abdelaziz E. Ibrahim

    2015-04-01

    Full Text Available Objective: Tilmicosin (TIL is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP administration against TIL-induced cardiotoxicity in mice. Materials and Methods: Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously. Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. Results: TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH, creatine kinase (CK, and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Conclusion: Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

    Directory of Open Access Journals (Sweden)

    Tania Martins-Marques

    2016-09-01

    Full Text Available Extracellular vesicles (EVs are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox, presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43 in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects.

  19. A Non-invasive Platform for Functional Characterization of Stem-Cell-Derived Cardiomyocytes with Applications in Cardiotoxicity Testing

    Directory of Open Access Journals (Sweden)

    Mahnaz Maddah

    2015-04-01

    Full Text Available We present a non-invasive method to characterize the function of pluripotent stem-cell-derived cardiomyocytes based on video microscopy and image analysis. The platform, called Pulse, generates automated measurements of beating frequency, beat duration, amplitude, and beat-to-beat variation based on motion analysis of phase-contrast images captured at a fast frame rate. Using Pulse, we demonstrate recapitulation of drug effects in stem-cell-derived cardiomyocytes without the use of exogenous labels and show that our platform can be used for high-throughput cardiotoxicity drug screening and studying physiologically relevant phenotypes.

  20. Protective effect of Emblica officinalis (amla) on isoproterenol-induced cardiotoxicity in rats.

    Science.gov (United States)

    Ojha, Shreesh; Golechha, Mahaveer; Kumari, Santosh; Arya, Dharamvir Singh

    2012-06-01

    Emblica officinalis, commonly known as amla, is an important medicinal plant reputed for its dietary and therapeutic uses. The aim of the present study was to investigate the protective role of E. officinalis against isoproterenol (ISP)-induced cardiotoxicity in rats and elucidate the possible mechanism involved. Rats were administered E. officinalis (100, 250 and 500 mg/kg, p.o.) or vehicle (normal saline) for 30 days, with concurrent subcutaneous injections of ISP (85 mg/kg, at 24 h interval) on 29th and 30th day. ISP-induced cardiac dysfunction as evidenced by decreased mean arterial pressure, heart rate, contractility (+LVdP/dt) and relaxation (-LVdP/dt) along with increased left ventricular end diastolic pressure. ISP significantly (p < 0.05) decreased antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase and myocyte-injury-specific marker enzymes, creatine phosphokinase-MB and lactate dehydrogenase in heart. A significant (p < 0.05) depletion of reduced glutathione and increase in thiobarbituric acid reactive substances along with histopathological alteration has further indicated the oxidative damage of myocardium. However, pretreatment with E. officinalis exhibited restoration of hemodynamic and left ventricular function along with significant preservation of antioxidants, myocytes-injury-specific marker enzymes and significant inhibition of lipid peroxidation. Furthermore, histopathological salvage of myocardium reconfirmed the protective effects of E. officinalis. Results of the present study demonstrate cardioprotective potential of E. officinalis attributed to its potent antioxidant and free radical scavenging activity as evidenced by favorable improvement in hemodynamic, contractile function and tissue antioxidant status.

  1. A Prospective Cohort Study on Cardiotoxicity of Adjuvant Trastuzumab Therapy in Breast Cancer Patients

    Science.gov (United States)

    Matos, Erika; Jug, Borut; Blagus, Rok; Zakotnik, Branko

    2016-01-01

    Background Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended. Objectives The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction. Methods In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab. Trastuzumab-related cardiac dysfunction was defined as a decline of ≥ 10% in left ventricular ejection fraction (LVEF). Results 92 patients (mean age, 53.6 ± 9.0 years) were included. Patients who developed trastuzumab-related LVEF decline ≥ 10% (20.6%) during treatment had significantly higher baseline LVEF (70.7 ± 4.4%) than those without (64.8 ± 5.5%) (p = 0.0035). All other measured baseline parameters (age, body mass index, arterial hypertension, level of NT-proBNP and other echocardiographic parameters) were not identified as significant. Conclusions Our findings suggest that baseline patient' characteristics, level of NT-proBNP and echocardiographic parameters, as long as they are within normal range, are not a reliable tool to predict early trastuzumab-related cardiac dysfunction in patients undergoing post-low dose anthracycline adjuvant trastuzumab therapy. A LVEF decline in patients with high-normal baseline level although statistically significant is not clinically relevant. PMID:27305108

  2. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property.

    Science.gov (United States)

    Naik, Suresh R; Thakare, Vishnu N; Patil, Snehal R

    2011-07-01

    The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

  3. Antihistamines modulate the integrin signaling pathway in h9c2 rat cardiomyocytes: Possible association with cardiotoxicity.

    Science.gov (United States)

    Yun, J S; Kim, S Y

    2015-08-01

    The identification of biomarkers for toxicity prediction is crucial for drug development and safety evaluation. The selective and specific biomarkers for antihistamines-induced cardiotoxicity is not well identified yet. In order to evaluate the mechanism of the life-threatening effects caused by antihistamines, we used DNA microarrays to analyze genomic profiles in H9C2 rat cardiomyocytes that were treated with antihistamines. The gene expression profiles from drug-treated cells revealed changes in the integrin signaling pathway, suggesting that cardiac arrhythmias induced by antihistamine treatment may be mediated by changes in integrin-mediated signaling. It has been reported that integrin plays a role in QT prolongation that may induce cardiac arrhythmia. These results indicate that the integrin-mediated signaling pathway induced by antihistamines is involved in various biological mechanisms that lead to cardiac QT prolongation. Therefore, we suggest that genomic profiling of antihistamine-treated cardiomyocytes has the potential to reveal the mechanism of adverse drug reactions, and this signal pathway is applicable to prediction of in vitro cardiotoxicity induced by antihistamines as a biomarker candidate.

  4. Protective effects of vitamin E and selenium against dimethoate-induced cardiotoxicity in vivo: biochemical and histological studies.

    Science.gov (United States)

    Amara, Ibtissem Ben; Soudani, Nejla; Hakim, Ahmed; Troudi, Afef; Zeghal, Khaled Mounir; Boudawara, Tahia; Zeghal, Najiba

    2013-11-01

    There is considerable interest in the study of free radical-mediated damage to biological systems due to pesticide exposure. However, there is a lack of consensus as to which determinations are best used to quantify future risks arising from xenobiotic exposure and natural antioxidant interventions. Our study investigated the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate cardiotoxicity induced by dimethoate. Female Wistar rats were exposed for 30 days either to dimethoate (0.2 g L⁻¹ of drinking water), dimethoate+selenium (0.5 mg kg⁻¹ of diet), dimethoate+vitamin E (100 mg kg⁻¹ of diet), or dimethoate+selenium+vitamin E. The exposure of rats to dimethoate promoted oxidative stress with a rise in malondialdehyde, advanced protein oxidation, and protein carbonyl levels. An increase of glutathione peroxidase, superoxide dismutase, and catalase activities was also noted. A fall in acetylcholinesterase and Na⁺ K⁺-ATPase activities, glutathione, nonprotein thiols, vitamins C and E levels was observed. Plasma levels of cholesterol, triglycerides, and low density lipoprotein-cholesterol increased and those of high density lipoprotein-cholesterol decreased. Coadministration of selenium or vitamin E to the diet of dimethoate-treated rats ameliorated the biochemical parameters cited above. The histopathological findings confirmed the biochemical results and the potential protective effects of selenium and vitamin E against cardiotoxicity induced by dimethoate.

  5. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Science.gov (United States)

    Wang, Min; Sun, Guibo; Wu, Ping; Chen, Rongchang; Yao, Fan; Qin, Meng; Luo, Yun; Sun, Hong; Zhang, Qiang; Dong, Xi; Sun, Xiaobo

    2013-01-01

    Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects. PMID:23662152

  6. Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Min Wang

    2013-01-01

    Full Text Available Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2 cells and human cervical cancer (HeLa cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects.

  7. 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.

  8. NT-proBNP as Early Marker of Subclinical Late Cardiotoxicity after Doxorubicin Therapy and Mediastinal Irradiation in Childhood Cancer Survivors

    Directory of Open Access Journals (Sweden)

    Amal Zidan

    2015-01-01

    Full Text Available Background. Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity. Aims of the Study. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP and tissue Doppler imaging (TDI as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation. Methods. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin’s lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. Results. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy. Conclusions. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.

  9. 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

    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...

  10. Subclinical Cardiotoxicity Detected by Strain Rate Imaging up to 14 months After Breast Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Erven, Katrien, E-mail: katrien.erven@uzleuven.be [Department of Radiotherapy, University Hospital Gasthuisberg, Leuven (Belgium); Iridium Cancer Network, Antwerp (Belgium); Florian, Anca [Department of Cardiology, University Hospital Gasthuisberg, Leuven (Belgium); Institute of Emergency for Cardiovascular Diseases, UMF “Carol Davila,” Bucharest (Romania); Slagmolen, Pieter [Medical Image Computing (ESAT/PSI), University Hospital Gasthuisberg, Leuven (Belgium); IBBT-KU Leuven Future Health Department, Leuven (Belgium); Sweldens, Caroline [Department of Radiotherapy, University Hospital Gasthuisberg, Leuven (Belgium); Jurcut, Ruxandra [Institute of Emergency for Cardiovascular Diseases, UMF “Carol Davila,” Bucharest (Romania); Wildiers, Hans [Department of Medical Oncology, University Hospital Gasthuisberg, Leuven (Belgium); Voigt, Jens-Uwe [Department of Cardiology, University Hospital Gasthuisberg, Leuven (Belgium); Weltens, Caroline [Department of Radiotherapy, University Hospital Gasthuisberg, Leuven (Belgium)

    2013-04-01

    Purpose: Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients. Methods and Materials: This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT. Results: Mean heart and left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (−17.5% ± 1.9% immediately after RT, −16.6% ± 1.4% at 8 months, and −17.7% ± 1.9% at 14 months vs −19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (−16.6% ± 2.3% immediately after RT, −16% ± 2.6% at 8 months, and −16.8% ± 3% at 14 months vs −19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected. Conclusions: In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical

  11. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Division of Drug Safety Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993 (United States); Moland, Carrie L.; Branham, William S. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); George, Nysia I. [Division Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2013-01-01

    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 B6C3F{sub 1} 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 B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

  12. Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

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    Coppola C

    2016-11-01

    Full Text Available Carmela Coppola,1 Gennaro Riccio,1 Antonio Barbieri,2 Maria Gaia Monti,3 Giovanna Piscopo,1 Domenica Rea,2 Claudio Arra,2 Carlo Maurea,1 Claudia De Lorenzo,4,5 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 2Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 3Department of Translational Medical Sciences, University Federico II, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy; 5CEINGE Biotecnologie Avanzate, Naples, Italy Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage.Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response.Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01. Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional

  13. Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

    Science.gov (United States)

    Yang, Hsiang-Yu; Ke, Hung-Yen; Hong, Gou-Jieng; Tsai, Yi-Ting; Lin, Chih-Yuan; Li, Chung-Yi; Tsai, Chien-Sung

    2009-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

  14. Progress of experimental research on cardiotoxicity of Chansu%蟾酥心脏毒性研究进展

    Institute of Scientific and Technical Information of China (English)

    李旻; 李华; 汪溪洁; 马璟

    2016-01-01

    近年来,人们对中药的不良反应日趋重视。蟾酥作为临床广泛应用和已知的具有心脏毒性的名贵中药,人们迫切希望明确其毒性机制以及与血药浓度的关系。蟾酥中主成分之一蟾蜍甾烯类物质的化学结构与地高辛类似,也属于强心苷类化合物。它具有兴奋和抑制心脏的双重效果,在低剂量时可兴奋心肌导致心动过速和快速心律失常,而在高剂量时可抑制心肌导致传导阻滞和缓慢心律失常。Na+-K+-ATP酶作为调节心肌能量和细胞内钙离子浓度的枢纽,蟾蜍甾烯类物质通过结合酶的α亚基可产生抑制作用,从而导致心肌细胞钙超载和能量紊乱,这可能是蟾酥心脏毒性的主要机制。本文分别从心脏毒性物质基础、整体动物实验、酶和离子通道、脂质代谢和离子稳态、药动学与心脏毒性的相关性等方面综述蟾酥心脏毒性的研究进展。%AS a result of a better understanding,people pay increasing attention to the adverse effect of traditional Chinese medicine. Chansu as a rare Chinese traditional medicine has been widely used in clinical treatment and known to have cardiotoxicity. The mechanism and relationships with blood drug concentrations need to be elucidated urgently. Bufadienolides,whose chemical structure is similar to that of digoxigenin,are the major component of Chansu and also belong to cardiac glycosides. They show both excitation and inhibition effects on the heart. Myocardial cells can not only be excited to trigger tachycardia and rapid arrhythmias at a low dose,but inhibited to induce heart block and slow arrhythmias at a high dose. As the key regulator of intracellular energy and calcium ion concentration , Na+/K+ATPase can be inhibited by bufadienolides through a combination of alpha subunits of the enzyme , resulting in calcium overload and energy disorders in myocardial cells. This might be the main mechanism of cardiotoxicity. In

  15. Rapid short term and gradual permanent cardiotoxic effects of vertebrate toxins from Chironex fleckeri (Australian box jellyfish) venom.

    Science.gov (United States)

    Chaousis, Stephanie; Smout, Michael; Wilson, David; Loukas, Alex; Mulvenna, Jason; Seymour, Jamie

    2014-03-01

    The vertebrate cardiotoxic components of the venom produced by the Australian box jellyfish, Chironex fleckeri, have not previously been isolated. We have uncovered for the first time, three distinct cytotoxic crude fractions from within the vertebrate cardiotoxic peak of C. fleckeri venom by monitoring viability of human muscle cells with an impedance based assay (ACEA xCELLigence system) measuring cell detachment as cytotoxicity which was correlated with a reduction in cell metabolism using a cell proliferation (MTS) assay. When the effects of the venom components on human cardiomyocytes and human skeletal muscle cells were compared, two fractions were found to specifically affect cardiomyocytes with distinct temporal profiles (labelled Crude Toxic Fractions (CTF), α and β). A third fraction (CTF-γ) was toxic to both muscle cell types and therefore not cardio specific. The vertebrate, cardio specific CTF-α and CTF-β, presented distinct activities; CTF-α caused rapid but short term cell detachment and reduction in cell metabolism with enhanced activity at lower concentrations than CTF-β. This activity was not permanent, with cell reattachment and subsequent increased metabolism of heart muscle cells observed when exposed to all but the highest concentrations of CTF-α tested. The cytotoxic effect of CTF-β took twice as long to act on the cells compared to CTF-α, however, the activity was permanent. Furthermore, we showed that the two fractions combined have a synergistic effect causing a much stronger and faster cell detachment (death) when combined than the sum of the individual effects of each toxin. These data presented here improves the current understanding of the toxic mechanisms of the Australian box jellyfish, C. fleckeri, and provides a basis for in vivo research of these newly isolated toxic fractions.

  16. Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.

    Science.gov (United States)

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Miguel-Carrasco, José L; Arias, José L; Arévalo, Miguel; Mate, Alfonso; Aramburu, Oscar; Vázquez, Carmen M

    2016-01-22

    Sunitinib (Su) is currently approved for treatment of several malignances. However, along with the benefits of disease stabilization, cardiovascular toxicities have also been increasingly recognized. The aim of this study was to analyze which mechanisms are involved in the cardiotoxicity caused by Su, as well as to explore the potential cardioprotective effects of l-carnitine (LC). To this end, four groups of Wistar rats were used: (1) control; (2) rats treated with 400mg LC/kg/day; (3) rats treated with 25mg Su/kg/day; and (4) rats treated with LC+Su simultaneously. In addition, cultured rat cardiomyocytes were treated with an inhibitor of nuclear factor kappa B (NF-κB), in order to examine the role of this transcription factor in this process. An elevation in the myocardial expression of pro-inflammatory cytokines, together with an increase in the mRNA expression of NF-κB, was observed in Su-treated rats. These results were accompanied by an increase in the expression of pro-fibrotic factors, nitrotyrosine and NOX 2 subunit of NADPH oxidase; and by a decrease in that of collagen degradation factor. Higher blood pressure and heart rate levels were also found in Su-treated rats. All these alterations were inhibited by co-administration of LC. Furthermore, cardiotoxic effects of Su were blocked by NF-κB inhibition. Our results suggest that: (i) inflammatory and fibrotic processes are involved in the cardiac toxicity observed following treatment with Su; (ii) these processes might be mediated by the transcription factor NF-κB; (iii) LC exerts a protective effect against arterial hypertension, cardiac inflammation and fibrosis, which are all observed after Su treatment.

  17. Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: A biochemical, histopathological, and immunohistochemical study.

    Science.gov (United States)

    Abdellatief, Suhair A; Galal, Azza A A; Farouk, Sameh M; Abdel-Daim, Mohamed M

    2017-02-01

    Cisplatin (cis-diamminedichloroplatinum, CDDP) is an effective DNA alkylating agent used in the treatment of different types of tumors; however, its clinical use is associated with hepato-cardiotoxicity. The current study was designed to assess the potential protective effect of parsley oil (PO) against CDDP-induced hepato-cardiotoxicity. For this purpose, 25 adult male rats were assigned into five groups, each containing five animals. Group I (control) was administered saline solution. Group II was administered PO at a dosage of 0.42ml/kg BW. Group III were administered CDDP at a dosage of 5mg/kg BW. Group IV was administered PO in addition to CDDP. Group V was administered saline solution in addition to CDDP, after which they were administered PO for five days. Oral administration of either saline solution or PO was performed each day for 10days, while administration of CDDP was via a single intraperitoneal injection five days following the commencement of the experiment. The recorded results revealed that CDDP induced obvious hepatic and cardiac injuries that were indicated by biochemical, histopathological, and immunohistochemical alterations, including elevation of serum hepatic and cardiac injury markers as well as proinflammatory cytokines. Moreover, CDDP induced an increase in the level of hepatic and cardiac injury biomarkers, decreases in the activities of antioxidant enzymes, a decrease in GSH concentration, and an increase in MDA concentration. CDDP also induced histopathological hepatocellular and myocardial changes, and overexpression of p53 and COX-2 in hepatic and cardiac tissues. Administration of PO either as a preventative medicine or as treatment significantly improved all the observed deleterious effects induced by CDDP in rat liver and heart. Thus, it may be concluded that PO, with its antioxidant, anti-inflammatory, and antiapoptotic activities, can potentially be used in the treatment of CDDP-induced hepatic and cardiac injuries.

  18. A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards.

    Science.gov (United States)

    Mordwinkin, Nicholas M; Burridge, Paul W; Wu, Joseph C

    2013-02-01

    Drug attrition rates have increased in past years, resulting in growing costs for the pharmaceutical industry and consumers. The reasons for this include the lack of in vitro models that correlate with clinical results and poor preclinical toxicity screening assays. The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. In this review, we discuss the use of pluripotent stem cell-derived cardiomyocytes for drug discovery and cardiotoxicity screening, as well as current hurdles that must be overcome for wider clinical applications of this promising approach.

  19. Changes in the levels of l-carnitine, acetyl-l-carnitine and propionyl-l-carnitine are involved in perfluorooctanoic acid induced developmental cardiotoxicity in chicken embryo.

    Science.gov (United States)

    Jiang, Qixiao; Wang, Chunbo; Xue, Chan; Xue, Lingfang; Wang, Meiting; Li, Changhao; Deng, Ziwen; Wang, Qian

    2016-12-01

    Perfluorooctanoic acid (PFOA), a persistent organic pollutant, is associated with developmental toxicity. This study investigated the mechanism of PFOA-induced developmental cardiotoxicity in chicken embryo, focusing on the interactions between developmental exposure to PFOA and the levels of l-carnitine (LC), acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC) in the heart. To evaluate the developmental cardiotoxicity, fertile chicken eggs were exposed to 0.1, 0.5, 1, 2 or 5mg/kg PFOA via air cell injection. Furthermore, exposure to 2mg/kg PFOA, with or without 100mg/kg LC were applied to investigate the effects of LC supplement. The results of functional and morphological assessments confirmed PFOA induced developmental cardiotoxicity in chicken embryo, which could be alleviated by co-exposure to LC. LC-MS/MS results also revealed remarkable decrease in LC, ALC and PLC levels in embryonic day six (ED6) chicken embryo hearts as well as LC level in embryonic day fifteen (ED15) chicken embryo hearts following developmental exposure to 2mg/kg PFOA. Meanwhile, co-exposure to 100mg/kg LC significantly elevated the levels of LC, ALC and PLC in chicken embryo hearts. Significantly elevated expression level of carnitine acetyltransferase (CRAT) in PFOA-exposed ED6 chicken embryo hearts was observed via western blotting, while LC co-exposure counteracted such changes. In conclusion, changes in the levels of LC, ALC and PLC in early embryonic stages are associated with PFOA induced developmental cardiotoxicity in chicken embryos.

  20. Antifungal miconazole induces cardiotoxicity via inhibition of APE/Ref-1-related pathway in rat neonatal cardiomyocytes.

    Science.gov (United States)

    Won, Kyung-Jong; Lin, Hai Yue; Jung, Soohyun; Cho, Soo Min; Shin, Ho-Chul; Bae, Young Min; Lee, Seung Hyun; Kim, Hyun-Jung; Jeon, Byeong Hwa; Kim, Bokyung

    2012-04-01

    Effects of miconazole, an azole antifungal, have not been fully determined in cardiomyocytes. We therefore identified the transcriptome in neonatal rat cardiomyocytes responding to miconazole using DNA microarray analysis and selected a gene and investigated its role in cardiomyocytes. Miconazole dose-dependently increased the levels of superoxide (O(2)(-)) and apoptosis in cardiomyocytes; these increases were inhibited by treatment with antioxidants. The DNA microarray revealed that 4163 genes were upregulated and 4829 genes downregulated by more than threefold in miconazole-treated cardiomyocytes compared with the vehicle-treated control. Moreover, redox homeostasis-, oxidative stress-, and reactive oxygen species (ROS)-related categories of genes were strongly affected by miconazole treatment. Among genes overlapped in all these categories, apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1), a redox-related gene, was prominent and was diminished in the miconazole-treated group. Changes in the O(2)(-) production and apoptosis induction in response to miconazole were inhibited in cardiomyocytes transfected with adenoviral APE/Ref-1. Overexpression of APE/Ref-1 reversed the reduction in beating frequency induced by miconazole. Our results demonstrate that miconazole may induce rat cardiotoxicity via a ROS-mediated pathway, which is initiated by the inhibition of APE/Ref-1 expression. This possible new adverse event in cardiomyocyte function caused by miconazole may provide a basis for the development of novel antifungal agents.

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

    Science.gov (United States)

    Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

    2013-04-01

    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-α, 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.

  2. 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.

  3. 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.

  4. 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.

  5. VARYING A V BLOCK COMPLICATING SNAKE BITE - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Vikas

    2014-02-01

    Full Text Available Snake venom toxicities comprise mainly bleeding disorders and nephrotoxicity. Cardiotoxicity is a rare manifestation of snake bite. We describe the case of a previously healthy 23 - year - old man who developed coagulopathy and AV node dysfunction following snake bite. Electrocardiography showed all variatio ns of AV conduction dysfunction . This is the first account of AV node dysfu nction caused by a snake bite with cardiotoxi city presenting as atrioventricular block

  6. Chewing the fat: A case report on intravenous lipid emulsion to reverse cardiotoxicity from intentional amitriptyline overdose.

    Directory of Open Access Journals (Sweden)

    J. Hellig

    2012-12-01

    Discussion: Toxicity was manifested as severe haemodynamic instability that did not respond to standard therapy, and was subsequently treated with intravenous fat emulsion (ILE therapy. The patient recovered with a survival to hospital discharge, neurologically intact.

  7. 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

  8. The Early Predictive Value of Right Ventricular Strain in Epirubicin-Induced Cardiotoxicity in Patients with Breast Cancer

    Science.gov (United States)

    Chang, Wei-Ting; Shih, Jhih-Yuan; Feng, Yin-Hsun; Chiang, Chun-Yen; Kuo, Yu Hsuan; Chen, Wei-Yu; Wu, Hong-Chang; Cheng, Juei-Tang; Wang, Jhi-Joung; Chen, Zhih-Cherng

    2016-01-01

    Background As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction. Methods A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale. Results Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (R2 = 0.8, p = 0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW were significantly impaired (-21.4 ± 4.12 vs. -16.94 ± 6.81%; -22.49 ± 4.97 vs. -16.86 ± 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose of epirubicin positively correlated with the development of dyspnea (R2 = 0.38, p = 0.04) and the decline of RVLS_FW (R2 = 0.53, p = 0.02). Notably, compared with the other echocardiographic parameters only RVLS_FW at the early stage (T2) significantly correlated with the development of dyspnea (odds ratio: 1.84, 95% confidence interval: 1.22-2.78, p = 0.04). Conclusions RVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival. PMID:27713603

  9. 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.

  10. Benefits of antihypertensive medications for anthracycline- and trastuzumab-induced cardiotoxicity in patients with breast cancer: Insights from recent clinical trials

    Directory of Open Access Journals (Sweden)

    Katarzyna Rygiel

    2016-01-01

    Full Text Available Advances in oncologic therapies have allowed many patients with breast cancer to achieve better outcomes and longer survival. However, this progress has been tempered by cardiotoxicity, associated with anticancer therapies, ranging from subclinical abnormalities to irreversible life-threatening complications, such as congestive heart failure or cardiomyopathy. In particular, exposure to chemotherapy (CHT, including anthracyclines and trastuzumab, can lead to cardiac dysfunction with short- or long-term consequences, among patients with breast cancer. The aim of this study is to highlight the potential role of commonly used cardiac medications in the prevention of anthracycline- and trastuzumab-mediated cardiotoxicity, in women with breast cancer, based on evidence from recent clinical trials. This overview is focused on the use of antihypertensive medications, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, outlining their cardioprotective effects in this patient population. In addition, the importance of biomarkers and modern imaging tests, as potential tools for detection and monitoring of cardiac dysfunction, induced by CHT, as well as some practical preventive and therapeutic strategies for cardio-oncology treatment teams, involved in the management of a growing number of women with breast cancer have been outlined. The content of this overview is based on a literature search of PubMed, within the last 5 years, mostly in relevance to the human epidermal growth factor receptor 2-positive patients with breast cancer, treated with anthracycline or trastuzumab therapy (in addition to surgery and/or radiation therapy [RT] regimen.

  11. Cardiotoxic and Arrhythmogenic Effects of Hemiscorpius lepturus Scorpion Venom in Rats

    Directory of Open Access Journals (Sweden)

    Khalil Pourkhalili

    2015-10-01

    Full Text Available Background: Envenomation by Hemiscorpius lepturus is not painful and the clinical manifestations include bloody urine due to hemoglobinuria or hematuria, dermonecrotic reactions,cardiac arrhythmia and in minority of cases acute renal failure which may lead to death following disseminated intravascular coagulation in infants. Cardiac effects of envenomation by H. lepturus venom including inotropic, chronotropic and arrhythmogenic properties are not studied as now in rat hearts with Langendorff apparatus.Methods: Rat hearts were allowed to equilibrate in its buffer and cardiotropic plus arrhythmogenic effects induced by injection of different doses of H. lepturus venom were detected and recorded by computer acquisition based data in Langendorff apparatus. The neutralizing effects of Razi Institute antivenom and autonomic drugs were assayed in parallel studies.Results: Hemiscorpius lepturus venom (25 μg/100 l treatment caused a negative inotropic (65.4 ± 3.2 versus 110.2 ± 3.4 and chronotropic effects (186.3 ± 4.2 versus 302 ± 6.3 in comparison to normal saline. Arrhythmogenic aspects including bradycardia, QRS widening and ST depression were induced by venom injection. Pre venom treatment (20 min of Razi Institute antivenom (10 μl neutralized cardiotropic effects but post venom injection (15 min later had no therapeutic role. Pre (10 min before and post (15 min after injection of adrenaline (10 μl neneutralized cardiotropic effects while pre venom injection (20 min of propanolol (10 μl had aggravating effects.Conclusion: Our study paves the way for further in vivo investigation of cardiovascular effects of this venom for finding suitable treatments instead of its ordinary antivenom medication in cardiogenic shock induced by the venom.

  12. 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

  13. Imatinib-induced decompensated heart failure in an elderly patient with chronic myeloid leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Hai-Hong Ran; Ran Zhang; Xue-Chun Lu; Bo Yang; Hui Fan; Hong-Li Zhu

    2012-01-01

    Because it is safe and well tolerated, imatinib is a standard first-line therapy for chronic myeloid leukemia (CML). Although there have been sporadic reports of imatinib-induced cardiotoxicity, including left ventricle (LV) dysfunction and heart failure, the evidence for it is contradictory. Here, we reported a case of an 88-year-old male patient with CML developed decompensated heart failure following imatinib therapy. Four days after the initiation of imatinib, the patient developed orthopnea, edema and a pleural effusion accompanied by abdominal distension, nausea and vomiting. The chest X-ray film showed an enlarged cardiac profile. The echocardiogram demonstrated a decreased LV ejection fraction and enlarged left-side cardiac chambers. B-type natriuretic peptide concentrations were markedly increased. The patient recovered soon after the withdrawal of imatinib and introduction of comprehensive therapy for heart failure. Imatinib-induced cardiotoxicity in elderly patients is a potentially serious complication that merits further evaluation.

  14. DHA derivatives of fish oil as dietary supplements: a nutrition-based drug discovery approach for therapies to prevent metabolic cardiotoxicity

    Science.gov (United States)

    Ma, Yonggang; Lindsey, Merry L.; Halade, Ganesh V.

    2014-01-01

    Introduction During the early 1970s, Danish physicians Jorn Dyerberg and colleagues observed that Greenland Eskimos consuming fatty fishes exhibited low incidences of heart disease. Fish oil is now one of the most commonly consumed dietary supplements. In 2004, concentrated fish oil was approved as a drug by the FDA for the treatment of hyperlipidemia. Fish oil contains two major omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). With advancements in lipid concentration and purification techniques, EPA- or DHA-enriched products are now commercially available, and the availability of these components in isolation allows their individual effects to be examined. Newly synthesized derivatives and endogenously discovered metabolites of DHA exhibit therapeutic utility for obesity, metabolic syndrome and cardiovascular disease. Areas covered This review summarizes our current knowledge on the distinct effects of EPA and DHA to prevent metabolic syndrome and reduce cardiotoxicity risk. Since EPA is an integral component of fish oil, we will briefly review EPA effects, but our main theme will be to summarize effects of the DHA derivatives that are available today. We focus on using nutrition-based drug discovery to explore the potential of DHA derivatives for the treatment of obesity, metabolic syndrome and cardiovascular diseases. Expert opinion The safety and efficacy evaluation of DHA derivatives will provide novel biomolecules for the drug discovery arsenal. Novel nutritional-based drug discoveries of DHA derivatives or metabolites may provide realistic and alternative strategies for the treatment of metabolic and cardiovascular disease. PMID:22724444

  15. Assessment of cardiotoxicity and effects of malathion on the early development of zebrafish (Danio rerio) using computer vision for heart rate quantification.

    Science.gov (United States)

    Simoneschi, Daniele; Simoneschi, Francesco; Todd, Nancy E

    2014-06-01

    Malathion, a common organophosphate insecticide, is a proven acetylcholinesterase inhibitor and is the most applied organophosphate insecticide in the United States. The use of zebrafish as a model to study the effects of pesticides on development is an innovative approach yielding relevant implications for determining the potential toxic effects of these pesticides on humans. In this study, a simple noninvasive technique was developed to investigate the cardiotoxicity of malathion on Danio rerio embryos, and to detect and quantify its effect on heart rate. Videos were recorded under a stereomicroscope and examined with our custom-made software (FishBeat) to determine the heart rate of the embryos. The pixel average intensity frequency (PI) of the videos was computed at its maximum probability to indicate the average number of heartbeats per second. Experimental observations successfully demonstrated that this method was able to detect the heart rate of zebrafish embryos as compared with manual stopwatch counting, with no significant difference. Embryos were treated acutely with increasing malathion concentrations (33.3 and 50 μg/mL malathion) at 52, 76, and 96 hpf. Embryos treated with 33.3 μg/mL malathion had significant bradycardia at 52 and 76 hpf, whereas embryos treated with 50 μg/mL malathion presented bradycardia at all hpf. These novel observations confirmed that malathion, acting as an acetylcholinesterase inhibitor, induced heartbeat irregularity in zebrafish embryos.

  16. [Takotsubo and surroundings. Step by step postpartum stress-induced cardiomyopathy shows its facet. A peculiar case of atypical takotasubo in the peripartum period].

    Science.gov (United States)

    Russo, Marco; Sappa, Roberta; Gianfagna, Enrico; Salame, Kareem; Sinagra, Gianfranco; Proclemer, Alessandro

    2014-01-01

    Takotsubo syndrome is an acquired cardiomyopathy with transient and reversible left ventricular dysfunction that can mimic an acute coronary syndrome. It is characterized by ECG abnormalities, including minimal ST-segment elevation and T-wave changes, mild troponin elevation, typical left ventricular regional wall motion abnormalities (apical ballooning) and atypical forms (midventricular or reverse apical ballooning) without significant coronary artery stenosis. Its etiology and pathophysiology remain unclear. The sympathetic system seems to play a central role: its exaggerated response to emotional or physical stress triggers may induce microvascular dysfunction and catecholamine-induced cardiotoxicity due to cyclic AMP-mediated calcium overload. We report our experience highlighting the possible pathophysiological and clinical overlap of emotional-triggered catecholamine cardiotoxicity, arterial hypertension and physiological cardiovascular overload in pregnancy describing an atypical case of takotsubo cardiomyopathy with diffuse left ventricular hypokinesia at onset and subsequent evolution to apical ballooning.

  17. Research progress on cardio-protective drug for preventing anthracycline cardiotoxicity%蒽环类药物心脏毒性防治药物研究进展

    Institute of Scientific and Technical Information of China (English)

    曲敬琨; 张佳; 张靖; 王健生

    2014-01-01

    Anthracyclines, which include doxorubicin, epirubicin, daunorubicin, and aclarubicin, are widely used chemotherapeu-tic agents for treating hematologic and solid tumors, such as acute leukemia, lymphoma, breast cancer, gastric cancer, soft tissue sarco-mas, and ovarian cancer. Anthracyclines can be combined with other chemotherapeutics and molecular targeted drugs for cancer treat-ment. The combination of anthracyclines with other chemotherapeutic drugs is usually the standard of first-line treatment. Anthracy-clines are efficacious and potent agents with broad antitumor effects. However, these drugs may cause adverse reactions, such as hair loss, myelotoxicity, and cardiotoxicity. Hematopoietic stimulating factors, such as granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin, can be used to control myelotoxicity. However, cardiotoxicity is the most serious anthracycline side effect. Clinical study results and practical observations indicate that the anthracycline cardiotoxicity is usually progressive and irreversible, especially after the first use of the drug, which may particularly cause heart damage. Therefore, the early detection and prevention of anthracy-cline-induced cardiotoxicity are important and have already gained considerable attention in clinical applications. Relevant experts from the China Society of Clinical Oncology and Hematology Branch of the Chinese Medical Association prepared the guidelines for the pre-vention and cure of anthracycline-induced cardiotoxicity in 2013. The authors reviewed the effective drugs currently used to prevent and cure anthracycline cardiotoxicity.%蒽环类药物包括阿霉素、表阿霉素、柔红霉素和阿克拉霉素等,广泛地用于治疗血液系统恶性肿瘤和实体肿瘤,如急性白血病、淋巴瘤、乳腺癌、胃癌、软组织肉瘤和卵巢癌等。蒽环类药物可以与其他化疗药物及分子靶向药物联合应用,以蒽环类药物为基础的联合治疗

  18. Toxic encephalopathy induced by capecitabine.

    Science.gov (United States)

    Niemann, B; Rochlitz, C; Herrmann, R; Pless, M

    2004-01-01

    Toxic encephalopathy is a rarely described side effect of 5-fluorouracil which usually presents with cerebellar, neuropsychiatric, and focal neurological symptoms. Magnetic resonance imaging findings are described as patchy white matter alterations. We report the 1st case of capecitabine-induced toxic encephalopathy with epilepsy-like symptoms and diffuse white matter alterations on magnetic resonance imaging.

  19. 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.

  20. Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

    Science.gov (United States)

    Vineetha, Vadavanath Prabhakaran; Girija, Seetharaman; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2014-03-01

    Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

  1. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression

    Directory of Open Access Journals (Sweden)

    Nagla A. El-Shitany

    2016-01-01

    Full Text Available The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1 control, (2 azithromycin, (3 azithromycin + carvedilol, and (4 azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β, tumor necrosis factor alpha (TNF-α, nuclear factor kappa beta (NF-κB, and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.

  2. 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.

  3. Successful usage of intravenous lipid emulsion in treatment of acute verapamil poisoning: A case report

    Directory of Open Access Journals (Sweden)

    Vuković-Ercegović Gordana

    2017-01-01

    Full Text Available Introduction. During the last few years, intravenous lipid emulsions have been effectively used in treatment of acute poisonings with lipophilic substances, including verapamil. Case report. A 37-year-old women presented 1 hour after ingestion of 2.8 g verapamil with hypotension and complete heart block. Because of the applied standard therapy failure and further patients impairment, Intralipid® 20% was used. Sinus rhythm was restored, arterial blood pressure increased and verapamile concentrations, both total and free decreased. Conclusion. Intravenous lipid emulsion can be important in treatment of severe acute intoxication and cardiotoxicity caused by verapamil.

  4. Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y. [Shimane Medical Univ., The Fourth Dept. of Internal Medicine, Izumo City, Shimane (Japan); Maruyama, R. [Shimane Medical Univ., Dept. of Laboratory Medicine, Izumo City, Shimane (Japan)

    2001-02-01

    Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

  5. Expression of the Cardiac Maintenance and Survival Factor FGF-16 Gene Is Regulated by Csx/Nkx2.5 and Is an Early Target of Doxorubicin Cardiotoxicity.

    Science.gov (United States)

    Wang, Jie; Jin, Yan; Cattini, Peter A

    2017-02-01

    The fibroblast growth factor (FGF) 16 gene (Fgf-16) is preferentially expressed by neonatal cardiomyocytes after birth, with levels increasing into adulthood. Null mice and isolated heart studies suggest a role for FGF-16 in cardiac maintenance and survival, including increased resistance to doxorubicin (DOX)-induced injury. However, the effect of DOX on endogenous FGF-16 synthesis and specifically regulation of cardiac Fgf-16 expression has not been reported. Here we assess the effect of DOX on FGF-16 RNA levels and stability as well as promoter activity and use sequence analysis, knockdown, and overexpression to investigate the role of cardiac transcription factor(s) implicated in the response. Endogenous FGF-16 RNA levels were reduced >70% in 8-week-old rats treated with 15 mg DOX/kg for 6 h. This was modeled in neonatal rat cardiomyocyte cultures, where an equivalent decrease was also seen within 6 h of 1 μM DOX treatment. Six kilobases of mouse Fgf-16 upstream flanking and promoter DNA was also assessed for DOX responsiveness in transfected cardiomyocytes. A decrease in FGF-16 promoter activity was seen with only 747 base pairs containing the Fgf-16 TATA box that includes a putative and highly conserved binding site for the cardiac transcription factor Csx/Nkx2.5. There was also no effect of DOX on FGF-16 RNA stability, consistent with transcriptional control. Levels and binding of Csx/Nkx2.5 to the FGF-16 promoter were reduced with DOX treatment. Knockdown of Csx/Nkx2.5 specifically decreased endogenous FGF-16 RNA and protein levels, whereas Csx/Nkx2.5 overexpression stimulated levels, and increased resistance to the rapid DOX-induced depletion of FGF-16. These observations indicate that Fgf-16 expression is directly regulated by Csx/Nkx2.5 in neonatal cardiomyocytes, and a negative effect of DOX on Csx/Nkx2.5 and, thus, endogenous FGF-16 synthesis may contribute indirectly to its cardiotoxic effects. Targeting FGF-16 levels could, however, offer

  6. The Cardiotoxicity of Terfenadine and Application Profile%特非那定的心脏毒性与国内外应用概况

    Institute of Scientific and Technical Information of China (English)

    毛璐; 王楠

    2012-01-01

    Objective The cardiotoxicity of Terfenadine and its application profile in the world were reviewed in this article. The references of clinical rational and safe use of the drug were provided. Methods We accessed relevant literature of Terfenadine withdrawal from the market in some countries and analysed the research on the cardiac toxicity of the drug, and summarized the application and adverse reactions of this drug in China. Results Analysis showed that Terfenadine has cardiac toxicity, when overdosed or increased blood concentration the adverse reaction was easy to happen. Although the drug was withdrawn or was restricted in use in the late 1990s, Terfenadine is still used in China as prescription drug, and the adverse reactions were reported in recent years. Conclusion The clinical adverse drug reactions should be alert. The dosage and combination drugs should be specified, in order to improve the safety and effectiveness for clinical medication.%目的 综述特非那定的心脏毒性与国内外应用概况,为临床安全、合理用药提供参考.方法 查阅国内外相关文献对特非那定在国内外上市及监管情况进行回顾并对其心脏毒性研究进展进行分析,对该药在我国的使用状况及出现的不良反应进行总结.结果 特非那定具有较为明确的心脏毒性,在过量或血药浓度增高时更为明显,该药于20世纪九十年代末在欧美等国家撤市或限制使用,目前在我国以处方药管理,也有相关的不良反应报道.结论 临床应警惕该药的不良反应,规范用药剂量及合并药物,提高临床用药的有效性和安全性.

  7. Oxidative Stress Mediates Doxorubicin-Induced Cardiotoxicity by Inhibiting Cystathionine-γ-Lyase%氧化应激通过抑制胱硫醚-γ-裂解酶介导阿霉素的心肌毒性

    Institute of Scientific and Technical Information of China (English)

    郑东诞; 冯鉴强; 王秀玉; 杨春涛; 莫利求; 兰爱平; 胡芬; 郭润民; 沈宁; 陈培熹

    2011-01-01

    目的 探讨氧化应激是否通过抑制胱硫醚-γ-裂解酶的表达及活性介导阿霉素的心肌毒性.方法 应用阿霉素处理大鼠胚胎H9c2心肌细胞以建立阿霉素心肌毒性的细胞模型.在阿霉素处理前60 min用活性氧清除剂N-乙酰半胱氨酸预处理H9c2心肌细胞以观察氧化应激在阿霉素心肌细胞损伤中的作用.应用CCK-8检测心肌细胞存活率;双氯荧光素酶染色及荧光显微镜照相术检测细胞内活性氧水平;Western blot检测胱硫醚-γ-裂解酶的表达;亚甲基蓝显色法检测胱硫醚-γ-裂解酶活性.结果 5 μmol/L阿霉素处理H9c2细胞24h引起明显的心肌毒性,使细胞存活率降低.阿霉素在促进细胞内活性氧生成的同时,还抑制胱硫醚-γ-裂解酶的表达及活性.N-乙酰半胱氨酸不仅抑制阿霉素对活性氧生成的促进作用,还减弱阿霉素的心肌毒性,并能阻断阿霉素对H9c2心肌细胞胱硫醚-γ-裂解酶表达及活性的抑制作用.结论 活性氧可通过抑制心肌细胞胱硫醚-γ-裂解酶的表达及活性介导阿霉素的心肌毒性.%Aim To explore whether oxidative stress mediates doxorubicin-induced cardiotoxicity by inhibiting cystathionine-γ-lyase ( CSE) expression and activity.MethodsH9c2 cells treated with doxorubicin were used as themodel of doxorubicin cardiototoxicity. H9c2 cells were pretreated with N-acetly-L-cysteine (NAC) 60 min prior to treatment with DOX so as to examine the role of oxidative stress in DOX-induced injury. Cell viability was measured by cell counter kit-8. The level of reactive oxygen species ( ROS) was tested by dichlorfluorescein staining and photofluorogra-phy. Expression of CSE was detected by Western blot assay. Activity of CSE was examined by methylene blue test assay. Results Exposure of H9c2 cells to 5 μmol/L doxorubicin induced significant cardiotoxicity, leading to a decrease in cell viability. Doxorubicin not only enhanced ROS generation, but also

  8. 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 <0.1 to 1.0 % and later (3-12 months) cardiomyopathy about 10 times less. Diagnosis rests on relatively nonspecific symptoms, 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.

  9. Maximizing the Benefit-Cost Ratio of Anthracyclines in Metastatic Breast Cancer: Case Report of a Patient with a Complete Response to High-Dose Doxorubicin

    Directory of Open Access Journals (Sweden)

    Kevin Shee

    2016-12-01

    Full Text Available Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2– mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit.

  10. Protective effects of oxymatrine on adriamycin-induced cardiotoxicity in rabbits and its mechanism%氧化苦参碱对兔阿霉素心肌损伤保护作用及其机制研究

    Institute of Scientific and Technical Information of China (English)

    马飞; 李小平; 顾建春; 章莉; 郑磊贞

    2009-01-01

    Objective To establish the in vivo models of adriamycin(ADR)-induced cardiotoxicity in rabbits, investigate the protective effect of oxymatrine (OMT) on ADR-induced cardiotoxicity, and explore the possible mechanism. Methods Twenty-six rabbits were randomly divided into ADR group (n=8, 2 mg/kg ADR), OMT group (n=5, 10 mg/kg OMT), ADR + OMT group (n=8, 10 mg/kg OMT was injected 30 min before ADR injection) and saline group (n=5, same quantity of normal saline), and rabbits in each group were infused with medicine or normal saline through ear marginal vein once a week for 8 weeks. The apoptosis of myocardial cells was detected by TUNEL methods, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) was determined. Results After treatment, the body weight of ADR group was significantly lower than that of the other groups(P < 0.05), the activity of SOD and GSH-Px significantly decreased and the apoptosis index (AI) was significantly higher than that of the other groups(P <0.01). There were similar while minor changes in ADR + OMT group. There was no significant adverse effects in OMT group. Conclusion OMT protects heart from adriamycin-induced injury in rabbits, which may relate to the decrease in level of antioxidant and apoptosis of myocardial cells.%目的 通过建立兔在体阿霉素(ADR)心肌损伤模型,研究氧化苦参碱(OMT)注射液对兔ADR损伤心肌功能的保护作用.并探索其可能机制.方法 26只新西兰大白兔随机分为4组,均经耳缘静脉缓慢注药,每周1次,共8周.①ADR组(n=8):注射2 mg/kg ADR;②OMT组(n=5):10 mg/kg OMT.③ADR+OMT组(n=8):每次注射ADR前30 min,先注射10 mg/kgOMT;④生理盐水(NS)组:以相同方法注射等量生理盐水.TUNEL法原位定性检测心肌细胞凋亡情况.心肌组织匀浆测定超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性.结果 ADR组用药后体质量明显低于其他组(P<0.05),SOD和GSH-Px活性明显降低(P<0.05),凋

  11. 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

  12. Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon and ribavirin treatment for chronic hepatitis C: case report and literature review

    Directory of Open Access Journals (Sweden)

    Wenxue Zhao

    2014-01-01

    Full Text Available Pegylated interferon alpha (Peg IFN-α in combination with ribavirin is the backbone of treatment in chronic hepatitis C (CHC. Cardiotoxicity due to interferon therapy is rare. The most frequent cardiovascular complications are arrhythmias and ischemic manifestations. Cardiomyopathy is extremely rare but can be life threatening. We present the case of a 41-year-old female patient with CHC in whom Peg IFN-α induced dilated cardiomyopathy and hypothyroidism. Chest radiography showed an enlarged and globular cardiac silhouette and pulmonary congestion. Echocardiography showed decreased left ventricular systolic function with an ejection fraction of 32% and fractional shortening of 15%. Cardiomyopathy had a complete remission after cessation of antiviral therapy with short-term heart failure medications and supportive care. Then we review the current literature about interferon induced cardiomyopathy in patients with HCV infection, as well as share our clinical experience in diagnosing and managing this rare complication.

  13. MicroRNAs regulatory networks in cardiotoxicity

    OpenAIRE

    2012-01-01

    A long time and many steps are needed to bring valuable drugs to patients. Drugs not only have to be effective against the disease which they are intended for, but also safe. All drugs cause toxic effects in proportion to the dose (Paracelsus, ca. XVI cent.). Therefore, assessing carefully the optimal dose at the desired benefit/risk ratio (Stevens and Baker, 2009) and characterizing mechanisms of toxicity are essential for maintaining high safety standards. The experimental strategies used t...

  14. Late cardiotoxicity after treatment for Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Aleman, Berthe M P; van den Belt-Dusebout, Alexandra W; De Bruin, Marie L;

    2007-01-01

    We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks...

  15. 超声药物透入疗法防治卡培他滨相关性手足综合征35例%Prevention and treatment of 35 cases with capecitabine hand-foot-related syndrome by ultrasound drug penetration therapy

    Institute of Scientific and Technical Information of China (English)

    闻飞飞; 赵美随

    2015-01-01

    目的:观察超声药物透入疗法预防及治疗卡培他滨所致手足综合征(hand foot s yndrom e , H FS)的疗效。方法:选取卡培他滨化疗患者共35例,35例均为经病理学或细胞学确诊的乳腺癌、结肠癌、胃癌患者。随机分为试验组18例和对照组17例。卡培他滨每日量为2500 mg/m2,分2次口服,连用14 d,休息7 d,21 d为1个周期。预防组18例,化疗同时运用超声药物透入仪导入维生素B6注射液,隔日1次。对照组17例,化疗同时给予维生素B6口服至化疗结束。结果:试验组18例患者中3例发生Ⅰ级手足综合征,发生率为16.7%,对照组手足综合征发生率为44.4%,两者有显著性差异(P<0.05)。结论:超声药物透入疗法可有效防治卡培他滨化疗所致手足综合征。%Objective:To investigate the effects of prevention and treatmentof ultrasound therapy drug penetration on capecitabine induced hand-footsyndrome (hand footsyndrome e, HFS) [1] . Methods:35 cases with capecitabine chemotherapy confirmed by pathology or cytology of breastcancer, colon cancer, stomach cancer were selected and randomly divided into an experimental group with 18 cases and a control group with 17 cases. The amountof capecitabine was 2500 mg/m2, twice orally, 14 days continuously, rest7 days, 21 days for a p eriod.18 pa tients in the prevention group were treated with ultrasound dru g pe netration i nstrumenti mported vi tamin B6 i njection, every other day, while 17 cases in the control group were treated with vitamin B6 oral chemotherapy until the end of chemotherapy. Results:3 cases among 18 patients in the experimental group occurredⅠgrade hand-footsyndrome, the rate was 16.7%, while thatin the control group hand-footsyndrome was 44.4%with significantdifference (P<0.05).Conclusion:Ultrasound drug penetration therapy can effectively control capecitabine chemotherapy induced hand-footsyndrome.

  16. [Acute oral suicidal intoxication with captan--a case report].

    Science.gov (United States)

    Chodorowski, Zygmunt; Sein Anand, Jacek; Waldman, Wojciech

    2004-01-01

    According to the best of our knowledge the second case of acute intoxication with captan was described. In this paper a 22-year old female was admitted to the Department of Toxicology with a nausea, weakness, numbness of upper limbs and substernal pain. She said that these symptoms began two hours after suicidal ingestion of 5.0 g of captan. At admission the patient was alert. Temperature was 37 degrees C, heart rate 100-120 b/min., BP 100-120/60-70 mm Hg and breathing rate 17/min. WBC were slightly elevated 12.4 x 10(3)/microl as well as the creatine kinase activity 329 U/L. ECG showed inversion of a T segment in V1-V4 leads. ECHO-sound made in 4th and 120th day after the onset of intoxication showed no changes, with EF--70%. Temporary increase of creatine kinase activity as well as the presence of inverted T segment in V1-V4 leads may suggest cardiotoxic effects of captan during acute intoxication.

  17. 四逆汤含药血清对心肌毒性大鼠乳鼠血清Bcl-2 Bax水平影响的研究%To Study of Effection of Blood Serum of Decoction for Treating Yang Exhaustion on Serum Baxand Bcl-2in Adriamycin Induced Cardio-toxicity in Myocardial Cell of Rat

    Institute of Scientific and Technical Information of China (English)

    王睿; 费洪新; 石小芳; 刘文华; 黄小义; 杨德助; 张腾腾

    2009-01-01

    目的:探讨四逆汤含药血清抗心肌毒性的疗效及其作用机制.方法:采用盐酸阿霉素(ADB)损伤Wistar大鼠乳鼠心肌导致心肌毒性为模型.随机分为正常组、心脏毒性ADR模型对照组、卡托普利组、四逆汤含药血清组.测定大鼠乳鼠血清Bcl-2、Bax水平,并应用光镜观察心肌组织的病理变化.结果:与正常组比较,阿霉素致心肌毒性大鼠乳鼠血清Bax水平显著降低.血清Bcl-2水平明显升高,四逆汤及卡托普利均能降低Bcl-2水平,升高Bax水平(P<0.05).光镜显示,四逆汤含药血清治疗组心肌细胞损伤程度明显低于模型组.结论:四逆汤含药血清能调节改善心肌毒性大鼠乳鼠的神经内分泌功能,拮抗过度激活的神经内分泌系统.%Objective:To explore the clinical effect and machenism of blood serum of decoction for treating yang ex-haustion on adriamycin induced cardio-toxicity in myocardial cell. Methods: Wistar rats were used to make cardio-toxicity in myocardial cell of rat model by injection of adriamyc into the peritoneum. The other 10 Wistar mrs were divided into the normal group. Model rats were randomly divided into model control group. Captopril group and blood serum of decoction for treating yang exhaustion group. Results : Compared with the normal group, serum baxlevel significantly decreased and Bcl -2level significantly increased. Compared with the model failure group, serum Bcl -2level significantly decreased and the level of baxsignificantly increased in the blood serum of decoction for treating yang exhaustion group and the Captopfil group(P < 0. 05). The degree of mycardial damage in the blood serum of decoction for treating yang exhaustion group was obviously lower than that in the model group. Conclusion: Blood senun of decoction for treating yang exhaustion can modify the nerval endocrine function of cardio - toxicity in myocardial cell failure rat and can antagonize the hyperactive nerval endocrine system.

  18. The First Case of Severe Takotsubo Cardiomyopathy Associated with 5-Fluorouracil in a Patient with Abnormalities of Both Dihydropyrimidine Dehydrogenase (DPYD) and Thymidylate Synthase (TYMS) Genes

    Science.gov (United States)

    Smith, Melissa; Maloney, Antonio

    2016-01-01

    5-Fluorouracil (5-FU) is the backbone of the chemotherapy regimens approved for treatment of many malignancies, especially colorectal cancer (CRC). The incidence of cardiotoxicity associated with 5-FU ranges between 1.5% to 18% and is most commonly manifested as anginal symptoms. Cardiomyopathy is very rarely reported with 5-FU and capecitabine. A 35-year-old Caucasian male with T3, N1, M0 rectal cancer after the initial neoadjuvant chemoradiation with 5FU/LV followed by surgical abdominoperineal resection (APR), began mFOLFOX6 in the adjuvant setting. Following the first treatment, he developed severe cardiomyopathy, with a drop in ejection fraction (EF) to 19% from normal. The cardiac workup showed no ischemic or other etiologies to explain this cardiac event. He was a nonsmoker and only occasionally drank alcohol. He had no previous or family history of heart disease and had normal cholesterol level. He was treated for severe congestive heart failure (CHF). When the patient presented to us for second opinion, we decided to examine him for dihydropyrimidine dehydrogenase (DPD) deficiency and thymidylate synthase (TYMS) polymorphism. The patient was found to be heterozygous for the c.85T>C mutation, resulting in reduced DPYD enzymatic activity and homozygous for TYMS 5’TSER genotype 2R/2R *f. Our group first identified and reported P453L (1358C>T) type DPYD germline mutation in a patient who developed 5-FU induced cardiotoxicity. In this paper, we describe the first case of cardiomyopathy related to DPD deficiency and homozygous polymorphism of TYMS in a patient with colon cancer following 5-FU containing regimen. Fluorouracil-related cardiomyopathy has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. The prospective testing for DPD deficiency in patients might prevent DPD-deficient patients from severe toxicity or even death, and therefore the development of a unified screening method is warranted. PMID:27752409

  19. Response to sorafenib after sunitinib-induced acute heart failure in a patient with metastatic renal cell carcinoma: case report and review of the literature.

    Science.gov (United States)

    Wong, Michael K K; Jarkowski, Anthony

    2009-04-01

    Cardiotoxicity is an emerging concern with a new class of drugs known as targeted agents, which include trastuzumab and sunitinib. Sunitinib is a small molecule that inhibits multiple tyrosine kinase receptors. This drug was approved by the United States Food and Drug Administration in 2006 for the treatment of clear cell metastatic renal cell carcinoma and advanced gastrointestinal stromal tumors. We describe a 65-year-old woman who was treated with sunitinib for metastatic clear cell renal cell carcinoma. After 5 months of therapy, she developed acute heart failure requiring hospitalization; sunitinib was immediately discontinued. The patient had classic symptoms of heart failure, including pleural effusion. An echocardiogram revealed a left ventricular ejection fraction of 30%. She received standard treatment for heart failure, including a beta-blocker, an angiotensin-converting enzyme inhibitor, and diuretics. Within 1 month, the patient's symptoms resolved, and subsequent cardiac evaluation showed that her left ventricular ejection fraction returned to normal. According to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute, her cardiac event associated with sunitinib was defined as grade III toxicity. One month later, sorafenib, another tyrosine kinase inhibitor, was started with the aim of continuing her previous response to sunitinib. After 7 months of sorafenib therapy, the patient had no evidence of heart failure, and her condition was responding to treatment. Clinicians should be aware that sunitinib-induced heart failure occurs occultly and that many--but not all--cases resolve with discontinuation of the drug. Use of sorafenib after sunitinib-induced heart failure appears to be safe and effective, which suggests that cardiotoxicity is not a general class effect of the tyrosine kinase inhibitors.

  20. Assurance Cases

    Science.gov (United States)

    2015-01-26

    2015 Carnegie Mellon University Assurance Cases Software Engineering Institute Carnegie Mellon University Pittsburgh, PA 15213 Charles B...1. REPORT DATE 26 JAN 2015 2. REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE Assurance Cases 5a. CONTRACT NUMBER 5b. GRANT NUMBER... Assurance Cases Charles B. Weinstock, January 2015 © 2015 Carnegie Mellon University Copyright 2015 Carnegie Mellon University This material is based upon

  1. 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...

  2. Late cardiotoxicity after treatment for a malignant bone tumor

    NARCIS (Netherlands)

    Postma, A; BinkBoelkens, MTE; BeaufortKrol, GCM; Kengen, RAM; Elzenga, NJ; SchasfoortvanLeeuwen, MJM; Kamps, WA; Schraffordt Koops, H.

    1996-01-01

    Cardiac function was assessed in longterm survivors of malignant bone tumors who were treated according to Rosen's T-5 or T-10 protocol, both including doxorubicin. Thirty-one patients, ages 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of

  3. 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...

  4. Trastuzumab (Herceptin)-associated cardiomyopathy presented as new onset of complete left bundle-branch block mimicking acute coronary syndrome: a case report and literature review.

    Science.gov (United States)

    Tu, Chung-Ming; Chu, Kai-Ming; Yang, Shin-Ping; Cheng, Shu-Mung; Wang, Wen-Been

    2009-09-01

    Trastuzumab (Herceptin) is well documented in reducing suffering and mortality from breast cancer. The clinically most important side effect of Herceptin is cardiotoxicity, which is reported in 2.6% to 4.5% of patients receiving trastuzumab alone and in as many as 27% of patients when trastuzumab is combined with an anthracycline in metastatic disease. We reported the case of a 50-year-old woman who presented to our emergency department (ED) because of chest pain and shortness of breath. On physical examination, holosystolic murmur over apex could be heard. Pulmonary and abdominal examinations were unremarkable. Twelve-lead electrocardiography showed sinus tachycardia and new onset of complete left bundle-branch block. Emergent transthoracic echocardiography revealed generalized hypokinesia of left ventricle and akinesia over interventricular septum and apex. She subsequently underwent immediate coronary angiography that revealed normal coronary angiography, and left ventriculogram revealed generalized hypokinesia with severe left ventricle dysfunction with ejection fraction of 33%. During right heart catheterization and endomyocardial biopsy, cardiac tamponade developed and was successfully relieved by pericardial window. She was discharged event-free 3 weeks later with conservative treatment. Although new onset of complete left bundle-branch block in a patient with chest pain may be acute coronary syndrome, careful review of medicine history is mandatory to avoid unnecessary procedure and complications.

  5. Dermatology case

    Directory of Open Access Journals (Sweden)

    Sandrina Carvalho

    2016-03-01

    Full Text Available Pilomatrixoma is a benign tumor of skin appendages with follicular differentiation most frequently found in children and adolescents, predominantly female. Clinically it is characterized by an erythematous-violaceous mobile nodule of hard consistency located on the head or neck. Although rare, multiple pilomatrixomas can be associated with other pathologies, particularly myotonic dystrophy or Steinert’s disease. In these cases, a prolonged follow-up should be maintained to rule out relapses and/or development of other diseases. We describe the case of a 9-year-old girl with multiple pilomatrixomas.

  6. 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...

  7. 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...

  8. 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...

  9. A Case for Case Report

    Directory of Open Access Journals (Sweden)

    Vivek Gharpure

    2010-11-01

    Full Text Available Evidence based medicine (EBM is becoming popular among clinicians and medical publishers; as clinical research is tested against the touchstone of EBM. Theory of Quality of Evidence, considers randomized controlled trials to be the best quality evidence, while case reports and expert opinions are considered at the lowest ebb

  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.

  11. Dermatology case

    Directory of Open Access Journals (Sweden)

    Catarina Dias

    2017-01-01

    Full Text Available Glomuvenous malformations, also known as glomangiomas, are tumor-like malformations or hamartomas of the glomus body. They can be sporadic or inherited as an autosomal dominant disease. Glomuvenous malformations tend to resemble hemangiomas. Clinical distinction between these entities is important due to their different therapeutic approaches. Surgical excision is the treatment of choice for isolated, painful glomuvenous malformations. We describe a case of a 7-year-old girl with multiple glomuvenous malformations.

  12. Dermatology case

    Directory of Open Access Journals (Sweden)

    Sandrina Carvalho

    2015-12-01

    and self-limiting dermatosis with characteristic clinical and histopathological pattern that justify its designation. It is characterized by annular or arciform erythematous plaques, preferably affecting the extensor surface of upper and lower limbs of younger patients. There are four main variants of granuloma annulare: localized, generalized, subcutaneous and perforating. In childhood, localized and subcutaneous forms are most commonly observed. We describe the case of a seven-year-old girl with localized granuloma annulare.

  13. Dermatology Case

    Directory of Open Access Journals (Sweden)

    Catarina Matos

    2017-01-01

    Full Text Available The authors describe a clinical case of a 5-months-old boy with widespread rash since the first month of life. Diffuse papular rash with intensive itching. The shaved skin was inconclusive so we performed biopsy to conÞ rm the diagnosis of scabies. It’s a dermatosis very contagious caused by the mite Sarcoptes scabiei var. hominis. In infants skin eruption may have a polymorphic presentation with characteristic distribution.

  14. Case04

    DEFF Research Database (Denmark)

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

    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...

  15. 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...

  16. Dermatology Case

    Directory of Open Access Journals (Sweden)

    Sandrina Carvalho

    2016-09-01

    Full Text Available Connective tissue nevus (CTN is a hamartomatous growth which can be associated to multiple syndromes, such as tuberous sclerosis, Buschke-Ollendorf syndrome, or Proteus syndrome. Familial cases of CTN have also been related to cardiac disease. Classically, CTN are characterized by asymptomatic, firm, multiple, skin-colored or yellowish plaques on the trunk or limbs, arising during childhood with no gender preference. A skin biopsy is usually necessary to confirm the diagnosis. Additional studies are oriented by signs or symptoms suggesting an underlying disease.

  17. 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.

  18. Dermatology case

    Directory of Open Access Journals (Sweden)

    Susana Vilaça

    2016-02-01

    Full Text Available Tinea corporis is a dermatophyte infection of the body. It usually begins as a pruritic circular or oval erythematous scaling patch or plaque that spreads centrifugally. Multiple lesions may run together to produce “flower petal” configurations. Tinea corporis contracted from infected animals is often intensely inflammatory. The history and clinical picture combination is characteristic, but the diagnosis could be confirmed by KOH (potassium hydroxide examination of scrapings from the lesions. Tinea corporis usually responds to the daily application of topical antifungals, but systemic therapy is needed in patients who have failed topical therapy. We report a case of a two -year old girl with tinea corporis of the vulvar region, initially misdiagnosed as irritant diaper dermatitis.

  19. Case study

    DEFF Research Database (Denmark)

    Milana, Marcella; Bernt Sørensen, Tore

    of several DHSs. Furthermore ?Udspil? was chosen for being a non-formal learning activity based on individual participation, even though linked to institutionalized learning practices, which were carried out in cooperation between several local institutions.Last but not least, the project represents...... that time Roskilde University Centre and Learning Lab Denmark, DK)3. The case here presented is based on results from research activity carried out over a 1 year period (spring 2006 - spring 2007). Detailed information concerning participation in the project was collected in two DHSs only: the Sports Day......Learning for democratic citizenship is embedded in the general popular education ideal(folkeoplysning), which is the primary source of inspiration for the Day High Schools (DHSs). DHSs are private institutions supported by local authorities, that host primarily low educated and unemployed young...

  20. Endoscopic case

    Directory of Open Access Journals (Sweden)

    Fernando Pereira

    2017-01-01

    Full Text Available We present the case of a ten-year-old female patient referred to Gastroenterolgy consultation for abdominal pain and cramping, usually worse after eating, recurring diarrhoea, hypochromic and microcytic anaemia with low serum iron and ferritin levels. Moderate to severe Crohn’s disease of the terminal ileum e right colon (L3 was diagnosed, based on endoscopic image and biopsy. The patient was treated with prednisone and azathioprine, but after one year of treatment she was steroids dependent and treatment was switched to infliximab. One year after beginning this treatment, the patient achieved remission (clinical and laboratorial parameters. A control colonoscopy showed mucosal healing with scars and deformation with stenosis of ileocecal valve (Figures 1-2. Surgical intervention will be probably necessary in near future.

  1. Case Study: Testing with Case Studies

    Science.gov (United States)

    Herreid, Clyde Freeman

    2015-01-01

    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 using case studies to test for knowledge or lessons learned.

  2. 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.

  3. 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...

  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. CASING DRILLING TECHNOLOGY

    OpenAIRE

    Nediljka Gaurina-Međimurec

    2005-01-01

    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-re...

  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. PSS Case Book

    DEFF Research Database (Denmark)

    Neugebauer, Line Maria; Mougaard, Krestine; Andersen, Jakob Bejbro;

    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.......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....

  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. Disaster Case Management

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Disaster Case Management Program (DCM) is a time-limited process that involves a partnership between a case manager and a disaster survivor (also known as a...

  12. Feasibibility study - cases

    DEFF Research Database (Denmark)

    Lund, Henrik; Hvelplund, Frede Kloster; Sukkumnoed, Decharut

    2004-01-01

    The chapter presents two case studies to show the tools of feasibiliy studies within the context of technological innovation.......The chapter presents two case studies to show the tools of feasibiliy studies within the context of technological innovation....

  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. Case Teaching and Evaluation

    Science.gov (United States)

    Patton, Michael Quinn; Patrizi, Patricia

    2005-01-01

    Experience and reflection on experience are the best teachers, yet rich cases that capture experience for reflection have largely eluded professional training in evaluation. The absence of high-quality, readily available teaching cases has been an important gap in the field. This article reviews the benefits of case teaching, examines evaluation…

  15. Portal cholangiopathy: case report

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Almeida Maia

    2014-01-01

    Full Text Available The present report describes the case of a child that after blunt abdominal trauma presented with portal thrombosis followed by progressive splenomegaly and jaundice. Ultrasonography and percutaneous cholangiography revealed biliary dilatation secondary to choledochal stenosis caused by dilated peribiliary veins, characterizing a case of portal biliopathy. The present case report is aimed at presenting an uncommon cause of this condition.

  16. Case study research.

    Science.gov (United States)

    Taylor, Ruth; Thomas-Gregory, Annette

    2015-06-10

    This article describes case study research for nursing and healthcare practice. Case study research offers the researcher an approach by which a phenomenon can be investigated from multiple perspectives within a bounded context, allowing the researcher to provide a 'thick' description of the phenomenon. Although case study research is a flexible approach for the investigation of complex nursing and healthcare issues, it has methodological challenges, often associated with the multiple methods used in individual studies. These are explored through examples of case study research carried out in practice and education settings. An overview of what constitutes 'good' case study research is proposed.

  17. Defining a periodontitis case

    DEFF Research Database (Denmark)

    Baelum, Vibeke; Lopez, Rodrigo

    2012-01-01

    of the 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....

  18. Haemospermia and 25 cases

    Directory of Open Access Journals (Sweden)

    Nikoubakht M

    1997-04-01

    Full Text Available During 3 years (1991-1994 25 cases were evaluated for hemospermia. 64% with primary management had improved. 36% that required more evaluation have at least one urologic problem in TRUS. Of these, adenocarcinoma of prostate, prostatic stone, seminal vesicle dilatation, each two cases, and verumontanum stone, urethral polyp, prostatic cyst each one case are diagnosed. According to this study the best method for evaluation of hemospermia is transrectal ultrasonography.

  19. 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…

  20. From Use Cases to Activity Cases

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2005-01-01

    Use cases can be used to capture requirements and to subdivide IT-systems into functionally coherent units. Information systems are activity systems that carry out important business activities. Many systems development methods recognize activity modeling as an important development activity. Use...

  1. 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

  2. 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...

  3. Examples and Case Studies

    NARCIS (Netherlands)

    Asbach, C.; Aguerre, O.; Bressot, C.; Brouwer, D.H.; Gommel, U.; Gorbunov, B.; Bihan, O. le; Jensen, K.A.; Kaminski, H.; Keller, M.; Koponen, I.K.; Kuhlbusch, T.A.J.; Lecloux, A.; Morgeneyer, M.; Muir, R.; Shandilya, N.; Stahlmecke, B.; Todea, A.M.

    2014-01-01

    Release of nanomaterials may occur during any stage of the life-cycle and can eventually lead to exposure to humans, the environment or products. Due to the large number of combinations of release processes and nanomaterials, release scenarios can currently only be tested on a case-by-case basis. Th

  4. 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.

  5. Objectivist case study research

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Fachner, Jörg

    2016-01-01

    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....

  6. 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...

  7. Muerte súbita en un corazón normal. Fibrilación ventricular idiopática: Revisión de la literatura a propósito de un caso Sudden death in a normal heart. Idiopathic ventricular fibrillation: Review of the literature concerning one case

    Directory of Open Access Journals (Sweden)

    J. García Fernández

    2003-04-01

    Full Text Available La fibrilación ventricular idiopática es aquella que se produce en ausencia de enfermedad cardíaca estructural y de otras causas identificables de fibrilación ventricular como cardiotoxicidad, alteraciones electrolíticas o predisposición hereditaria. Comentamos el caso de un varón sano de 37 años de edad asintomático hasta el día de su ingreso en el cual presentó múltiples episodios de fibrilación ventricular sin ningún desencadenante previo, no encontrándose en el estudio ninguna causa que lo justificase, implantándose finalmente un desfibrilador automático implantable. Comentamos los requisitos para su diagnóstico, la estratificación de riesgo y la utilidad de las pruebas utilizadas, así como los tratamientos propuestos.Idiopathic ventricular fibrillation is that which is produced in the absence of structural cardiac disease and of other identifiable causes of ventricular fibrillation such as cardiotoxicity, electrolytical alterations or hereditary predisposition. The case of a healthy male, aged 37, who was asymptomatic until the day he was admitted to hospital where he showed numerous episodes of ventricular fibrillation without any previous triggering, is discussed. In the examination no cause was found to explain this, and an automatic defibrillator was implanted. The requirements for its diagnosis, risk stratification and the usefulness of the tests employed, as well as the treatments proposed are discussed.

  8. 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...

  9. The Space for Case

    Science.gov (United States)

    Shafto, Michael

    1973-01-01

    Research supported by grants from the National Institute of Mental Health, the National Science Foundation, and the Educational Testing Service; examines the psychological validity of Fillmore's theory of case grammar. (DD)

  10. Case report: Perinephric lymphangiomatosis

    Directory of Open Access Journals (Sweden)

    Gorantla Rajani

    2010-01-01

    Full Text Available Perirenal lymphangiomatosis is a rare benign malformation of the lymphatic system. We report here a case of bilateral perirenal and parapelvic involvement with a normal excretory collecting system.

  11. Recent Case Law

    DEFF Research Database (Denmark)

    Petz, Thomas; Sagaert, Vincent; Østergaard, Kim

    2004-01-01

    In this section authors from various European countries report the recent case law in their country on the field of private patrimonial law, that is decisions on the law of property, juridical acts, the law of obligations, contract law and prescription. The European Review of Private Law (ERPL......) started this section in 2003. The section aims to give our readers an overview of what is happening in the most recent European case law. We have asked the national reporters to report the juridical essence of the decisions given by the highest courts in their country. These national reports...... not relate the facts of the decision, nor the personal opinion of the reporter. One can find discussions on the most important decisions of European courts in ERPL’s case note section. The recent case law section gives overviews of decisions published in periods of four months. The period of January...

  12. Parathyroid carcinoma: case report

    Science.gov (United States)

    STURNIOLO, G.; GAGLIANO, E.; TONANTE, A.; TARANTO, F.; PAPALIA, E.; CASCIO, R.; DAMIANO, C.; VERMIGLIO, F.; STURNIOLO, G.

    2013-01-01

    Summary: The authors present a case of parathyroid carcinoma in a patient with primary hyperparathyroidism. Following a literature review, the clinical and diagnostic profile, treatment and prognosis of this rare disease are discussed. PMID:23837957

  13. ACROMEGALY: A CASE REPORT

    OpenAIRE

    -()

    2015-01-01

    Acromegaly is a rare disease caused due to hyper secretion of growth hormone. Most of the cases of acromegaly are caused by pitutary adenoma which can be microadenoma or macroadenomas. These adenomas are never malignant, but can have significant morbidity and mortality. We report a 35 year old female patient presented herewith classical presentation of acromegaly with chief complain of weight gain, excessive sweating , widening of both hands and feet and was diagnosed as a case of acromega...

  14. Autoerotic deaths: four cases.

    Science.gov (United States)

    Cooke, C T; Cadden, G A; Margolius, K A

    1994-07-01

    We describe the circumstances and post mortem medical findings of 4 unusual fatalities where death occurred during autoerotic practice. Three cases occurred in young to middle-aged men--hanging, electrocution and inhalation of a zucchini. The manner of death in each was accidental. The fourth case was an elderly man who died of ischemic heart disease, apparently whilst masturbating with a vacuum cleaner and a hair dryer.

  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. Case for diagnosis

    OpenAIRE

    Calistru,Ana Maria; Lisboa, Carmen; Bettencourt, Herberto; Azevedo, Filomena

    2012-01-01

    Riga-Fede disease is a rare, benign disorder characterized by reactive ulceration of the oral mucosa associated with repetitive dental traumatism. It was first described in children with neurologic disorders and is very rare in adults. This case report describes the occurrence of a large ulcer of the tongue, resembling squamous cell carcinoma, in an adult with hemiparesis. The lesion cleared after neurologic recovery. This case highlights the importance of considering this disorder in the dif...

  17. 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

  18. 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.

  19. Writing of Patient Case History

    Institute of Scientific and Technical Information of China (English)

    Tian Junying

    2016-01-01

    This paper introduces the language features, structure and contents of case history. Good patient case history contributes to correct diagnosis and formulation of a treatment plan, therefore, it is important for physicians to learn how to write case history.

  20. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation.

    Science.gov (United States)

    Young, Amy C; Schwarz, Evan; Medina, Genevieve; Obafemi, Adebisi; Feng, Sing-Yi; Kane, Colin; Kleinschmidt, Kurt

    2012-09-01

    Synthetic cannabinoids have been popular recreational drugs of abuse for their psychoactive properties. Five of the many synthetic cannabinoids have been recently banned in the United States because of their unknown and potentially harmful adverse effects. Little is known about these substances. They are thought to have natural cannabinoid-like effects but have different chemical structures. Adverse effects related to synthetic cannabinoids are not well known. We provide clinical effects and patient outcome following K9 use. In addition, we briefly review synthetic cannabinoids. We present a 17-year-old adolescent boy with chest pain, tachycardia, and then bradycardia associated with smoking K9. Two synthetic cannabinoids, JWH-018 and JWH-073, were confirmed on laboratory analysis. In addition to the limited current data, we demonstrate harmful adverse effects related to toxicity of 2 synthetic cannabinoids. Further studies are needed.

  1. 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...

  2. 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.

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

    Science.gov (United States)

    Nascimento, Maria Carolina M O; Matsubara, Beatriz B; Matsubara, Luiz S; Correa, Camila R; Pereira, Elenize J; Moreira, Priscila L; Carvalho, Flavio A; Burini, Caio H; Padovani, Carlos R; Yeum, Kyung-Jin; Ferreira, Ana Lucia A

    2011-10-01

    The effect of pharmacological dose of α-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (α-tocopherol, n = 11) group. Animals received corn oil (C) or α-tocopherol dissolved in corn oil (250 mg α-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac α-tocopherol absorption at the end of the study period. As compared to the C group, α-tocopherol-supplemented group showed significantly (p rats.

  4. A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.

    Science.gov (United States)

    Chang, Sung-A; Lim, Byung-Kwan; Lee, You Jung; Hong, Mi-Kyung; Choi, Jin-Oh; Jeon, Eun-Seok

    2015-05-01

    Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.

  5. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

    Science.gov (United States)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (Pzinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (Pzinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (Pzinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation.

  6. Cardiotoxicity associated with the use of trastuzumab in breast cancer patients

    NARCIS (Netherlands)

    Perik, Patrick J.; de Korte, Maarten Alexander; van Veldhuisen, Dirk J.; Gietema, Jourik A.; Sleijfer, Dirk T.; de Vries, Elisabeth G. E.

    2007-01-01

    The monoclonal antibody against HER2, trastuzumab (Herceptin (R)), has become an important player in the treatment of patients with HER2-positive breast cancer. Both in the metastatic and adjuvant setting, the addition of trastuzumab to other systemic treatments has led to a striking increase in tum

  7. The mechanism underlying the cardiotoxic effect of the toxin from the jellyfish Chironex fleckeri.

    Science.gov (United States)

    Mustafa, M R; White, E; Hongo, K; Othman, I; Orchard, C H

    1995-08-01

    We have investigated the mechanisms underlying the cardiac effects of the toxin from the box jellyfish Chironex fleckeri. Papillary muscles isolated from the hearts of ferrets and ventricular myocytes isolated from the hearts of ferrets and rats were used. Force, intracellular [Ca2+], and membrane potential were monitored in the papillary muscles; contraction, intracellular [Ca2+], intracellular [Na+], and membrane currents were monitored in the isolated myocytes. Application of the toxin to these preparations resulted in a large increase in intracellular [Ca2+] and the adverse symptoms of Ca2+ overload (aftercontractions, spontaneous contractions, a decrease in developed force, and an increase in resting force). The response of papillary muscles to the toxin was not inhibited by blockers of Ca2+ or Na+ channels or by inhibitors of the sarcoplasmic reticulum, Na+/K+ ATPase, or Na+/H+ exchange. The response to the toxin was, however, blocked by prior exposure to a solution which contained no Na+ and by Ni2+. In the isolated myocytes, as well as an increase in intracellular [Ca2+], the toxin also caused an increase in intracellular [Na+] and the appearance of a current which was inward at negative potentials and reversed at about -10 mV. These data can be explained by the toxin increasing Na+ influx into the cell. The increase in intracellular [Na+] will then increase intracellular [Ca2+] via the Na+/Ca2+ exchange mechanism, thus producing the observed Ca2+ overload.

  8. 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.

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

    OpenAIRE

    2006-01-01

    Extracted venoms from two species of cubozoan, Chironex fleckeri (C. fleckeri)and 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 t...

  10. The role of nitric oxide in Doxorubicin-induced cardiotoxicity: experimental study.

    Science.gov (United States)

    Bahadır, Ayşenur; Kurucu, Nilgün; Kadıoğlu, Mine; Yenilme, Engin

    2014-03-01

    Amaç: Bu çalışmada sıçanlarda doksorubisinin (DOX) tek başına ve nitrik oksit sentaz (NOS) inhibitörleri ile birlikte kullanımının kalp kası üzerinde yarattığı hasar araştırıldı.Gereç ve Yöntemler: Çalışmada 12 haftalık 24 adet erkek “Sprague Dawley” sıçanı (ortalama ağırlık 262±18 gr) rastgele dört gruba (n=6) dağıtıldı. Grup I kontrol grubu olarak ayırıldı. Grup II’ye haftada bir kez intraperitoneal (ip) 3 mg/kg, beş hafta DOX uygulandı. Grup III’e DOX enjeksiyonundan 30 dakika önce ip 30 mg/kg L-NAME (nonselektif NOS inhibitörü) 5 hafta uygulandı. Grup IV’e DOX enjeksiyonundan 30 dakika önce ip 3 mg/kg L-NIL (indüklenebilir NOS inhibitörü) 5 hafta uygulandı. Çalışma süresince sıçanlar haftada iki kez tartıldı. Altıncı haftada kalbin sol ventrikülünden alınan parçalardan elektron ve ışık mikroskobik inceleme ve lipit peroksidasyonu tayini (malondialdehid) yapıldı. Plazma lipit peroksidasyonunun belirlenmesi amacı ile sıçanlardan kan alındı.Bulgular: Grup II, Grup III ve Grup IV’te kilo kaybı gözlendi. DOX uygulanan grupta istatistiksel olarak anlamlı kilo kaybı saptandı. Miyokard hasarı bulguları tek başına DOX alan hayvanlarda kontrol grubuna oranla daha yüksek oranda izlendi. DOX’le beraber L-NAME ve L-NIL verilen sıçanlarda kardiyotoksitenin histopatolojik bulguları kontrol grubundan farklı değildi. Plazma malondialdehid düzeyi DOX grubunda (9,3± 3,4), diğer tüm gruplara göre daha yüksek olarak ölçüldü. Sonuç: Bizim çalışmamızda DOX’la beraber NOS inhibitörleri uygulandığında DOX’a bağlı kardiyak toksisite bulgularında anlamlı azalma olduğu gösterilmiştir.

  11. Capparis spinosa reduces Doxorubicin-induced cardio-toxicity in cardiomyoblast cells

    Directory of Open Access Journals (Sweden)

    Seyed Hadi Mousavi

    2016-08-01

    Full Text Available Objective: Doxorubicin (DOX is an effective anticancer drug but its clinical application is limited because it induces apoptosis in cardiomyocytes and leads to permanent degenerative cardiomyopathy and heart failure possibly due to oxidative stress. Recent studies showed that Capparis spinosa (C. spinoseexhibits potent antioxidant activity. So, in this study, we explored the protective effect of hydro-alcoholic extract of C. spinosa against DOX-induced cytotoxicity in H9c2 cells. Materials and Methods: Cell viability was quantified by MTT assay. Apoptotic cells were determined using flow cytometry (sub-G1 peak evaluation of DNA fragmentation following PI staining. Cells were cultured with 5 μM DOX for 24 hr to induce cell damage. H9c2 cells were pretreated with different concentrations (6-200 μg/ml of C. spinosa extract for 4 hr before DOX treatment in all trials. Results:  Pretreatment with 25, 50, 100 and 200 µg/ml of C. spinosa could increase the viability of H9C2 cells to 72.63 ± 2.8% (p< 0.05, 77.37 ± 1.8% (p< 0.05, 83.56 ± 2.6% (p< 0.001 and 90.9 ± 0.5% (p< 0.001 of control, respectively. Also, C. spinosa decreased apoptotic induction significantly, at the doses of 50 µg/ml (p

  12. 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/[...

  13. 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.

  14. 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.

  15. 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.

  16. Case Studies in Biology.

    Science.gov (United States)

    Zeakes, Samuel J.

    1989-01-01

    A case study writing exercise used in a course on parasitology was found to be a powerful learning experience for students because it involved discipline-based technical writing and terminology, brought the students in as evaluators, applied current learning, caused interaction among all students, and simulated real professional activities. (MSE)

  17. Destroy The Bank! (case)

    NARCIS (Netherlands)

    Star, G.J. Van der; Maas, A.

    2016-01-01

    DZ Bank faces some significant challenges for the near future. One of them is the way payments are being made. This case is about Stefan, the Strategic Management Consultant of DZ Bank. He struggles with innovations and new technologies, such as Bitcoins. What does this mean for the future of the ba

  18. Case report 537: Chondroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Pignatti, G.; Nigrisoli, M.

    1989-05-01

    A case is reported of a 10-year-old girl who presented with pain in the left hip. Radiologically, a well-defined lytic lesion with a sclerotic border was present in the neck of the femur, with no epiphyseal involvement. The rarity of a metaphyseal site of origin of a chondroblastoma was stressed and the literature reviewed. (orig./GDG).

  19. [Renal leiomyoma. Case report].

    Science.gov (United States)

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  20. 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.

  1. [Thoracic actinomycosis: three cases].

    Science.gov (United States)

    Herrak, L; Msougar, Y; Ouadnouni, Y; Bouchikh, M; Benosmane, A

    2007-09-01

    Actinomycosis is a rare condition which, in the thoracic localisation, can mimic cancer or tuberculosis. We report a series of three case of thoracic actinomycosis treated in the Ibn Sina University Thoracic Surgery Unit in Rabat, Morocco. CASE N degrees 1: This 45-year-old patient presented a tumefaction on the left anterior aspect of the chest. Physical examination identified a parietal mass with fistulisation to the skin. Radiography demonstrated a left pulmonary mass. Transparietal puncture led to the pathological diagnosis of actinomycosis. The patient was given medical treatment and improved clinically and radiographically. CASE N degrees 2: This 68-year-old patient presented repeated episodes of hemoptysis. The chest x-ray revealed atelectasia of the middle lobe and bronchial fibroscopy demonstrated the presence of a bud in the middle lobar bronchus. Biopsies were negative. The patient underwent surgery and the histology examination of the operative specimen revealed pulmonary actinomycosis. The patient recovered well clinically and radiographically with antibiotic therapy. CASE N degrees 3: This 56-year-old patient presented cough and hemoptysis. Physical examination revealed a left condensation and destruction of the left lung was noted on the chest x-ray. Left pleuropulmonectomy was performed. Histological analysis of the surgical specimen identified associated Aspergillus and Actinomyces. The outcome was favorable with medical treatment. The purpose of this work was to recall the radiological, clinical, histological, therapeutic, outcome aspects of this condition and to relate the problems of differential diagnosis when can suggest other diseases.

  2. Nasal tooth: case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Si Hyun; Kim, Ji Hye; Hwang, Hee Young; Yang, Dal Mo; Kim, Hyung Sik; Park, Chol Heui [Gachon Medical School, Inchon (Korea, Republic of)

    2002-12-01

    Ectopic tooth is not uncommon and usually occurs in the palate and maxillary sinus. We report a case of ectopic tooth located in the nasal cavity, a rare site. The mass depicted by CT was highly attenuated, and central lucency was observed.

  3. [Ledderhose disease (case considerations)].

    Science.gov (United States)

    Bottinelli, N F

    1982-12-01

    After a preliminary note, the Author gives the casuistic survey of 30 patients, surgically treated during 12 years about. Moreover, a per cent analysis is done about the different possibilities of incidence of Ledderhose's disease in the cases considered. As a conclusion, the Author remembers the operative technique which gave the best results. Wide partial aponeurectomy.

  4. 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

  5. SCLERODERMA: A CASE REPORT*

    Directory of Open Access Journals (Sweden)

    Gülay Altan

    2015-04-01

    Full Text Available Scleroderma is an autoimmune connective tissue disorder which is characterized by fibrosis of visceral organs, skin and blood vessels. This condition can be localized or systemic. Its estimated prevalence is 250 cases in a million and it is more common in women than in men. Resorption of the mandibular angle and coronoid process can be observed in patients with scleroderma. Pressure of fibrous mucocutaneous tissues is thought to be the cause of the resorption. Decreased number of wrinkles due to sclerosis and distinct facial features because of the atrophy of ala nasi are among common clinical characteristics of this condition. The aim of this case report is to present a 40-year-old female patient with scleroderma who presented with signs of resorption at the angle of mandible, coronoid process, as well as widening of the periodontal space.

  6. The Case of CUL

    DEFF Research Database (Denmark)

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

    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....... management support. Keywords: pedagogical courses, faculty, organisation, managemental support......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...

  7. 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.

  8. Multiple pregnancy. Case report.

    Directory of Open Access Journals (Sweden)

    Práxedes Regla Rojas Quintana

    2009-11-01

    Full Text Available We present a case of a 34-year-old white female patient, of rural origins, with a history of 3rd degree bronchial asthma and respiratory arrests for that cause, who has required several admissions in the ICU. Gestation history 1, no deliveries, 1 abortion and secondary infertility, for which she was treated, along with her spouse, in the infertility consultation, in which ovulation disorders were diagnosed, consisting of bilateral tubaric obstruction on her and severe oligospermia on her spouse, for which they underwent combined surgical treatment. Tubaric permeability with hydrotubation was first accomplished, then ovulation and spermatogenesis with clomiphene citrate and then low-technology fertilization was performed, resulting in a quadruple pregnancy, which satisfactorily arrived to full term at 34 weeks of gestation. Due to the mother’s medical history, the risks involved in this type of pregnancy and its happy outcome, we decided to publish the case.

  9. ACROMEGALY: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    10.5958/2319-5886.2015.00183.6

    2015-10-01

    Full Text Available Acromegaly is a rare disease caused due to hyper secretion of growth hormone. Most of the cases of acromegaly are caused by pitutary adenoma which can be microadenoma or macroadenomas. These adenomas are never malignant, but can have significant morbidity and mortality. We report a 35 year old female patient presented herewith classical presentation of acromegaly with chief complain of weight gain, excessive sweating , widening of both hands and feet and was diagnosed as a case of acromegaly due to macroadenoma of pirtutary gland, on the basis of typical clinical features and hormonal parameters also radiological findings. Patient underwent transsphenoidal surgical resection of macroadenoma and recovered completely from the disease. Early recognition and diagnosis will help to avoid the complications of disease.

  10. Eagle syndrome: case report.

    Science.gov (United States)

    Uludağ, İrem Fatma; Öcek, Levent; Zorlu, Yaşar; Uludağ, Burhanettin

    2013-01-01

    Eagle syndrome is an aggregate of symptoms caused by an elongated styloid process, most frequently resulting in headache, facial pain, dysphagia and sensation of foreign body in throat. The proper diagnosis is not difficult with clinical history, physical examination and radiographic assessment if there is a sufficient degree of suspicion. The treatment is very effective. We report here a typical case of Eagle syndrome which was misdiagnosed as trigeminal neuralgia for many years and was treated with carbamazepine. We aim to point the place of Eagle syndrome in the differential diagnosis of facial pain. We also re-emphasize the usefulness of the three-dimensional computed tomography in the diagnosis of Eagle syndrome. Even though Eagle syndrome is a rare condition, in cases of facial pain refractory to treatment or unexplained complaints of the head and neck region, it should be considered in the differential diagnosis as it has therapeutic consequences.

  11. 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.

  12. Case report: Morgagni hernia.

    Science.gov (United States)

    Rogers, Frederick B; Rebuck, Jill A

    2006-03-01

    The case reported here is a 32-year-old man with a sudden onset of chest pain and an acute deterioration of lung function. An incarcerated Morgagni hernia was diagnosed with a computer tomographic CT scan, and repaired electively via a midline laparotomy. Morgagni hernia is a rare type of congenital diaphragmatic hernia, which may not be symptomatic until adulthood when the patient presents with acute symptoms or incarceration.

  13. Scleroderma. A case presentation.

    Directory of Open Access Journals (Sweden)

    Rubén Bembibre Taboada

    2005-08-01

    Full Text Available This article presents a brief review about generalized sclerosis (sclerodermia and reports a case with such disease talking into consideration that the patient received clinical intensive care assistaance and had a clinical diagnosis supoported by lab test for a clinical and differential diagnosis. Medical treatment was applied for the disease and for the possible complications, but the patients follow up was wrong due to multi organ failure as a consequence of derlying disease.

  14. Gastric syphilis - Case report*

    Science.gov (United States)

    Guimarães, Tais Ferreira; Novis, Camila Freitas Lobo; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Gastric syphilis is an uncommon extracutaneous manifestation of syphilis, occurring in less than 1% of patients, presenting nonspecific clinical manifestations. In general, it occurs on secondary stage. The critical point is the recognition of the syphilitic gastric involvement, without which there may be incorrect diagnosis of malignancy of the digestive tract. In this report, a case of secondary syphilis with gastric involvement that had complete remission with benzathine penicillin will be described. PMID:27828649

  15. LARYNGOCELE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Umakanth Goud

    2015-04-01

    Full Text Available Laryngoceles are rare, cystic dilatation of saccule of ventricle of larynx. Three types are recognized – internal, external and mixed types. Many of the laryngoceles are asymptomatic; few require surgical excision via internal/endoscopic or external approach. Contrast CT is the investigation of choice. A 40year old male presented to our OPD with a neck Scar, later diagnosed as laryngocele. Here is the case report about presentation, di agnosis and management of a large mixed layngocele.

  16. Combustible Cartridge Case Characterization

    Science.gov (United States)

    1984-02-01

    University (NYU) has resulted in the selection of two cross-linked melamine / formaldehyde acrylic styrene resin systems that can be used in the beater additive... melamine resin Akaradit II stabilizer 20. ABSTRACT (con) Test coupons of combustible cartridge case material were fabricated using these recommended...and agitated for 30 min before the pH was slowly lowered to 3 with p-toluene sulfonic acid. In order to maintain this pH in the felting tank, it was

  17. 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.

  18. Esthesioneuroblastoma A Case Report

    OpenAIRE

    Chadha, Snya; Pannu, Kulwant Kaur

    2011-01-01

    Esthesioneuroblastoma (ENB) also known as olfactory neuroblastoma is an uncommon malignant neoplasm arising in the roof of nasal cavity. It is now understood to originate from the olfactory epithelium. Case reports published worldwide have been very few. Common presenting symptoms of Esthesioneuroblastoma include nasal obstruction, epistaxis, facial pain, diplopia, proptosis, and anosmia. Apart from being locally aggressive, it metastasizes widely by both hematogenous and lymphatic routes.

  19. [Obstructive anuria. Thirty cases].

    Science.gov (United States)

    Bennani, S; Debbagh, A; Joual, A; el Mrini, M; Benjelloun, S

    1995-01-01

    The authors report 30 cases of obstructive anuria during the last fifteen years. The anuria was secondary to lithiasis in 60 per cent, in 26.6 per cent to pelvic cancer and in 13.4 per cent to retroperitoneal fibrosis. The diagnosis was facilitated by ultrasonography. Emergency treatment of obstructive anuria is based on urinary diversion by ureteral stent or by percutaneous nephrostomy under ultrasound control. Later the treatment depend of etiology.

  20. IPEX syndrome: Case report

    OpenAIRE

    Radlović Nedeljko; Janić Dragana; Sajić Silvija; Janković Srđa; Ješić Maja; Leković Zoran; Petrović Rada

    2008-01-01

    INTRODUCTION IPEX syndrome, namely, a hereditary (X-linked) immunodysregulation with autoimmune polyendocrinopathy and enteropathy, as the basic manifestations, presents a rare and exceptionally severe disease. It develops due to gene mutation responsible for the synthesis of a specific protein (FOXP3), which, by differentiation and activation of regular T-lymphocytic CD4+CD25+, has the key role in the induction and maintenance of the peripheral tolerance of one's own tissue. CASE OUTLINE We ...

  1. Cystosarcoma phyllodess. Case presentation

    Directory of Open Access Journals (Sweden)

    Lidia Torres Ajá

    2006-08-01

    Full Text Available A 12 year-old patient is presented, with tumor of the left breast of 11,7 cms, of quick growth, without another accompanying sintomatology, which was diagnosed as cystosarcoma phyllodess benign. In the twenty-five years of existence of our hospital, it is the first tumor phyllodes detected in girl, for that is considered a curious and interesting case that can enrich the experience of other professionals of the health.

  2. Malignant histiocytosis. Case report

    OpenAIRE

    RUIZ, OSCAR; Instituto de Investigaciones Clínicas, UNMSM; Servicio Hematologia Clínica, Hospital Dos de Mayo; QUIÑONES, WILLY; Servicio Hematologia Clínica, Hospital Dos de Mayo; MISAD, OSCAR; Laboratorio de Anatomia Patológica “Oscar Misad; Delgado, Carlos; Instituto de Investigaciones Clínicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú.; Ronceros, Sergio; Instituto de Investigaciones Clínicas, Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima, Perú. médico patólogo.; MARANGONI, MANUELA; Departamento de Enfermería, Hospital Dos de Mayo; BARDALES, LUZ; Servicio Hematologia Clínica, Hospital Dos de Mayo; REYES, RAFAEL; Servicio Hematologia Clínica, Hospital Dos de Mayo; CASTILLO, ALFREDO; Servicio Hematologia Clínica, Hospital Dos de Mayo; URRUTIA, KATIA; Servicio Hematologia Clínica, Hospital Dos de Mayo

    2013-01-01

    Fourteen year-old male patient referred from Huancayo who presented one month gastric intolerance, jaundice, fever and a lymph proliferative syndrome. Laboratory tests revealed severe pancytopenia due to phagocytosis. Haematologic and anatomy-pathology diagnosis was human malignant histiocytosis. We present this case due to its low frequency and the emergency character of the disease. Paciente varón de 14 años, procedente de Huancayo, que presenta un mes antes de su hospitalización intoler...

  3. OMC Compressor Case

    Science.gov (United States)

    Humphrey, W. Donald

    1997-01-01

    This report summarizes efforts expended in the development of an all-composite compressor case. Two pre-production units have been built, one utilizing V-CAP and one utilizing AFR-700B resin systems. Both units have been rig tested at elevated temperatures well above design limit loads. This report discusses the manufacturing processes, test results, and Finite Element Analysis performed. The V-CAP unit was funded by NASA-Lewis Research Center in 1994 under contract number NAS3- 27442 for Development of an All-Composite OMC Compressor Case. This contract was followed by an Air Force study in 1996 to build and identical unit using the AFR-700B resin system in place of the V-CAP system. The second compressor case was funded under U.S. Air Force contract F33615-93-D-5326, Advanced Materials for Aerospace Structures Special Studies (AMAS3), Delivery Order 0021 entitled "Advanced Polymeric Composite Materials and Structures Technology for Advanced High Temperature Gas Turbine Engines.' Initial studies using the V-CAP resin system were undertaken in 1993 under a NASA Lewis contract (NAS3-26829). A first prototype unit was developed in a joint program between Textron-Lycoming (now Allied Signal) and Brunswick (now Lincoln Composites). This unit included composite end closures using low density, high temperature molded end closures. The units was similar in size and shape to a titanium case currently used on the PT-21 0 engine and was funded as part of the integrated High Performance Turbine Engine Technology (EHPTET) initiative of DOD and NASA.

  4. 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....

  5. 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.

  6. Case report: pelvic actinomycosis.

    Science.gov (United States)

    Maxová, K; Menzlová, E; Kolařík, D; Dundr, P; Halaška, M

    2012-01-01

    A case of pelvic actinomycosis is presented. The patient is 42-year-old female with a 5 weeks history of pelvic pain. An intrauterine device (IUD) was taken out 3 weeks ago. There is a lump length 9 cm between rectus muscles. Ultrasound, magnetic resonance imaging (MRI) and histology are used to make the diagnosis. Actinomycosis can mimic the tumour disease. The definitive diagnosis requires positive anaerobic culture or histological identification of actinomyces granulas. A long lasting antibiotic therapy is performed.

  7. Case Study - Alpha

    Directory of Open Access Journals (Sweden)

    Stephen Leybourne

    2016-11-01

    Full Text Available This case study was developed from an actual scenario by Dr. Steve Leybourne of Boston University.  The case documents the historical evolution of an organization, and has been used successfully in courses dealing with organizational and cultural change, and the utilization of ‘soft skills’ in project-based management. This is a short case, ideal for classroom use and discussion.  The issues are easily accessible to students, and there is a single wide ranging question that allows for the inclusion of many issues surrounding strategic decision-making, and behavioural and cultural change. Alpha was one of the earlier companies in the USA to invest in large, edge-of-town superstores, with plentiful free vehicle parking, selling food and related household products. Alpha was created in the 1950s as a subsidiary of a major publicly quoted retail group.  It started business by opening a string of very large discount stores in converted industrial and warehouse premises in the south of the United States. In the early days shoppers were offered a limited range of very competitively priced products. When Alpha went public in 1981 it was the fourth largest food retailer in the US, selling an ever-widening range of food and non-food products.  Its success continued to be based on high volume, low margins and good value for money, under the slogan of ‘Alpha Price.’

  8. Boerhaave syndrome - case report

    Directory of Open Access Journals (Sweden)

    Biljana Radovanovic Dinic

    Full Text Available ABSTRACT CONTEXT: Boerhaave syndrome consists of spontaneous longitudinal transmural rupture of the esophagus, usually in its distal part. It generally develops during or after persistent vomiting as a consequence of a sudden increase in intraluminal pressure in the esophagus. It is extremely rare in clinical practice. In 50% of the cases, it is manifested by Mackler's triad: vomiting, lower thoracic pain and subcutaneous emphysema. Hematemesis is an uncommon yet challenging presentation of Boerhaave's syndrome. Compared with ruptures of other parts of the digestive tract, spontaneous rupture is characterized by a higher mortality rate. CASE REPORT: This paper presents a 64-year-old female patient whose vomit was black four days before examination and became bloody on the day of the examination. Her symptoms included epigastric pain and suffocation. Physical examination showed hypotension, tachycardia, dyspnea and a swollen and painful abdomen. Auscultation showed lateral crackling sounds on inspiration. Ultrasound examination showed a distended stomach filled with fluid. Over 1000 ml of fresh blood was extracted by means of nasogastric suction. Esophagogastroduodenoscopy was discontinued immediately upon entering the proximal esophagus, where a large amount of fresh blood was observed. The patient was sent for emergency abdominal surgery, during which she died. An autopsy established a diagnosis of Boerhaave syndrome and ulceration in the duodenal bulb. CONCLUSION: Boerhaave syndrome should be considered in all cases with a combination of gastrointestinal symptoms (especially epigastric pain and vomiting and pulmonary signs and symptoms (especially suffocation.

  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. 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...

  11. 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.

  12. Tracheobronchopathia osteochondroplastica: four cases

    Institute of Scientific and Technical Information of China (English)

    Dursun Tatar; Gunes Senol; Atike Demir; Gulru Polat

    2012-01-01

    Tracheobronchopathia osteochondroplastica (TO) is a rare and benign disorder of unknown cause affecting the large airways.It is characterized by the presence of multiple osseous and cartilaginous nodules in the submucosa of the trachea and main bronchi that is characterized by the progression of submucosal bone and/or cartilage including nodules through the lumen of trachea and bronchus.We present four cases that were diagnosed TO while investigating for the causes of hemoptysis and chronic cough.We plan to emphasize TO in differential diagnosis in proper patients.

  13. 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.

  14. 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.

  15. Hypertrophic pachymeningitis: case report

    Directory of Open Access Journals (Sweden)

    Deus-Silva Leonardo de

    2003-01-01

    Full Text Available Hypertrophic pachymeningits is an unusual cause of neurological symptoms and is often secondary to infections, carcinomatosis or inflammatory diseases. It may also be idiopathic. We report a case of pachymeningitis which was manifested primarily by psychosis and visual loss with optic atrophy and destruction of nasal septum. The patient, a 45 year old woman was submitted to extensive investigation without evidence of any underlying disease. A meningeal biopsy was performed and showed a mostly unspecific inflammatory process with extensive fibrosis of the dura and few early stage granulomas. These findings suggest either neurosarcoidosis or idiopathic hypertrophic pachymeningitis.

  16. A case of peeling

    DEFF Research Database (Denmark)

    Nielsen, Anders

    2016-01-01

    Peeling of paint and plaster from building facades is a well-known phenomenon. This contribution analyses a case of peeling on a villa and its gardens walls, Figure 1. The walls were levelled with cement plaster, before painted with a formally very dense acrylic paint. - The analysis shows...... that the present layer of acryl paint is not very dense because it is applied on a rough plaster surface. - However, the main reason of the peeling seems to be the difference in thermal expansion between the masonry and the cement plaster. It is shown that the peeling takes place both winter and summer....

  17. 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.

  18. 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.

  19. Final report on case studies

    DEFF Research Database (Denmark)

    Ljungberg, Daniel; McKelvey, Maureen; Lassen, Astrid Heidemann

    2012-01-01

    Case study as a research design means investigating a single or multiple instance(s) or setting(s) (i.e. a case) and its entire context to explain a phenomenon and its processes. This is achieved through detailed understanding, usually comprised of multiple sources of information. In this way, case...... studies attempt to provide as a complete an understanding of a (complex) phenomenon as possible. Within the AEGIS project, survey and case study research are complementary. They are complementary in the sense that the former can provide more generalizable evidence on a phenomenon in terms of cross......-sectional data, while the latter can provide more in-depth (qualitative) understanding on specific issues. In systematically examining the case studies, however, this report goes beyond a typical single case study. Here we provide a synthesis of 86 case studies. Multiple case studies, following similar focus...

  20. Autopsy profiles of malpractice cases.

    Science.gov (United States)

    Pakis, Isil; Yayci, Nesime; Karapirli, Mustafa; Gunce, Elif; Polat, Oguz

    2009-01-01

    Claims for medical malpractice and the number of lawsuits filed thereafter are increasing in Turkey as is the case throughout the world. In the present study all files issued by the associated boards of the Council of Forensic Medicine between 2001 and 2005 were studied and of those, 525 death cases in which there was a medical malpractice claim were included. 303 of the cases (57.7%) were male, 215 (41%) were female, while no gender was mentioned in seven cases (1.3%). The age of the subjects ranged between 0 and 90, with an average of 26.8. 147 cases (28%) were related to Emergency Units. 92% of the cases (482 cases) were resolved in the Council of Forensic Medicine, Ministry of Justice. 167 of the resolved cases were concluded as medical malpractice.

  1. 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

  2. Regional odontodysplasia: case report

    Directory of Open Access Journals (Sweden)

    Ana Carolina Magalhães

    2007-12-01

    Full Text Available Regional odontodysplasia (RO is a rare developmental anomaly involving both mesodermal and ectodermal dental components in a group of contiguous teeth. It affects the primary and permanent dentitions in the maxilla and mandible or both jaws. Generally it is localized in only one arch. The etiology of this dental anomaly is uncertain. Clinically, affected teeth have an abnormal morphology, are soft on probing and typically discolored, yellow or yellowish-brown. Radiographically, the affected teeth show a "ghostlike" appearance. This paper reports the case of a 5-year-old girl presenting this rare anomaly on the left side of the maxillary arch, which crossed the midline. The primary maxillary left teeth (except for the canine and the primary maxillary right central incisor were missing due to previous extractions. The permanent teeth had a "ghostlike" appearance radiographically. The treatment performed was rehabilitation with temporary partial acrylic denture and periodic controls. In the future, the extraction of affected permanent teeth and rehabilitation with dental implants will be evaluated. The presentation of this case adds valuable information to pediatric dentists to review special clinical and radiographic features of RO, which will facilitate the diagnosis and treatment of patients with this condition.

  3. Humeral lengthening: Case report

    Directory of Open Access Journals (Sweden)

    Gajdobranski Đorđe

    2013-01-01

    Full Text Available Introduction. Difference in length of upper extremities has mainly esthetic significance and is therefore not so often a subject of operative treatment, compared to lower extremities. Case Outline. We are presenting a case of a 16­year­old patient in whom a shortening of 9 cm of the right humerus was determined at the end of growth. This shortening was the result of surgical treatment of solitary bone cyst at the proximal end of the humerus done at the age of 10 years. In order to correct the length of the humerus we applied distraction osteogenesis with a compressive­distracting device according to Mitkovic (Traffix, and we achieved the lengthening of 7.5 cm. During the period of distraction we encountered the following complications: minimal suppuration at the site of the wedges that was successfully resolved with intensive local treatment, while pain and paresthesias along the N. radialis were resolved with a temporarily slowing of the distraction process. Fixation with a plate, i.e. bone grafting was not necessary, and final functional and esthetic result was excellent. Conclusion. Successful lengthening of the shortened humerus can be achieved with a unilateral compressive­distracting device according to Mitkovic as its application up to a complete bone reconstruction does not require additional plate fixation or bone grafting. The patient was capable of performing usual daily activities during application of the device.

  4. 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.

  5. 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.

  6. 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

  7. Ureterocele. A Case Report

    Directory of Open Access Journals (Sweden)

    Andrés Gualpa Jácome

    2013-12-01

    Full Text Available Ureterocele is a dilation of the distal end of the ureter that occurs during fetal stage. Its incidence varies according to the series between 1/500 to 1/4000 patients, predominantly in girls. A case of a 50-year-old white female patient with a history of recurrent urinary tract infections is presented. She attended the family doctor’s office due to the exacerbation of her condition by some episodes of dysuria, urinary frequency and urgency for several months. Abdominal ultrasound was recommended. A complex structure in the middle part of the right kidney was disclosed by a multislice ultrasonography of the abdominal region performed in the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos. Ureteropyelocaliectasis with good corticomedullary differentiation was observed in the left kidney, as well as dilation of the ureter until its entry into the bladder as a cystic intravesical mass. It was decided to report this case given its rare occurrence.

  8. 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

  9. Program evaluation and case study

    OpenAIRE

    Kushner, S

    2009-01-01

    This entry looks at the convergence of case study methodology and program evaluation. An early insight of some educational evaluation theorists was of the convergence of case study and program evaluation – the fusion of method with purpose. Program evaluation and case study came to be mutually-bracketed. In the educational evaluation field 'Responsive', 'Democratic', 'Illuminative' methodologies were developed in parallel with case study methods - the same authors contributing freely to both ...

  10. 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 ...

  11. 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…

  12. 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.

  13. Emotion, Engagement, and Case Studies

    Science.gov (United States)

    Herreid, Clyde Freeman; Terry, David R.; Lemons, Paula; Armstrong, Norris; Brickman, Peggy; Ribbens, Eric

    2014-01-01

    Three college faculty taught large general biology classes using case studies and personal response systems (clickers). Each instructor taught the same eight cases in two different sections, except the questions within the cases differed. In one section the questions were lower order (LO) factual inquiries, and in the other they were largely…

  14. Perioral gustatory sweating: case report.

    NARCIS (Netherlands)

    Kayser, S.C.; Ingels, K.J.A.O.; Hoogen, F.J.A. van den

    2012-01-01

    OBJECTIVE: Presentation of a case of perioral Frey syndrome. DESIGN: Case report. SUBJECT: A 72-year-old woman with hyperhidrosis around the mouth and chin. RESULTS: This patient suffered from bilateral perioral gustatory sweating following a mandibular osteotomy; such a case has not previously been

  15. Disulfiram neuropathy: two case reports

    OpenAIRE

    2016-01-01

    Background Neuropathy is a rare adverse side effect of disulfiram therapy and is under-recognized. There have been few case reports documenting this side effect. Case presentation Two cases of disulfiram peripheral neuropathy are discussed. The first case is that of a 25-year-old Caucasian woman who was exposed to disulfiram therapy for a total of 8 months and developed pain and stiffness that prevented her from walking. The second case is that of a 46-year-old Caucasian woman who developed s...

  16. Mucormycosis: 2 Case Report

    Directory of Open Access Journals (Sweden)

    M. Faruk Oktay

    2007-01-01

    Full Text Available Mucormycosis is a rare, saprophytic, invasive and fulminant fungal disease. It is infective to patients with underlying immunocompromised conditions. We presented two cases of mucormycosis, one of which occured in the nose and the other on the auricle. A two-year-old female patient with diabetic ketoacidosis revealed necrosis and surrounding hyperemia in the nasal vestibule, nasal septum and dorsum of nose. A 17-year-old female diabetic patient had been suffering from black-colored lesion on the auricle. Physical examination presented necrosis on the auricle. Facial paralysis occured in the patient with auricular mucormycosis. Systemic amphotericin B was empirically administered after the sample was obtained for microbiologic and histopathologic examination in both patients. Necrotic tissues was also debrided in the second patient. The first patient died on the second day of treatment, and the second patient on the seventh day. We discussed the bacteriologic characteristics, histological peculiarities, and alternative treatments.

  17. Parathyroid adenoma. Case presentation

    Directory of Open Access Journals (Sweden)

    Daniel Olivera Fajardo

    2016-10-01

    Full Text Available Parathyroid Adenoma is a non-malignant tumor of the thyroid glands, which increases the levels of parathormone. This hormone regulates blood and bone levels of calcium, phosphorus and Vitamin D. Its classic triad is characterized by the increase of the levels of parathormone, hyperkalimia and Hipophosphatemia. This entity affects between 500-1000 inhabitants and is the main cause of primary Hyperparathyroidism in about 80-85% of the patients. It is presented a case of a 69 year old female patient, admitted due to pathologic fractures of hip, clavicle, and fingers, caused by primary hyperparathyroidism originated by parathyroid adenoma. For the low incidence of this entity, its publication is considered of interest for the scientific staff.

  18. Choroidal osteoma - case reports.

    Science.gov (United States)

    Khan, N; Rahman, N A; Uddin, M S

    2014-07-01

    Choroidal osteoma is a rare disease. In this article four case histories were described. All were female and young patient. One patient had bilateral and other three had unilateral involvement. They had no family history. One patient reported at eye department in Bangabandhu Sheikh Mujib Medical University (BSMMU) and the other three patients reported in Bangladesh Eye Hospital. Choroidal osteoma is a benign tumor. It is diagnosed by fundoscopy, ocular B-scan ultrasonography, x-ray orbit, FFA, OCT and CT-scan of orbit. Most patients do not require treatment. Hemorrhage on the lesion suggests the presence of sub-retinal neovascularization which are typically treated with laser or intra-vitreal anti-VEGF.

  19. Tuberous sclerosis. Case presentation.

    Directory of Open Access Journals (Sweden)

    Graciela Caridad Cabrera Acea

    2009-03-01

    Full Text Available A mixed race female, 34 years of age was attended due to papule lesions in the facial area between one and ten mm of diameter. These lesions were flat, with skin colour, symmetrically distributed in the central part of the face (cheeks, chin and nose, of soft texture with telangiectasia. She referred to present these lesions since she was seven years of age, and three months before attending to consultation she noticed an increase in the number and size of these lesions. The patient has a normal intelligence coefficient and declared family history of these lesions. The diagnosis was sebaceous adenoma. Since this is not a frequent disease and due to the patient’s age we decided to publish this case.

  20. Hemihydranencephaly; a Case Report

    Directory of Open Access Journals (Sweden)

    Amit Agrawal

    2009-04-01

    Full Text Available Background:Hemihydranencephaly is a rare disorder of the brain characterized by complete or almost complete unilateral absence of cerebral cortex with preservation of meninges, basal ganglia, pons, medulla, cerebellum, and falx. Case Presentation:Thirteen year-old male child presented with left sided upper and lower limb weakness with facial asymmetry since the age of six months. His magnetic resonance imaging (MRI scans demonstrated a nearly complete absence of the right cerebral hemisphere including basal ganglion, which was replaced by cerebrospinal fluid with a small residual rim of the occipital cortex. The imaging features were suggestive of right-sided hemihydranencephaly. Conclusion:Patients with hemihydranencephaly provide an experiment of nature with potential implications for normal cognitive development and illustrate how much there is still to be learned about human development.

  1. 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.

  2. A case of acromegaly.

    Science.gov (United States)

    Siddiqui, N I; Chowdhury, K S; Rahman, S; Sarker, C B; Rahman, K M

    2003-01-01

    A fifty years old woman hailing from Purbadhala of Netrokona district complaining of gradual enlargement of hands, feet, nose and other acral parts of the body for about last eight years. She noticed coarsening of the skin and gradual protrusion of her lower jaw. She complained of headache, vertigo, frequent passage of urine, increased thirst, weight loss and fatiguability. She was found hypertensive having blood pressure 200/110 mm of Hg. Her appearance was coarse with rough skin. There were enlargement of hands, feet, nose, lower jaw with prognathism and enlargement of other acral parts. Investigations revealed high plasma glucose level, both fasting and 2 hrs. after glucose, high level of growth hormone, failure of suppression of growth hormone during OGTT. Thyroid function tests of the patient were found normal with increased heel pad size and enlarged sella turcica in all diameters. She was diagnosed as a case of acromegaly due to growth hormone hypersecretion.

  3. Iniencephaly: Case Report

    Directory of Open Access Journals (Sweden)

    Hernando R Alvis-Miranda

    2015-01-01

    Full Text Available The iniencephaly involves a variable defect in the occipital bone, resulting in a large foramen magnum, partial or total absence of the cervical and thoracic vertebrae, accompanied by incomplete closure of arcs and/or vertebral bodies, significant shortening of the spinal column and hyperextension of the malformed cervicothoracic spine; the individual′s face is deviated upward, the mandibular skin is directly continuous with anterior thorax due to the absence of neck. Its incidence is about 1:1000-1:2000 births, so this is a pretty rare neural tube defect. We present a case of iniencephaly in association with cardiovascular, spinal cord, and intracranial malformations that ended demonstrating the low survival of patients affected with this condition.

  4. 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

  5. CADASIL: case report

    Directory of Open Access Journals (Sweden)

    Julio Cesar Vasconcelos da Silva

    Full Text Available ABSTRACT Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL is a hereditary cerebral arteriopathy caused by mutations in the Notch-3 gene. The diagnosis is reached by skin biopsy revealing presence of granular osmiophílic material (GOM, and/or by genetic testing for Notch-3. We report a case of a 52-year-old man with recurrent transient ischemic attacks (TIA, migraine, in addition to progressive sensory, motor and cognitive impairment. He was submitted to a neuropsychological assessment with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease battery along with other tests, as well as neuroimaging and genetic analysis for Notch-3, confirming the diagnosis. Executive function, memory, language and important apraxic changes were found. Imaging studies suggested greater involvement in the frontal lobes and deep areas of the brain.

  6. Executable Use Cases

    DEFF Research Database (Denmark)

    Jørgensen, Jens Bæk; Bossen, Claus

    2004-01-01

    Many software experts argue that when we design a new system, we should create an explicit description of the environment in which the proposed system is to be used. The argument becomes crucial for pervasive computing, which aims to tightly integrate systems into their environments and into the ......Many software experts argue that when we design a new system, we should create an explicit description of the environment in which the proposed system is to be used. The argument becomes crucial for pervasive computing, which aims to tightly integrate systems into their environments...... and into the work processes they're to support. However, prototypes typically provide an explicit representation only of the system itself. Executable use cases, on the other hand, can also describe the environment. EUCs are designed to: narrow the gap between informal ideas about requirements and the formalization...

  7. Lamellar Ichtyosis: Case Report

    Directory of Open Access Journals (Sweden)

    Kamer Gündüz

    2009-12-01

    Full Text Available Introduction: Ichtyosiform dermatoses are a group of hereditary disorders characterized by excessive scaling on the skin. Lamellar ichtyosis is an autosomal recessive disorder. The clinical findings are seen at birth and become widespread and prominent in time; gray-brown scales are seen all over the body. Emollients and keratolytics containing salicylic acid or glycolic acid are used topically. Symptoms are improved significantly by acitretin usage. Case Report: Here we present a 5-year-old girl with lamellar ichtyosis. She was born in a collodion membrane. Besides the skin scales, ectropion and deformities of the nails and ears were observed. Significant clinical improvement was seen with acitretin (10 mg/day therapy. Conclusion: Lamellar ichtyosis is a severe form of ichtyosiform dermatoses and topical agents may be insufficient. Systemic acitretin treatment improves the symptoms significantly but long term side effects limit its usage. (Journal of Current Pediatrics 2009; 7: 154-7

  8. Migraine Infarction. Case Report

    Directory of Open Access Journals (Sweden)

    Yoany Mesa Barrera

    2015-03-01

    Full Text Available Migraine is considered like a risk factor for ischemic ictus in adult young people. In spite of the criteria established for the treatment of the migraine infarct, they are not always fulfilled strictly, permitting certain flexibility in the aforementioned treatment. The case of a patient with a background of migraine with auras, who suffers an ischemic cerebral migraine infarct at the course of a migraine crisis, is presented. The ictus was manifested like an especial right hemiparesis of the female sex in fertile age. The prognosis is good with low risk of recurrence, with unstable disorders and dysarthria. The laboratories studies were normal and the cerebral infarct was detected in the magnetic resonance, at the half left cerebral artery's territory. The patient had favorable evolution without sequel.

  9. Unusual case of tuberculosis

    Directory of Open Access Journals (Sweden)

    Vatsal Bachkaniwala

    2015-12-01

    Full Text Available Though commonly encountered, extrapulmonary tuberculosis (TB can sometimes present with variable clinical picture intricating the diagnosis. The nonspecific symptoms include pyrexia of unknown origin, hepatosplenomegaly, lymphadenopathy, meningitis, and, rarely, variety of hematological abnormalities, namely, anemia, pancytopenia, and leukemoid reaction. When it presents with bone marrow (BM involvement, prognosis is usually poor. We, hereby, report a case of unusual TB presentation with a 4 month history of fever associated with fatigability, and diarrhea. During the hospital stay and follow up, the patient showed a spectrum of interesting hematological findings, including pancytopenia on peripheral smear, caseating granulomas consistent with TB on bone marrow examination. The patient showed a good clinical as well as hematological response to anti-tuberculosis treatment. This paper highlights the significance of a hematological picture in the final confirmation of TB, which may otherwise be passed off as nutritional or other unrelated causes. [Int J Res Med Sci 2015; 3(12.000: 3921-3923

  10. 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.

  11. [Pheochromocytoma. Report of 10 cases].

    Science.gov (United States)

    Rabii, R; Joual, A; Rais, H; Bennani, S; el Mrini, M; Benjelloun, S

    1999-01-01

    We report 10 cases of adrenal pheochromocytoma seen over a period 15-years. A female predominance was noted (8 women/2 men). Patients were aged between 16-46 years with a mean of 34 years. Clinical manifestations consisted of hypertension observed in all cases, with vasomotor symptoms (90%). Time to consultation was prolonged (mean: 23 months). CT scan performed in 7 cases showed pheochromocytoma in all cases, located on the right side in 6 cases, while one pheochromocytoma was located in Zukerkandal organ. All patients were operated via anterior approach and adrenalectomy was performed. A favourable course was observed in 90% of cases with normalisation blood pressure. One death was noted. Histological examination showed no malignancy in all cases.

  12. 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.

  13. 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.

  14. Safety Cases for Advanced Control Software: Safety Case Patterns

    Science.gov (United States)

    2007-10-15

    Classification Argument (from [14]) The classification of software failure modes can be useful for adaptive systems. Kurd in [15] shows how HAZOPS ...Safety Cases for Advanced Control Software : Safety Case Patterns Robert Alexander, Tim Kelly, Zeshan Kurd, John...5a. CONTRACT NUMBER FA8655-07-1-3025 5b. GRANT NUMBER 4. TITLE AND SUBTITLE Safety Cases for Advanced Control Software 5c. PROGRAM ELEMENT

  15. IPEX syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2008-01-01

    Full Text Available INTRODUCTION IPEX syndrome, namely, a hereditary (X-linked immunodysregulation with autoimmune polyendocrinopathy and enteropathy, as the basic manifestations, presents a rare and exceptionally severe disease. It develops due to gene mutation responsible for the synthesis of a specific protein (FOXP3, which, by differentiation and activation of regular T-lymphocytic CD4+CD25+, has the key role in the induction and maintenance of the peripheral tolerance of one's own tissue. CASE OUTLINE We present a male infant with classic clinical features of IPEX syndrome, which manifested by the end of the first month after birth, first with type 1 diabetes mellitus and chronic diarrhoea followed by dehydration and disordered development, and then with facial eczema and laboratory signs of thyroiditis without thyroid dysfunction (antithyreoglobulin antibodies 1:5500, antimicrosomal antibodies 1:40. In addition, plasma IgE level was high (517 IU/l, while antibodies to tissue transglutaminase were mildly increased (IgA 7.5 U/ml, and anti-smooth muscle and anti-DNA antibodies were absent. Based on the typical clinical features, as well as the laboratory findings, IPEX syndrome was diagnosed, which was further confirmed by proved IVS7+5G>A mutations in the FOXP3 gene. Therapy with insulin and Pronison, combined with parenteral and semielementary nutrition resulted in the patient's clinical improvement. At the age of 9 months, despite Pronison and hypoallergenic nutrition, the child had a relapse of severe and persistent diarrhoeal disorder followed by dehydration, weight loss and deterioration of general condition. Beside the complete parenteral nutrition, as well as other measures, azathioprine was introduced into the treatment, but without the desired effect. At the age of 12.5 months, due to bacteraemia and disseminated intravascular coagulation as complications, the patient ended lethally. CONCLUSION IPEX syndrome should be kept in mind in all the cases of

  16. Celiac disease - case report

    Directory of Open Access Journals (Sweden)

    Bojković Gradimir

    2002-01-01

    Full Text Available Introduction Celiac disease (nontropical sprue, gluten-sensitive enteropathy, chronic intestinal malabsorption disorder is caused by gluten intolerance. This hereditary disorder is caused by sensitivity to gliadin. Because the body's own immune system causes the damage, celiac disease is considered to be an autoimmune disorder. However, it is also classified as a disease of malabsorption because nutrients are not absorbed. When people with celiac disease eat foods containing gluten, their immune system responds by damaging the small intestine. Specifically, tiny finger-like protrusions, called villi, on the lining of the small intestine are lost. The diagnosis is suspected on the basis of symptoms and signs, enhanced by laboratory and x-ray studies, and confirmed by biopsy revealing flat mucosa and subsequent clinical and histologic improvement on a gluten-free diet. Gluten must be excluded from diet. Supplementary vitamins, minerals and hematinics may be given depending on deficiency. Case report This is a case report of a 23-year old female patient with a mineralization defect (osteomalacia and secondary osteoporosis caused by long-time unrecognized celiac disease. The patient had many symptoms: short stature, steatorrhea, anemia, weight loss and chronic bone pain. Laboratory and x-ray studies and jejunal biopsy revealed a chronic intestinal malabsorption disorder caused by gluten intolerance. Gluten-free diet and supplementary vitamins, minerals and hematinics were included with apparent clinical remission. Discussion and Conclusion Some people with celiac disease may not have symptoms. The undamaged part of their small intestine is able to absorb enough nutrients to prevent symptoms. However, people without symptoms are still at risk for complications of celiac disease. Biopsy of the small intestine is the best way to diagnose celiac disease. Decreased bone density (osteoporosis and osteomalacia is a serious problem for celiacs. If calcium

  17. 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.

  18. 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,

  19. Patellar osteochondroma: case report,

    Directory of Open Access Journals (Sweden)

    Frederico Barra de Moraes

    2014-04-01

    Full Text Available The aim was to report on a rare case of patellar osteochondroma. A 60-year-old man presented a tumor on his left patella that had developed over a 10-year period, which is a rare occurrence, considering the patient's age and the site at which the tumor appeared. The clinical condition comprised mild pain and the presence of a mass, without limitation of flexion-extension or any neurovascular deficit. The tumor dimensions were 8 cm longitudinally × 6 cm transversally × 3 cm anteroposteriorly. It was hardened and was adhering to the patellar bone plane. On radiographs and tomographic scans, we observed areas of greater density corresponding to bone and other less dense areas that could correspond to slow-growing cartilage, with irregularities on the patellofemoral joint surface. Simple resection of the tumor was performed, and the anatomopathological examination confirmed that it was a patellar osteochondroma. Osteochondroma, or osteocartilaginous exostosis, includes a large proportion of the benign bone tumors. It results from cell alterations that trigger unregulated production of spongy bone. It is basically treated by means of surgical removal of the tumor mass. This is not essential, but is recommended in order to avoid lesions caused by contiguity and the risk of malignant transformation.

  20. 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.

  1. [Broncholithiasis: six cases].

    Science.gov (United States)

    Ghraïri, H; Ketata, W; Kartas, S; Ayadi, A; Ammar, J; Abid, H; Kilani, T; Hamzaoui, A

    2007-04-01

    Broncholithiasis is an exceptional condition characterized by the presence of stony formations in the bronchial lumen. We report six cases. Mean age was 41 years. Revealing signs were hemoptysis (n=5), cough (n=5), fever (n=1) and recurrent lower respiratory tract infections (n=1). Physical examination found sonorous rales in two patients and was normal in four. The chest x-ray showed a parenchymal opacity suggestive of calcification in one patient, atelectasia in two, and alveolar images in three. Bronchial endoscopy demonstrated broncholithiasis in one patient, an endobronchial blood clot in one patient with abundant hemoptysis, an endoluminal bud simulating a tumor in two, an inflammatory aspect in one, and was normal in one. Thoracic computed tomography demonstrated broncholithiasis in three patients. Treatment consisted in lobectomy in five patients. The pathology specimen confirmed broncholithiasis in all five and in one revealed caseofollicular lesions of the hillar nodes. Anti-tuberculosis treatment was prescribed for this patient. Therapeutic abstention with regular surveillance was chosen for one patient with an uncomplicated broncholithiasis. Broncholithiasis is an exceptional condition with potentially serious consequences. Certain diagnosis is based on high-resolution computed tomography and endoscopic findings but can nevertheless be a surgical discovery.

  2. Case consultation: ablatio penis.

    Science.gov (United States)

    Money, J

    1998-01-01

    In male infants, traumatic ablation of the penis, with or without loss of the testicles may occur as a sequel to mutilatory violence, accidental injury, or circumcision error. Post-traumatically, one program of case management is surgical sex reassignment to live as a girl, with female hormonal therapy at the age of puberty. The other program is genital reconstructive surgery to live as a boy, with male hormonal therapy at puberty if the testicles are missing. In both programs, the long term outcome is less than perfect and is contingent on intervening variables that include societal ideology; surgical technology; juvenile and adolescent timing and frequency of hospital admissions construed by the child as nosocomial abuse; development of body image; health and sex education; fertility versus sterility; coitus and orgasm; possible lesbian orientation if living as a girl; and long-term cost accounting, including the psychic cost of being a pawn in possible malpractice litigation on whose disability a very large fortune in compensation may devolve. There is, as yet, no unanimously endorsed set of guidelines for the treatment of genital trauma and mutilation in infancy, and no provision for a statistical depository for outcome data.

  3. Multiple myeloma: 45 cases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hee Chul; Suh, Jin Suck; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1990-10-15

    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.

  4. 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.

  5. Perilunar Luxation. Case Report

    Directory of Open Access Journals (Sweden)

    Yaniel Truffín Rodríguez

    2015-06-01

    Full Text Available Within the specter of injuries found in dorsal perilunar luxation or injuries of the bigger arch, the one belonging to bigger frequency reciprocates with the fracture luxation trasescafo dorsal perilunar. Much less frequent are the luxations that associate the big bone's fractures and those with displaced fractures of the pyramidal. Throughout the above, the case of a 19 year old patient is presented, that came to the emergency room of Gustavo Aldereguía Lima, Cienfuegos Hospital, after suffering a fall on his left hand with background of previous health. Great increase of volume in the left-handed wrist, acute pain in spite of immobilization and absolute functional impotence were verified. Manual reduction under general anesthesia of the perilunar luxation of the carpus was accomplished. By means of X-ray pictures of control, anteroposterior and lateral of the wrist, escafoides's fracture and its characteristics were verified. For the marked angulation and conminution of the fracture surgical open-cast treatment was decided, using the technique of Ruse, that was postpone to the tenth day from the initial lesion, when the wrist was less inflamed and the risks of complications were less. The patient was discharged of the consultation of orthopedics to the six months of operated showing functional acceptable results.

  6. Dioxin: a case study.

    Science.gov (United States)

    Bond, G G

    1993-01-01

    The need to notify individuals of a possible health risk from their past exposure to potentially hazardous agents frequently extends beyond workers to include community groups. The issues to consider in community notification are frequently similar to those that are important for worker notification but may include some that are unique. This case study traces the evolution of one company's strategy for communicating with the public about possible dioxin contamination associated with its operations. Early communications tended to emphasize the technical aspects of the issues in the fashion of scientists talking to other scientists. This was interpreted by some to be symptomatic of an arrogant and uncaring attitude. Beginning in the early 1980s, the company's management recognized the need to reach out to a variety of audiences on multiple levels, and shifted to a more comprehensive communications strategy. A similar shift is now occurring throughout the chemical manufacturing industry as top managers realize that, if they expect to continue to operate, they must become more accountable and responsive to the public.

  7. 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.

  8. Three cases of pulmonary varix

    Energy Technology Data Exchange (ETDEWEB)

    Takishima, Teruo; Sakuma, Hajime; Tajima, Tsunemi; Okimoto, Takao; Yamamoto, Keiichiro; Dohi, Yutaka (Saitama Medical School (Japan))

    1982-06-01

    Three cases of pulmonary varix associated with valvular heart disease were reported. Round shadows were clearer on first oblique or lateral films of chest x-ray in all 3 cases. On chest tomograms, the shadows were substantial and round-elliptical. RI angiography with sup(99m)Tc-RBC demonstrated these shadows in agreement with the site of influx of the pulmonary vein into the left atrium in Cases 1 and 3 and with the pulmonary vein slightly apart from the left atrium in Case 2. On CT scans in Cases 1 and 3, enhancement with a contrast medium visualized dilatation of the pulmonary vein close to, and in continuation with, the shadow of the left atrium. The diagnosis of pulmonary varix in agreement with the venous phase of pulmonary angiography was made for all 3 cases. Non-surgical examinations (especially CT scan) proved highly useful for the diagnosis of pulmonary varix.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Theory Testing Using Case Studies

    DEFF Research Database (Denmark)

    Møller, Ann-Kristina Løkke; Dissing Sørensen, Pernille

    2014-01-01

    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......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...... research paths....

  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. Building theories from case study research: the progressive case study

    NARCIS (Netherlands)

    Steenhuis, Harm-Jan; Bruijn, de Erik J.

    2006-01-01

    Meredith (1998) argues for more case and field research studies in the field of operations management. Based on a literature review, we discuss several existing approaches to case studies and their characteristics. These approaches include; the Grounded Theory approach which proposes no prior litera

  17. Demystifying Instructional Innovation: The Case of Teaching with Case Studies

    Science.gov (United States)

    Kantar, Lina D.

    2013-01-01

    Issues emerging from instructional innovation are inevitable, yet basing any curriculum shift on a theoretical framework is paramount. This paper grounds the case-based pedagogy in three learning theories: behaviorism, cognitivism, and constructivism. The three theories are described and situated in relation to the case study method. An…

  18. Esthesioneuroblastoma: a case report.

    Science.gov (United States)

    Shukla, R C; Singh, P K; Senthil, S; Pathak, R

    2010-06-01

    Esthesioneuroblastoma (olfactory neuroblastoma) is an uncommon neuroectodermal tumor. Its biological activity ranges from indolent growth to local recurrence and rapid widespread metastasis. Treatment options consist of surgical resection followed by radiation therapy for primary lesions and the addition of chemotherapy for advanced, recurrent, or metastatic lesions. Patients often present with nasal obstruction, rhinorrhea, recurrent epistaxis, hyposmia, or anosmia. We report a case of esthesioneuroblastoma involving bilateral nasal cavity leading to bilateral nasal obstruction, epistaxis and proptosis of the right eye associated with decreased visual acquity on that eye and loss of smell. A diffuse nontender, 6x6 cms swelling with illdefined margins was seen over the nasal bridge, extending superiorly to glabella and laterally to right maxillary region. X-ray PNS showed soft tissue mass in the nasal cavity with destruction of nasal septum, intense periosteal reaction with destruction of right maxillary wall and extension to right orbit. CT scan of paranasal sinuses showed 8.5 x 4.9 x 7.8 cms irregularly marginated heterogeneous iso- to hyper dense soft tissue mass lesion with extensive adjacent bony destruction and spiculated periosteal reaction involving bilateral nasal cavity and anterior cranial fossa. Biopsy from right nasal mass showed neuroblastoma. The patient received radiotherapy and chemotherapy. The modified Kadish staging system, lymph node status, treatment modality, and age are useful predictors of survival in patients who present with esthesioneuroblastoma. Excellent outcomes for esthesioneuroblastoma are achievable. Long-term follow-up is necessary because of the extended interval for recurrent disease; unlike most sinonasal malignancies, surgical salvage is possible.

  19. A case of testicular rupture

    OpenAIRE

    野俣, 浩一郎; 林, 幹男

    1987-01-01

    A case of testicular rupture is reported. A 26-year-old man was referred to our hospital because of testicular trauma. Ultrasound of the testis was performed preoperatively. Ultrasonography revealed a disruption of the tunica albuginea and dense clusters of echoes in the tunica vaginalis. In the case of acute testicular trauma, this echo pattern suggests testicular rupture.

  20. 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.

  1. Instructional Computing: Ten Case Studies.

    Science.gov (United States)

    Hargan, Carol; Hunter, Beverly

    These case studies are written for educational institutions that wish to plan, extend, or improve their use of computers for learning and teaching. Each case study includes a brief description of each of the following: profile of the institution, history of the development of instructional computing, organization and management, student access to…

  2. 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.

  3. 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.……

  4. Periodontal considerations in veneer cases.

    Science.gov (United States)

    Peto, David

    2015-04-01

    Porcelain veneers are a minimally invasive technique to enhance patients' smiles. A crucial component in these cases is the supporting periodontal apparatus and its interaction with the restorations. This article addresses basic concepts such as biologic width, altered eruption patterns, appropriate gingival contouring and smile design to give practitioners the tools to diagnose, evaluate and treat cases successfully and predictably.

  5. Proliferative periostitis: a case report.

    Science.gov (United States)

    Zand, Vahid; Lotfi, Mehrdad; Vosoughhosseini, Sepideh

    2008-04-01

    Proliferative periostitis of Garré represents a periosteal reaction to the presence of infection or other irritants. This can be odontogenic or nonodontogenic. This is a case report of an odontogenic periostitis resulting from endodontic origin. It was successfully treated by nonsurgical root canal therapy without using antibiotic therapy during the treatment of this case.

  6. Intracortical chondrosarcoma: a case report.

    Directory of Open Access Journals (Sweden)

    Khodamorad Jamshidi

    2014-02-01

    Full Text Available Chondrosarcoma is the second most common primary mesenchymal malignant tumor of the bone. The most common form is central chondrosarcoma and the rarest is intracortical chondrosarcoma. Here, we describe the clinical, pathological, and imaging features of a case of intracortical chondrosarcoma as well as the outcome of surgical treatment. This is the third case reported in the literature.

  7. 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…

  8. 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…

  9. Dermatomyositis panniculitis: a case report.

    Science.gov (United States)

    Carroll, Melissa; Mellick, Nick; Wagner, Godfrey

    2015-08-01

    Dermatomyositis-related panniculitis is a rare cutaneous manifestation of dermatomyositis. There are few reported cases in the medical literature. We present the case of a 60-year-old woman with a 2-year history of dermatomyositis and recent biopsy-confirmed panniculitis treated with prednisone, cyclophosphamide and i.v. immunoglobulin.

  10. 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....

  11. 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

  12. 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 in a progressive...

  13. 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.

  14. Case Study: A Picture Worth a Thousand Words? Making a Case for Video Case Studies

    Science.gov (United States)

    Pai, Aditi

    2014-01-01

    A picture, they say, is worth a thousand words. If a mere picture is worth a thousand words, how much more are "moving pictures" or videos worth? The author poses this not merely as a rhetorical question, but because she wishes to make a case for using videos in the traditional case study method. She recommends four main approaches of…

  15. A case of cerebral paragonimiasis in Denmark. Case report.

    Science.gov (United States)

    Møller, A; Settnes, O P; Jensen, N O; Kruse-Larsen, C

    1995-01-01

    A case of cerebral paragonimiasis with severe neurological symptoms is presented. The patient, a 45-year-old woman, recovered completely after resection of a large cyst at the C3 level. The pathogenesis is discussed.

  16. [Ectopic breast fibroadenoma. Case report].

    Science.gov (United States)

    Senatore, G; Zanotti, S; Cambrini, P; Montroni, I; Pellegrini, A; Montanari, E; Santini, D; Taffurelli, M

    2010-03-01

    Among the rare anomalies of the breast development, polythelia is the most common, between 1% and 5% of women and men present supernumerary nipples. Polymastia, usually presenting as ectopic breast tissue without areola-nipple complex, is seen mostly along the milk line, extending from the axilla to the pubic region. Ectopic breast tissue is functionally analogous to mammary gland and it is subjected to the same alterations and diseases, whether benign or malignant, that affect normal breast tissue. We report the case of a 21 years-old female evaluated by the medical staff after founding a solid nodular mass by suspect axillary lymphadenopathy. Differential diagnosis with lymphoma is the major problem in these cases. The mass was removed and the intraoperative histological examination showed fibroadenoma in axillary supernumerary breast. Presence of ectopic breast tissue is a rare condition; development of benign mass or malignant degeneration is possible, but it is very unusual. In case of polymastia diagnosis is simple; in case of isolated nodule, without local inflammation or infection, there are greater difficulties. Ultrasonography is diagnostic in case of breast fibroadenoma, but it might be inadequate in ectopic localizations owing to the shortage of mammary tissue around the mass. Preoperative diagnosis is important to plan an adequate surgical treatment; lumpectomy is indicated in case of benign tissue; in case of malignancy, therapy is based on the standard treatment used for breast cancer (surgery, chemotherapy and radiation therapy).

  17. Health policy and case management.

    Science.gov (United States)

    Mark, D D

    2000-01-01

    The purpose of this article is to analyze the performance of and support for case management using a policy framework in order to increase case managers' awareness of policy making and facilitate successful planning for future policy initiatives. Feldstein's (1996) theory of opposing legislative outcomes indicates that legislation can be viewed on a continuum, ranging from legislation that meets the needs of the public to legislation considered to be in the self-interest of the participants and legislators. The current health care system requires that case managers working for publicly funded health care organizations balance the need for stewardship of U.S. tax dollars and the health care needs of consumers. It is apparent from the literature that case managers are successfully achieving this balance. However, certain conditions should exist that allow for case manager decision-making that promotes effective and efficient utilization of health care resources. Case managers must work within the context of the health care policy environment. Realizing that it is more likely that the conflicts between stewardship and the provision of health care services will continue, case managers' knowledge and influence regarding policy making becomes imperative in order to ensure that these conflicting goals do not become mutually exclusive.

  18. Two cases of rheumatoid meningitis.

    Science.gov (United States)

    Magaki, Shino; Chang, Edward; Hammond, Robert R; Yang, Isaac; Mackenzie, Ian R A; Chou, Benedict T; Choi, Soo I; Jen, Joanna C; Pope, Whitney B; Bell, David A; Vinters, Harry V

    2016-02-01

    Central nervous system (CNS) involvement by rheumatoid arthritis (RA) in the form of rheumatoid meningitis (RM) is rare and most commonly occurs in the setting of longstanding severe RA. Due to a wide range of clinical presentations and nonspecific laboratory findings, it presents a diagnostic challenge often requiring brain biopsy. Only a few histopathologically confirmed cases have been described in the literature. Our aim is to describe two cases of RM and review the literature. The first case is of a previously healthy 37-year-old man who presented with severe headaches and focal neurologic deficits. Magnetic resonance imaging demonstrated abnormal leptomeningeal enhancement in the left frontal and parietal sulci. The second case is of a 62-year-old woman with a history of mild chronic joint pain who presented with confusion, personality changes and seizures. Both patients ultimately underwent brain biopsy which demonstrated RM on pathologic examination. Administration of corticosteroids resulted in significant clinical improvement in both cases. To our knowledge, our unusual case of RM in the young man is the fifth reported case of rheumatoid meningitis in a patient with no prior history of RA. Such an atypical presentation makes diagnosis even more difficult and highlights the need for awareness of this entity in the diagnostic consideration of a patient presenting with unexplained neurologic symptoms. Our literature review underscores the clinical and pathologic heterogeneity of CNS involvement in RA.

  19. Influence of Casing Shoe Depth on Sustained Casing Pressure

    OpenAIRE

    2012-01-01

    In 2006 the Petroleum Safety Authority Norway (PSA) performed a well integrity survey. The survey indicated that about 20 % of wells on the Norwegian Continental shelf (NCS) may suffer from well integrity issues. Most of the problems were related to deficiency in annulus safety valve, tubing, cement and casing. Pressure build-up in annulus, i.e. sustained casing pressure, is one of the main indicators of a significant well integrity problem. Increased understanding on the field may help engin...

  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. Renal myxoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Henrique C Souza

    2015-04-01

    Full Text Available Myxomas are rare tumors that can appear in many anatomical locations. There are only 14 cases of renal involvement documented in the literature. This article reports a case of renal myxoma in an elderly woman with recurrent cystitis. After five years of follow-up, the computed tomography (CT revealed a large solid tumor mass in the left kidney. Tumor resection was performed preserving the affected kidney with histopathological diagnosis of renal myxoma. The objective of this study is to report a rare case of renal myxoma, emphasizing the importance of the differential diagnosis from other benign and malignant mesenchymal tumors.

  3. Emphysematous cystitis: 3 cases report

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ho Jong; Byun, Jae Young; Lee, Jae Moon; Ro, Hee Jung; Shinn, Kyung Sub [Catholic University Medical College, Seoul (Korea, Republic of)

    1995-09-15

    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.

  4. Five cases of cystic osteoechinococcosis

    Institute of Scientific and Technical Information of China (English)

    JIANG Ci-peng

    2005-01-01

    @@ Osseous cystic echinococcosis (CE) is a rare disease caused by the larval stage of Echinococcus granulosus (E. granulosus) and CE is different from alveolar echinococcosis (AE) caused by the larva of E. multilocularis. During a period of 20 years (1983-2003), a total of 364 cases of echinococcosis, including 263 CE and 101 AE cases were diagnosed at Hydatidos Research Laboratory (HRL), Basic Medical College, Lanzhou University, China. Of them, 5 cases of osseous CE (1.37%) were encountered and now reported as follows.

  5. [Congenital retinal folds in different clinical cases].

    Science.gov (United States)

    Munteanu, M

    2005-01-01

    We present 12 clinical cases of congenital retinal folds with different etiologies: posterior primitive vitreous persistency and hyperplasia (7 cases),retinocytoma (1 case). retinopathy of prematurity (1 case), astrocytoma of the retina (1 case), retinal vasculitis (1 case), Goldmann-Favre syndrome (1 case). Etiopathogenic and nosological aspects are discussed; the congenital retinal folds are interpreted as a symptom in a context of a congenital or acquired vitreo-retinal pathology.

  6. Worst Case Efficient Data Structures

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting

    . The first problem we consider is how to make bounded in-degree and out-degree data structures partially persistent, i.e., how to remember old versions of a data structure for later access. A node copying technique of Driscoll et al. supports update steps in amortized constant time and access steps in worst...... case constant time. The worst case time for an update step can be linear in the size of the structure. We show how to extend the technique of Driscoll et al. such that update steps can be performed in worst case constant time on the pointer machine model. We present two new comparison based priority......We study the design of efficient data structures. In particular we focus on the design of data structures where each operation has a worst case efficient implementations. The concrete problems we consider are partial persistence, implementation of priority queues, and implementation of dictionaries...

  7. Teaching Ethics by Case Analysis.

    Science.gov (United States)

    Fromer, Margot Joan

    1980-01-01

    Starting with basic philosophic positions and principles, nursing students can be helped to analyze ethical dilemmas of increasing complexity. A hypothetical situation is presented and discussed as an example of a case study used to teach these principles. (CT)

  8. Updated Cases for Medical Microbiology

    Directory of Open Access Journals (Sweden)

    Brinda Govindan

    2015-08-01

    Full Text Available Review of: Cases in Medical Microbiology and Infectious Diseases, 4th ed.; Peter H. Gilligan, Daniel S. Shapiro, and Melissa B. Miller; (2014. ASM Press, Washington, DC. 589 pages.

  9. 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.

  10. 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...

  11. The Japanese "Internment" Cases Revisited.

    Science.gov (United States)

    Robinson, Edward T.

    2003-01-01

    Reviews topics discussed in the OAH article, "Incarcerating Japanese Americans" (Roger Daniels). States that the three internment cases were correct. Asks whether internment could re-occur given the climate in U.S. society since September 11, 2001. (CMK)

  12. 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

  13. On Kindling Flames with Cases

    Science.gov (United States)

    Fuchs, H. O.

    1974-01-01

    Describes how case studies, involving written accounts of engineering jobs as they were actually done or problems as they were actually encountered, can be effectively used to motivate engineering students. (JR)

  14. Case Studies in Strategic Planning

    Science.gov (United States)

    1990-03-06

    Contains developed case studies in strategic planning on The Navy General Board, Joint Service War Planning 1919 to 1941, Navy Strategic Planning , NASA...in Strategic Planning NPS-56-88-031-PR of September 1988. Strategic planning , Strategic Management.

  15. Case Study: del Amo Bioventing

    Science.gov (United States)

    The attached presentation discusses the fundamentals of bioventing in the vadose zone. The basics of bioventing are presented. The experience to date with the del Amo Superfund Site is presented as a case study.

  16. 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...

  17. Paroxysmal upgaze deviation: case report

    OpenAIRE

    Echeverría-Palacio CM; Benavidez-Fierro MA

    2012-01-01

    The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck...

  18. [Heterolateral renal dystopia (2 cases)].

    Science.gov (United States)

    Anastasov, G; Peneva, S; Mushmov, D; Salambashev, L

    1982-01-01

    The authors observed two cases with crossed renal dystopia, to which venous urography, renal scintigraphy, echographic and gamma-chamber investigations were performed. The venous urography, in case of the appropriate symptomatics, is stressed to be able to establish the presence of heterolateral dystopia by as far as the distributional function of the anomaly is concerned--the gamma-chamber investigation is with the highest information value.

  19. Abdominal pregnancy- a case report.

    Science.gov (United States)

    Okafor, Ii; Ude, Ac; Aderibigbe, Aso; Amu, Oc; Udeh, Pe; Obianyo, Nen; Ani, Coc

    2011-01-01

    A case of abdominal pregnancy in a 39 year old female gravida 4, para 0(+3) is presented. Ultrasonography revealed a viable abdominal pregnancy at 15 weeks gestational age. She was initially managed conservatively. Surgical intervention became necessary at 20 weeks gestational age following Ultrasound detection of foetal demise. The maternal outcome was favourable. This case is presented to highlight the dilemma associated with diagnosis and management of abdominal pregnancy with a review of literature.

  20. 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.

  1. Supernumerary Jawbone Tooth: Clinical Case

    OpenAIRE

    Rivas Gutiérrez, Jesús; Carlos Sánchez, María Dolores

    2016-01-01

    Introduction: supernumerary teeth are dental development anomalies, alsoknown as hyperdontia or extra teeth. Their prevalence ranges between 0.3% and 3.8%.Their morphology may be normal or dismorphic and are associated to the etiology ofocclusal alterations. It is important to make an early diagnostic through a radiographicalstudy. Case presentation:this article presents a clinical case of a supernumerary tooth thatcaused rotation and crowding of the anterior bottom teeth, which was addressed...

  2. Cutaneous actinomycosis: A rare case

    Directory of Open Access Journals (Sweden)

    Metgud S

    2007-01-01

    Full Text Available Cutaneous actinomycosis is a rare presentation. Here we present a case of cutaneous actinomycosis with no history of trauma or systemic dissemination. The isolate was identified as Actinomyces viscosus by standard methods. The isolate was found to be penicillin resistant by Kirby Bauer disc diffusion method. Therefore, the patient was treated with cotrimoxazole and improved. Thus, this case highlights the importance of isolation and susceptibility testing in actinomycotic infection. The sinuses have healed, and the patient has recovered.

  3. Toxoplasmosis Neuroretinitis: A Case Report

    OpenAIRE

    2016-01-01

    Introduction Neuroretinitis (NR) is considered to be an inflammatory condition which is characterized by optic disc edema and, as a result, formation of a macular star figure. NR is an atypical presentation of toxoplasmosis infection, and such cases are quite rare. Case Presentation A 13-year-old girl presented with painless subacute visual loss in her right eye for a week at Khatam-Al-Anbia eye hospital in Mashhad, Iran. Following comprehensive evaluation, a diagnosis of toxoplasmic NR was m...

  4. 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)

  5. Pulmonary artery sling: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Gil Hyun; Lee, Sun Wha; Cha, Sung Ho [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1993-09-15

    Aberrant left-sided pulmonary artery(pulmonary artery sling) is an uncommon anomaly,which may cause significant respiratory abnormality. We report a case of pulmonary artery sling which is combined with persistent left superior vena cava and dextrocardia. This case were identified by esophagogram and CT and confirmed by MRI and angiography. We consider that MRI is a valuable new method for the diagnosis of aberrant left-sided pulmonary artery.

  6. [Malignant fibrous histiocytoma. Case report].

    Science.gov (United States)

    Morlino, A; Rossi, M T; Fabrizio, T; Scutari, F

    2010-03-01

    Malignant fibroous histiocytoma (MFH) is an aggressive soft tissue sarcoma, that most frequently occurs in the muscles of the extremities and in abdominal or in retroperitoneal space of young adults. It is seldom confined to the skin and subcutaneous tissue. It is rarely diagnosed before excision and pathological exam, and has an unfavorable prognostic in some cases. This work reports the case of a 94 years old patient with originally cutaneous MFH stressing the importance of the early diagnosis.

  7. A case of complicated otomastoiditis

    Directory of Open Access Journals (Sweden)

    Mario Atzeni

    2015-12-01

    Full Text Available We describe the case of a child who, at her first episode of clinically evident acute otitis media, has developed a bilateral mastoiditis, though with unilateral simptomatology. The mastoiditis was complicated by the spontaneous drainage of the postauricular abscess in the subcutaneous tissue. According to the literature, we believe that the temporal bone computed tomography scan is the fundamental examination to properly define an anusual case of mastoiditis, plan adequate therapy (medical o surgical, and rule out other possible complications.

  8. Making a case for case studies in psychotherapy training

    DEFF Research Database (Denmark)

    Mackrill, Thomas Edward; Iwakabe, Shigeru

    2013-01-01

    The evidence debate in psychotherapy pays little attention to developing an evidence base for training practices. Understanding effective training requires an examination of what makes training work. This article examines the role of case studies in psychotherapy training. This has not been...... articulated explicitly or researched systematically in spite of its cardinal importance. An analysis of the role of case studies in psychotherapy training is presented. Reading, watching, or hearing about cases can offer novice psychotherapists access to a closed world; access to psychological theory...... in action; access to whole courses of therapy; access to different approaches; access to significant moments; access to the therapeutic relationship; access to a wide range of client types; access to working in different contexts; and the opportunity of identifying with therapists and clients. Writing...

  9. [Primary hepatic actinomycosis: a case of inflammatory pseudotumor (case report)].

    Science.gov (United States)

    Tamsel, Sadik; Demirpolat, Gülgün; Killi, Refik; Elmas, Nevra

    2004-06-01

    Actinomycosis is an uncommon chronic infection in which primary liver involvement accounts for 5% of all actinomycotic infections. Abdominal actinomycosis is a severe and progressive peritoneal infection due to an anaerobic gram-positive bacterium, Actinomyces israelii. The presence of a long-standing intrauterine device (IUD) is a well-known risk factor in young women. Although hepatic lesions are present in 15% of cases of abdominal actinomycotic infection, liver involvement in the majority of these cases is attributable to metastatic spread from other evident intraabdominal sites. Hepatic actinomycosis presents most commonly as a single abscess. However, hepatic actinomycosis can closely mimic a malignant tumor on clinical and radiological examination. Such lesions have been termed inflammatory pseudotumors. Tissue specimens for microscopic examination are necessary for diagnosis. We report a rare case of inflammatory pseudotumor of the liver caused by actinomycotic infection.

  10. Imported Case of Melioidosis in Oman: Case Report

    Science.gov (United States)

    Tamtami, Nada AL; Khamis, Faryal; Al-Jardani, Amina

    2017-01-01

    Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. It is most commonly described in Southeast Asia and Northern Australia and some imported cases in non-endemic areas. We describe the case of a 55-year-old Omani man with fulminant sepsis who worked in Laos, Cambodia. B. pseudomallei was isolated from the patient’s blood and was identified by means of microbiological and biochemical tests. We highlight the importance of careful attention to non-fermentative gram-negative rods in a septic patients who have worked or travelled to Southeast Asia. PMID:28042405

  11. A Case of Orbital Histoplasmosis.

    Science.gov (United States)

    Krakauer, Mark; Prendes, Mark Armando; Wilkes, Byron; Lee, Hui Bae Harold; Fraig, Mostafa; Nunery, William R

    2016-01-01

    Histoplasma capsulatum var capsulatum is a dimorphic fungus endemic to the Ohio and Mississippi River Valleys of the United States. In this case report, a 33-year-old woman who presented with a right orbital mass causing progressive vision loss, diplopia, and facial swelling is described. Lateral orbitotomy with lateral orbital wall bone flap was performed for excisional biopsy of the lesion. The 1.5 × 1.8 × 2.3 cm cicatricial mass demonstrated a granulomatous lesion with necrosis and positive staining consistent with Histoplasma capsulatum var capsulatum infection. To the authors' knowledge, this is the first case of orbital histoplasmosis to be reported in the United States and the first case worldwide of orbital histoplasmosis due to Histoplasma capsulatum var capsulatum.

  12. RARE CASE OF COLONIC METASTASIS

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-04-01

    Full Text Available Colon cancer is the second most common type of cancer in females and the third in males worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this case report, an extremely rare case of colon adenocarcinoma with metastasis to the philtrum with extensive peritoneal and bowel involvement is presented. A 44 year old male presented with a change in bowel habits, melena and weight loss . Diagnosed to have carcinoma rectum underwent Abdominoperenial resection (APR two y ears back. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Now presented with swelling over philtrum . Fine needle aspiration (FNAC was done suggestive of adenocarcinoma. This case presented for its uncommon presentation.

  13. Menstruation angina: a case report

    Directory of Open Access Journals (Sweden)

    Choo Wai Kah

    2009-03-01

    Full Text Available Abstract Introduction Menstruation is commonly associated with migraine and irritable bowel but is rarely correlated with angina or myocardial ischaemia. Only a small number of cases have been reported suggesting a link between menstruation and myocardial ischaemic events. Case presentation A case of menstruation angina is reported in order to raise awareness of this association. A 47-year-old South Asian woman presented with recurrent chest pains in a monthly fashion coinciding with her menstruations. Each presentation was associated with troponin elevation. Angioplasty failed to resolve her symptoms but she eventually responded to hormonal therapy. Conclusions The possibility of menstruation angina should always be taken into account in any female patients from puberty to menopause presenting with recurrent chest pains. This can allow an earlier introduction of hormonal therapy to arrest further myocardial damage.

  14. 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.

  15. GORDON SYNDROME: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Rita

    2015-03-01

    Full Text Available BACKGROUND: Gordon Syndrome is an extremely rare disorder and it is part of a group of genetic disorders known as Arthrogryposis multiplex congenita. There are congenital contractures in at least two or more areas of body. Gordon Syndrome is characterized by congenital Camptodactyly, Clubfoot and Cleft Palate. CASE CHARACTERISTICS: One month female baby presented with congenital distal contra ctures in hands ( C amptodactyly, talipes equinovarus deformity in both lower limbs ( C lub feet, hyperextension of left leg at knee joint, central cleft palate, oral thrush. INTERVENTION: Treatment of oral thrush, feeding advice and physiotherapy. OUTCOME: Relieved of oral thrush, weight gain started and attached to Plastic Surgery, Orthopedic and Physiotherapy Specialties. MESSAGE: Sporadic cases of this rare disorder do occur and not many cases have been reported from India.

  16. 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.

  17. Thoracic endometriosis: 3 case reports

    Institute of Scientific and Technical Information of China (English)

    Song Ying-na; Lang Jing-he; Zhu Lan

    2006-01-01

    Abstract:Thoracic endometriosis is a rare disorder. It can be divided into pleural and pulmonary parenchymal endometriosis according to the site of the lesion. In this article 3 typical cases of thoracic endometriosis (case 1 is pleural endometriosis, case 2 and 3 are pulmonary parenchymal endometriosis) were described, and the various presentations, pathogenesis, diagnosis, and therapies of thoracic endometriosis were reviewed. The pathogenesis of thoracic endometriosis has not been established clearly yet. Recurrent right-sided pneumothorax or hemoptysis that occurs within days of the onset of menstruation is the most common manifestation. The correlation between the patient's symptoms and menses is essential to establish the diagnosis. Radiographic studies, bronchoscopy, and thoracoscopy may support the diagnosis. Pathologic evidence is not present universally. Therapeutic interventions include medical and surgical options, which should be individualized for each patient.

  18. High frequency welded (ERW) casing

    Energy Technology Data Exchange (ETDEWEB)

    Duisberg, J. (Hoesch Roehrenwerke A.G., Hamm (Germany, F.R.))

    1980-09-01

    Due to the up-to-date standard in welding and testing techniques, the significance of ERW-casing is growing rapidly. The basic items of ERW-pipe are explained in detail. The forming mechanism, the high frequency welding by induction and contact welding processes is explained in detail as well as destructive and non-destructive testing methods. Finishing the ends as threading, thread control (gauging), power tight connection, pressure test and final quality control are rounding up the picture of the production of ERW-casing. Last but not least the test results from the joint strength- and collapse tests which are of outstanding interest for casings, are compared with API requirements in order to demonstrate compliance with API requirements.

  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. Clinical Approach in Orbital Cellulitis Cases: Case Series

    Directory of Open Access Journals (Sweden)

    Altan Atakan Özcan

    2012-07-01

    Full Text Available Pur po se: To evaluate the etiological factors, diagnosis, follow-up and treatment procedures in cases of orbital cellulitis. Ma te ri al and Met hod: A retrospective review was performed on medical records of patients with orbital cellulitis treated between 2009 and 2011 in our clinic. The patients were studied for age, ophthalmologic examination features, laboratory and radiology results, treatment modalities and the response to these treatments. Re sults: Eleven patients (7 male, 4 female having an average age of 9.7 years (6 months-25 years participated in the study. All patients had eyelid oedema, hyperemia and ocular pain; with chemosis in 3, gaze restriction in 6, relative afferent pupillary defect and proptosis in 4 cases. Orbital cellulitis was observed to occur secondary to paranasal sinusitis in 10 patients (90.9% and 1 patient had only history of superior respiratory tract infection. Sinus infection was localized in ethmoid and maxillary sinuses in all except one case. Laboratory tests showed leukocytosis in 8 patients. Surgical drainage was performed in 7 of 8 patients with abscess formation observed with radiological imaging. The remainder of the patients were followed with sole medical treatment. All patients recovered without any vision loss or life-threatening complication. Dis cus si on: Orbital cellulitis cases must be followed with radiologic imaging for any complication that may occur and patients with abscess should be evaluated for surgical drainage besides antimicrobial treatment.(Turk J Ophthalmol 2012; 42: 284-7

  1. Faster Case Retrieval Using Hash Indexing Technique

    OpenAIRE

    2011-01-01

    The main objective of case retrieval is to scan and to map the most similar old cases in case base with a new problem. Beside accurateness, the time taken to retrieve case is also important. With the increasing number of cases in case base, the retrieval task is becoming more challenging where faster retrieval time and good accuracy are the main aim. Traditionally, sequential indexing method has been applied to search for possible cases in case base. This technique worked fast when the number...

  2. 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

  3. 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.

  4. MIRROR MOVEMENT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    AA. Momen

    2008-11-01

    Full Text Available Mirror movement is an interesting but often overlooked neurological soft sign;these movements are described as simultaneous contralateral, involuntary, identical movements that accompany voluntary movements. This neurologic problem is very rarely seen in children; in familial cases there is a positive history of these movements in parents, diminishing with time. Here, we have presented the case of an 11-year old girl with mirror movements in her upper limbs which interfered with her hand writing. Her neurological examination revealed normal results. In this report, we have tried to explain some of the pathophysiologic mechanisms related to these abnormal movements.Keywords:Mirror Movements, Children, Soft neurologic sign

  5. 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.

  6. Granulomatous orchitis - a case report

    Directory of Open Access Journals (Sweden)

    Nitin M Gadgil

    2001-01-01

    Full Text Available Clinically seminoma and granulomatous orchitis are difficult to separate. The present case highlights this aspect. 50-year-old male presented with mass & pain in right testis since 6 to 8 months. Right testis was enlarged, hard & tender: Laboratory investigations were within normal limits. Orchiectomy specimen revealed homogenous appearance with yellow grey colour Sections studied showed multiple non-caseating granulomas mainly within seminiferous tubules. Differential diagnosis of non-caseating granulomas mainly includes sarcoidosis & granulomatous orchitis. Restriction of granulomas to seminiferous tubules as in our case is a characteristic feature of granulomatous orchitis.

  7. Neonatal acute apendicitis, case report

    OpenAIRE

    Romero Rojas, Nery; Instituto de Patología, UNMSM; Sánchez García, Luis; Hospital Nacional Docente de Cajamarca

    2016-01-01

    Introduction. Acute appendicitis is a rare disease in newborns with a high mortality because of unspecific clinical features. We report a case of non-perforated acute appendicitis in a newborn at the San Bartolome Hospital in Lima. Case report. A female newborn weighing 3 170 g in the first day repelled maternal lactation; at the third day, she presented 39°C fever, and later, abdominal distention, constipation, and abundant vomiting. The X-ray films showed a distended gastric camera and para...

  8. Secretory breast cancer. Case report.

    Science.gov (United States)

    Lombardi, A; Maggi, S; Bersigotti, L; Lazzarin, G; Nuccetelli, E; Amanti, C

    2013-04-01

    Secretory carcinoma of the breast is a rare tumor initially described in children but occurring equally in adult population. This unusual breast cancer subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases. However, surgery is still considered the most appropriate treatment for this pathology. We describe the case of a 50 -year-old woman who has undergone a breast conservative surgery for a little tumor, preoperatively diagnosticated by a fine needle aspiration biopsy (FNAB) as a well differentiated infiltrating carcinoma.

  9. 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.

  10. Case management: unraveling the confusion.

    Science.gov (United States)

    Bower, K

    1998-01-01

    I'm going to close with some of my ideas about the characteristics that case managers exhibit. I have a great deal of professional respect for case managers. I think that you are a tenacious lot. One of the major things that case managers do is help create new alternatives to problems. You open doors; no ... you first build the door and then you open it. You're creative, persistent, and resourceful. You are sometimes asked to solve all of an organization's problems. I think that is a tremendous burden, and that you can get confused because of that role conflict and confusion. What model is best for my organization? Within that is my patient population. What is it that they need? What are the current issues that you are seeing? How is my case management role different from other roles? How large a scope of practice can I handle and be reasonably successful with the patients with whom I'm dealing? How many different kinds of approaches and models are needed within my organization? Look toward the future; think about the future in terms of your crystal balls. What trends do you see building in either the demographics or the health and social environments that are going to influence health care in the future? What effect will the aging of our population have on you and your case management practice? What issues are going to be related to those trends? How many more people do we have living in fragmented families? What's going to happens in terms of resources available for patients? How can case management influence those changes? I don't think we're going to see the pace of change in the health care industry slow down. We will continue to have health care organizations address social issues in addition to pathophysiologic ones. No matter what the role and how it evolves, case management will always be at the junction of change in health care. This will be difficult at times to deal with. It will also be a source of satisfaction for those in the role because of the

  11. 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....

  12. 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.

  13. What's funny about case management?

    Science.gov (United States)

    Saxton, S E

    1997-01-01

    Humor is an effective tool to prevent and resolve burnout, a common problem associated with the practice of case management. Easily accessed by almost everyone, humor has many physiological and psychological benefits. The conscious use of humor in an organization requires a commitment at all levels in order for the organization to benefit as a whole. Offering formal seminars, using humor in company newsletters, and encouraging cartoon or joke sharing impacts on the physical and mental health of the employees. Techniques for bringing laughter to the workplace are outlined, as well as examples from the practice of case management.

  14. [Rare cases of bladder stones].

    Science.gov (United States)

    Sampalmieri, Gregorio; Moretti, Antonello; Sampalmieri, Matteo

    2014-01-01

    We present here two special cases of urolithiasis. The first one shows a giant bladder lithiasis resulting in severe renal insufficiency in a 63-year-old patient, who had previously had nicturia (2-3 times), occasional episodes of urinary frequency and burning micturition, in the absence of renal colic, hematuria or interrupted urination. The second case referes to an 85-year-old man suffering from prostatic enlargement and bladder stones, hospitalized to undergo intervention of trans-vesical prostatic adenomectomy, during which two star-shaped stones were found without obvious symptoms.

  15. Primary ciliary dyskinesiatwo cases reports

    Directory of Open Access Journals (Sweden)

    Mohammad Sadegh Rezaee1

    2009-01-01

    Full Text Available (Received 22 December, 2009 ; Accepted 10 March, 2010AbstractPrimary ciliary dyskinesia and Kartagener's syndrome are rare genetic disorders. There is a ciliary dysfunction in these disorders that cause recurrent infections in respiratory and sinus tracts associated with dextrocardia, chronic vasomotor rhinitis and dextrocardia. The aim of this paper is to report two rare cases of Primary ciliary dyskinesia, including one case of primary ciliary dyskinesia and Kartagener's syndrome for additional knowledge. J Mazand Univ Med Sci 2009; 19(73: 85-89 (Persian.

  16. 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.

  17. 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

    2015-10-16

    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.

  18. "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.

  19. Neonatal brucellosis: A case report.

    Science.gov (United States)

    Alnemri, Abdul Rahman M; Hadid, Adnan; Hussain, Shaik Asfaq; Somily, Ali M; Sobaih, Badr H; Alrabiaah, Abdulkarim; Alanazi, Awad; Shakoor, Zahid; AlSubaie, Sarah; Meriki, Naema; Kambal, Abdelmageed M

    2017-02-28

    Although brucellosis is not uncommon in Saudi Arabia, neonatal brucellosis has been infrequently reported. In this case of neonatal brucellosis, Brucella abortus was isolated by blood culture from both the mother and the neonate. Serology was positive only in the mother.

  20. Evans Syndrome: A case report

    Directory of Open Access Journals (Sweden)

    F. Porcaro

    2014-08-01

    Full Text Available We describe a case of a 14-years old caucasian female affected by autoimmune hemolytic anemia and thrombocytopenia successfully treated with intravenous immunoglobulin and steroids. Nevertheless, neutropenia occurred during follow-up period. Positivity of direct antiglobulin test and sieric anti-neutrophil antibodies suggested the diagnosis of Evans syndrome trilineage.

  1. Necrotizing faciitis: report of case.

    Science.gov (United States)

    Mruthyunjaya, B

    1981-01-01

    A case of necrotizing fasciitis following infection of a mandibular third molar is reported. Necrotizing fasciitis is a relatively rare but fulminating clinical entity characterized by necrosis of fascia with widespread undermining of the superficial tissue and extreme systemic toxicity. Prompt recognition and proper management can reduce the morbidity and mortality in this severe soft tissue infection.

  2. 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…

  3. 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...

  4. Gestational diabetes insipidus. Case Report.

    Science.gov (United States)

    Ejmocka-Ambroziak, Anna; Grzechocińska, Barbara; Jastrzebska, Helena; Kochman, Magdalena; Cyganek, Anna; Wielgoś, Mirosław; Zgliczyński, Wojciech

    2015-01-01

    Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

  5. 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.

  6. Task descriptions versus use cases

    DEFF Research Database (Denmark)

    Lauesen, Søren; Kuhail, Mohammad Amin

    2011-01-01

    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...

  7. Use cases versus task descriptions

    DEFF Research Database (Denmark)

    Lauesen, Søren; Kuhail, Mohammad Amin

    2011-01-01

    to specify require-ments for the same project: Acquire a new system to support a hotline. [Princi-pal ideas/results] Among the 15 replies, eight used traditional use cases that specified a dialog between users and system. Seven used a related technique, task description, which specified the customer's needs...

  8. 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.

  9. 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.

  10. The Case Study of Frank

    Science.gov (United States)

    Eynde, Peter Op't; Hannula, Markku S.

    2006-01-01

    As a unifying feature of this Special Issue, we have asked proponents of each framework to analyse an empirical classroom account of one student's process of solving a mathematical problem. Here, for the case study of "Frank", we give the main data that were available to all authors.

  11. Case report and literature review

    Science.gov (United States)

    Flahault, Adrien; Vignon, Marguerite; Rabant, Marion; Hummel, Aurélie; Noël, Laure-Hélène; Canioni, Danielle; Knebelmann, Bertrand; Suarez, Felipe; El Karoui, Khalil

    2016-01-01

    Abstract Introduction: We report the case of a multicentric Castleman disease (MCD) with initial renal involvement. Although the renal involvement in this case was typical of MCD, it constitutes a rare presentation of the disease, and in our case the renal manifestations led to the haematological diagnosis. Clinical Findings/Patient Concerns: The patient was admitted for fever, diarrhea, anasarca, lymphadenopathies and acute renal failure. Despite intravenous rehydration using saline and albumin, renal function worsened and the patient required dialysis. While diagnostic investigations were performed, right hemiplegia occurred. There was no anemia or thrombocytopenia. Diagnoses: Kidney biopsy was consistent with glomerular thrombotic microangiopathy (TMA). Lymph node histology was consistent with hyalin-vascular variant of Castleman disease. Outcomes: Given the renal and neurological manifestations of this MCD-associated TMA, the patient was treated with plasma exchange during one month, and six courses of rituximab, cyclophosphamide and dexamethasone. The evolution was favorable. Conclusion: Although rare, this diagnosis is worth knowing, as specific treatment has to be started as soon as possible and proved to be efficient in our case as well as in other reports in the literature. PMID:27741115

  12. Case Studies in Sports Nutrition.

    Science.gov (United States)

    Clark, Nancy

    1988-01-01

    This article presents case studies of two athletes who wanted to affect a change in their body weight in order to enhance athletic performance. Each athlete's problem and the nutrition approach used to solve it are discussed. Caloric values of fast foods are listed. (JL)

  13. Beer potomania: a case report

    Science.gov (United States)

    Bhattarai, Nimesh; Kafle, Poonam; Panda, Mukta

    2010-01-01

    A syndrome of hyponatraemia associated with excessive beer drinking was first recognised in 1971. This syndrome has been referred to as beer potomania. Dilutional hyponatraemia occurs due to excessive consumption of an exclusive beer diet which is poor in salt and protein. We report a case of beer potomania who improved dramatically with introduction of solute load, with no subsequent neurological sequelae. PMID:22736559

  14. [Intraabdominal paraganglioma--case report].

    Science.gov (United States)

    Ordeanu, C; Mărginean, A

    2011-01-01

    Paraganglioma is a rare neuroendocrine neoplasm that may develop in the head, neck, torax or abdomen, with a not specified symptoms and the accurate diagnose is established histopathological. The authors present a case of one intraabdominal paraganglioma, incidentally found during ultrasonographic evaluation and diagnose with histopathological examination of excised pieces.

  15. 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.

  16. 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...

  17. Emphysematous Cystitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Suleyman Tagci

    2014-12-01

    Full Text Available Emphysematous cystitis is an infectious disease, which is characterized by accumulation of air within the lumen and wall of the bladder. Diabetes mellitus, neurogenic bladder and advanced age are important risk factors for the development of the disease. In this case report, we present a young diabetic male patient with neurogenic bladder, who was treated with the diagnosis of emphysematous cystitis.

  18. Chondroblastoma of rib : case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hun; Kim, Kyung Rae; Ryu, Sang Wan [Kwangju Hospital, Kwangju (Korea, Republic of)

    2004-07-01

    Chondroblastoma is an uncommon, benign, cartilaginous neoplasm originating in an epiphysis or apophysis of a long tubular bone. The rib is an unusual site for chondroblastoma. The authors describe a case of chondroblastoma of the rib and present a brief review of the literature.

  19. 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...

  20. Overview of the Case Studies

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul

    2011-01-01

    A series of case studies are used to illustrate many of the underlying modelling principles within the book. To facilitate this, the ICAS-MoT modelling tool has been used. A wide range of application areas have been chosen to ensure that the principal concepts of effective and efficient modelling...

  1. [Emphysematous pyelonephritis: a case report].

    Science.gov (United States)

    Rabii, R; Fekak, H; Mezzour, H; Joual, A; Moufid, K; el Mrini, M; Benjelloun, S; Cherkab, R; Bensaid, A; el Kettani, C; Barrou, L

    2003-04-01

    Diabetic patients with urinary tract infections had a certain risk of developping emphysematous pyelonephritis with gas producting bacteria. This disease was accompagned with high mortalité. We will report one case who was treated successfully by high dose antibiotic regim and emergency nephrectomy.

  2. 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.

  3. Dermatology case: segmental lichen aureus

    OpenAIRE

    Fernandes, I.; S. Carvalho; Machado, S.; Alves,R.; Selores, M.

    2012-01-01

    ABSTRACT The authors describe a clinical case of a six-year-old boy with history of a segmental brownish maculopapular skin eruption on his left thoracic and lumbar wall, since the last four months. Based on clinical and histological findings he was diagnosed with segmental lichen aureus.

  4. 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.

  5. Hemifacial Microsomia - A Case Report

    Directory of Open Access Journals (Sweden)

    Sushma Rao

    2005-01-01

    Clinically one sees facial asymmetry, macrostomia, micrognathia, and microtia to anotia of the external ear, preauricular skin tags, and Epibulbar tumors in the eyes. One such case of Hemifacial Microsomia seen in a boyaged 9 years, who complained of facial asymmetry on the right side of the face since birth and an extra auricle on the same side, is reported here.

  6. 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.

  7. Beer potomania: a case report

    OpenAIRE

    Bhattarai, Nimesh; Kafle, Poonam; Panda, Mukta

    2010-01-01

    A syndrome of hyponatraemia associated with excessive beer drinking was first recognised in 1971. This syndrome has been referred to as beer potomania. Dilutional hyponatraemia occurs due to excessive consumption of an exclusive beer diet which is poor in salt and protein. We report a case of beer potomania who improved dramatically with introduction of solute load, with no subsequent neurological sequelae.

  8. Beer potomania: a case report.

    Science.gov (United States)

    Bhattarai, Nimesh; Kafle, Poonam; Panda, Mukta

    2010-04-29

    A syndrome of hyponatraemia associated with excessive beer drinking was first recognised in 1971. This syndrome has been referred to as beer potomania. Dilutional hyponatraemia occurs due to excessive consumption of an exclusive beer diet which is poor in salt and protein. We report a case of beer potomania who improved dramatically with introduction of solute load, with no subsequent neurological sequelae.

  9. Webbed penis: a rare case.

    Science.gov (United States)

    Agrawal, R; Chaurasia, D; Jain, M

    2010-01-01

    Webbed penis belongs to a rare and little-known defect of the external genitalia. The term denotes the penis of normal size for age hidden in the adjacent scrotal and pubic tissues. Though rare, it can be treated easily by surgery. A case of webbed penis is presented with brief review of literature.

  10. Lithium nephropathy: a case report

    OpenAIRE

    Raphael Reis Pereira-Silva; Debora Esperancini-Tebar

    2014-01-01

    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.

  11. 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.

  12. The Case for Forensic Toxicology

    Science.gov (United States)

    Baker, William P.; DeBeus, Elizabeth; Jones, Carleton

    2006-01-01

    Understanding natural and human-induced hazards is an important part of the standards-based science curriculum. Experience, however, indicates that the topic is a difficult one for many students. We have developed an exciting investigative laboratory exercise that uses simulated food-based case studies to promote critical thinking and improve…

  13. Plunging Ranula: A Case Report

    OpenAIRE

    F. R. Karjodkar; Ambika Gupta

    2011-01-01

    Plunging ranulas, also known as deep, diving, cervical or deep plunging ranula, usually appear in conjunction with oral ranula. Rarely, these ranulas may arise independent of oral swelling. A rare case of plunging ranula without oral swelling is discussed along with review of literature.

  14. 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.

  15. Equatorial jet - a case study

    Digital Repository Service at National Institute of Oceanography (India)

    Muraleedharan, P.M.; PrasannaKumar, S.

    Detailed EOF analysis of wind data reportEd. by Wunsch over Gan (00 degrees 41'S; 73 degrees 10'E) is made for the period 1963-70. The year 1964, which exhibited least variability from mean wind structure, has been chosen for the case study. EOF...

  16. 5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity

    DEFF Research Database (Denmark)

    Jensen, Søren Astrup; Sørensen, Jens Benn

    2012-01-01

    This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia.......This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia....

  17. Protective effects of fullerenol against chronic doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Injac Rade

    2009-01-01

    Full Text Available Since the introduction of Doxorubicin (Dox for the treatment of cancer in 1969, this compound has demonstrated high antitumor efficacy. Dox's use in chemotherapy has been limited largely due to its diverse toxicities, including cardiac, liver, renal, pulmonary, hematological and testicular toxicity. Various attempts have been made to reduce Dox-induced toxicity. These include dosage optimization, synthesis and use of analogues. Moreover, a number of agents have been investigated as protective agents during Dox therapy. Polyhydroxilated derivatives of fullerene, named fullerenols C60(OHn, are being extensively studied due to their great potential as antioxidants. It is proposed that they might act as free radical scavengers in biological systems, in xenobiotics-induced oxidative stress as well as against radioactive irradiation. We have investigated the effects of fullerenol C60(OH24 (Frl at doses of 25, 50 and 100 mg kg-1 week (for a time-span of three weeks on heart and liver tissue after Doxorubicin (Dox-induced toxicity in rats with colorectal cancer. In the present study, in vivo Wistar male rat model was used to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for three weeks chronic cardio- and hepatotoxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for three weeks. Commercially available methods were used for blood and pathohystological analysis and for the measurement of enzyme activity (SOD, MDA, GSH, GSSH, GPx, GR, CAT, CK, LDH, α-HBDH, AST, ALT in serum and homogenate samples of heart and liver tissues. According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.

  18. The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

    Directory of Open Access Journals (Sweden)

    Seyed Vahid Shetab Boushehri

    2010-10-01

    Full Text Available This is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50. Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects.

  19. Strategies for early detection of cardiotoxicities from anticancer therapy in adults: evolving imaging techniques and emerging serum biomarkers.

    Science.gov (United States)

    Akhter, Nausheen; Murtagh, Gillian; Yancy, Clyde

    2015-01-01

    Significant advances have been made in detecting cancer therapeutics-related cardiac dysfunction with serum biomarkers, cardiovascular MRI, echocardiography and multi-modality approaches. Serum biomarkers, notably cardiac troponins and natriuretic peptides, have been evaluated for their prognostic ability in predicting left ventricular dysfunction. Imaging modalities, such as cardiovascular MRI and echocardiography, have been used for cardiac surveillance of patients with cancer undergoing chemotherapy. Developments in imaging, specifically myocardial deformation imaging, also known as strain, have been shown to be sensitive tools in detecting early changes in cardiac function. This review aims to synthesize the evidence that supports emerging serum biomarkers and complementary imaging modalities that continue to enhance the detection of cancer therapeutics-related cardiac dysfunction.

  20. Effect of Piper betle on cardiac function, marker enzymes, and oxidative stress in isoproterenol-induced cardiotoxicity in rats.

    Science.gov (United States)

    Arya, Dharamvir Singh; Arora, Sachin; Malik, Salma; Nepal, Saroj; Kumari, Santosh; Ojha, Shreesh

    2010-11-01

    The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300 mg/kg) and P. betle (75, 150, and 300 mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300 mg/kg) or saline was orally administered for 30 days. ISP (85 mg/kg, s.c.) was administered at an interval of 24 h on the 28(th) and 29(th) day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (-LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (-LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300 mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.

  1. Electrophysiological and molecular mechanisms of protection by iron sucrose against phosphine-induced cardiotoxicity: a time course study.

    Science.gov (United States)

    Solgi, Reza; Baghaei, Amir; Golaghaei, Ali; Hasani, Shokoufeh; Baeeri, Maryam; Navaei, Mona; Ostad, Seyyed Nasser; Hosseini, Rohollah; Abdollahi, Mohammad

    2015-01-01

    The present study was designed for determining the exact mechanism of cytotoxic action of aluminum phosphide (AlP) in the presence of iron sucrose as the proposed antidote. Rats received AlP (12 mg/kg) and iron sucrose (5-30 mg/kg) in various sets and were connected to cardiovascular monitoring device. After identification of optimum doses of AlP and iron sucrose, rats taken in 18 groups received AlP (6 mg/kg) and iron sucrose (10 mg/kg), treated at six different time points, and then their hearts were surgically removed and used for evaluating a series of mitochondrial parameters, including cell lipid peroxidation, antioxidant power, mitochondrial complex activity, ADP/ATP ratio and process of apoptosis. ECG changes of AlP poisoning, including QRS, QT, P-R, ST, BP and HR were ameliorated by iron sucrose (10 mg/kg) treatment. AlP initiated its toxicity in the heart mitochondria through reducing mitochondrial complexes (II, IV and V), which was followed by increasing lipid peroxidation and the ADP/ATP ratio and declining mitochondrial membrane integrity that ultimately resulted in cell death. AlP in acute exposure (6 mg/kg) resulted in an increase in hydroxyl radicals and lipid peroxidation in a time-dependent fashion, suggesting an interaction of delivering electrons of phosphine with mitochondrial respiratory chain and oxidative stress. Iron sucrose, as an electron receiver, can compete with mitochondrial respiratory chain complexes and divert electrons to another pathway. The present findings supported the idea that iron sucrose could normalize the activity of mitochondrial electron transfer chain and cellular ATP level as vital factors for cell escaping from AlP poisoning.

  2. Sildenafil and Phosphodiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumor Cells to Doxorubicin

    Science.gov (United States)

    2010-07-01

    promotes nor ame- liorates Adriamycin-induced cytotoxicity against either bone marrow cells or macrophages. Serafini et al. found that sildenafil reversed...Immunol 108(5):671–680 29. Serafini P et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived

  3. What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment.

    Science.gov (United States)

    Bronte, Enrico; Bronte, Giuseppe; Novo, Giuseppina; Bronte, Fabrizio; Bavetta, Maria Grazia; Lo Re, Giuseppe; Brancatelli, Giuseppe; Bazan, Viviana; Natoli, Clara; Novo, Salvatore; Russo, Antonio

    2015-11-01

    The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation.

  4. The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

    Directory of Open Access Journals (Sweden)

    Seyed Vahid Shetab Boushehri

    2010-09-01

    Full Text Available "nThis is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50. Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects.

  5. p21{sup WAF1/Cip1/Sdi1} knockout mice respond to doxorubicin with reduced cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Terrand, Jerome; Xu, Beibei; Morrissy, Steve; Dinh, Thai Nho [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Williams, Stuart [Biomedical Engineering Program, College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States); Chen, Qin M., E-mail: qchen@email.arizona.edu [Department of Pharmacology,College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724 (United States)

    2011-11-15

    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 p21{sup WAF1/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, IFN{gamma} and TNF{alpha} 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: Black-Right-Pointing-Pointer Doxorubicin induces p21 elevation in the myocardium. Black-Right-Pointing-Pointer Doxorubicin causes dilated cardiomyopathy in wild type mice. Black-Right-Pointing-Pointer p21 Knockout mice are resistant against doxorubicin induced cardiomyopathy. Black-Right-Pointing-Pointer Lack of inflammatory response correlates with the resistance in p21 knockout mice.

  6. Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity.

    Science.gov (United States)

    Hall, Michael E; Smith, Grant; Hall, John E; Stec, David E

    2012-12-15

    Although disruption of leptin signaling is associated with obesity as well as cardiac lipid accumulation and dysfunction, it has been difficult to separate the direct effects of leptin on the heart from those associated with the effects of leptin on body weight and fat mass. Using Cre-loxP recombinase technology, we developed tamoxifen-inducible, cardiomyocyte-specific leptin receptor-deficient mice to assess the role of leptin in regulating cardiac function. Cre recombinase activation in the heart resulted in transient reduction in left ventricular systolic function which recovered to normal levels by day 10. However, when cardiomyocyte leptin receptors were deleted in the setting of Cre recombinase-induced left ventricular dysfunction, irreversible lethal heart failure was observed in less than 10 days in all mice. Heart failure after leptin receptor deletion was associated with marked decreases of cardiac mitochondrial ATP, phosphorylated mammalian target of rapamycin (mTOR), and AMP-activated kinase (pAMPK). Our results demonstrate that specific deletion of cardiomyocyte leptin receptors, in the presence of increased Cre recombinase expression, causes lethal heart failure associated with decreased cardiac energy production. These observations indicate that leptin plays an important role in regulating cardiac function in the setting of cardiac stress caused by Cre-recombinase expression, likely through actions on cardiomyocyte energy metabolism.

  7. In vitro cardiotoxicity screening of silver and metal oxide nanoparticles using human induced pluripotent stem cell-derived cardiomyocytes

    Science.gov (United States)

    Exposure risk to silver and metal oxide nanoparticles (NPs) continues to increase due to their widespread use in products and applications. In vivo studies have shown Ag, TiO2 and CeO2 NPs translocate to the heart following various routes of exposure. Thus, it is critical to asse...

  8. SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Yang Ruan

    2015-02-01

    Full Text Available Background: SIRT1, which belongs to the Sirtuin family of NAD-dependent enzymes, plays diverse roles in aging, metabolism, and disease biology. It could regulate cell survival and has been shown to be a protective factor in heart function. Hence, we verified the mechanism by which SIRT1 regulates doxorubicin induced cardiomyocyte injury in vivo and in vitro. Methods: We analyzed SIRT1 expression in doxorubicin-induced neonatal rat cardiomyocyte injury model and adult mouse heart failure model. SIRT1 was over-expressed in cultured neonatal rat cardiomyocyte by adenovirus mediated gene transfer. SIRT1 agonist resveratrol was used to treat the doxorubicin-induced heart failure mouse model. Echocardiography, reactive oxygen species (ROS production, TUNEL, qRT-PCR, and Western blotting were performed to analyze cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results: SIRT1 expression was down-regulated in doxorubicin induced cardiomocyte injury, accompanied by elevated oxidative stress and cell apoptosis. SIRT1 over-expression reduced doxorubicin induced cardiomyocyte apoptosis with the attenuated ROS production. SIRT1 also reduced cell apoptosis by inhibition of p38MAPK phosphorylation and caspase-3 activation. The SIRT1 agonist resveratrol was able to prevent doxorubicin-induced heart function loss. Moreover, the SIRT1 inhibitor niacinamide could reverse SIRT1's protective effect in cultured neonatal rat cardiomyocytes. Conclusions: These results support the role of SIRT1 as an important regulator of cardiomyocyte apoptosis during doxorubicin-induced heart injury, which may represent a potential therapeutic target for doxorubicin-induced cardiomyopathy.

  9. Five misunderstandings about Case-study Research

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent

    This article examines five common misunderstandings about case-study research: (1) Theoretical knowledge is more valuable than practical knowledge; (2) One cannot generalize from a single case, therefore the single case study cannot contribute to scientific development; (3) The case study is most...

  10. Five misunderstandings about case study research

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent

    2004-01-01

    This article examines five common misunderstandings about case-study research: (1) Theoretical knowledge is more valuable than practical knowledge; (2) One cannot generalize from a single case, therefore the single case study cannot contribute to scientific development; (3) The case study is most...

  11. PHAKOMATOSIS PIGMENTOVASCULARIS: REPORT OF A CASE

    Directory of Open Access Journals (Sweden)

    Mostafa Mirshams-Shahshahani

    1995-06-01

    Full Text Available The present study introduces a rare case of phakomatosispigmenJovascularis, which is charaderiud by the existence ofpigmentary naevus ond vascular naevus. Until 1985, 63 cases ofthis syndrome have been reported, mostly in Japon (56 cases. This is the first case of phakomatosis pigmentovascularis, reported in Iran.

  12. The Managerial Nature of Case Management.

    Science.gov (United States)

    Wolk, James L.; And Others

    1994-01-01

    Contends that case managers engage in the practice of management. Employs Mintzberg's seminal research on chief executive behavior to argue that case managers' work is similarly characterized by brevity, variety, and fragmentation. Notes that case managers perform the 10 roles developed by Mintzberg. Describes roles and presents case managers'…

  13. Learning with Multimedia Cases: An Evaluation Study

    Science.gov (United States)

    Van Den Berg, Ellen; Jansen, Leanne; Blijleven, Peter

    2004-01-01

    This article is about the relation between case-based learning and transfer in teacher education. Through a design research approach a multimedia case has been developed. The topic of the case is "outdoor activities in science education." The core of the case is a 17 minute video that is supplemented by all kinds of background information. Results…

  14. Cerebral paragonimiasis--report of five cases.

    Science.gov (United States)

    Toyonaga, S; Kurisaka, M; Mori, K; Suzuki, N

    1992-03-01

    Five cases of cerebral paragonimiasis presenting with hemianopsia, convulsion, and gait disturbance are discussed. The cases were all in the chronic stage. The intradermal paragonimiasis reaction, complement fixation, and Ouchterlony tests were not useful for diagnosis. Computed tomography demonstrated calcifications in all cases in sites consistent with the foci of symptoms. Surgical treatment in two cases failed to improve symptoms.

  15. Using Correspondence Analysis in Multiple Case Studies

    NARCIS (Netherlands)

    Kienstra, Natascha; van der Heijden, Peter G.M.

    2015-01-01

    In qualitative research of multiple case studies, Miles and Huberman proposed to summarize the separate cases in a so-called meta-matrix that consists of cases by variables. Yin discusses cross-case synthesis to study this matrix. We propose correspondence analysis (CA) as a useful tool to study thi

  16. Using correspondence analysis in multiple case studies

    NARCIS (Netherlands)

    Kienstra, N.H.H.; van der Heijden, P.G.M.

    2015-01-01

    In qualitative research of multiple case studies, Miles and Huberman proposed to summarize the separate cases in a so-called meta-matrix that consists of cases by variables. Yin discusses cross-case synthesis to study this matrix. We propose correspondence analysis (CA) as a useful tool to study thi

  17. Higher rank case of Dwork's conjecture

    CERN Document Server

    Wan, D

    2000-01-01

    This is the final version of ANT-0142 ("An embedding approach to Dwork's conjecture"). It reduces the higher rank case of the conjecture over a general base variety to the rank one case over the affine space. The general rank one case is completed in ANT-0235 "Rank one case of Dwork's conjecture". Both papers will appear in JAMS.

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

    Directory of Open Access Journals (Sweden)

    Kyriakides Theodoros

    2011-08-01

    Full Text Available 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 presentation A 23-year-old Caucasian man presented to an orthopedic surgeon with a history of left shoulder weakness of several weeks' duration. The patient complained of pain and inability to lift minimal weight, such as a glass of water, following an appendectomy. His orthopedic clinical examination revealed obvious atrophy of the supraspinatus and infraspinatus muscles and 2 of 5 muscle strength scores on flexion resistance and external rotation resistance. Magnetic resonance imaging showed diffuse high signal intensity within the supraspinatus and infraspinatus muscles and early signs of minimal fatty infiltration consistent with denervation changes. No compression of the suprascapular nerve in the suprascapular or spinoglenoid notch was noted. Electromyographic studies showed active denervation effects in the supraspinatus muscle and more prominent in the left infraspinatus muscle. The findings were compatible with damage to the suprascapular nerve, especially the part supplying the infraspinatus muscle. On the basis of the patient's history, clinical examination, and imaging studies, the diagnosis was suspected to be associated with a possible traction injury of the suprascapular nerve that could have occurred during the patient's transfer from the operating table following an appendectomy. Conclusion Our case report may provide important insight into patient transfer techniques used by hospital personnel, may elucidate the clinical significance of careful

  19. CASE REPORT: Chorangiophagus Parasiticus: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Ranjit Kangle

    2012-07-01

    Full Text Available Malformations are common in twin pregency compared to singleton pregnancy. One such rare anomaly is Chorangiophagus parasiticus also known as twin to twin transfusion which is an asymmetric abnormality of monozygotic twins, where asymmetric twin survive by parasitisizing normal twin. It’s a rare condition with an incidence of 1 in 35.000 deliveries. We report such a case with complete autopsy findings.

  20. A CYTOLOGICALLY DIAGNOSED CASE OF GIANT FIBROADENOMA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Metta Raja Gopal

    2015-02-01

    Full Text Available Fibroadenomas are benign solid tumors which occur most frequently in child bearing age with 68% occurrence in adolescents. Giant fibroadenomas are uncommon variants of fibroadenomas usually presenting in adolescents characterized by massive and rapid enlargement of bre ast tissue which may be quite alarming to the young girls. We present a case of giant fibroadenoma diagnosed by FNAC in the 14 yr adolescent who presented with large unilateral left breast enlargement which grew rapidly over a period of 10 months.