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31.
Rabbit model for in vivo study of anthracycline-induced heart failure and for the evaluation of protective agents 总被引:4,自引:0,他引:4
Simůnek T Klimtová I Kaplanová J Mazurová Y Adamcová M Sterba M Hrdina R Gersl V 《European journal of heart failure》2004,6(4):377-387
BACKGROUND: Cardiac toxicity associated with chronic administration of anthracycline (ANT) antibiotics represents a serious complication of their use in anticancer chemotherapy, but can also serve as a useful experimental model of cardiomyopathy and congestive heart failure. AIMS: In this study, a model of chronic ANT cardiotoxicity induced by repeated i.v. daunorubicin (DAU) administration to rabbits was tested. METHODS: Three groups of animals were used: (1) control group-10 animals received i.v. saline; (2) 11 animals received DAU (3 mg/kg, i.v.); (3) 5 animals received the model cardioprotective agent dexrazoxane (DEX, 60 mg/kg, i.p.), 30 min prior to DAU. All substances were administered once weekly, for 10 weeks. The DAU-induced heart damage and protective action of DEX were determined and quantitated with the use of histopathology, invasive haemodynamic measurements (e.g. left ventricular pressure changes-dP/dt(max), dP/dt(min)), non-invasive systolic function examinations (left ventricular ejection fraction, PEP/LVET index) and biochemical analysis of cardiac troponin T plasma concentrations. RESULTS: All the employed methods showed unambiguously pronounced heart impairment in the DAU group, with the development of both systolic and diastolic heart failure, as well as significant reduction of DAU-cardiotoxicity in DEX-pretreated animals. Other toxicities were acceptable. CONCLUSION: The presented model has been approved to be consistent and reliable and it can serve as a basis for future determinations and comparisons of chronic cardiotoxic effects of various drugs, as well as for the evaluation of potential cardioprotectants. 相似文献
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33.
Zadák Z Hyspler R Tichá A Solichová D Bláha V Melichar B 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2006,49(1):23-26
The objective of this work was to review nutritional components of the Mediterranean diet. The Mediterranean diet is not a specific diet plan or diet program but a collection of eating habits that are traditionally followed by the people of the Mediterranean region. There are at least 16 countries bordering the Mediterranean Sea and food habits vary between these countries according to culture, ethnic background and religion. The Mediterranean diet, containing olive oil, fish, fruits and vegetable is associated with a low rate of cardivascular and cancer diseases. This diet is rich in phytosterols, squalene, dietary fibre, antioxidants, phenolic substances and polyunsaturated acids. 相似文献
34.
Zadák Z Hyspler R Hronek M Tichá A 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2010,53(3):131-137
Measurement of parameters of energy requirement, respiratory quotient (RQ), rate of oxygen consumption (VO2) and rate of carbon dioxide production (VCO2) reveal Ringerfundin as an excellent and metabolically stable-acting balanced ionic solution, which does not increase the consumption of O2 or the total energy requirement. In conclusion, Ringerfundin was very well tolerated and in no case were observed undesirable effects. 相似文献
35.
Hana Kalábová Bohuslav Melichar Leoš Ungermann Jiří Doležal Lenka Krčmová Markéta Kašparová Jiří Plíšek Radomír Hyšpler Miroslav Pecka Dagmar Solichová 《Medical oncology (Northwood, London, England)》2011,28(4):1281-1287
An increased incidence of complications of atherosclerosis has been noted in cancer survivors. The aim of the present study
was to evaluate, in patients with breast carcinoma, the effect of antracycline-based chemotherapy on carotid intima-media
thickness (IMT), myocardial perfusion, assessed by single-photon emission tomography (SPECT) and laboratory parameters associated
with the risk of atherosclerosis. Thirty-six patients with breast cancer were evaluated before and after anthracycline-based
chemotherapy. Retinol, alpha-tocopherol, glycosylated hemoglobin and urinary neopterin were measured by high-performance liquid
chromatography. Peripheral blood cell count, D-dimers, fibrinogen, antithrombin, glucose, magnesium, creatinine, uric acid,
albumin, C-reactive protein, lipoprotein (a), cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein
(LDL) cholesterol, triglycerides, homocysteine, urinary albumin and N-acetyl-beta-d-glucosaminidase (NAG) were determined with routine methods. No significant differences were observed between patients and
16 controls. Compared to the measurement before the start of therapy, peripheral blood leukocyte and platelet count, hemoglobin,
creatinine, HDL cholesterol, retinol, albumin, urinary albumin and NAG decreased, and total cholesterol, LDL cholesterol,
triglycerides, neopterin and mean IMT increased significantly after the treatment. Of the 36 patients who had SPECT after
treatment, perfusion defects were noted only in two cases, including the patient who had perfusion defects at baseline examination
and a patient who did not have a baseline SPECT. In conclusion, a significant increase in carotid IMT, total cholesterol,
LDL cholesterol, triglycerides and urinary neopterin and a decrease of peripheral blood leukocyte and platelet counts, hemoglobin,
creatinine, HDL cholesterol, retinol, albumin and NAG were observed after the treatment. 相似文献
36.
Simůnek T Klimtová I Adamcová M Gersl V Hrdina R Sterba M Kaplanová J Mazurová Y 《Cancer chemotherapy and pharmacology》2003,52(5):431-434
Purpose Cardiac troponin T (cTnT) plasma concentration is considered a useful marker of anthracycline-induced cardiomyopathy. In this study we used daunorubicin-treated Chinchilla rabbits as a model to investigate the relationship between left ventricular contractility and cTnT plasma concentrations.Methods Two groups of animals were used: a control group (n=8) received i.v. saline, and an experimental group (n=11) received daunorubicin (3 mg/kg, i.v.). The substances were administered once weekly for 10 weeks, and 5–7 days after the last administration, left ventricular cardiac contractility (dP/dtmax) was invasively measured as a contractility index and blood was sampled for cTnT concentration determination (Elecsys Troponin T STAT immunoassay).Results Cardiac contractility was significantly lower in seven surviving daunorubicin-treated animals than in control animals (745.7±69.3 vs 1393.4±25.5 kPa/s; P<0.001), while cTnT plasma concentrations were significantly increased (medians 0.278 vs 0.000 ng/ml; P<0.001). When the dP/dtmax values of individual daunorubicin-treated animals were plotted against the corresponding cTnT plasma concentrations, a close negative linear correlation was found (R=–0.910; P<0.005; regression equation: dP/dtmax=–1861*cTnT+1234).Conclusions This study suggests that determination of cTnT plasma levels, which is simple and inexpensive, could be used in anthracycline-treated patients for left ventricular systolic function assessment and contractility estimation. 相似文献
37.
Josef Dvořák Bohuslav Melichar Radomír Hyšpler Lenka Krčmová Lubor Urbánek Hana Kalábová Markéta Kašparová Dagmar Solichová 《Medical oncology (Northwood, London, England)》2010,27(3):690-696
Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment
of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods
of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal
permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated
with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin
in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by
capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by
high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment.
Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed
in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed
between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using
the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients
with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol. 相似文献
38.
Melichar B Krcmová L Kalábová H Holecková P Kasparová M Plísek J Hyspler R Studentová H Solichová D 《Journal of nutritional science and vitaminology》2010,56(4):222-226
Cetuximab is a chimeric antibody registered for the therapy of advanced colorectal carcinoma. Cancer and anticancer therapy are associated with oxidative stress, and disorders of antioxidant balance may be involved in the toxicity associated with anticancer treatment. The aim of the present study was to investigate the changes of serum retinol, alpha-tocopherol and C-reactive protein during the first month of treatment with cetuximab and chemotherapy. Twenty-five consecutive patients with metastatic colorectal carcinoma treated with a combination of chemotherapy and cetuximab were included in the present study. Serum retinol and alpha-tocopherol were determined by high-performance liquid chromatography and serum C-reactive protein was determined using commercial kits. Significant correlation was observed between baseline concentrations of retinol and C-reactive protein (r(s)=-0.54, p<0.01). Median survival of patients who had baseline serum retinol below 1.25 μmol/L was 10 mo compared to 18 mo for patients who had serum retinol equal or above 1.25 μmol/L (p<0.05); median survival of patients who had serum C-reactive protein below 24 mg/L was significantly longer compared to patients with C-reactive protein levels equal or above 24 mg/L (18 vs. 7 mo, p<0.05), but no difference in survival was observed based on alpha-tocopherol levels. Twenty-two patients had evaluation of retinol, alpha-tocopherol and C-reactive protein at least once during the follow up. Serum concentration of alpha-tocopherol decreased significantly during the therapy, but retinol and C-reactive protein concentrations remained unchanged. In conclusion, a significant correlation was observed between serum retinol and C-reactive protein. Serum alpha-tocopherol decreased significantly during the first month of combination therapy with cetuximab. Low retinol and high C-reactive protein concentrations were predictive of poor prognosis in this patient population. 相似文献
39.
Naveen Ashish Marcas M. Bamman Frank J. Cerny Dan M. Cooper Pierre D'Hemecourt Joey C. Eisenmann Dawn Ericson John Fahey Bareket Falk Davera Gabriel Michael G. Kahn Han C.G. Kemper Szu‐Yun Leu Robert I. Liem Robert McMurray Patricia A. Nixon J. Tod Olin Paolo T. Pianosi Mary Purucker Shlomit Radom‐Aizik Amy Taylor 《CTS Clinical and Translational Science》2015,8(1):67-76
In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health. 相似文献
40.
Hrdina R Gersl V Klimtová I Simůnek T Mazurová Y Machácková J Adamcová M 《Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové》2002,45(3):99-105
A possible protective action of DMPS (a dithiol chelating agent) against chronic daunorubicin toxicity in rabbits in comparison with dexrazoxane was investigated. The rabbits were divided into five groups: control (saline, 1 ml/kg i.v.), daunorubicin (3 mg/kg i.v.), DMPS (50 mg/kg i.v.); the remaining two groups were pre-treated either with dexrazoxane (60 mg/kg i.p.) or DMPS (50 mg/kg i.v.) 30 min before administration of daunorubicin (3 mg/kg i.v.). Drugs were given once a week for 10 weeks. Routine biochemical parameters were determined in weeks 1, 5 and 11. In the 11th week, invasive haemodynamic parameters were measured, then the rabbits underwent autopsy, cardiac tissue was examined by light microscopy and scored semiquantitatively. The contents of calcium, potassium, magnesium, iron and selenium were measured in the left heart ventricle. DMPS administered alone was well tolerated and did not cause any major signs of toxicity. It decreased the cardiac content of calcium, but did not affect the iron concentration. In contrast to dexrazoxane, DMPS pre-treatment did not prevent the decline in body weight in weeks 8-11 caused by daunorubicin, actually worsened mortality (26.7% vs 40.0%), did not ameliorate daunorubicin-induced nephrotic syndrome, and did not prevent the occurrence of the severe myocardial lesions. Unlike dexrazoxane, a lack of protective effect of DMPS against chronic daunorubicin toxicity in rabbits was demonstrated. The underlying cause may consist in the fact that DMPS does not efficiently chelate tissue iron and thus may not prevent the formation of oxygen free radicals. 相似文献