Effect of nicorandil on the myocardial tissue perfusion and myocardial cell injury in patients with diabetes after PCI

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Xue-Li Ren1

2017-04-01

Full Text Available Objective: To study the effect of nicorandil on the myocardial tissue perfusion and myocardial cell damage in patients with diabetes after percutaneous coronary intervention (PCI. Methods: 68 patients with coronary heart disease and type 2 diabetes mellitus who received PCI in our hospital between May 2011 and September 2015 were collected and then divided into observation group and control group (n=34 according to the single-blind randomized control method. Control group of patients received PCI alone, and the observation group of patients received nicorandil therapy after PCI. After treatment, real-time myocardial ultrasound contrast was used to evaluate the myocardial perfusion of two groups of patients; blood biochemical analyzer was used to detect the contents of peripheral blood myocardial enzyme spectrum indexes; the ELISA method was used to detect the contents of serum oxidative stress indicators; RIA method was used to detect the contents of serum apoptosis molecules. Results: After treatment, the myocardial tissue perfusion parameters plateau peak intensity (A, slope rate of curve (β and myocardial blood flow (A×β levels of observation group were significantly higher than those of control group (P<0.05; peripheral blood myocardial enzyme spectrum indexes creatine kinase (CK, lactate dehydrogenase (LDH, troponin I (cTnI and glutamic oxalacetic transaminase (GOT contents of observation group were significantly lower than those of control group (P<0.05; serum vitamin E (VitE and vitamin C (VitC contents of observation group were significantly higher than those of control group while malondialdehyde (MDA, advanced oxidation protein products (AOPPs, soluble apoptosis-associated factor (sFas and soluble apoptosis-associated factor ligand (sFasL contents were lower than those of control group (P<0.05. Conclusion: Adjuvant nicorandil therapy can improve the myocardial perfusion and reduce the myocardial cell injury in patients with coronary

Myocardial damage in successful vessel coronary angioplasty as assessed by creatinine kinase and its myocardium band isoenzyme levels

International Nuclear Information System (INIS)

Abbas, S.; Samor, N.A.; Kayani, A.M.

2008-01-01

To determine the frequency of myocardial damage in elective, successful, single vessel percutaneous coronary angioplasty by assessing myocardial band (MB), creatinine kinase levels and to find out the association of common modifiable risk factors with myocardial damage in patients undergoing single vessel coronary angioplasty. Fifty patients undergoing elective and successful single vessel percutaneous coronary angioplasty were evaluated with creatinine kinase and creatinine kinase MB levels before and after 8 hours and 1st day following coronary angioplasty. Studied variables included the length of stent deployed, maximum deployment pressure and total balloon inflation time, apart from hypertension, cholesterol level, smoking and diabetes mellitus. Out of 50 patients, 9 had raised creatinine kinase at 8 hours (18%) and 10 had raised creatinine kinase (20%) on 1st day following coronary angioplasty, 7 (14%) patients and 8 (16%) patients had raised creatinine kinase MB levels at 8 hours and 1st day following coronary angioplasty respectively. The rise of either was equal to or more than 3 times the normal limits. Modifiable risk factors, significantly associated with myocardial damage, were diabetes mellitus (p=0.006) and LDL levels (p=0.009) in patients undergoing single vessel coronary angioplasty. Successful elective, uncomplicated, single vessel coronary angioplasty resulted in some myocardial damage evident by mild rise in cardiac enzymes but rise of creatinine kinase MB above 3 times of normal, which signifies percutaneous coronary angioplasty-related myocardial infarction, was not seen. There was a significant association between diabetes mellitus, LDL levels and myocardial damage in patients undergoing coronary angioplasty but no significant association was found between hypertension, smoking and myocardial damage. (author)

Relation between myocardial damage and disease activity in patients with systemic lupus erythematosus by exercise {sup 201}Tl scintigraphy

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Kuzumoto, Masayuki [Nara Medical Univ. (Japan)

1997-08-01

Myocardial damage in patients with systemic lupus erythematosus (SLE) was evaluated using exercise thallium-201 myocardial scintigraphy, and the relationship between myocardial damage and disease activity of SLE was examined. Twenty-seven patients (26 women and 1 man, mean age 43 years), in whom extramural coronary artery lesions were excluded by coronary angiogram or presumed to be excluded by exercise electrocardiogram, were enrolled in this study. The mean duration of disease and the mean duration of corticosteroid therapy in these patients were 94 and 77 months, respectively. Exercise thallium-201 scintigraphy was performed twice (mean interval, 30 months) to evaluate the progression of myocardial damage. Myocardial ischemia as an index of myocardial damage was evaluated by visual analysis and ischemic score (IS). The changes in myocardial ischemia were categorized into 3 groups: improved, unchanged or worsened. The disease activity of SLE was determined by the SLE Disease Activity Index (SLEDAI), and the changes in this index were classified into the same three categories, as evaluated every six months between the two scintigraphic examinations. Disease activity was significantly correlated with myocardial ischemia (p<0.05), and with myocardial ischemia as diagnosed by {Delta}IS (difference in ischemic score between the first and second thallium-201 scintigrams: p<0.005). But neither the duration of disease nor the duration of corticosteroid therapy was correlated with IS at the first scintigraphy. These results indicate that control of SLE disease activity may be critical in the treatment of myocardial damage resulting from vascular lesions, especially intramyocardial small-artery disease, in patients with SLE. (author)

Impact of Insulin Resistance on Silent and Ongoing Myocardial Damage in Normal Subjects: The Takahata Study

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Taro Narumi

2012-01-01

Full Text Available Background. Insulin resistance (IR is part of the metabolic syndrome (Mets that develops after lifestyle changes and obesity. Although the association between Mets and myocardial injury is well known, the effect of IR on myocardial damage remains unclear. Methods and Results. We studied 2200 normal subjects who participated in a community-based health check in the town of Takahata in northern Japan. The presence of IR was assessed by homeostasis model assessment ratio, and the serum level of heart-type fatty acid binding protein (H-FABP was measured as a maker of silent and ongoing myocardial damage. H-FABP levels were significantly higher in subjects with IR and Mets than in those without metabolic disorder regardless of gender. Multivariate logistic analysis showed that the presence of IR was independently associated with latent myocardial damage (odds ratio: 1.574, 95% confidence interval 1.1–2.3 similar to the presence of Mets. Conclusions. In a screening of healthy subjects, IR and Mets were similarly related to higher H-FABP levels, suggesting that there may be an asymptomatic population in the early stages of metabolic disorder that is exposed to myocardial damage and might be susceptible to silent heart failure.

Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

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Lobo, Reema Orison; Shenoy, Chandrakala K

2015-07-01

Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

Cell therapy in myocardial infarction: emphasis on the role of MRI

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Ye, Yuxiang; Bogaert, Jan

2008-01-01

Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points. (orig.)

Utility of Cardiac Magnetic Resonance to assess association between admission hyperglycemia and myocardial damage in patients with reperfused ST-Segment Elevation Myocardial Infarction

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Wolf Jean-Eric

2008-01-01

Full Text Available Abstract Aims to investigate the association between admission hyperglycemia and myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI using Cardiac Magnetic Resonance (CMR. Methods We analyzed 113 patients with STEMI treated with successful primary percutaneous coronary intervention. Admission hyperglycemia was defined as a glucose level ≥ 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP, providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE, reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores. Results Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and 1c (p = 0.01 and 0.04, peak plasma Creatine Kinase (p In a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores. Conclusion Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR.

Plain computed tomography for assessment of early coronary microcirculatory damage after revascularization therapy in acute myocardial infarction

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Kato, Masaya; Dote, Keigo; Sasaki, Shota

2006-01-01

Coronary microcirculatory damage is an important factor for the prognosis for acute myocardial infarction (MI) after revascularization. The myocardial enhancement area with contrast media infused during coronary revascularization therapy, detected by computed tomography (CT) just after revascularization, has been reported to correspond to the area of hemorrhagic infarction. The relationship between myocardial contrast enhancement and coronary microcirculatory damage was investigated in the present study. Thirteen patients with acute anterior MI underwent successful coronary revascularization within 6 h of symptom onset were enrolled. The coronary flow velocity pattern was measured using a Doppler guidewire and chest CT assessments were performed immediately after coronary revascularization. The ratio of mean CT number of the highest-enhanced myocardial area and the lumen of the left ventricle was defined as a relative CT number. The relative CT number significantly correlated with coronary diastolic deceleration time (r=-0.78, p<0.002) and coronary diastolic deceleration rate (r=0.74, p<0.04). It also correlated with peak myocardial enzyme release in plasma. Myocardial contrast enhancement detected using plain CT just after coronary reperfusion therapy implies coronary microcirculatory damage in acute MI. The relative CT number is useful in evaluating the impaired coronary microcirculatory state. (author)

Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

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Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

2008-03-01

Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

QRS slopes for assessment of myocardial damage in chronic chagasic patients

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Pueyo, E; Laciar, E; Anzuola, E; Laguna, P; Jane, R

2007-01-01

In this study the slopes of the QRS complex are evaluated for determination of the degree of myocardial damage in chronic chagasic patients. Previous studies have demonstrated the ability of the slope indices to reflect alterations in the conduction velocity of the cardiac impulse. Results obtained in the present study show that chronic chagasic patients have significantly flatter QRS slopes as compared to healthy subjects. Not only that but the extent of slope lessening turns out to be proportional to the degree of myocardial damage caused by the disease. Additionally, when incorporating the slope indices into a classification analysis together with other indices indicative of the presence of ventricular late potentials obtained from high resolution electrocardiography, results show that the percentages of correct classification increase up to 62.5%, which means eight points above the percentages obtained prior to incorporation of the slope indices. It can be concluded that QRS slopes have great potential for assessing the degree of severity associated with Chagas' disease

Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

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Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

2017-09-01

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

The myocardial perfusion imaging of bone marrow mesenchymal stem cell transplantation treated acute myocardial infarction in pig

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He Miao; Hou Xiancun; Li Yaomei; Zhou Peng; Qi Chunmei; Wu Weihuan; Li Li

2006-01-01

Objective: To evaluate the clinical value of bone marrow mesenchymal stem cell transplantation on acute myocardial infarction in pig with myocardial perfusion imaging. Methods: Acute myocardial infarction models were established by 21 minitype Chinese pigs and were divided into two groups. After 10 days, experimental group (n=11) was transplanted with bone marrow mesenchymal stem cell at the infarct areas, and the control group (n=10) with incubation solution. Before and eight weeks after transplantation, both groups were examined by 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging and with semi-quantitative analysis. Besides, echocardiogram and immunohistochemistry were also performed. Results: There was significant difference of total myocardial perfusion abnormal segments (46 vs 26), infarct areas [(34±12)% vs (21±10)%] and myocardial ischemia score [(20.0±4.3) vs (12.1±3.6)] between two groups (P<0.05). Also, there were accordant results with echocardiogram and immunohistochemistry findings. Conclusions: Bone marrow mesenchymal stem cell transplantation may improve blood perfusion and viability of the ischemic areas: Myocardial perfusion imaging can accurately observe the survival of bone marrow mesenchymal stem cell transplanted at the infarct areas. (authors)

Histochemical and immunohistochemical analyses of the myocardial scar fallowing acute myocardial infarction

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Tatić Vujadin

2012-01-01

were positive to CD34 and CD31, and smooth muscle cells to SMA. Oval and elongated cells were positive to PCNA and Ki-67. The preserved muscle fibers in the scar were positive to myosin, myoglobin and desmin as well as elongated and oval cells. Other cells were negative to these markers. Conclusion. Our findings speak that myocardial regeneration is maybe possible and develops in human ischemic heart damages and that the myocardium is not a static organ without capacity of cell regeneration.

Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy

International Nuclear Information System (INIS)

Clubb, F.J. Jr.; Bishop, S.P.

1984-01-01

The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms. Results indicated that the growth of myocardial cells in period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells

NF-κB involvement in hyperoxia-induced myocardial damage in newborn rat hearts.

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Zara, Susi; De Colli, Marianna; Rapino, Monica; Di Valerio, Valentina; Marconi, Guya Diletta; Cataldi, Amelia; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

2013-11-01

Premature newborns are frequently exposed to hyperoxia ventilation and some literature data indicate the possibility of hyperoxia-induced myocardial damage. Since nuclear factor κB (NF-κB) is a crucial signaling molecule involved in physiological response to hyperoxia in different cell types as well as in various tissues, our attention has been focused on the role played by NF-κB pathway in response to moderate and severe hyperoxia exposure in rat neonatal heart tissue. Akt and IκBα levels, involved in NF-κB activation, along with the balance between apoptotic and survival pathways have also been investigated. Experimental design of the study has involved exposure of newborn rats to room air (controls), 60 % O2 (moderate hyperoxia), or 95 % O2 (severe hyperoxia) for the first two postnatal weeks. Morphological analysis shows a less compact tissue in rat heart exposed to moderate hyperoxia and a decreased number of nuclei in samples exposed to severe hyperoxia. A significant increase of NF-κB positive nuclei percentage and p-IκBα expression in samples exposed to 95 % hyperoxia compared to control and to 60 % hyperoxia is evidenced; in parallel, an increase of pAkt/Akt ratio in both samples exposed to 95 and 60 % hyperoxia is shown. Furthermore, a more evident cytochrome c/Apaf-1 immunocomplex and a decreased Bcl2 expression in 95 % hyperoxia-exposed sample compared to 60 % exposed one is evidenced. In conclusion, our findings suggest the involvement of the NF-κB pathway and Akt signaling in the mechanisms of myocardial hyperoxic damage in the newborns, with particular reference to the induction of oxidative stress-related apoptosis.

Effect of fast-track cardiac anesthesia on myocardial oxidative damage, inflammation and nerve related peptides of patients undergoing cardiac operation

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Xing-Tao Cai

2016-01-01

Full Text Available Objective: To study the effect of fast-track cardiac anesthesia on myocardial oxidative damage, inflammation and nerve related peptides of patients undergoing cardiac operation. Methods: Sixty patients with rheumatic heart disease undergoing heart valve surgery were randomly divided into the fast track group (n=30 and conventional group (n=30. Then myocardial injury indicators, mitochondrial oxidative stress indicators, inflammation indicators and nerverelated peptides of both groups were analyzed. Results: cTnI contents at T2-T4 points in time of both groups showed an increasing trend and the increasing trend of fast track group was weaker than that of conventional group; SOD contents as well as mitochondrial tristate respiratory function, respiratory control ratios and phosphorus oxygen ratios in myocardial tissue of fast track group were higher than those of conventional group, and MDA contents was lower than those of conventional group; plasma TNF-α, IL-6, IL-8, NSE, S100β and Aβ contents of fast track group were lower than those of conventional group. Conclusions: Fasttrack cardiac anesthesia can protect myocardial cells, reduce mitochondrial oxidative stress, relieve inflammation and improve nerve function; it is an ideal anesthesia method for cardiac operation.

Cardioprotection against experimental myocardial ischemic injury using cornin

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Y. Xu

2016-01-01

Full Text Available Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

The usefulness of the nuclear cardiology in the cellular implant in patients with severe myocardial damage; La utilidad de la cardiologia nuclear en el implante celular en pacientes con dano miocardico severo

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Omelas A, M.; Arguero S, R.; Garrido G, M.H.; Rodriguez C, A.; Careaga, G.; Castano G, R.; Nambo, M.J.; Pascual P, J.; Ortega R, A.; Gaxiola A, A.; Magana S, J.A.; Estrada A, H.; Equipo de Tecnicos en Medicina Nuclear [Centro Medico Nacional Siglo XXI IMSS Hospital de Cardiologia-Servicio de Medicina Nuclear Mexico DF (Mexico)

2005-07-01

The recent therapeutic advances as the cellular implant as well as those different protocols of image acquisition in the field of the Nuclear Cardiology its have allowed that the patient with severe myocardial damage and without some possibility of revascularization is benefited with these advances. Doubtless the Tl-201 par excellence has an important paper for standardize the more appropriate therapeutic behavior for the heart attack patient; reason by this investigation protocol was developed. The objective of the study was to identify the heart attack regions without viable tissue with SPECT in patient with important myocardial damage without some possibility of traditional revascularization; for the 'Stem cell' cellular implantation therapy. The methodology it was carried out by a study of myocardial perfusion in 10 patients with important myocardial damage previous cellular implants, with PICANUC/ SPECT methodology and using a software (Emory Tool Box) for the image processing validated by the University of Emory Atlanta GA; and using as tracer the Tl - 201 to identify the heart attack regions without presence of viable tissue with an analysis model of 17 segments standardized for the left ventricle; qualifying this way the myocardial perfusion in: 0 (normal), 1 (light), 2 (moderate), 3 (severe), 4 (absent) and x (bad technique). The conclusions were that the SPECT study with PICANUC methodology with Tl-201 is safe and effective for the precise localization for the cellular implantation via direct intra myocardial. (Author)

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways

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Jun Yang

2015-07-01

Full Text Available Background: Myocardial apoptosis is heavily implicated in the myocardial damage caused by ischemia-reperfusion (I/R. Toll-like receptor 4 (TLR4 is a potent inducer of these apoptotic cascades. In contrast, the radioprotective 105 kDa protein (RP105 is a specific negative regulator of TLR4 signaling pathways. However, the precise mechanisms by which RP105 inhibits myocardium apoptosis via TLR4-associated pathways during I/R is not fully understood. Methods: We utilized a rat model of myocardial ischemic reperfusion injury (MIRI. Animals were pre-treated with Ad-EGFP adenovirus, Ad-EGFP-RP105 adenovirus, saline, or nothing (sham. After three days, rats underwent a 30min left anterior descending coronary artery occlusion and a 4h reperfusion. Mycardial tissue was assessed by immunohistochemistry, TUNEL-staining, Western blot, quantitative RT-PCR, and a morphometric assay. Results: RP105 overexpression resulted in a reduction in infarct size, fewer TUNEL-positive cardiomyocytes, and a reduction in mitochondrial-associated apoptosis cascade activity. Further, RP105 overexpression repressed I/R-induced myocardial injury by attenuating myocardial apoptosis. This was mediated by inhibiting TLR4 activation and the phosphorylation of P38MAPK and the downstream transcription factor AP-1. Conclusion: RP105 overexpression leads to the de-activation of TLR4, P38MAPK, and AP-1 signaling pathways, and subsequently represses apoptotic cascades and ensuing damage of myocardial ischemic reperfusion. These findings may become the basis of a novel therapeutic approach for reducing of cardiac damage caused by MIRI.

Association of myocardial cell necrosis with experimental cardiac hypertrophy

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Revis, N W; Cameron, A J.V.

1979-01-01

Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

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Rui Guo

2010-01-01

Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

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Guo, Rui; Ren, Jun

2010-01-18

Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

Three-dimension structure of ventricular myocardial fibers after myocardial infarction

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Li Libin

2010-11-01

Full Text Available Abstract Background To explore the pathological changes of three-dimension structure of ventricular myocardial fibers after anterior myocardial infarction in dog heart. Methods Fourteen acute anterior myocardial infarction models were made from healthy dogs (mean weight 17.6 ± 2.5 kg. Six out of 14 dogs with old myocardial infarction were sacrificed, and their hearts were harvested after they survived the acute anterior myocardial infarction for 3 months. Each heart was dissected into ventricular myocardial band (VMB, morphological characters in infarction region were observed, and infarct size percents in descending segment and ascending segment were calculated. Results Six dog hearts were successfully dissected into VMB. Uncorresponding damages in myocardial fibers of descending segment and ascending segment were found in apical circle in anterior wall infarction. Infarct size percent in the ascending segment was significantly larger than that in the descending segment (23.36 ± 3.15 (SD vs 30.69 ± 2.40%, P = 0.0033; the long axis of infarction area was perpendicular to the orientation of myocardial fibers in ascending segment; however, the long axis of the infarction area was parallel with the orientation of myocardial fibers in descending segment. Conclusions We found that damages were different in both morphology and size in ascending segment and descending segment in heart with myocardial infarction. This may provide an important insight for us to understand the mechanism of heart failure following coronary artery diseases.

Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging

International Nuclear Information System (INIS)

Yamada, Kiyoyasu; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Sawada, Ken; Isobe, Satoshi; Ohshima, Satoru; Murohara, Toyoaki; Hirai, Makoto

2012-01-01

To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. (orig.)

Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

International Nuclear Information System (INIS)

Arimoto, Takanori; Takeishi, Yasuchika; Niizeki, Takeshi

2005-01-01

Iodine-123-metaiodobenzylguanidine ( 123 I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage. The aim of the present study was to compare cardiac sympathetic nervous activity assessed by 123 I-MIBG imaging with serum levels of H-FABP in patients with heart failure. Fifty patients with chronic heart failure were studied. 123 I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay. Heart to mediastinum (H/M) ratios of 123 I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r=-0.296, p=0.029) and BNP (r=-0.335, p=0.0213). Myocardial washout rate of 123 I-MIBG was also correlated with H-FABP (r=0.469, p 123 I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart. (author)

Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

Science.gov (United States)

Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

2009-11-24

Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

Infarct-like acute myocarditis: relation between electrocardiographic findings and myocardial damage as assessed by cardiac magnetic resonance imaging.

Science.gov (United States)

Nucifora, Gaetano; Miani, Daniela; Di Chiara, Antonio; Piccoli, Gianluca; Artico, Jessica; Puppato, Michela; Slavich, Gianaugusto; De Biasio, Marzia; Gasparini, Daniele; Proclemer, Alessandro

2013-03-01

Acute myocarditis (AM) may occasionally have an infarct-like presentation. The aim of the present study was to investigate the relation between electrocardiographic (ECG) findings in this group of patients and myocardial damage assessed by cardiac magnetic resonance imaging (MRI) with the late gadolinium enhancement (LGE) technique. Myocardial damage may be associated with ECG changes in infarct-like AM. Forty-one consecutive patients (36 males; mean age, 36 ± 12 years) with diagnosis of AM according to cardiac MRI Lake Louise criteria and infarct-like presentation were included. The relation between site of ST-segment elevation (STE), sum of STE (sumSTE), time to normalization of STE, and development of negative T wave with the extent of LGE (expressed as % of left ventricular mass [%LV LGE]), was evaluated. Most (80%) patients presented with inferolateral STE; mean sumSTE was 5 ± 3 mm. Normalization of STE occurred within 24 hours in 20 (49%) patients. Development of negative T wave occurred in 28 (68%) patients. Cardiac MRI showed LGE in all patients; mean %LV LGE was 9.6 ± 7.2%. Topographic agreement between site of STE and LGE was 68%. At multivariate analysis, sumSTE (β = 0.42, P 24 hours (β = 0.39, P 24 hours, and development of negative T wave) may help to identify patients with larger areas of myocardial damage. © 2012 Wiley Periodicals, Inc.

Myocardial SPECT in children with sickle cell disease

International Nuclear Information System (INIS)

Maunoury, C.; Hallaj, I.; Barritault, L.; Acar, P.; Montalembert, M. de

2002-01-01

Aim: While cerebral and bones strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Conventional techniques such as exercise testing and echocardiography have a low sensitivity and specificity to detect myocardial ischemia in patients with SCD. The aim of this prospective study was to assess myocardial perfusion with 201 Tl SPECT in children with SCD. Materials and Methods: Twenty-two patients, aged 12 ± 4 years, were included. Myocardial perfusion was assessed by 201 Tl SPECT after stress and 3 hours later after reinjection on a single head gammacamera equipped with a LEAP collimator (64x64 matrix size format, 30 projections over 180 0 , 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Results: Myocardial perfusion was impaired in 13/22 patients: 8 had reversible defects and 5 had fixed defects. The left ventricular cavity was dilated in 13/22 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. Conclusion: Myocardial perfusion is frequently impaired in children with SCD. Treatment with hydroxyurea should be considered in SCD patients with perfusion defects

Implantation of stem cells in the treatment of acute myocardial infarction

International Nuclear Information System (INIS)

Obregon Santos, Angel; Wilford de Leon, Mario; Aroche Aportela, Ronald; Isla Garcia, Rosa; Conde Cerdeira, Hector; Vila Garcia, Elena

2007-01-01

A lot of investigations demonstrate the possibility of regeneration of the cardiomiocity from stem cells. A longitudinal, prospective, observational study was conducted in patients with acute myocardial infarction in CIMEQ'S hospital since January 2004 up to January 2007 with the purpose to evaluate the security and efficacy of the intracoronary transfer of autologous bone-marrow-cells during acute myocardial infarction. Patients within seven days of the onset of symptoms of a first ST-segment elevation myocardial infarction, and between 18 and 70 years old. The patients are evaluated previous to apply the procedure and 6 months for clinic, electrocardiography, echocardiography, ergometry and coronariography. The drug eluting stent is placed on the culprit lesion and the bone marrow is stimulated with granulocyte colony-stimulating factor (G-CSF). The mononuclear's cells which are obtained have been implanted using the intracoronary way. The implantation by means of the intracoronary way of stem cells, after of stimulation of bone marrow during acute myocardial infarction demonstrated to be an effective and safety procedure

Impact of a modified Maze procedure on the atrial hormonal function and level of myocardial damage markers

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S. I. Zheleznev

2015-10-01

Full Text Available Surgical treatment of atrial fibrillation (AF in patients with valvular heart disease remains one of the most pressing problems in cardiac surgery. The purpose of the study was to determine the dynamics of proANP and myocardial damage markers depending on a modification of the radiofrequency (RF Maze procedure used. The study involved 86 patients operated over a period from November 2007 to December 2010. A concomitant RF Maze procedure during mitral valve (MV surgery was performed in two groups of the cohort; in group 1 it was the standard Maze IV scheme, in group 2 it was the modified one. In both groups we assessed the levels of proANP and myocardial damage markers. In group 1 a more significant decrease in proANP (by 4 times was seen as compared to group 2 (by half. In group 1, the pleural effusion rate was 46.2%, and thoracocentesis rate reached 25.6%. In group 2, the corresponding rates were lower,14.9% and 27.7%. During the first postoperative day there was an increase in creatine phosphokinase MB fraction and Troponin T in both groups, and the rise was significantly higher in group 1. It should be noted that modified Maze IV RF ablation results in 80% freedom from AF, which is consistent with that of the standard Maze IV scheme. In patients with left atrial ablation the proANP secretion is less prominent early after surgery, and myocardial damage is lower in comparison with biatrial ablation.

Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

International Nuclear Information System (INIS)

Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

2017-01-01

Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

DETECTION OF MYOCARDIAL VIABILITY IN ISСHAEMIC DAMAGE USING MAGNETIC RESONANCE AND EMISSION TOMOGRAPHY

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V. Yu. Ussov

2013-01-01

Full Text Available A review of modern methods of magnetic resonance imaging (MRI and emission tomography (singlephoton emission and positron emission computer tomography – SPECT and PET as toos for diagnosis and prognosis of myocardial ischaemic damage, in particular in coronary revascularization. The definition of term “myocardial viability” is discussed. It has been shown that the integrity of blood-tissue barrier between myocardium and microcirculatory vessels is the most sensitive marker of tissue viability and of functional integrity of myocardium. It’s evaluation by means of contrast-enhanced MRI of myocardium is the most available and most precise technique of diagnosis and prognosis both in patients with postinfarction myocardiosclerosis and in patients with coronary disease without myocardial infarction. It is proposed that in the nearest future the combination of MR-coronarography and contrast-enhanced MRI of myocardium will provide a possibility to obtain the full set of data necessary for planning of endovascular and surgical treatment of various forms of coronary heart disease. PET and SPECT techniques currently are of some essential interest for pathophysiologic research of coronary ishaemia in clinical and experimental studies as well as for qualitative visual studies of pharmacokinetics.

Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

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Jeehoon Kang

2016-11-01

Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

Diagnosis of early human myocardial ischemic damage with electron probe microanalysis

International Nuclear Information System (INIS)

Singh, S.; Abraham, J.L.; Raasch, F.; Wolf, P.; Bloor, C.M.

1983-01-01

We determined the Na/K x-ray intensity ratio in frozen sections of myocardial tissues obtained at autopsy from patients who died from various causes, using electron probe analysis. We have been able to distinguish between the ischemically injured and normal cells. The method is simple, fast, and dependable even when the duration of ischemia is only 30 minutes

Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

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Ramón Rodrigo

2013-01-01

Full Text Available Acute myocardial infarction (AMI is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress. These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage.

Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

Science.gov (United States)

Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

2013-01-01

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

DEFF Research Database (Denmark)

Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

2014-01-01

Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

Energy Technology Data Exchange (ETDEWEB)

Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

2017-12-15

Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

Impairment of myocardial perfusion in children with sickle cell disease

International Nuclear Information System (INIS)

Maunoury, C.; Acar, P.; Montalembert, M. de

2003-01-01

While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 ± 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

Heart-type fatty acid binding protein is an early marker of myocardial damage after radiofrequency catheter ablation.

Science.gov (United States)

Giannessi, Daniela; Piacenti, Marcello; Maltinti, Maristella; Rossi, Andrea; Di Cecco, Pietro; Startari, Umberto; Cabiati, Manuela; Panchetti, Luca; Del Ry, Silvia; Morales, Maria-Aurora

2010-10-01

Radiofrequency (RF) ablation of arrhythmias induces myocardial damage and release of biomarkers. This study aimed to assess the kinetics of heart-type fatty acid-binding protein (h-FABP), a cytosolic protein released after myocardial injury incurred by both atrial and ventricular RF ablation, compared to other markers of myocardial injury. h-FABP, cTnI, CK-MB(mass) and myoglobin were evaluated in 30 patients with atrial or ventricular tachyarrhythmias before, immediately after and at 3, 6 and 24h after the procedure. h-FABP increased immediately after the procedure in all subjects (6.6 ± 1.2 μg/L vs 2.7 ± 0.3, pvalues of time for mean power of RF application in both the entire patient cohort and in ventricular ablations. h-FABP may be an early parameter for monitoring RF-induced lesions and the site of ablation was relevant for biomarker increase. Copyright © 2010 Elsevier Inc. All rights reserved.

NMR study of damage on isolated perfused rat heart exposed to ischemia and hypoxia

International Nuclear Information System (INIS)

Luo Xuechun; Yan Yongbin; Zhang Riqing; Fan Lili

2001-01-01

Myocardial ischemia is the most common and primary cause of myocardium damage. Numerous conventional techniques and methods have been developed for ischemia and reperfusion studies. However, because of damage to the heart sample, most of these techniques can not be used to continuously monitor the full dynamic course of the myocardial metabolic pathway. The nuclear magnetic resonance (NMR) surface coil technique, which overcomes the limitations of conventional instrumentation, can be used to quantitatively study every stage of the perfused heart (especially after perfusion stoppage) continuously, dynamically, and without damage under normal or designed physiological conditions at the molecular level. In this paper, 31 P-NMR was used to study the effects of ischemia and hypoxia on isolated perfused hearts. The results show that complete hypoxia caused more severe functional damage to the myocardial cells than complete ischemia

The diagnostic value of Tc-99m PYP, Tl-201 dual isotope SPECT to predict the viability of damaged myocardium in the acute phase of myocardial infarction

International Nuclear Information System (INIS)

Matsuo, Hitoshi; Watanabe, Sachiro; Arai, Masazumi

1991-01-01

To assess the diagnostic value of Tc-99m pyrophosphate (PYP), Tl-201 dual isotope SPECT for the evaluation of myocardial viability, segmental comparison between dual isotope SPECT and exercise, delayed, and reinjected Tl study were performed with 18 acute myocardial infarction (AMI) patients. Among 72 damaged myocardial segments, 48 segments (67%) were judged as viable by chronic phase Tl studies. The segments with severely reduced Tl uptake by dual SPECT showed significantly lower prevalence of viable myocardium than the segments with reduced and normal Tl uptake (p<0.001). The segments with PYP accumulation localized to the subendocardium represented the favorable outcome compared with the transmural accumulation (p<0.001). And overlap segments show better prognosis than the segments without overlap (p<0.05). Most importantly, we can get better predictive accuracy of myocardial scar by dual isotope SPECT than the judgement by Tl or PYP SPECT alone (83.3% vs 77.8%, 68.1%). Thus, we conclude that Tc-99m PYP, Tl-201 dual isotope SPECT is useful to assess the severity of myocardial damage in the acute phase of myocardial infarction. (author)

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

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Raúl Enrique Cuevas-Durán

2017-11-01

Full Text Available Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co and Rosmarinus officinalis (Ro extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a sham; (b vehicle-treated myocardial infarction (MI (MI-V; (c Ro extract-treated myocardial infarction (MI-Ro; (d Co extract-treated myocardial infarction (MI-Co; or (e Ro+Co-treated myocardial infarction (MI-Ro+Co. Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2′-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1, increased vasodilators agents (angiotensin 1–7 and bradikinin and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

Cells involved in extracellular matrix remodeling after acute myocardial infarction

International Nuclear Information System (INIS)

Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

2015-01-01

Evaluate the effects of VEGF_1_6_5 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF_1_6_5 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF_1_6_5. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF_1_6_5, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF_1_6_5 seems to provide a protective effect in the treatment of acute myocardial infarct

Cells involved in extracellular matrix remodeling after acute myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

2015-07-01

Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

Myocardial Damage in Patients With Deferred Stenting After STEMI

DEFF Research Database (Denmark)

Lønborg, Jacob; Engstrøm, Thomas; Ahtarovski, Kiril Aleksov

2017-01-01

BACKGROUND: Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in pa...

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.

The Influence of Autologous Bone Marrow Stem Cell Transplantation on Matrix Metalloproteinases in Patients Treated for Acute ST-Elevation Myocardial Infarction

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Eline Bredal Furenes

2014-01-01

Full Text Available Background. Matrix metalloproteinase-9 (MMP-9, regulated by tissue inhibitor of metalloproteinase-9 (TIMP-1 and the extracellular matrix metalloproteinase inducer (EMMPRIN, contributes to plaque instability. Autologous stem cells from bone marrow (mBMC treatment are suggested to reduce myocardial damage; however, limited data exists on the influence of mBMC on MMPs. Aim. We investigated the influence of mBMC on circulating levels of MMP-9, TIMP-1, and EMMPRIN at different time points in patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI trial (n=100. Gene expression analyses were additionally performed. Results. After 2-3 weeks we observed a more pronounced increase in MMP-9 levels in the mBMC group, compared to controls (P=0.030, whereas EMMPRIN levels were reduced from baseline to 2-3 weeks and 3 months in both groups (P<0.0001. Gene expression of both MMP-9 and EMMPRIN was reduced from baseline to 3 months. MMP-9 and EMMPRIN were significantly correlated to myocardial injury (CK: P=0.005 and P<0.001, resp. and infarct size (SPECT: P=0.018 and P=0.008, resp.. Conclusion. The results indicate that the regulation of metalloproteinases is important during AMI, however, limited influenced by mBMC.

Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction.

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El Gammal, Zaynab H; Zaher, Amr M; El-Badri, Nagwa

2017-09-01

Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635-804 nm), power density (6-50 mW/cm 2 ), duration (20-150 s), energy density (0.96-1 J/cm 2 ), delivery time (20 min-3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low

Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

International Nuclear Information System (INIS)

Horton, J.W.

1987-01-01

An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h or hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [ 14 C]inulin, values (ml H 2 O/g dry wt) for control nonshocked myocardial slices were 4.03 /plus minus/ 0.11 (SE) for total water, 2.16 /plus minus/ 0.07 for inulin impermeable space, and 1.76 /plus minus/ 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation. After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

NARCIS (Netherlands)

ter Horst, Kasper W.

2010-01-01

The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by

Uptake and release of 99mTc-CPI in cultured myocardial cells

International Nuclear Information System (INIS)

Li Shengting; Xiao Yanling; Yu Qifu; Zhang Hongyuan; Tang Jingrong

1991-01-01

The uptake and release of 99m Tc-CPI were studied in cultured monolayer neonatal rat myocardial cells incubated under normal condition (37 deg C, pH 7.4). The plateau level of uptake (4291.6 cpm/mg cell protein) was reached at 41.4 min when incubated with 37 kBq 99m Tc-CPI. The 99m Tc-CPI release was composed of at least two components. The fast component had a half-time (t 1/2 ) of 3.3 min and the slow one 198.0 min. It was suggested by the authors that the uptake of 99m Tc-CPI by cultured myocardial cells might be related to passive diffusion

Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

International Nuclear Information System (INIS)

Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

1985-01-01

To study kinetics and principles of cellular uptake of 13 N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of 13 N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract 13 N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. 13 N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of 13 N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of 13 N-ammonia may not always provide a valid measurement of myocardial perfusion

Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

Science.gov (United States)

Zhao, Shuting; Xu, Zhaobin; Wang, Hai; Reese, Benjamin E.; Gushchina, Liubov V.; Jiang, Meng; Agarwal, Pranay; Xu, Jiangsheng; Zhang, Mingjun; Shen, Rulong; Liu, Zhenguo; Weisleder, Noah; He, Xiaoming

2016-10-01

It is difficult to achieve minimally invasive injectable cell delivery while maintaining high cell retention and animal survival for in vivo stem cell therapy of myocardial infarction. Here we show that pluripotent stem cell aggregates pre-differentiated into the early cardiac lineage and encapsulated in a biocompatible and biodegradable micromatrix, are suitable for injectable delivery. This method significantly improves the survival of the injected cells by more than six-fold compared with the conventional practice of injecting single cells, and effectively prevents teratoma formation. Moreover, this method significantly enhances cardiac function and survival of animals after myocardial infarction, as a result of a localized immunosuppression effect of the micromatrix and the in situ cardiac regeneration by the injected cells.

Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models.

Science.gov (United States)

Lim, Sun Ha; Kim, Yaesil; Yun, Ki Na; Kim, Jin Young; Jang, Jung-Hee; Han, Mee-Jung; Lee, Jongwon

2016-12-08

Many cohort studies have shown that consumption of diets containing a higher composition of foods derived from plants reduces mortality from coronary heart disease (CHD). Here, we examined the active components of a plant-based diet and the underlying mechanisms that reduce the risk of CHD using three rat models and a quantitative proteomics approach. In a short-term myocardial infarction (MI) model, intake of wheat extract (WE), the representative cardioprotectant identified by screening approximately 4,000 samples, reduced myocardial injury by inhibiting apoptosis, enhancing ATP production, and maintaining protein homeostasis. In long-term post-MI models, this myocardial protection resulted in ameliorating adverse left-ventricular remodelling, which is a predictor of heart failure. Among the wheat components, arabinose and xylose were identified as active components responsible for the observed efficacy of WE, which was administered via ingestion and tail-vein injections. Finally, the food components of plant-based diets that contained cell wall polysaccharides rich in arabinose, xylose, and possibly fucose were found to confer protection against myocardial injury. These results show for the first time that specific monosaccharides found in the cell wall polysaccharides in plant-based diets can act as active ingredients that reduce CHD by inhibiting postocclusion steps, including MI and heart failure.

Comparative Analysis of Changes of Myocardial Angiogenesis and Energy Metabolism in Postinfarction and Diabetic Damage of Rat Heart

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Sergey A. Afanasiev

2014-01-01

Full Text Available Comparative study of changes in myocardial activity of lactate dehydrogenase (LDH, succinate dehydrogenase (SDH, and capillary density distribution in the experimental models of diabetic and postinfarction damage of rat heart was performed. Data showed that decrease in LDH and SDH activities was observed in both pathologies which can suggest abnormal processes of glycolysis and oxidative phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined pathologies was comparative with the corresponding values of these parameters in control group. The authors hypothesize that these differences can be caused by specifics of myocardial vascularization. The results of the study showed that an increase in capillary density was found in all groups of rats with pathologies compared with control group. However, no significant differences in the intensity of angiogenesis processes were found between groups with pathologies.

Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease

International Nuclear Information System (INIS)

Virtanen, K.S.; Nikkinen, P.; Lindroth, L.; Kuikka, J.T.

2002-01-01

Aim: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. Methods: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of 123 I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. Results: The more reduced post-exercise FFA metabolic rate (-63±18%, mean ±1 SD) compared to flow (-36±16%) was related to the severity of myocardial ischemia and wall motion abnormalities. Conclusion: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease. (orig.) [de

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

Science.gov (United States)

Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

Quantitative Assessment of Myocardial Infarction by In-111 Antimyosin Antibody

Energy Technology Data Exchange (ETDEWEB)

Lee, Myung Chul; Lee, Kyung Han; Choi, Yoon Ho; Chung, June Key; Park, Young Bae; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon, Dae Hyuk [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

1991-03-15

Infarct size is a major determinant of prognosis after acute myocardial infarction. Up to date, however, clinically available tests to estimate this size have not been sufficiently accurate. Twelve lead electrocardiogram and wall motion abnormality measurement are not quantitative, and creatine phosphokinase (CPK) measurement is inaccurate in the presence of reperfusion or right ventricular infarction. Methods have been developed to localize and size acute myocardial infarcts with agents that are selectively sequestered in areas of myocardial damage, but previously used agents have lacked sufficient specificity. Antibodies that bind specifically only to damaged myocardial cells may resolve this problem and provide an accurate method for noninvasively measuring infarct size. We determined the accuracy with which infarcted myocardial mass can be measured using single photon emission computed tomography (SPECT) and radiolabeled antimyosin antibodies. Seven patients with acute myocardial infarction and one stable angina patient were injected with 2 mCi of Indium-111 labeled antimyosin antibodies. Planar image and SPECT was performed 24 hours later. None of the patients had history of prior infarcts, and none had undergone reperfusion techniques prior to the study, which was done within 4 days of the attack. Planar image showed all infarct patients to have positive uptakes in the cardiac region. The location of this uptake correlated to the infarct site as indicated by electrocardiography in most of the cases. The angina patient, however, showed no such abnormal uptake. Infarct size was determined from transverse slices of the SPECT image using a 45% threshold value obtained from a phantom study. Measured infarct size ranged from 40 to 192 gr. There was significant correlation between the infarct size measured by SPECT and that estimated from serial measurements of CPK (r=0.73, p<0,05). These date suggest that acute myocardial infarct size can be accurately measured

The relationship between clinical stage, prognosis and myocardial damage in patients with Duchenne-type muscular dystrophy. Five-year follow-up study

International Nuclear Information System (INIS)

Naruse, Hitoshi; Miyagi, Junko; Arii, Tohru; Ohyanagi, Mitsumasa; Iwasaki, Tadaaki; Jinnai, Kenji

2004-01-01

The evaluation of myocardial damage by [ 123 I]15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) imaging, which represents free fatty acid metabolism, has not been reported in patients with Duchenne-type muscular dystrophy (DMD). To date, the relationship between clinical stage, prognosis and myocardial damage has not been evaluated by radionuclear cardiac imaging. The main goal of this study was to elucidate the relationship of quantitative indices of myocardial damage obtained by radionuclear cardiac imaging ([ 201 Tl] and [ 123 I]BMIPP) to clinical stage and incidence of severe cardiac events in patients with Duchenne-type muscular dystrophy (DMD). The study population consisted of 28 male patients with DMD. The average age at the beginning of observation was 19.1±7.4 yrs. Nuclear tomographic imaging was performed using [ 201 Tl] and [ 123 I]BMIPP. The mid-ventricular short axial slices were classified into four anatomical regions, and the normalized count data in these areas (TL, BM) were obtained. The endpoint was the occurrence of heart failure during the follow up period. Thirteen cases of heart failure occurred during the 5-year follow-up period, including three cases with cardiac death due to congestive heart failure. Clinical staging correlated directly with TL (p=0.0118) and BM (p=0.0401) in the whole left ventricle. In regional TL analysis, an association was observed only in the septum (p=0.0151), and in the anterior (p=0.0361) region. The only discrepancy between the tracer parameters (TL-BM) in the septum was observed with the radionuclear cardiac values, which exhibited a relationship with cardiac events (p=0.0124). This discordance, TL 201 Tl] in this area was representative of the clinical stage, and TL-BM correlated well with the prognosis. (author)

Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

Science.gov (United States)

Sui, Xizhong; Gao, Changqing

2014-01-01

Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

Cell damage evaluation of mammalian cells in cell manipulation by amplified femtosecond ytterbium laser

Science.gov (United States)

Hong, Z.-Y.; Iino, T.; Hagihara, H.; Maeno, T.; Okano, K.; Yasukuni, R.; Hosokawa, Y.

2018-03-01

A micrometer-scale explosion with cavitation bubble generation is induced by focusing a femtosecond laser in an aqueous solution. We have proposed to apply the explosion as an impulsive force to manipulate mammalian cells especially in microfluidic chip. Herein, we employed an amplified femtosecond ytterbium laser as an excitation source for the explosion and evaluated cell damage in the manipulation process to clarify the application potential. The damage of C2C12 myoblast cell prepared as a representative mammalian cell was investigated as a function of distance between cell and laser focal point. Although the cell received strong damage on the direct laser irradiation condition, the damage sharply decreased with increasing distance. Since the threshold distance, above which the cell had no damage, was consistent with radius of the cavitation bubble, impact of the cavitation bubble would be a critical factor for the cell damage. The damage had strong nonlinearity in the pulse energy dependence. On the other hand, cell position shift by the impact of the cavitation bubble was almost proportional to the pulse energy. In balance between the cell viability and the cell position shift, we elucidated controllability of the cell manipulation in microfluidic chip.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

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Yuanyuan Zhao

2015-01-01

Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

Dietary broccoli sprouts protect against myocardial oxidative damage and cell death during ischemia-reperfusion.

Science.gov (United States)

Akhlaghi, Masoumeh; Bandy, Brian

2010-09-01

Cruciferous vegetables are known for antioxidant and anti-carcinogenic effects. In the current study we asked whether dietary broccoli sprouts can protect the heart from ischemia-reperfusion. Rats were fed either control diet (sham and control groups) or a diet mixed with 2% dried broccoli sprouts for 10 days. After 10 days the isolated hearts were subjected to ischemia for 20 min and reperfusion for 2 h, and evaluated for cell death, oxidative damage, and Nrf2-regulated phase 2 enzyme activities. Broccoli sprouts feeding inhibited markers of necrosis (lactate dehydrogenase release) and apoptosis (caspase-3 activity) by 78-86%, and decreased indices of oxidative stress (thiobarbituric acid reactive substances and aconitase inactivation) by 82-116%. While broccoli sprouts increased total glutathione and activities of the phase 2 enzymes glutamate cysteine ligase and quinone reductase in liver, they did not affect these in ischemic-reperfused heart. While the mechanism is not clear, the results show that a relatively short dietary treatment with broccoli sprouts can strongly protect the heart against oxidative stress and cell death caused by ischemia-reperfusion.

Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

DEFF Research Database (Denmark)

Zohlnhofer, D.; Dibra, A.; Koppara, T.

2008-01-01

OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

Right Ventricular Function After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention : (from the Glycometabolic Intervention as Adjunct toPrimary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction III Trial)

NARCIS (Netherlands)

Gorter, Thomas M; Lexis, Chris P H; Hummel, Yoran M; Lipsic, Erik; Nijveldt, Robin; Willems, Tineke P; van der Horst, Iwan C C; van der Harst, Pim; Melle, van J.P.; van Veldhuisen, Dirk J

2016-01-01

Right ventricular (RV) dysfunction is a powerful risk marker after acute myocardial infarction (MI). Primary percutaneous coronary intervention (PCI) has markedly reduced myocardial damage of the left ventricle, but reliable data on RV damage using cardiac magnetic resonance imaging (MRI) are

E2/ER β Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis

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Kuan-Ho Lin

2017-04-01

Full Text Available Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2, for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs. In addition, protein phosphatase such as protein phosphatase 1 (PP1 and calcineurin (PP2B are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation. In this study, we observed that E2/ERβ inhibited isoproterenol (ISO-induced myocardial cell apoptosis, cytochrome c release and downstream apoptotic markers. Moreover, we found that E2/ERβ blocks ISO-induced apoptosis in H9c2 cells through the enhancement of calcineurin protein degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that supplementation with estrogen and/or overexpression of estrogen receptor β gene may prove to be effective means to treat stress-induced myocardial damage.

Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris.

Science.gov (United States)

Yan, Wenwen; Zhou, Lin; Wen, Siwan; Duan, Qianglin; Huang, Feifei; Tang, Yu; Liu, Xiaohong; Chai, Yongyan; Wang, Lemin

2015-01-01

To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (Pangina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (Pangina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.

Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

Science.gov (United States)

Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

2015-01-01

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Effect of bionic electrical stimulation on the differentiation of embryonic stem cells into cardiomyocytes in the presence myocardial cells in vitro

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Li-na ZHENG

2011-08-01

Full Text Available Objective To investigate the effects of electrical stimulation on the differentiation of embryonic stem cells(ESCs into cardiomyocytes in the presence of myocardial cells in vitro.Methods ESCs and neonate rat cardiomyocytes were isolated and cultured.These cells of primary culture were divided into 5 groups according to whether or not electric stimulation was given and the presence of cardiomyocytes: control group,stimulation group,cardiomyocytes group,stimulation+ cardiomyocyte conditioned medium group,and stimulation+cardiomyocytes group.Expression of troponin T(cTnT in the differentiated cells from ESCs was examined by immunofluoresence on the 5th,7th and 14th day.Results In the group co-cultured with myocardial cell and electrical stimulation,the differentiating ratio of cardiomyocytes derived from ESCs and expressing cTnT was 40.00%±2.39%,and it was higher than that in control group(2.00%±1.60%,stimulation group(3.00%±2.00%,cardiomyocytes group(28.70%±4.06%,stimulation+cardiomyocyte conditioned medium group(17.10%±2.23%,P < 0.05.Conclusion Bionic electric stimulation promotes the differentiation of ESCs into cardiomyocyte in a microenvironment consisting of myocardial cells.

Chronic inflammatory cells and damaged limbal cells in pterygium ...

African Journals Online (AJOL)

Background: Chronic inflammation in pterygium occurrence has not been explained. Whether damaged limbal basal epithelial cells are associated with pterygium occurrence in black Africans is not clear. Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells ...

Repair of radiation damage in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Setlow, R.B.

1981-01-01

The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

Repair of radiation damage in mammalian cells

International Nuclear Information System (INIS)

Setlow, R.B.

1981-01-01

The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

Science.gov (United States)

Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

2015-01-01

Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

Myocardial scintigraphy: methods and indications

International Nuclear Information System (INIS)

Knapp, W.H.

1993-01-01

Myocardial scintigraphy comprises perfusion imaging using TI-201 or - more recently - Tc-99m-labeled compounds with high affinity to myocytes. Imaging with these agents has become an important procedure in the detection of coronary artery disease, particularly in patients with non-diagnostic stress-ECG, in the functional evaluation of coronary stenoses after angiographical documentation in order to meet the adequate therapy decision, in therapy monitoring and follow-up, in the post infarction assessment of myocardial viability and differentiation between severe ischemia and scar and, occasionally, in acute ischemia. The use of positron emitters does not offer significant advantages for mere perfusion imaging, but is indispensable for the scintigraphic investigation of certain aspects of myocardial metabolism, particularly for the differentiation of viable ischemic wall segments from irreversibly damaged tissue. Imaging of myocardial necrosis has been improved by the introduction of labeled antimyosin antibody fragments and offers a considerable clinical potential in the diagnosis of myocarditis and cardiac transplant rejection. Neurohumoral aspects are increasingly involved in our understanding of myocardial failure. Scintigraphy of innervation/neurotransmission contributes to the investigation of pathophysiological alterations in myocardial insufficiency and in heart transplants. (orig.) [de

[Effects of moxibustion with seed-sized moxa cone on apoptosis of myocardial cells after sport fatigue in mice].

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Xu, Huiqian; Hu, Yin; Gu, Yihuang; Zhang, Hongru

2015-03-01

To observe the effects of moxibustion on factors related with apoptosis of myocardial cells after sports fatigue in mice as well as the relationship among histone acetyltransferases p300 (p300), CREB binding protein (CBP) and cell apoptosis to discuss the role of p300 and CBP in moxibustion against apoptosis of myocardial cells. Sixty clean-grade male Kunming mice were randomly divided into a control group, a sport group and a moxibustion group, 20 cases in each one. Mice in all group received identical feeding environment. Mice in the control group did not received sport nor moxibustion; mice in the sport group and moxibustion group received non-weight swimming training which lasted from 30 min per day to 90 min per day gradually for 21 days; 1 h after swimming training, mice in the moxibustion group received moxibustion with seed-sized moxa cone at "Zusanli" (ST 36) and "Guanyuan" (CV 4), 5 cones at each acupoint, once a day for 21 days. 24 h after the final swimming training, cardiac muscle tissue was collected to test factor associated suicide (Fas), B cell lymphoma/lewkmia-2 (Bcl-2) by immunohistochemical method and expression of p300 and CBP. Compared with the control group, the apoptosis rate of myocardial cells in the sport group was significantly increased (Pprotein was significantly increased (Psport group, the apoptosis rate of myocardial cells in the moxibustion group was significantly reduced (Pprotein was significantly reduced (Psports fatigue in mice to inhibit the starting of apoptotic process, therefore reducing the apoptosis of myocardial cells after heavy exercise and protecting heart function.

Mechanisms of dealing with DNA damage in terminally differentiated cells

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Fortini, P. [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, E., E-mail: eugenia.dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy)

2010-03-01

To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

Mechanisms of dealing with DNA damage in terminally differentiated cells

International Nuclear Information System (INIS)

Fortini, P.; Dogliotti, E.

2010-01-01

To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

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Yihua Liu

2017-11-01

Full Text Available Background: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs. This study sought to address (i the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI in rats. Methods: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27 or hypoxic conditions (5% O2, n=27 until Passage 4 (P4. Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6 or hypoxia (n=6 were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG positron emission tomography (PET imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Results: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Conclusion: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction.

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Liu, Yihua; Yang, Xiaoxi; Maureira, Pablo; Falanga, Aude; Marie, Vanessa; Gauchotte, Guillaume; Poussier, Sylvain; Groubatch, Frederique; Marie, Pierre-Yves; Tran, Nguyen

2017-01-01

The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats. rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis. © 2017 The Author(s). Published by S. Karger AG

Follow-up of regional myocardial T2 relaxation times in patients with myocardial infarction evaluated with magnetic resonance imaging

International Nuclear Information System (INIS)

Krauss, X.H.; Wall, E. van der; Laarse, A. van der; Dijkman, P.R.M. van; Bruschke, A.V.G.; Doornbos, J.; Roos, A. de; Voorthuisen, A.E. van

1990-01-01

Multi-echo spin-echo cardiac magnetic resonance imaging studies (echo times 30, 60, 90 and 120 ms) were performed in 19 patients with a 7-14-day (mean 10) old myocardial infarction and were repeated in 13 patients 4-7 months (mean 6) later. Also, 10 normal subjects were studied with magnetic resonance imaging. T2 relaxation times of certain left ventricular segments were calculated from the signal intensities at echo times of 30 and 90 ms. Compared to normal individuals, the mean T2 values on the early magnetic resonance images of the patients with inferior infarction showed significantly prolonged T2 times in the inferiorly localized segments, while on the follow-up magnetic resonance images the T2 times had almost returned to the normal range. Also the patients with anterior infarction showed significantly prolonged T2 times in the anteriorly localized segments on the early nuclear magnetic resonance images, but the T2 times remained prolonged at the follow-up magnetic resonance images. For every patient a myocardial damage score was determined, which was defined as the sum of the segmental T2 values in the patients minus the upper limit of normal T2 values obtained from the normal volunteers (= mean normal+2SD). The damage score on both the early and late magnetic resonance imaging study correlated well with the infarction size determined by myocardial enzyme release. Only the patients with an inferior infarction showed a significant decrease in damage score at follow-up magnetic resonance imaging. It is concluded that the regional T2 relaxation times are increased in infarcted myocardial regions and may remain prolonged for at least up to 7 months after the acute event, particularly in patients with an anterior infarction. These findings demonstrate the clinical potential of T2-weighted magnetic resonance imaging studies for detecting myocardial infarction, and estimating infarct size for an extended period after acute myocardial infarction. (author). 29 refs

Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

DEFF Research Database (Denmark)

Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

2016-01-01

BACKGROUND: Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased...... troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction...... was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...

Pacemaker Implantation Associated Myocardial Micro-Damage: A Randomised Comparison between Active and Passive Fixation Leads.

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Blažek, Patrick; Ferri-Certić, Jerko; Vražić, Hrvoje; Lennerz, Carsten; Grebmer, Christian; Kaitani, Kazuaki; Karch, Martin; Starčević, Boris; Semmler, Verena; Kolb, Christof

2018-03-20

Fixation of the pacemaker leads during pacemaker implantation leads to an increase of cardiac Troponin T (cTnT) that can be interpreted as a sign of minimal myocardial damage. This trial evaluates whether the mechanism type of lead fixation influences the magnitude of cTnT release. Patients having a de-novo cardiac pacemaker implantation or a lead revision were centrally randomized to receive either a ventricular lead with an active (screw) or passive (tine) fixation mechanism. High-sensitive Troponin T (hsTnT) was determined on the day of the procedure beforehand and on the following day. 326 Patients (median age (IQR) 75.0 (69.0-80.0) years, 64% male) from six international centers were randomized to receive ventricular leads with an active (n = 166) or passive (n = 160) fixation mechanism. Median (IQR) hsTnT levels increased by 0.009 (0.004-0.021) ng/ml in the group receiving screw-in ventricular leads and by 0.008 (0.003-0.030) ng/ml in the group receiving tined ventricular leads (n.s.). In conclusion pacemaker implantations are followed by a release of hsTnT. The choice between active or passive fixation ventricular leads does not have a significant influence on the extent of myocardial injury and the magnitude of hsTnT release.

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

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Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

2015-01-01

Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

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Gülay Kip

2015-09-01

Full Text Available Objective: Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R. Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods: Diabetes was induced with streptozotocin (55 mg/kg in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC, diabetes plus ischaemia-reperfusion (DIR, and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg; the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA levels were evaluated in the lung tissues of all rats. Results: Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively. The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively. The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT

Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

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Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

2017-12-01

Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model

DEFF Research Database (Denmark)

Schuh, A.; Kroh, A.; Konschalla, S.

2012-01-01

Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells...... into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left...... compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted...

The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

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Hasan Ali Kiraz

2015-12-01

Full Text Available Objective: Ischemia/reperfusion (I/R injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg were randomly divided into three equal groups as follows: the diabetic I/R group (DIR in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL, which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC which underwent sham operations without tightening of the coronary sutures. As a control group (C, six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008. Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively. Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001. Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively. Also, myocardial tissue edema was significantly different among groups (p=0.006. The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively. Conclusion: Taken together, our data

Clinical study on myocardial imaging with β-methyl-p-(123I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy

International Nuclear Information System (INIS)

Kihara, Koichi; Nakajo, Masayuki; Shono, Hirohisa

1992-01-01

Myocardial imaging with β-methyl-p-( 123 I)-iodophenyl-pentadecanoic acid ( 123 I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201 Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123 I-BMIPP compared to 201 Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123 I-BMIPP was higher than that of 201 Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123 I-BMIPP was lower than that of 201 Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 123 I-BMIPP, these results suggest that 123 I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy. (author)

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity.

Science.gov (United States)

Shuvy, Mony; Shifman, Oshrat E Tayer; Nusair, Samir; Pappo, Orit; Lotan, Chaim

2009-01-01

Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

Investigation of solar cell radiation damage

International Nuclear Information System (INIS)

Bernard, J.; Reulet, R.; Arndt, R.A.

1974-01-01

Development of communications satellites has led to the requirement for a greater and longer lived solar cell power source. Accordingly, studies have been undertaken with the aim of determining which solar cell array provides the greatest power at end of life and the amount of degradation. Investigation of the damage done to thin silicon and thin film CdS solar cells is being carried out in two steps. First, irradiations were performed singly with 0.15, 1.0 and 2.0MeV electrons and 0.7, 2.5 and 22MeV proton. Solar cells and their cover materials were irradiated separately in order to locate the sites of the damage. Diffusion length and I.V. characteristics of the cells and transmission properties of the cover materials were measured. All neasurements were made in vacuum immediately after irradiation. In the second part it is intended to study the effect of various combinations of proton, electron and photon irradiation both with and without an electrical load. The results of this part show whether synergism is involved in solar cell damage and the relative importance of each of three radiation sources if synergism is found [fr

Assessment of Myocardial Contractile Function Using Global and Segmental Circumferential Strain following Intracoronary Stem Cell Infusion after Myocardial Infarction: MRI Feature Tracking Feasibility Study

International Nuclear Information System (INIS)

Bhatti, Sabha; Al-Khalidi, Hussein; Hor, Kan; Hakeem, Abdul; Taylor, Michael; Quyyumi, Arshed A.; Oshinski, John; Pecora, Andrew L.; Kereiakes, Dean; Chung, Eugene; Pedrizzetti, Gianni; Miszalski-Jamka, Tomasz; Mazur, Wojciech

2012-01-01

Background. Magnetic resonance imaging (MRI) strain analysis is a sensitive method to assess myocardial function. Our objective was to define the feasibility of MRI circumferential strain (ε cc ) analysis in assessing subtle changes in myocardial function following stem cell therapy. Methods and Results. Patients in the Amorcyte Phase I trial were randomly assigned to treatment with either autologous bone-marrow-derived stem cells infused into the infarct-related artery 5 to 11 days following primary PCI or control. MRI studies were obtained at baseline, 3, and 6 months. ε cc was measured in the short axis views at the base, mid and apical slices of the left ventricle (LV) for each patient (13 treatments and 10 controls). Mid-anterior LV ε cc improved between baseline −18.5 ± 8.6 and 3 months −22.6 ± 7.0, P = 0.03. There were no significant changes in ε cc at 3 months and 6 months compared to baseline for other segments. There was excellent intraobserver and interobserver agreement for basal and mid circumferential strain. Conclusion. MRI segmental strain analysis is feasible in assessment of regional myocardial function following cell therapy with excellent intra- and inter-observer variability's. Using this method, a modest interval change in segmental ε cc was detected in treatment group

Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

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Ford, Jordan; McEndaffer, Laura; Renshaw, Randall; Molesan, Alex; Kelly, Kathleen

2017-11-01

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

Stem cell therapy for ischemic heart diseases.

Science.gov (United States)

Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

2017-01-01

Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

Science.gov (United States)

Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

2015-04-01

Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

Human adipose stem cell and ASC-derived cardiac progenitor cellular therapy improves outcomes in a murine model of myocardial infarction

Directory of Open Access Journals (Sweden)

Davy PMC

2015-10-01

Full Text Available Philip MC Davy,1 Kevin D Lye,2,3 Juanita Mathews,1 Jesse B Owens,1 Alice Y Chow,1 Livingston Wong,2 Stefan Moisyadi,1 Richard C Allsopp1 1Institute for Biogenesis Research, 2John A. Burns School of Medicine, University of Hawaii at Mānoa, 3Tissue Genesis, Inc., Honolulu, HI, USA Background: Adipose tissue is an abundant and potent source of adult stem cells for transplant therapy. In this study, we present our findings on the potential application of adipose-derived stem cells (ASCs as well as induced cardiac-like progenitors (iCPs derived from ASCs for the treatment of myocardial infarction. Methods and results: Human bone marrow (BM-derived stem cells, ASCs, and iCPs generated from ASCs using three defined cardiac lineage transcription factors were assessed in an immune-compromised mouse myocardial infarction model. Analysis of iCP prior to transplant confirmed changes in gene and protein expression consistent with a cardiac phenotype. Endpoint analysis was performed 1 month posttransplant. Significantly increased endpoint fractional shortening, as well as reduction in the infarct area at risk, was observed in recipients of iCPs as compared to the other recipient cohorts. Both recipients of iCPs and ASCs presented higher myocardial capillary densities than either recipients of BM-derived stem cells or the control cohort. Furthermore, mice receiving iCPs had a significantly higher cardiac retention of transplanted cells than all other groups. Conclusion: Overall, iCPs generated from ASCs outperform BM-derived stem cells and ASCs in facilitating recovery from induced myocardial infarction in mice. Keywords: adipose stem cells, myocardial infarction, cellular reprogramming, cellular therapy, piggyBac, induced cardiac-like progenitors

Acute myocardial infarction

International Nuclear Information System (INIS)

RISCHPLER, Christoph

2016-01-01

Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans.

Phagocytic response of astrocytes to damaged neighboring cells.

Directory of Open Access Journals (Sweden)

Nicole M Wakida

Full Text Available This study aims to understand the phagocytic response of astrocytes to the injury of neurons or other astrocytes at the single cell level. Laser nanosurgery was used to damage individual cells in both primary mouse cortical astrocytes and an established astrocyte cell line. In both cases, the release of material/substances from laser-irradiated astrocytes or neurons induced a phagocytic response in near-by astrocytes. Propidium iodide stained DNA originating from irradiated cells was visible in vesicles of neighboring cells, confirming phagocytosis of material from damaged cortical cells. In the presence of an intracellular pH indicator dye, newly formed vesicles correspond to acidic pH fluorescence, thus suggesting lysosome bound degradation of cellular debris. Cells with shared membrane connections prior to laser damage had a significantly higher frequency of induced phagocytosis compared to isolated cells with no shared membrane. The increase in phagocytic response of cells with a shared membrane occurred regardless of the extent of shared membrane (a thin filopodial connection vs. a cell cluster with significant shared membrane. In addition to the presence (or lack of a membrane connection, variation in phagocytic ability was also observed with differences in injury location within the cell and distance separating isolated astrocytes. These results demonstrate the ability of an astrocyte to respond to the damage of a single cell, be it another astrocyte, or a neuron. This single-cell level of analysis results in a better understanding of the role of astrocytes to maintain homeostasis in the CNS, particularly in the sensing and removal of debris in damaged or pathologic nervous tissue.

Impact of genomic damage and ageing on stem cell function

Science.gov (United States)

Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

2014-01-01

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

Energy Technology Data Exchange (ETDEWEB)

Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Tabibzadeh, Siamak, E-mail: fbs@bioscience.org [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Dept of Oncologic Radiology, University of California, Irvine, CA (United States)

2014-06-13

Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells.

Science.gov (United States)

Burke, Russell T; Marcus, Joshua M; Orth, James D

2017-06-13

Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE. In multiple cell models, selinexor treatment results in the formation of clustered DNA damage foci in 30-40% of cells within 8 hours that is dependent upon cysteine-528. DNA damage strongly correlates with G1/S-phase and decreased DNA replication. Live cell microscopy reveals an association between DNA damage and cell fate. Cells that form damage in G1-phase more often die or arrest, while those damaged in S/G2-phase frequently progress to cell division. Up to half of all treated cells form damage foci, and most cells that die after being damaged, were damaged in G1-phase. By comparison, non-transformed cell lines show strong cell cycle effects but little DNA damage and less death than cancer cells. Significant drug combination effects occur when selinexor is paired with different classes of agents that either cause DNA damage or that diminish DNA damage repair. These data present a novel effect of exportin-1 inhibition and provide a strong rationale for multiple combination treatments of selinexor with agents that are currently in use for the treatment of different solid cancers.

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

DEFF Research Database (Denmark)

Ripa, RS; Jorgensen, E; Wang, Y

2006-01-01

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of......: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group...

Clinical study on myocardial imaging with. beta. -methyl-p-( sup 123 I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy

Energy Technology Data Exchange (ETDEWEB)

Kihara, Koichi; Nakajo, Masayuki; Shono, Hirohisa (Kagoshima Univ. (Japan). Faculty of Medicine) (and others)

1992-04-01

Myocardial imaging with {beta}-methyl-p-({sup 123}I)-iodophenyl-pentadecanoic acid ({sup 123}I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with {sup 201}Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of {sup 123}I-BMIPP compared to {sup 201}Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of {sup 123}I-BMIPP was higher than that of {sup 201}Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of {sup 123}I-BMIPP was lower than that of {sup 201}Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of {sup 123}I-BMIPP, these results suggest that {sup 123}I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy. (author)

Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

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Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2015-01-15

Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

DNA damage responses in human induced pluripotent stem cells and embryonic stem cells.

Directory of Open Access Journals (Sweden)

Olga Momcilovic

2010-10-01

Full Text Available Induced pluripotent stem (iPS cells have the capability to undergo self-renewal and differentiation into all somatic cell types. Since they can be produced through somatic cell reprogramming, which uses a defined set of transcription factors, iPS cells represent important sources of patient-specific cells for clinical applications. However, before these cells can be used in therapeutic designs, it is essential to understand their genetic stability.Here, we describe DNA damage responses in human iPS cells. We observe hypersensitivity to DNA damaging agents resulting in rapid induction of apoptosis after γ-irradiation. Expression of pluripotency factors does not appear to be diminished after irradiation in iPS cells. Following irradiation, iPS cells activate checkpoint signaling, evidenced by phosphorylation of ATM, NBS1, CHEK2, and TP53, localization of ATM to the double strand breaks (DSB, and localization of TP53 to the nucleus of NANOG-positive cells. We demonstrate that iPS cells temporary arrest cell cycle progression in the G(2 phase of the cell cycle, displaying a lack of the G(1/S cell cycle arrest similar to human embryonic stem (ES cells. Furthermore, both cell types remove DSB within six hours of γ-irradiation, form RAD51 foci and exhibit sister chromatid exchanges suggesting homologous recombination repair. Finally, we report elevated expression of genes involved in DNA damage signaling, checkpoint function, and repair of various types of DNA lesions in ES and iPS cells relative to their differentiated counterparts.High degrees of similarity in DNA damage responses between ES and iPS cells were found. Even though reprogramming did not alter checkpoint signaling following DNA damage, dramatic changes in cell cycle structure, including a high percentage of cells in the S phase, increased radiosensitivity and loss of DNA damage-induced G(1/S cell cycle arrest, were observed in stem cells generated by induced pluripotency.

An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

Directory of Open Access Journals (Sweden)

Ying Huang

2013-11-01

Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage. Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and

Myocardial infarction after near drowning.

Science.gov (United States)

Chen, Li-Bang; Lai, Yen-Chun; Chen, Chang-Chih; Chang, Wen-Han; Su, Yu-Jang

2008-06-01

During summer, near drowning is a common accident in Taiwan. It may lead to multiple organ damages in cases where severe hypothermia and hypoxemia occur. We present a case of myocardial infarction after near drowning. The patient was sent to our ED by the emergency medical services called by the witness. On arrival to our ED, hypothermia and hypoxemia overcame him. Endotracheal intubation and warm intravenous fluid were applied at once owing to drowsy consciousness, respiratory distress, and hypothermia. Electrocardiogram showed diffuse ST-segment elevation over the precordial leads V2-V6. The initial level of cardiac enzymes was within normal limit but elevated in troponin I on the second day after hospitalization. We presumed that the possibility of myocardial infarction resulted from near drowning-related hypoxemia. To our knowledge, this is the first case describing myocardial injury with electrocardiogram changes after near drowning.

Differential Mechanisms of Myocardial Conduction Slowing by Adipose Tissue-Derived Stromal Cells Derived From Different Species

NARCIS (Netherlands)

ten Sande, Judith N.; Smit, Nicoline W.; Parvizi, Mojtaba; van Amersfoorth, Shirley C. M.; Plantinga, Josee A.; van Dessel, Pascal F. H. M.; de Bakker, Jacques M. T.; Harmsen, Marco C.; Coronel, Ruben

: Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine

Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells.

Science.gov (United States)

Bru, Samuel; Samper-Martín, Bàrbara; Quandt, Eva; Hernández-Ortega, Sara; Martínez-Laínez, Joan M; Garí, Eloi; Rafel, Marta; Torres-Torronteras, Javier; Martí, Ramón; Ribeiro, Mariana P C; Jiménez, Javier; Clotet, Josep

2017-09-01

Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitamin E deficiency fails to affect myocardial performance during in vivo ischemia-reperfusion.

Science.gov (United States)

Coombes, J S; Powers, S K; Demirel, H A; Hamilton, K L; Jessup, J; Vincent, H K; Shanely, R A

2000-12-01

Vitamin E content of cardiac tissue has been proposed to play a major role in the damage caused by myocardial ischemia-reperfusion (I-R). Previous studies using in vitro models have examined vitamin E deficiency and I-R-induced myocardial damage with equivocal results. The purpose of this study was to use an in vivo model of myocardial I-R to determine the effects of vitamin E deficiency on myocardial I-R-induced damage. Female Sprague-Dawley rats (4-mo old) were assigned to either: 1) control diet (CON), or 2) vitamin E deficient diet (VE-DEF). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU vitamin E/kg diet. The VE-DEF diet was the AIN-93M diet prepared with tocopherol stripped corn oil and no vitamin E. Following a 14-week feeding period, significant differences (p CON = 48.2 +/- 3.5; VE-DEF = 12.4 +/- 1.4 micrograms VE/g wet weight). Animals from both experimental groups were subjected to an in vivo I-R protocol consisting of 25 minutes of left coronary artery occlusion followed by 10 minutes of reperfusion. No group differences (p > 0.05) existed in cardiac performance (peak arterial pressure or ventricular work) or the incidence of ventricular arrhythmias during the I-R protocol. VE-DEF animals had significantly higher (p CON animals. These data suggest that although vitamin E deficiency increases oxidative damage resulting from myocardial I-R, it does not affect cardiac performance during the insult.

Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

Directory of Open Access Journals (Sweden)

Khayat Andre

2011-01-01

Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

Damage-recognition proteins as a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to ultraviolet radiation

International Nuclear Information System (INIS)

Chao, C.C.-K.

1992-01-01

The authors compared damage-recognition proteins in cells expressing different sensitivities to DNA damage. An increase in damage-recognition proteins and an enhancement of plasmid re-activation were detected in HeLa cells resistant to cisplatin and u.v. However, repair-defective cells derived from xeroderma-pigmentosum (a rare skin disease) patients did not express less cisplatin damage-recognition proteins than repair-competent cells, suggesting that damage-recognition-protein expression may not be related to DNA repair. By contrast, cells resistant to DNA damage consistently expressed high levels of u.v.-modified-DNA damage-recognition proteins. The results support the notion that u.v. damage-recognition proteins are different from those that bind to cisplatin. Findings also suggest that the damage-recognition proteins identified could be used as potential indicators of the sensitivity or resistance of cells to u.v. (author)

Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

Science.gov (United States)

Chao, Hui Xiao; Poovey, Cere E; Privette, Ashley A; Grant, Gavin D; Chao, Hui Yan; Cook, Jeanette G; Purvis, Jeremy E

2017-11-22

Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that, within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell-cycle arrest. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes and clinical significance of liver function and myocardial zymogram in children with rotavirus enteritis

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Lan-Ping Yang

2016-12-01

Full Text Available Objective: To explore the changes and clinical significance of liver function and myocardial zymogram in children with rotavirus (RV enteritis. Methods: A total of 70 children with RV enteritis who were admitted in our hospital were included in the study and served as the observation group. The liver function and myocardial zymogram before and after treatment were detected. The proportion of RV enteritis children with liver and myocardial damage was calculated. The effect of dehydration on the liver function and myocardial zymogram in children with RV enteritis was analyzed. A total of 65 children with non-RV enteritis who were admitted in our hospital at the same stage were served as the control group. Results: The serum ALT, AST, CK, CK-MB, LDH, and α-HBDH levels, and liver myocardial damage children proportion in the observation group were significantly higher than those in the control group (P<0.05. The serum ALT, AST, CK, CK-MB, LDH, and α-HBDH levels in the observation group were significantly elevated with the acceleration of dehydration degree (P<0.05. In the observation group, 45 children had liver and myocardial damage, whose ALT, AST, CK, CKMB, LDH, and α-HBDH levels after treatment were significantly reduced when compared with before treatment (P<0.05. Conclusions: Early detection of liver function and myocardial zymogram can accurately reflect the condition in children with RV enteritis, which can provide an evidence for the formulation of clinical treatment protocol.

Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

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Enrique Gallego-Colon

2015-01-01

Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

Science.gov (United States)

Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

2004-06-29

There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

Early myocardial damage assessment in dystrophinopathies using 99Tcm-MIBI gated myocardial perfusion imaging

Directory of Open Access Journals (Sweden)

Zhang L

2015-12-01

Full Text Available Li Zhang,1,* Zhe Liu,2,* Ke-You Hu,3 Qing-Bao Tian,3 Ling-Ge Wei,4 Zhe Zhao,5 Hong-Rui Shen,5 Jing Hu5 1Department of Cardiovascular Disorders, 2Department of Geriatrics, The Third Hospital of Hebei Medical University, 3The Public Health Department, Hebei Medical University, 4Department of Nuclear Medicine, 5Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China *Li Zhang and Zhe Liu are first coauthors of this paper Background: Early detection of muscular dystrophy (MD-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m-methoxyisobutylisonitrile (99Tcm-MIBI gated myocardial perfusion imaging (G-MPI for MD.Methods and results: Ninety-one patients underwent 99Tcm-MIBI G-MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD (n=77 or Becker muscular dystrophy (BMD; n=14. 99Tcm-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using 99Tcm-MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (rs=0.534 [P<0.05] and rs=0.784 [P<0.05], respectively. Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05, but not in BMD patients.Conclusion: 99Tcm-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Science.gov (United States)

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

Directory of Open Access Journals (Sweden)

Juan Carlos Chachques

2011-01-01

Full Text Available Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

Autologous bone marrow concentrate enriched in progenitor cells — An adjuvant in the treatment of acute myocardial infarction

Directory of Open Access Journals (Sweden)

Vinay Sanghi

2016-06-01

Full Text Available Despite advances in revascularization techniques, acute myocardial infarction (AMI still carries significant morbidity and mortality. Over the past decade, the use of regenerative medicine methodologies, and specifically bone marrow derived progenitor cell therapy has been tested in more than 35 Phase I and Phase II clinical studies demonstrating overall safety and measurable clinical benefit, 12–61 months post-treatment as evaluated by improvement in the Left Ventricular Ejection Fraction (LVEF and changes in infarct size post AMI. Recent meta-analysis on the subject highlighted several important parameters that include timing of the cell therapy post AMI, the cell dose, and the baseline LVEF on enrollment. We further postulate that the mythologies and timing for cell handling and delivery including the specific devices are essential for clinical efficacy. Addressing this we have developed a rapid 60 to 90 minute process and integrated system which is carried out in the heart catheter lab, using a combination product (U.S. Food and Drug broadly defined as the combination of co-labeled optimized “cell friendly” devices, effective cell/biological formulation and dose for harvesting, processing, verifying, and delivering an autologous dose of bone marrow progenitor/stem cells via the intracoronary artery proximal to the infarct myocardial region. The methodology has been demonstrated to be safe and feasible for autologous in vivo use and presented by our groups' earlier studies1–3 and most recently used in a Phase Ib critical limb ischemia trial of 17 subjects (NCT01472289 (manuscript under preparation. This is the first case study prior to beginning the AMIRST trial [Acute Myocardial Infarction Rapid Stem cell Therapy], specific to our proprietary combination product kit for acute myocardial infarction, and was completed under the Independent Ethics Committee and Institutional Committee for Stem Cell Research and Therapy approval (TIEC

Primary radiation damage and disturbance in cell divisions

International Nuclear Information System (INIS)

Kim, Jin Kyu; Lee, Yun-Jong; Kim, Jae-Hun; Petin, Vladislav G.; Nili, Mohammad

2008-01-01

Survived cells from a homogeneous population exposed to ionizing radiation form various colonies of different sizes and morphology on a solid nutrient medium, which appear at different time intervals after irradiation. Such a phenomenon agrees well with the modern theory of microdosimetry and classical hit-and-target models of radiobiology. According to the hit-principle, individual cells exposed to the same dose of radiation are damaged in different manners. It means that the survived cells can differ in the content of sublethal damage (hits) produced by the energy absorbed into the cell and which is not enough to give rise to effective radiation damage which is responsible for cell killing or inactivation. In diploid yeast cells, the growth rate of cells from 250 colonies of various sizes appeared at different time intervals after irradiation with 600 Gy of gamma radiation from a 60 Co isotopic source was analyzed. The survival rate after irradiation was 20%. Based on the analyses results, it was possible to categorize the clones grown from irradiated cells according to the number of sub-lesions from 1 to 4. The clones with various numbers of sub-lesions were shown to be different in their viability, radiosensitivity, sensitivity to environmental conditions, and the frequency of recombination and respiratory deficient mutations. Cells from unstable clones exhibited an enhanced radiosensitivity, and an increased portion of morphologically changed cells, nonviable cells and respiration mutants, as well. The degree of expression of the foregoing effects was higher if the number of primary sublethal lesions was greater in the originally irradiated cell. Disturbance in cell division can be characterized by cell inactivation or incorrect distribution of mitochondria between daughter cells. Thus, the suggested methodology of identification of cells with a definite number of primary sublethal lesions will promote further elucidation of the nature of primary radiation

Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

International Nuclear Information System (INIS)

Roper, Katherine; Coverley, Dawn

2012-01-01

In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naïve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naïve nuclei. At the same time, H2AX is phosphorylated in naïve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naïve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: ► A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. ► Damage-activated extracts impose the cellular response to DNA damage on naïve nuclei. ► PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. ► Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. ► LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening approach.

Myocardial scintigraphy with I-123 labeled fatty acids

International Nuclear Information System (INIS)

Dudczak, R.

1983-01-01

This study presents experimental and clinical data in the use of I-123 labeled aromatic and aliphatic fatty acids. I-123 p-phenylpentadecanoic acid (p-IPPA) and I-123 heptadecanoic acid (HDA) were applied for myocardial scintigraphy. The feasibility of p-IPPA and HDA for myocardial scintigraphy was substantiated in animal experiments. Clinical studies were performed in patients with coronary artery disease (CAD) and cardiomyopathy (CMP). In CAD the results of fatty acid studies were compared with those of Tl-201. I-123 labeled fatty acids proved to be a useful tool for myocardial scintigraphy. The possibility to evaluate non invasively the myocardial metabolic function in man may add a complementary diagnostic tool in the clinical follow up of patients with heart disease. In CAD studies with I-123 p-IPPA and I-123 HDA might provide a means to assess the degree of myocardial viability and to identify a subgroup of patients who are at increased risk for irreversible myocardial damage. In patients with CMP it is probable that these studies may be used as a means of separating groups of patients with this disease. (Author)

Bacterial Cell Surface Damage Due to Centrifugal Compaction

NARCIS (Netherlands)

Peterson, Brandon W.; Sharma, Prashant K.; van der Mei, Henny C.; Busscher, Henk J.

Centrifugal damage has been known to alter bacterial cell surface properties and interior structures, including DNA. Very few studies exist on bacterial damage caused by centrifugation because of the difficulty in relating centrifugation speed and container geometry to the damage caused. Here, we

Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

Directory of Open Access Journals (Sweden)

Sudhira Begum

2007-12-01

Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

Effects of different components of serum after radiation, burn and combined radiation-burn injury on inward rectifier potassium channel of myocardial cells

International Nuclear Information System (INIS)

Ye Benlan; Cheng Tianmin; Xiao Jiasi

1997-01-01

Objective: To study the effects of different components of serum in rats inflicted with radiation, burn and combined radiation-burn injury on inward rectifier potassium channel of cultured myocardial cells. Method: Using patch clamp method to study the action of single ion channel. Results: The low molecular and lipid components of serum after different injuries models could all activate the inward rectifier potassium channel in cultured myocardial cells. The components of serum after combined radiation-burn injury showed the most significant effect, and the way of this effect was different from that from single injury. Conclusion: The serum components post injury altered the electric characteristic of myocardial cells, which may play a role in the combined effect of depressed cardiac function after combined radiation-burn injury

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

Science.gov (United States)

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

DNA damage in synchronized hela cells irradiated with ultraviolet

International Nuclear Information System (INIS)

Downes, C.S.; Collins, A.R.S.; Johnson, R.T.

1979-01-01

The lethal effect of uv radiation on HeLa cells is least in mitosis and greatest in late G 1 -early S. Photochemical damage to HeLa DNA, as measured by thymine-containing dimer formation and by alkaline sucrose sedimentation, also increases from mitosis towards early S phase. Computer simulations of uv absorption by an idealized HeLa cell at different stages of the cell cycle indicate that changes in damage could be due solely to changes in chromatin geometry. But survival is not exclusively a function of damage

Aging of hematopoietic stem cells: DNA damage and mutations?

Science.gov (United States)

Moehrle, Bettina M; Geiger, Hartmut

2016-10-01

Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase in and nature of DNA mutations in the hematopoietic system with age, the quality of the DNA damage response in aged HSCs, and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or three-dimensional architecture of the cell as major cell intrinsic factors of HSCs aging. Aging of HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSC aging in the light of these novel mechanisms of aging of HSCs. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Quantification of DNA damage by single-cell electrophoresis

International Nuclear Information System (INIS)

Ikushima, Takaji

1990-01-01

A simple technique of micro-agarose gel electrophoresis has been developed to quantify DNA damage in individual cells. Cells are embedded in agarose gel on microscope slides, lysed by detergents and then electrophoresed for a short time under neutral or alkaline condition. In irradiated cells, DNA migrates from the nucleus toward the anode, displaying commet-like pattern by staining with DNA-specific fluorescence dye. DNA damage is evaluated by measuring the distance of DNA migration. The technique was applied for measuring DNA damage in single cells exposed to 60 Co γ-rays, or to KUR radiation in the presence or absence of 10 B-enriched boric acid. The enhanced production of double-stranded DNA breaks by 10 B(n,α) 7 Li reaction was demonstrated here. The significant increase in the length of DNA migration was observed in single cells exposed to such a low dose as 20 cGy after alkaline micro electrophoresis. (author)

CD4+ Foxp3+ T-cells contribute to myocardial ischemia-reperfusion injury.

Science.gov (United States)

Mathes, Denise; Weirather, Johannes; Nordbeck, Peter; Arias-Loza, Anahi-Paula; Burkard, Matthias; Pachel, Christina; Kerkau, Thomas; Beyersdorf, Niklas; Frantz, Stefan; Hofmann, Ulrich

2016-12-01

The present study analyzed the effect of CD4 + Forkhead box protein 3 negative (Foxp3 - ) T-cells and Foxp3 + CD4 + T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4 + T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34.5±4.7% in MHCII KO versus 59.4±4.9% in wildtype (WT)) and better preserved ejection fraction determined by magnetic resonance tomography (56.9±2.8% in MHC II KO versus 39.0±4.2% in WT). MHC-II KO mice also displayed better microvascular perfusion than WT mice after 24hours of reperfusion. Also CD4 + T-cell sufficient OT-II mice, which express an in this context irrelevant T-cell receptor, revealed smaller infarct sizes compared to WT mice. However, MHC-II blocking anti-I-A/I-E antibody treatment was not able to reduce infarct size indicating that autoantigen recognition is not required for the activation of CD4 + T-cells during reperfusion. Flow-cytometric analysis also did not detect CD4 + T-cell activation in heart draining lymph nodes in response to 24hours of ischemia-reperfusion. Adoptive transfer of CD4 + T-cells in CD4 KO mice increased the infarct size only when including the Foxp3 + CD25 + subset. Depletion of CD4 + Foxp3 + T-cells in DEREG mice enabling specific conditional ablation of this subset by treatment with diphtheria toxin attenuated infarct size as compared to diphtheria toxin treated WT mice. CD4 + Foxp3 + T-cells enhance myocardial ischemia-reperfusion injury. CD4 + T-cells exert injurious effects without the need for prior activation by MHC-II restricted autoantigen recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytomegalovirus-Induced Effector T Cells Cause Endothelial Cell Damage

NARCIS (Netherlands)

van de Berg, Pablo J. E. J.; Yong, Si-La; Remmerswaal, Ester B. M.; van Lier, René A. W.; ten Berge, Ineke J. M.

2012-01-01

Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial cell damage, but definitive proof for a direct cytopathic effect of CMV in these diseases is lacking. CMV infection is associated with a strong increase in both CD4(+) and CD8(+) T cells

Basic study on a lower-energy defibrillation method using computer simulation and cultured myocardial cell models.

Science.gov (United States)

Yaguchi, A; Nagase, K; Ishikawa, M; Iwasaka, T; Odagaki, M; Hosaka, H

2006-01-01

Computer simulation and myocardial cell models were used to evaluate a low-energy defibrillation technique. A generated spiral wave, considered to be a mechanism of fibrillation, and fibrillation were investigated using two myocardial sheet models: a two-dimensional computer simulation model and a two-dimensional experimental model. A new defibrillation technique that has few side effects, which are induced by the current passing into the patient's body, on cardiac muscle is desired. The purpose of the present study is to conduct a basic investigation into an efficient defibrillation method. In order to evaluate the defibrillation method, the propagation of excitation in the myocardial sheet is measured during the normal state and during fibrillation, respectively. The advantages of the low-energy defibrillation technique are then discussed based on the stimulation timing.

G-CSF therapy with mobilization of bone marrow stem cells for myocardial recovery after acute myocardial infarction - a relevant treatment?

DEFF Research Database (Denmark)

Ripa, R.S.; Kastrup, J.

2008-01-01

-CSF treatment. Current controversies in interpretation of the results include 1) importance of direct cardiac effect of G-CSF vs indirect through bone marrow stem and progenitor cell mobilization, 2) importance of timing of G-CSF therapy, 3) importance of G-CSF dose, and 4) importance of cell types mobilized...... from the bone-marrow. Cell-based therapies to improve cardiac function remain promising and further experimental and clinical studies are warranted to determine the future role of G-CSF Udgivelsesdato: 2008/6......This review of adjunctive therapy with subcutaneous granulocyte-colony stimulating factor (G-CSF) to patients with acute myocardial infarction (AMI) focus on the cardioprotective effects and potential mechanisms of G-CSF and discuss the therapeutic potential of G-CSF. All clinical trials published...

Quantitative aspects of repair of potentially lethal damage in mammalian cells

International Nuclear Information System (INIS)

Iliakis, G.; Pohlit, W.

1979-01-01

Stationary cultures of Ehrlich ascites tumour cells were irradiated with X-rays and then immediately or after a time interval tsub(rep) plated to measure the survival. The increase in survival observed after delayed plating was interpreted as repair of potentially lethal damage. A cybernetic model was used to analyse these data. Three states of damage were assumed for the cells. In state A the cells could grow to macrocolonies, in state B the cells suffered potentially lethal damage and could grow to macrocolonies only if they were allowed to repair the damage and in state C the cells were lethally damaged. A method of deriving the values of the parameters of the model from the experimental data was given. The dependence of the reaction rate constant of the repair potentially lethal damage on the dose D was used to derive a possible mechanism for the production of the shoulder in the dose effect curve. Finally this model was compared with other models of radiation action in living cells. (author)

Track structure model of cell damage in space flight

Science.gov (United States)

Katz, Robert; Cucinotta, Francis A.; Wilson, John W.; Shinn, Judy L.; Ngo, Duc M.

1992-01-01

The phenomenological track-structure model of cell damage is discussed. A description of the application of the track-structure model with the NASA Langley transport code for laboratory and space radiation is given. Comparisons to experimental results for cell survival during exposure to monoenergetic, heavy-ion beams are made. The model is also applied to predict cell damage rates and relative biological effectiveness for deep-space exposures.

Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

Science.gov (United States)

Yang, Yang; Yang, Ming; Ai, Fen; Huang, Congxin

2017-06-01

The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

Old tools for sophisticated diagnosis: Electrocardiography for the assessment of myocardial viability

International Nuclear Information System (INIS)

Margonato, A.; Chierchia, S.

1996-01-01

The identification of residual myocardial viability in patients with a previous myocardial infarction has important clinical implications. Various methods have been developed for the detection of viable myocardium, however most of them are expensive and available only to high-tech centers. In the attempt to obtain reliable information at a low cost, exercise-ECG has been proposed as a useful technique. The results of a series of studies show that ST segment elevation and ventricular arrhythmias elicited by exercise are reliable signs of the presence of reversible myocardial damage

Myocardial injury and protection related to cardiopulmonary bypass

NARCIS (Netherlands)

de Hert, Stefan; Moerman, Anneliese

2015-01-01

During cardiac surgery with cardiopulmonary bypass, the heart is isolated from the circulation. This inevitably induces myocardial ischemia. In addition to this ischemic insult, an additional hit will occur upon reperfusion, which may worsen the extent of tissue damage and organ dysfunction. Over

Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

Science.gov (United States)

Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

2014-02-01

Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

Impairment of myocardial perfusion in children with sickle cell disease; Alteration de la perfusion myocardique chez l'enfant drepanocytaire

Energy Technology Data Exchange (ETDEWEB)

Maunoury, C. [Hopital Necker-Enfants-Malades, Service de Medecine Nucleaire, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Hopital des Enfants, Service de Cardiologie Pediatrique, 31 - Toulouse (France); Montalembert, M. de [Hopital Necker-Enfants-Malades, Service de Pediatrie Generale, 75 - Paris (France)

2003-10-01

While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 {+-} 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 {+-} 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

Science.gov (United States)

Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

2013-06-21

We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

Expression of assayable residual stem cell damage in erythroid differentiation

International Nuclear Information System (INIS)

Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

1985-01-01

In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

Evaluation of myocardial abnormalities in collagen diseases by thallium-201 myocardial scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Yamano, Shigeru; Kagoshima, Tadashi; Sugihara, Kiyotaka (Nara Medical Univ., Kashihara (Japan)) (and others)

1993-12-01

This study was performed to evaluate myocardial abnormalities in patients with collagen diseases by exercise and rest thallium-201 myocardial scintigrams. A total of 65 patients without ischemic ECG changes, consisting of 18 with systemic lupus erythematosus (SLE), 18 with polymyositis (PM), 8 with progressive systemic sclerosis (PSS), and 21 with Sjoegren's syndrome (SjS), was enrolled in this study. Reversible exercise-induced defects scintigraphically suggesting myocardial ischemia were noted in 8 cases of SLE, 4 cases of PM, 4 cases of PSS, and 3 cases of SjS. Nineteen patients had exercise-induced defects and underwent cardiac catheterization, 8 of whom had normal coronary angiograms. Fixed hypoperfusion areas were observed in one case of SLE, 6 cases of PM and 3 cases of SjS. Rest thallium-201 myocardial scintigram disclosed hypoperfusion areas which were not induced by exercise in 2 cases of SLE, 3 cases of PM, one case of PSS and 5 cases of SjS. Echocardiogram showed no significant differences in ejection fraction and % fractional shortening between the disease groups and healthy control group. These findings suggest that patients with collagen diseases have abnormalities of coronary circulation at the level of the intramural vasculature before cardiac function impairment, myocardial fibrosis and functional abnormalities at the cell membrane. (author).

Myocardial perfusion in silent myocardial ischemia

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Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

1989-01-01

To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (Tl) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n=36) or absence (Silent Group, n=49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30±10 % in Silent Group, 28±12 % in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial Tl washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4±10% vs -16±14%, p<0.001). The study in patients who exhibited both silent and symptomatic ischemia showed the same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia. (author)

Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

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Gehrau, Ricardo C.; D' Astolfo, Diego S.; Andreoli, Veronica [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Bocco, Jose L., E-mail: jbocco@fcq.unc.edu.ar [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Koritschoner, Nicolas P. [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

2011-02-10

The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC{sub 50}). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p < 0.0001) in KLF6 mRNA levels were observed depending on the cellular p53 status upon cell damage. KLF6 expression was significantly increased in 63% of p53-deficient cells (122/195). Conversely, KLF6 mRNA level decreased nearly 4 fold in more than 70% of p53+/+ cells. In addition, klf6 gene promoter activity was down-regulated by DNA damaging agents in cells expressing the functional p53 protein whereas it was moderately increased in the absence of functional p53. Consistent results were obtained for the endogenous KLF6 protein level. Results indicate that human klf6 gene expression is responsive to external cell damage mediated by IC{sub 50} concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable

Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells.

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Karpov, Andrey A; Udalova, Daria V; Pliss, Michael G; Galagudza, Michael M

2017-04-01

Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury. © 2016 John Wiley & Sons Ltd.

Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

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Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

2013-06-01

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death.

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Zhang, Jianhui; Sun, Hong; Salvi, Richard; Ding, Dalian

2018-07-01

Paraquat (PQ), one of the most widely used herbicides, is extremely dangerous because it generates the highly toxic superoxide radical. When paraquat was applied to cochlear organotypic cultures, it not only damaged the outer hair cells (OHCs) and inner hair cells (IHCs), but also caused dislocation of the hair cell rows. We hypothesized that the dislocation arose from damage to the support cells (SCs) that anchors hair cells within the epithelium. To test this hypothesis, rat postnatal cochlear cultures were treated with PQ. Shortly after PQ treatment, the rows of OHCs separated from one another and migrated radially away from IHCs suggesting loss of cell-cell adhesion that hold the hair cells in proper alignment. Hair cells dislocation was associated with extensive loss of SCs in the organ of Corti, loss of tympanic border cells (TBCs) beneath the basilar membrane, the early appearance of superoxide staining and caspase-8 labeling in SCs below the OHCs and disintegration of E-cadherin and β-catenin in the organ of Corti. Damage to the TBCs and SCs occurred prior to loss of OHC or IHC loss suggesting a form of detachment-induced apoptosis referred to as anoikis. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival

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Ana Belén Herrero

2017-05-01

Full Text Available Human myeloma cell lines (HMCLs and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS, leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR, the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM, since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ, using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it

The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

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Edward B. Thorp

2012-01-01

Full Text Available Heart failure is a progressive and disabling disease. The incidence of heart failure is also on the rise, particularly in the elderly of industrialized societies. This is in part due to an increased ageing population, whom initially benefits from improved, and life-extending cardiovascular therapy, yet ultimately succumb to myocardial failure. A major cause of heart failure is ischemia secondary to the sequence of events that is dyslipidemia, atherosclerosis, and myocardial infarction. In the case of heart failure postmyocardial infarction, ischemia can lead to myocardial cell death by both necrosis and apoptosis. The extent of myocyte death postinfarction is associated with adverse cardiac remodeling that can contribute to progressive heart chamber dilation, ventricular wall thinning, and the onset of loss of cardiac function. In cardiomyocytes, recent studies indicate that myocardial ischemic injury activates the unfolded protein stress response (UPR and this is associated with increased apoptosis. This paper focuses on the intersection of ischemia, the UPR, and cell death in cardiomyocytes. Targeting of the myocardial UPR may prove to be a viable target for the prevention of myocyte cell loss and the progression of heart failure due to ischemic injury.

Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ

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Yi YANG

2017-12-01

Full Text Available Objective To investigate the role of mitochondrial calcium uptake 1 (MICU1 in myocardial hypertrophy of mice and underlying mechanism. Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM with 300nmol/L angiotensin Ⅱ (Ang Ⅱ for 48 hours in vitro. After that, MICU1 specific small interfering RNA (siRNA was delivered to knockdown MICU1 levels in MCM. On the other hand, adenovirus-mediated over-expression of MICU1 was transfected into MCM. Accordingly, the expressions of ANP and BNP in myocardial cells were measured by qRT- PCR. Mitochondrial membrane potential and ATP contents were detected by JC-1 assay kit and ATP assay kit, respectively. Then, Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells. The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy. The size of myocardial cells was determined by α-actinin staining. Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by AngⅡ were both decreased. Meanwhile, myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels. With the method of genetic intervention, we found that MICU1 deficiency exacerbated mitochondrial Ca2+ overload, increased cell surface and elevated the expression of BNP. Conversely, the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload, cell surface of MCM and expressions of ANP and BNP. Conclusion MICU1 alleviates AngⅡ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload. DOI: 10.11855/j.issn.0577-7402.2017.12.05

Toll-Like Receptors and Myocardial Inflammation

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Yan Feng

2011-01-01

Full Text Available Toll-like receptors (TLRs are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1 TLRs, TLR ligands, and the signal transduction system and (2 the important role of TLR signaling in these critical cardiac conditions.

Evaluation of the damage of cell wall and cell membrane for various extracellular polymeric substance extractions of activated sludge.

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Guo, Xuesong; Liu, Junxin; Xiao, Benyi

2014-10-20

Extracellular polymeric substances (EPS) are susceptible to contamination by intracellular substances released during the extraction of EPS owing to the damage caused to microbial cell structures. The damage to cell walls and cell membranes in nine EPS extraction processes of activated sludge was evaluated in this study. The extraction of EPS (including proteins, carbohydrates and DNA) was the highest using the NaOH extraction method and the lowest using formaldehyde extraction. All nine EPS extraction methods in this study resulted in cell wall and membrane damage. The damage to cell walls, evaluated by 2-keto-3-deoxyoctonate (KDO) and N-acetylglucosamine content changes in extracted EPS, was the most significant in the NaOH extraction process. Formaldehyde extraction showed a similar extent of damage to cell walls to those detected in the control method (centrifugation), while those in the formaldehyde-NaOH and cation exchange resin extractions were slightly higher than those detected in the control. N-acetylglucosamine was more suitable than KDO for the evaluation of cell wall damage in the EPS extraction of activated sludge. The damage to cell membranes was characterized by two fluorochromes (propidium iodide and FITC Annexin V) with flow cytometry (FCM) measurement. The highest proportion of membrane-damaged cells was detected in NaOH extraction (26.54% of total cells) while membrane-damaged cells comprised 8.19% of total cells in the control. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of chemical-induced DNA damage on male germ cells

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Holme, J.A.; Bjoerge, C.; Trbojevic, M.; Olsen, A.K.; Brunborg, G.; Soederlund, E.J. [National Inst. of Public Health, Oslo (Norway). Dept. of Environmental Medicine; Bjoeras, M.; Seeberg, E. [National Hospital, Oslo (Norway). Dept. of Microbiology; Scholz, T.; Dybing, E.; Wiger, R. [National Hospital, Oslo (Norway). Inst. for Surgical Research and Surgical Dept. B

1998-12-31

Several recent studies indicate declines in sperm production, as well as increases in the incidence of genitourinary abnormalities such as testicular cancer, cryptorchidism and hypospadias. It is not known if these effects are due to exposure to chemical pollutants or if other ethiological factors are involved. Animal studies indicate that chemicals will induce such effects by various genetic, epigenetic or non-genetic mechanisms. Recently, much attention has been focused on embryonic/fetal exposure to oestrogen-mimicking chemicals (Toppari et al., 1996). However, the possibility that chemicals may cause reproductive toxicity by other mechanisms such as interactions with DNA, should not be ignored. DNA damage in germ cells may lead to the production of mutated spermatozoa, which in turn may result in spontaneous abortions, malformations and/or genetic defects in the offspring. Regarding the consequences of DNA alterations for carcinogenesis it is possible that genetic damage may occur germ cells, but the consequences are not expressed until certain genetic events occur in postnatal life. Transmission of genetic risk is best demonstrated by cancer-prone disorders such as hereditary retinoblastoma and the Li-Fraumeni syndrome. A number of experiments indicate that germ cells and proliferating cells may be particularly sensitive to DNA damaging agents compared to other cells. Furthermore, several lines of evidence have indicated that one of the best documented male reproductive toxicants, 1,2-dibrome-3-chloropropane (DBCP), causes testicular toxicity through DNA damage. It is possible that testicular cells at certain maturational stages are more subject to DNA damage, have less efficient DNA repair, or have different thresholds for initiating apoptosis following DNA damage than other cell types. (orig.)

Link between DNA damage and centriole disengagement/reduplication in untransformed human cells.

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Douthwright, Stephen; Sluder, Greenfield

2014-10-01

The radiation and radiomimetic drugs used to treat human tumors damage DNA in both cancer cells and normal proliferating cells. Centrosome amplification after DNA damage is well established for transformed cell types but is sparsely reported and not fully understood in untransformed cells. We characterize centriole behavior after DNA damage in synchronized untransformed human cells. One hour treatment of S phase cells with the radiomimetic drug, Doxorubicin, prolongs G2 by at least 72 h, though 14% of the cells eventually go through mitosis in that time. By 72 h after DNA damage we observe a 52% incidence of centriole disengagement plus a 10% incidence of extra centrioles. We find that either APC/C or Plk activities can disengage centrioles after DNA damage, though they normally work in concert. All disengaged centrioles are associated with γ-tubulin and maturation markers and thus, should in principle be capable of reduplicating and organizing spindle poles. The low incidence of reduplication of disengaged centrioles during G2 is due to the p53-dependent expression of p21 and the consequent loss of Cdk2 activity. We find that 26% of the cells going through mitosis after DNA damage contain disengaged or extra centrioles. This could produce genomic instability through transient or persistent spindle multipolarity. Thus, for cancer patients the use of DNA damaging therapies raises the chances of genomic instability and evolution of transformed characteristics in proliferating normal cell populations. © 2014 Wiley Periodicals, Inc.

Impact of system delay on infarct size, myocardial salvage index, and left ventricular function in patients with ST-segment elevation myocardial infarction

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Lønborg, Jacob Thomsen; Schoos, Mikkel Malby; Kelbæk, Henning Skov

2012-01-01

The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less...

Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction

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Michelle R. Santoso

2016-01-01

Full Text Available Stem cell therapy has broad applications in regenerative medicine and increasingly within cardiovascular disease. Stem cells have emerged as a leading therapeutic option for many diseases and have broad applications in regenerative medicine. Injuries to the heart are often permanent due to the limited proliferation and self-healing capability of cardiomyocytes; as such, stem cell therapy has become increasingly important in the treatment of cardiovascular diseases. Despite extensive efforts to optimize cardiac stem cell therapy, challenges remain in the delivery and monitoring of cells injected into the myocardium. Other fields have successively used nanoscience and nanotechnology for a multitude of biomedical applications, including drug delivery, targeted imaging, hyperthermia, and tissue repair. In particular, superparamagnetic iron oxide nanoparticles (SPIONs have been widely employed for molecular and cellular imaging. In this mini-review, we focus on the application of superparamagnetic iron oxide nanoparticles in targeting and monitoring of stem cells for the treatment of myocardial infarctions.

DNA-repair, cell killing and normal tissue damage

International Nuclear Information System (INIS)

Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

1998-01-01

Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

Transplantation of mesenchymal stem cells overexpressing IL10 attenuates cardiac impairments in rats with myocardial infarction.

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Meng, Xin; Li, Jianping; Yu, Ming; Yang, Jian; Zheng, Minjuan; Zhang, Jinzhou; Sun, Chao; Liang, Hongliang; Liu, Liwen

2018-01-01

Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI. © 2017 Wiley Periodicals, Inc.

Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

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Møller, Peter; Jensen, Ditte Marie; Christophersen, Daniel Vest

2015-01-01

-reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations...... of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure...... and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc....

Effect of acupuncture on the genetic expression of myocardial endothelin-1 and atrial natriuretic peptide in rats with stress-induced prehypertension

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Wenrui Jia

2017-01-01

Conclusion: Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats, suggesting a protective effect of acupuncture against myocardial damage.

Damage effect of γ-rays on bacillus subtilis vegetative Cells

International Nuclear Information System (INIS)

Chen Xiaoming; Liu Fang; Zhang Jianguo; Yan Wanli; Zheng Chun; Li Xiaoyan

2011-01-01

In order to investigate the damage effects of γ-rays at cell and molecular level, Bacillus subtilis vegetative cells were irradiated by 60 Co γ-rays at different absorbed doses. The cell survival rate was examined with the standard plate-count method. The intracellular SOD activity was measured by SOD kit through xanthine oxidase method. DNA double-strand breaks were analyzed by pulsed-field gel electrophoresis (PFGE). The cell survival rate decreases when γ-rays dose increases. A clear relation could not be found between intracellular SOD activity and absorbed dose. The DNA release percentage value and break level value increase obviously with γ-rays dose. Cell survival rate is related to DNA double-strand breaks level. It can be concluded that γ-rays have obviously damage effect on Bacillus subtilis vegetative cell, and the damage effect changes with SOD activity and DSB. (authors)

Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

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Kimura M

2012-01-01

Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

Mitochondrial DNA damage and oxidative damage in HL-60 cells exposed to 900 MHz radiofrequency fields

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Sun, Yulong; Zong, Lin; Gao, Zhen [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Zhu, Shunxing [Laboratory Animal Center, Nantong University, Nantong, Jiangsu Province (China); Tong, Jian [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Cao, Yi, E-mail: yicao@suda.edu.cn [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China)

2017-03-15

Highlights: • Increased reactive oxygen species. • Decreased mitochondrial transcription Factor A and polymerase gamma. • Decreased mitochondrial transcripts (ND1 and 16S) and mtDNA copy number. • Increased 8-hydroxy-2′deoxyguanosine. • Decreased adenosine triphosphate. - Abstract: HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm{sup 2} power intensity for 4 h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2′-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions. The results indicated a significant increase in ROS and significant decreases in mitochondrial transcription factor A, mtDNA polymerase gamma, mtDNA transcripts and mtDNA copy number in RF-exposed cells compared with those in sham-exposed control cells. In addition, there was a significant increase in 8-OHdG and a significant decrease in ATP in RF-exposed cells. The response in positive control cells exposed to gamma radiation (GR, which is also known to induce ROS) was similar to those in RF-exposed cells. Thus, the overall data indicated that RF exposure was capable of inducing mtDNA damage mediated through ROS pathway which also induced oxidative damage. Prior-treatment of RF- and GR-exposed the cells with melatonin, a well-known free radical scavenger, reversed the effects observed in RF-exposed cells.

Mechanism of the Protective Effect of Yulangsan Flavonoid on Myocardial Ischemia/Reperfusion Injury in Rats

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Xudong Zhang

2014-09-01

Full Text Available Aims: Effect and mechanism of Yulangsan flavonoid (YLSF on rat myocardial ischemia/reperfusion injury (MI/RI has been investigated. Methods: Sprague-Dawley (SD rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1 mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR. Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS, caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS as well as constitutive nitric oxide synthase (cNOS. Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

Hypoxia-ischemia and retinal ganglion cell damage

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Charanjit Kaur

2008-08-01

Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

Radioadaptive response. Efficient repair of radiation-induced DNA damage in adapted cells

International Nuclear Information System (INIS)

Ikushima, Takaji; Aritomi, Hisako; Morisita, Jun

1996-01-01

To verify the hypothesis that the induction of a novel, efficient repair mechanism for chromosomal DNA breaks may be involved in the radioadaptive response, the repair kinetics of DNA damage has been studied in cultured Chinese hamster V79 cells with single-cell gel electrophoresis. The cells were adapted by priming exposure with 5 cGy of γ-rays and 4-h incubation at 37C. There were no indication of any difference in the initial yields of DNA double-strand breaks induced by challenging doses from non-adapted cells and from adapted cells. The rejoining of DNA double-strand breaks was monitored over 120 min after the adapted cells were challenged with 5 or 1.5 Gy, doses at the same level to those used in the cytogenetical adaptive response. The rate of DNA damage repair in adapted cells was higher than that in non-adapted cells, and the residual damage was less in adapted cells than in non-adapted cells. These results indicate that the radioadaptive response may result from the induction of a novel, efficient DNA repair mechanism which leads to less residual damage, but not from the induction of protective functions that reduce the initial DNA damage

Ultrastructural study of mitochondrial damage in CHO cells exposed to hyperthermia.

Science.gov (United States)

Cole, A; Armour, E P

1988-09-01

A unique direct-view stereo electron microscope technique was used to visualize the structure and three-dimensional distributions of mitochondria in CHO cells in situ following hyperthermic treatments. Aberrations induced by various heating regimens were recorded. The protocol included a trypsin digestion that may have enhanced the expression of the initial heat damage. The developed damage was observed as increasing levels of mitochondrial distortion, swelling, and dissociation. Minimal damage was induced at 42 degrees C for exposures of up to 4 h, while significant damage was induced at 43 degrees C for exposures of more than 30 min and at 45 degrees C for exposures of more than 10 min. For moderate exposures, a partial recovery of mitochondrial integrity was observed when the heat treatment was followed by incubation at 37 degrees C for 24 h. Mitochondrial damage was related to the heat dose in that increasing treatment temperature resulted in greater damage, but when compared to cell survival the damage did not parallel cell killing under all time-temperature conditions.

Nuclear cardiological investigations in patients classified as physically disabled following myocardial infarction

International Nuclear Information System (INIS)

Mester, Janos; Zolnay, Imre; Csernay, Laszlo

1988-01-01

110 patients classified as physically disabled as a consequence of myocardial infarction were reinvestigated by means of nuclear cardiological methods. Resting 201 Tl perfusion scintigraphy showed a normal distribution of radioactivity, while radionuclide ventriculography revealed a normal left ventricular ejection fraction and a normokinetic left ventricle in 20 patients. The investigation of a further 19 patients demonstrated only minimal pathological changes. The results in 34 patients revealed severe myocardial damage, and in a further 19 cases the development of left ventricular aneurysm. The results clearly show the value of 201 Tl scintigraphy and radionuclide ventriculography in assessments of the degree of physical disability after myocardial infarction. (author) 15 refs.; 3 tabs

Use of clopidogrel in the reduction of myocardial damage during percutaneous coronary intervention

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Arijit Dasgupta

2009-03-01

Full Text Available Arijit Dasgupta, Debabrata MukherjeeGill Heart Institute, University of Kentucky, Lexington, KY, USAAbstract: It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK/creatinine kinase myocardial band (CK-MB elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI. Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of clopidogrel is considered to be at least 300 mg given 6 to 15 hours prior to PCI but there is considerable evidence to suggest that a loading dose of 600 mg given 2 to 6 hours prior to PCI may be more efficacious in limiting post-coronary intervention events. The benefit obtained from clopidogrel appears independent of and incremental to that of other antiplatelet and antithrombotic agents used during and after coronary intervention.Keywords: percutaneous coronary intervention, myonecrosis, clopidogrel, antiplatelet agents, myocardial infarction 

Radiation damage evaluation on AlGaAs/GaAs solar cells

International Nuclear Information System (INIS)

Moreno, E.G.; Alcubilla, R.; Prat, L.; Castaner, L.

1988-01-01

A piecewise model to evaluate radiation damage on AlGaAs based solar cells has been developed, which gives complete electrical parameters of the cells in the operating temperature range. Different structures, including graded band gap and double heteroface can be analyzed. The cell structure is sliced into layers of constant parameters, allowing the model to take into account nonuniform damage produced by low energy protons without excess computer time. Proton damage coefficients as well as proton damage ratios can be calculated for energies between 30 and 10/sup 4/ keV with only two adjustable parameters. In addition, coirradiation experiments with different energy protons can be simulated, by improving the conventional method of degradation computering

Acute myocardial infarction: 'telomerasing' for cardioprotection

OpenAIRE

Sanchís-Gomar, Fabián; Lucía Mulas, Alejandro

2015-01-01

Reactivating the telomerase gene through gene therapy after acute myocardial infarction (AMI) has been recently reported to improve survival in mice. Given that regular physical exercise also activates this gene, therapeutic and lifestyle interventions targeting telomerase need to be explored as possible additions to the current armamentarium for myocardial regeneration. 9.292 JCR (2015) Q1, 17/289 Biochemistry & mollecular biology, 17/187 Cell biology, 8/124 Medicine, research & experimen...

[Myocardial ultrastructural changes in rats following different levels of acute +Gz exposure].

Science.gov (United States)

Zheng, Jun; Liu, Cheng-gang; Ren, Li; Xiao, Xiao-guang; Xu, Shu-xuan; Wang, Ping; Ji, Gui-ying

2004-06-01

To observe the effects of different levels of acute +Gz exposure on myocardial ultrastructure of rats and provide experimental basis for further development of anti-G measures. Twenty male Wistar rats were randomly divided into 4 groups (n=5): normal control group, +20 Gz group, +10 Gz group and +5 Gz group. Profile of the centrifuge +Gz exposure was trapezoidal, in which +20 Gz lasted for 30 s, +10 Gz for 1.5 min. +5 Gz exposure was repeated for 3 times with 30 min interval and each for 1.5 min. Myocardial tissue of left ventricle was sampled for transmission electron microscopy 5 h after exposure. +20 Gz and +10 Gz exposure caused obvious edema of myocardial and endothelial cells, myofibril disorder and injuries of mitochondria and nucleus. Breaks of myocardial fiber, formation of contraction bands and rupture of mitochondria were also observed in +20 Gz group. In +5 Gz group, there was still slight edema of myocardial and endothelial cells, while organic changes of myocardial ultrastructure were not observed. High +Gz exposure can cause myocardial ultrastructural injury in rats. Slight reversible injured response can also be observed in myocardial cell after repeated moderate level of +Gz exposure. This indicates that attention should be paid to the study of the effect of high +Gz on heart in pilots.

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

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Qing Li

2013-09-01

Full Text Available Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX, a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180 cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl-2, 5-diphenyltetrazoliumbromide (MTT assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore. Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

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Brum Patricia C

2011-04-01

Full Text Available Abstract Background Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI, in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV and autonomic functions in streptozotocin (STZ diabetic rats. Methods Male Wistar rats were divided into 4 groups: control (C, n = 15, diabetes (D, n = 16, MI (I, n = 21, and diabetes + MI (DI, n = 30. MI was induced 15 days after diabetes (STZ induction. Ninety days after MI, LV and autonomic functions were evaluated (8 animals each group. Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins. Results MI area was similar in infarcted groups (~43%. Ejection fraction and +dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased Na+-Ca2+ exchange and phospholamban expression (164% and decreased phosphorylated phospholamban at serine16 (65% and threonine17 (70% expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups. Conclusions LV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory

Myocardial imaging in the noninvasive evaluation of patients with suspected ischemic heart disease

International Nuclear Information System (INIS)

Pitt, B.; Strauss, H.W.

1976-01-01

Three noninvasive radioactive tracer techniques for evaluating patients with ischemic heart disease are described: (1) myocardial perfusion imaging, (2) acute infarct imaging, and (3) the gated blood pool scan. Myocardial perfusion imaging with tracers that distribute in the myocardium in relation to regional blood flow allows detection of patients with transmural and nontransmural infarction by the finding of decreased tracer concentration in the affected region of the myocardium. If these tracers are injected at the time of maximal stress to patients with significant coronary arterial stenosis but without infarction, areas of transient ischemia can be identified as zones of decreased tracer concentration not found when an examination is performed at rest. Acute infarct imaging with tracers that localize in acutely damaged tissue permits separation of patients with acute myocardial necrosis from those without infarction and those with more chronic damage. The gated blood pool scan permits assessment of left ventricular function and regional wall motion. The measurement of ventricular volumes, ejection fraction and regional wall motion adds significantly to the determination of hemodynamic variables in assessing patients with acute infarction. The technique also permits detection of right ventricular dysfunction. Performance of a combination of these radioactive tracer techniques is often advantageous, particularly in patients with suspected infarction. The techniques can establish whether infarction is present, whether it is acute, where the damage is located and how extensive it is; they can also provide a measure of the effect of this damage on left ventricular function

Role of calcium and free fatty acids in epinephrine-induced myocardial necrosis

International Nuclear Information System (INIS)

Mallov, S.

1983-01-01

A possible mechanism by which large doses of catecholamines produce myocardial necrosis was investigated. Male Sprague-Dawley rats, 275 to 325 g in weight, were injected once, sc, with 3 mg/kg epinephrine (E) or infused iv for 1 hr with E at a rate of 1.2 or 1.7 micrograms/min, and also injected iv with either 45Ca or [3H]palmitic acid (3H-PA) at the same time as or at various periods of time after E administration but exactly 0.5 or 1 hr before death. Controls were injected with saline solution. Heart/plasma ratios of radioactivity (H/P) were determined. The ratios increased in the case of both 45Ca and [3H]PA within 0.5 hr after E, reached peak values after 18 to 24 hr with 45Ca and 3 to 6 hr with [3H]PA, and remained above values for the controls for at least 72 hr with 45Ca and 48 hr with [3H]PA. The rate of 45Ca influx into heart 20 hr after E administration paralleled the severity of the myocardial damage that had been produced. When 45Ca and E were injected simultaneously, H/P increased progressively with time to 30 times control values, indicating the accumulation and retention of Ca in the heart. Under the same conditions, H/P values with [3H]PA also rose but remained constant at a level two to three times that in controls. Total cardiac free fatty acids (FFA) rose slightly and remained constant at the elevated level. It was not possible to distinguish a given point in time at which the increase in either Ca or FFA influx, initially due to the normal pharmacological effect of E, began to occur as a consequence of damage produced by the latter. It is concluded that high concentrations of catecholamines promote the deposition of Ca and FFA in myocardial cells in various forms, and that the deposition of these substances as soaps in the plasma membranes may cause permeability changes that lead to cell injury

Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice.

Science.gov (United States)

Dimomeletis, Ilias; Deindl, Elisabeth; Zaruba, Marc; Groebner, Michael; Zahler, Stefan; Laslo, Saskia M; David, Robert; Kostin, Sawa; Deutsch, Markus A; Assmann, Gerd; Mueller-Hoecker, Josef; Feuring-Buske, Michaela; Franz, Wolfgang M

2010-11-01

Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes. We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction. Human MAPCs were selected by negative depletion of CD45(+)/glycophorin(+) BM cells and plated on fibronectin-coated dishes. In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction. In vivo, we transplanted human MAPCs (5 × 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice. Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo. Heart tissues were analyzed immunohistochemically. Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency. In later passages, cardiac markers (Nkx2.5, GATA4, MLC-2v, MLC-2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22α) were expressed. Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%). Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC integrated in the peri-infarct region. The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor-sensitive SCID model. Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs. Lack of

Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

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Bjarke Follin

2018-01-01

Full Text Available Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls, 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI and 82rubidium positron emission tomography (PET. Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.. After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.

Sulphonated hypocrellin B sensitized photo damage to ascetic hepatoma cells

International Nuclear Information System (INIS)

Yue Jiachang; Wang Tiandun; Pang Suzhen; An Jingyi; Jiang Lijing

1994-01-01

The cellular uptake of sulphonated hypocrellin (S-HB), as well as photo damage on cellular viability, lipid peroxidation and intrinsic fluorescence quenching of membrane protein was studied. It was found that S-HB suitable dissolved in aqueous solution, its cellular uptake is slower than HB. The photo damage on cellular viability both photo sensitizers was close to each other, however the photo sensitizers were different in physical and chemical properties. The HB photo damage target of cells was membrane, but the sulphonated HB photo damage target of cells may be part of organelles, besides the membrane. the experiments showed the sulphonated HB would be suggested as a potential advantage for photodynamic therapy of tumor in clinical application

Value of Tl-201 in evaluating myocardial damage and ischemia in transplant patients

International Nuclear Information System (INIS)

Jazmati, B.; Tumeh, S.S.; Holman, L.B.

1989-01-01

Orthotopic heart transplant recipients suffer from graft rejection and accelerated coronary artery disease. The authors have evaluated 29 recipients of orthotopic heart transplants who had multiple biopsy-proved episodes of rejection and underwent annual T1-201 exercise myocardial scintigraphy and coronary angiography. Of 43 pairs of nuclear scans and coronary angiograms, 39 showed normal radiotracer uptake and coronary arteries. In four scans, there were ischemic changes, and in only one case was there significant two-vessel coronary artery disease. The nuclear scans correlated with the coronary angiograms in 93% of the cases. The authors conclude that T1-201 myocardial scintigraphy is insensitive in the early detection of graft rejection and can reliably rule out significant coronary artery disease in transplant recipients

Effect of methylprednisolone upon technetium-99m pyrophosphate assessment of myocardial necrosis in the canine countershock model

International Nuclear Information System (INIS)

Schneider, R.M.; Hayslett, J.P.; Downing, S.E.; Berger, H.J.; Donabedian, R.K.; Zaret, B.L.

1977-01-01

RRepeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-/sup 99m/ pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P < 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in MP dogs, resulting in accelerated urinary excretion of PYP (46.9 +- 3.6 vs 35.8 +- 2.4 percent injected dose in one hour, P < 0.01), and reduced blood PYP. Thus, MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data

Myocardial Bridge

Science.gov (United States)

... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

Repair processes for photochemical damage in mammalian cells

International Nuclear Information System (INIS)

Cleaver, J.E.

1974-01-01

Repair processes for photochemical damage in cells following uv irradiation are reviewed. Cultured fibroblast cells from human patients with xeroderma pigmentosum were used as an example to illustrate aspects of repair of injuries to DNA and proteins. (250 references) (U.S.)

Evaluation of myocardial abnormalities in patients with collagen diseases by thallium-201 myocardial scintigram

Energy Technology Data Exchange (ETDEWEB)

Yamano, Shigeru (Nara Medical Univ., Kashihara (Japan))

1992-08-01

This study was performed to evaluate myocardial lesions in patients with collagen diseases by rest and exercise thallium-201 myocardial scintigraphies. A total of 76 patients without ischemic ECG changes, consisting of 27 cases of systemic lupus erythematosus (SLE), 17 cases of polymyositis or dermatomyositis (PM[center dot]DM), 11 cases of progressive systemic sclerosis (PSS), and 21 cases of Sjoegren's syndrome (SjS), were enrolled in this study. Reversible exercise-induced defects suggesting myocardial ischemia were noted in 12 cases of SLE, 5 cases of PM[center dot]DM, 3 cases of PSS, and 3 cases of SjS. Of the 23 patients who had exercise-induced defects, 9 patients showed normal coronary angiograms by cardiac catheterization. Fixed hypoperfusion areas were observed in 5 cases of SLE, 6 cases of PM[center dot]DM, 4 cases of PSS and 3 cases of SjS. Rest thallium-201 myocardial scintigraphy disclosed hypoperfusion areas, which were not induced by exercise, in 1 case of SLE, 4 cases of PM[center dot]DM, 1 case of PSS and 5 cases of SjS. Endomyocardial biopsy was performed on 20 patients. Myocardial lesions in PM[center dot]DM and PSS were more severe and wide spread than in SLE. Ejection fraction and fractional shortening evaluated by echocardiography had no significant differences between each disease group and the healthy control group. These findings suggest that patients with collagen diseases show the presence of abnormalities of coronary circulation at the level of the intramyocardial vasculature in the stage before impairment of cardiac function, myocardial fibrosis and functional abnormalities of the cell membrane level that were not dependent on myocardial ischemia. (author).

Stem Cells and Tissue Engineering

CERN Document Server

Pavlovic, Mirjana

2013-01-01

Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

Recovery and functional activity of mononuclear bone marrow and peripheral blood cells after different cell isolation protocols used in clinical trials for cell therapy after acute myocardial infarction

NARCIS (Netherlands)

van Beem, Rachel T.; Hirsch, Alexander; Lommerse, Ingrid M.; Zwaginga, Jaap Jan; Noort, Willy A.; Biemond, Bart J.; Piek, Jan J.; van der Schoot, C. Ellen; Voermans, Carlijn

2008-01-01

AIMS: Clinical trials showed contradictory results in functional recovery after intracoronary infusion of autologous mononuclear (bone marrow) cells in patients with acute myocardial infarction. A recent study suggests that this might be related to the isolation protocol used. In The Netherlands, a

Processing of radiation-induced clustered DNA damage generates DSB in mammalian cells

International Nuclear Information System (INIS)

Gulston, M.K.; De Lara, C.M.; Davis, E.L.; Jenner, T.J.; O'Neill, P.

2003-01-01

Full text: Clustered DNA damage sites, in which two or more lesions are formed within a few helical turns of the DNA after passage of a single radiation track, are signatures of DNA modifications induced by ionizing radiation in mammalian cell. With 60 Co-radiation, the abundance of clustered DNA damage induced in CHO cells is ∼4x that of prompt double strand breaks (DSB) determined by PFGE. Less is known about the processing of non-DSB clustered DNA damage induced in cells. To optimize observation of any additional DSB formed during processing of DNA damage at 37 deg C, xrs-5 cells deficient in non-homologous end joining were used. Surprisingly, ∼30% of the DSB induced by irradiation at 37 deg C are rejoined within 4 minutes in both mutant and wild type cells. No significant mis-repair of these apparent DSB was observed. It is suggested that a class of non-DSB clustered DNA damage is formed which repair correctly within 4 min but, if 'trapped' prior to repair, are converted into DSB during the lysis procedure of PFGE. However at longer times, a proportion of non-DSB clustered DNA damage sites induced by γ-radiation are converted into DSB within ∼30 min following post-irradiation incubation at 37 deg C. The corresponding formation of additional DSB was not apparent in wild type CHO cells. From these observations, it is estimated that only ∼10% of the total yield of non DSB clustered DNA damage sites are converted into DSB through cellular processing. The biological consequences that the majority of non-DSB clustered DNA damage sites are not converted into DSBs may be significant even at low doses, since a finite chance exists of these clusters being formed in a cell by a single radiation track

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

Science.gov (United States)

Ding, Xue-feng; Wu, Yan; Qu, Wen-rui; Fan, Ming; Zhao, Yong-qi

2018-01-01

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine (20 and 40 mM) and irradiated them with 50 mW/cm2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation. PMID:29623929

The imaging research of myocardial damage in Duchenne muscular dystrophy

International Nuclear Information System (INIS)

Fu Peng; Wei Lingge; Hu Jing; Huang Jianmin; Liu Xiaomei

2011-01-01

It is common that Duchenne muscular dystrophy (DMD) patients can suffer from cardiac damage, which performed variously. Cardiac damage in DMD often be paid no attention in early stage,since the clinical symptoms is slight. With the decline of cardiac function, the quality of life, treatment and rehabilitation training of patients will be affected significantly. Furthermore, the progress of the disease will be speeded up and the difficulty of treatment will be increased. Therefore, there will be important significance in delaying the progression of cardiac damage and prolonging the life of patients by the early diagnosis and intervention treatment of cardiac damage in DMD. For the convenience of the clinician to choose suitable imaging methods, to improve the cardiac damage in patients of DMD, imaging researches which are applied to the DMD cardiac damage are reviewed. (authors)

Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

International Nuclear Information System (INIS)

Gehrau, Ricardo C.; D'Astolfo, Diego S.; Andreoli, Veronica; Bocco, Jose L.; Koritschoner, Nicolas P.

2011-01-01

The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC 50 ). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p 50 concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable marker for the efficiency of cell death upon cancer treatment.

[Plasma cell dyscrasias and renal damage].

Science.gov (United States)

Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

2012-01-01

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

Acute myocardial infarction associated with intravenous dipyridamole for rubidium-82 PET imaging

International Nuclear Information System (INIS)

Marwick, T.H.; Hollman, J.

1990-01-01

This report describes the occurrence of chest pain and electrocardiographic features of acute myocardial infarction following intravenous dipyridamole-handgrip stress. Myocardial perfusion imaging (Rb-82 PET) demonstrated a stress-induced perfusion defect. Following failure to respond to medical therapy, urgent cardiac catheterization demonstrated total occlusion of the left anterior descending coronary artery. The vessel was revascularized, with limitation of myocardial damage evidenced by failure to develop anterior Q waves and only modest elevation of cardiac enzyme levels. Complications of intravenous dipyridamole stress are rare, this case constituting the first major problem in over 500 such procedures at this institution. However, this experience demonstrates the importance of vigilant observation during the performance of this technique

Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction.

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Lu, Li-Fen; Wang, Chao-Ping; Yu, Teng-Hung; Hung, Wei-Chin; Chiu, Cheng-An; Chung, Fu-Mei; Tsai, I-Ting; Yang, Chih-Ying; Cheng, Ya-Ai; Lee, Yau-Jiunn; Yeh, Lee-Ren

2012-01-01

Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage. Copyright © 2011 Elsevier Ltd. All rights reserved.

Non-Q-wave myocardial infarction: impaired myocardial energy metabolism in regions with reduced 99mTc-MIBI accumulation.

Science.gov (United States)

Moka, D; Baer, F M; Theissen, P; Schneider, C A; Dietlein, M; Erdmann, E; Schicha, H

2001-05-01

Reduced regional technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) accumulation in patients with chronic non-Q-wave infarction (NQWI) but without significant coronary artery stenosis indicates non-transmural damage of the myocardial wall. The aim of this study was to characterise cardiac energy metabolism after NQWI using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and to compare the biochemical remodelling with changes in regional 99mTc-MIBI uptake and with morphological and functional parameters assessed by magnetic resonance imaging (MRI). Fifteen patients with a history of NQWI, exclusion of significant coronary artery stenosis (energy metabolism. Spectroscopic measurements were performed in the infarct-related myocardial region. Corresponding gradient-echo MR images and myocardial 99mTc-MIBI single-photon emission tomography images were acquired for exact localisation of the infarct region. All examinations were performed at rest under anti-ischaemic medication. Data were compared with those of patients in whom coronary artery disease had been excluded by angiography (group B, n=10). All patients of group A displayed anterior wall hypokinesia in the infarcted area on both ventriculography and MRI, with a reduced myocardial accumulation of 99mTc-MIBI (66.3%+/-11.8% vs 95.6%+/-2.2% in group B). The mean wall thickness during the complete cardiac cycle (9.5+/-1.8 mm vs 13.1+/-1.1 mm in group B, Penergy metabolism.

DNA damage-inducible transcripts in mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Alamo, I. Jr.; Hollander, M.C.

1988-01-01

Hybridization subtraction at low ratios of RNA to cDNA was used to enrich for the cDNA of transcripts increased in Chinese hamster cells after UV irradiation. Forty-nine different cDNA clones were isolated. Most coded for nonabundant transcripts rapidly induced 2- to 10-fold after UV irradiation. Only 2 of the 20 cDNA clones sequenced matched known sequences (metallothionein I and II). The predicted amino acid sequence of one cDNA had two localized areas of homology with the rat helix-destabilizing protein. These areas of homology were at the two DNA-binding sites of this nucleic acid single-strand-binding protein. The induced transcripts were separated into two general classes. Class I transcripts were induced by UV radiation and not by the alkylating agent methyl methanesulfonate. Class II transcripts were induced by UV radiation and by methyl methanesulfonate. Many class II transcripts were induced also by H2O2 and various alkylating agents but not by heat shock, phorbol 12-tetradecanoate 13-acetate, or DNA-damaging agents which do not produce high levels of base damage. Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury

The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

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Yanjun Zhang

2014-07-01

Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

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Palasubramaniam Dharshan

2011-09-01

Full Text Available Abstract Background Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a and monocyte chemotactic factor 1(MCP-1 are detectable in peripheral blood after myocardial infarction (MI. It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium. Methods Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous blood from patients with normal coronary arteries, stable coronary artery disease (CAD, unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI. Results Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model. Conclusions SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.

Mycolactone cytotoxicity in Schwann cells could explain nerve damage in Buruli ulcer.

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Junichiro En

2017-08-01

Full Text Available Buruli ulcer is a chronic painless skin disease caused by Mycobacterium ulcerans. The local nerve damage induced by M. ulcerans invasion is similar to the nerve damage evoked by the injection of mycolactone in a Buruli ulcer mouse model. In order to elucidate the mechanism of this nerve damage, we tested and compared the cytotoxic effect of synthetic mycolactone A/B on cultured Schwann cells, fibroblasts and macrophages. Mycolactone induced much higher cell death and apoptosis in Schwann cell line SW10 than in fibroblast line L929. These results suggest that mycolactone is a key substance in the production of nerve damage of Buruli ulcer.

Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells.

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Luca A Petruccelli

Full Text Available Histone deacetylase inhibitors (HDACi are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents.

Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

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Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

2011-01-01

Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

Polymyxin B Nephrotoxicity: From Organ to Cell Damage.

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Maria de Fátima Fernandes Vattimo

Full Text Available Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p. once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 μM, 75 μM and 375 μM polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B.

Novel strategies for enhancing myocardial infarction

NARCIS (Netherlands)

Liu, J.

2011-01-01

Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Massive cell loss initiated a series of cascade events upon ischemic injury. Enourmous effort has been put to investigate strategies for enhancing myocardial healing. Cell therapy emerges as a promising strategy for

Chronic inflammatory cells and damaged limbal cells in pterygium

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells were ..... Jiang Y, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 2002; 21: 2245-2252. 6. Kato S, Aoshima H, Saitoh Y, Miwa N. Fullerene-.

Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

International Nuclear Information System (INIS)

Tsubouchi, Susumu; Oohara, Hiroshi.

1989-01-01

Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

Circulating endothelial cells: a potential parameter of organ damage in sickle cell anemia?

NARCIS (Netherlands)

Strijbos, Michiel H.; Landburg, Precious P.; Nur, Erfan; Teerlink, Tom; Leebeek, Frank W. G.; Rijneveld, Anita W.; Biemond, Bart J.; Sleijfer, Stefan; Gratama, Jan W.; Duits, Ashley J.; Schnog, John-John B.

2009-01-01

Objective laboratory tools are needed to monitor developing organ damage in sickle cell disease (SCD). Circulating endothelial cells (CECs) are indicative of vascular injury. We determined whether elevated CEC can be detected in asymptomatic SCD with the CellSearch system and whether the CEC count

Removal of radiation damage by subpopulations of plateau-phase Chinese hamster ovary cells

International Nuclear Information System (INIS)

Nelson, J.M.; Metting, N.F.; Braby, L.A.; Roesch, W.C.

1987-01-01

Specific cellular radiobiology studies are often required to test aspects of the mathematical models developed in the Radiation Dosimetry program. These studies are designed to determine whether specific mathematical expressions, which characterize the expected effect of biochemical mechanisms on observable biological responses, are consistent with the behavior of selected cell lines. Since these tests place stringent requirements on the cellular system, special techniques and culture conditions are required to minimize biological variability. The use of specialized cell populations is providing data on the extent of repair following low doses, and on the changes in the types of damage that can be repaired as the cell progresses toward mitosis. The stationary-phase Chinese hamster ovary (CHO) cells are composed primarily of G(1)-phase cells (83%), with the remainder comprising both G(2) and S phases. Removal of radiation damage by cells was studied in split-dose experiments. To date, we have observed no significant differences in cellular repair rate. This suggests, therefore, that each of the repair processes found in stationary-phase cells is cell-age independent. However, cellular radiation sensitivity does change rapidly and considerably as the cells progress from one phase to the next through the cell cycle. Since the rate of damage removal appears invariant, the change in survival must reflect the efficiency of producing that damage. The experimental data suggest that production of one or another sort of damage probably dominates during specific phases of the cell cycle, while the capacity for removal of all types of damage remains relatively constant

The fine structure of sheep myocardial cells; sarcolemmal invaginations and the transverse tubular system.

Science.gov (United States)

SIMPSON, F O; OERTELIS, S J

1962-01-01

An electron microscope study of sheep myocardial cells has demonstrated the presence of a transverse tubular system, apparently forming a network across the cell at each Z band level. The walls of these tubules resemble the sarcolemma in consisting of two dense layers-plasma membrane and basement menbrane; continuity of the tubule walls with the sarcolemma can be seen when longitudinal sections of a cell are obtained between two subsarcolemmal myofibrils and at the same time perpendicular to the cell surface. The demonstration of communication between the lumen of the transverse tubular system and the extracellular space appears to be more definite in this study than in any work hitherto published. It provides anatomical evidence of a possible direct pathway for transmission of the activating impulse from the sarcolemma to the myofibril Z bands.

Damage-induced DNA repair processes in Escherichia coli cells

International Nuclear Information System (INIS)

Slezarikova, V.

1986-01-01

The existing knowledge is summed up of the response of Escherichia coli cells to DNA damage due to various factors including ultraviolet radiation. So far, three inducible mechanisms caused by DNA damage are known, viz., SOS induction, adaptation and thermal shock induction. Greatest attention is devoted to SOS induction. Its mechanism is described and the importance of the lexA recA proteins is shown. In addition, direct or indirect role is played by other proteins, such as the ssb protein binding the single-strand DNA sections. The results are reported of a study of induced repair processes in Escherichia coli cells repeatedly irradiated with UV radiation. A model of induction by repeated cell irradiation discovered a new role of induced proteins, i.e., the elimination of alkali-labile points in the daughter DNA synthetized on a damaged model. The nature of the alkali-labile points has so far been unclear. In the adaptation process, regulation proteins are synthetized whose production is induced by the presence of alkylation agents. In the thermal shock induction, new proteins synthetize in cells, whose function has not yet been clarified. (E.S.)

Consideration of myocardial FDG uptake in differentiation of mediastinal lymph node of non-small cell lung cancer

International Nuclear Information System (INIS)

Eo, Jae Seon; Lee, Won Woo; Chung, Jin Haeng; So, Young; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2004-01-01

The whole body FDG PET suffers from poor diagnostic competency in differentiation of mediastinal lymph node (LN) in non-small cell lung cancer. In addition to LN FDG uptake. We considered myocardial FDG uptake in mediastinal lymph node staging. Thirty-nine non-small cell lung cancer patients (male: female = 32: 7, age = 63±11 years) who underwent preoperative whole body FDG PET were enrolled. There were 18 squamous cell cancer, 13 adenocarcinoma, and 8 others. Maximum standard uptake values (maxSUVs) of myocardium and LNs using lean body weight were measured and compared with pathological results. Among 187 LNs which were confirmed postoperatively, 31 were malignant, and 156 benign. Of 31 malignant LNs, only 11 were visible on FDG PET (sensitivity : 35.5% = 11/31) but majority of 20 nonvisible metastatic LNs had relevant cause of false negative (11 peribroncheal, 3 mucine producing adenocarcinoma, or 6 low amount of tumor cells). Of 156 benign LNs, 137 were nonvisible (specificity : 87.8% 137/156) and 19 visible. Under subgroup analysis of 30 visible LNs on whole body FDG PET (11 malignant, and 19 benign), maxSUV of myocardium (p = 0.020) as well as maxSUV of LN (p = 0.002) were significant predictor of malignant LN in multivariate analysis. Using the ROC curve, a cut-off value of LN maxSUV > 2.4 provided sensitivity of 81.8% and specificity of 63.2% (AUC 0.775, 95% confidence interval = 0.586 to 0.906). Meanwhile, the composite criterion of LN maxSUV plus square root of myocardial maxSUV > 4.65 provided slightly improved diagnostic competencies (sensitivity 90.9%, specificity 84.2%, AUC 0.876, 95% confidence interval 0.704 to 0.966) (p = 0.08). Taking into consideration myocardial FDG uptake may improve the diagnostic competency of whole body FDG PET in differentiation of mediastinal LNs of non-small cell lung cancer

Photooxidative damage to mammalian cells and proteins by visible light

International Nuclear Information System (INIS)

Packer, L.; Kellogg, E.W. III

1980-01-01

In the present article, studies carried out in our laboratory on the effects of visible irradiation and O 2 in a variety of target systems ranging from cultured mammalian cells to purified catalase are reviewed. We will relate these studies of photooxidative damage to a scheme for the propagation of intracellular damage which traces a number of the possible pro-oxidant and anti-oxidant pathways found in the cell

Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

International Nuclear Information System (INIS)

Kamp, Hennicke G.; Eisenbrand, Gerhard; Schlatter, Josef; Wuerth, Kirsten; Janzowski, Christine

2005-01-01

Ochratoxin A (OTA) is a nephrotoxic/-carcinogenic mycotoxin, produced by several Aspergillus- and Penicillium-strains. Humans are exposed to OTA via food contamination, a causal relationship of OTA to human endemic Balkan nephropathy is still under debate. Since DNA-adducts of OTA or its metabolites could not be identified unambiguously, its carcinogenic effectiveness might be related to secondary effects, such as oxidative cell damage or cell proliferation. In this study, OTA mediated induction of (oxidative) DNA damage, cytotoxicity (necrosis, growth inhibition, apoptosis) and modulation of glutathione were investigated in cell lines (V79, CV-1) and primary rat kidney cells. After 24 h incubation, viability of V79 cells was strongly decreased by OTA concentrations >2.5 μmol/L, whereas CV-1 cells were clearly less sensitive. Strong growth inhibition occurred in both cell lines (IC 50 ∼2 μmol/L). Apoptosis, detected with an immunochemical test and with flow cytometry, was induced by >1 μmol/L OTA. Oxidative DNA damage, detected by comet assay after additional treatment with repair enzymes, was induced in all cell systems already at five-fold lower concentrations. Glutathione in CV-1 cells was depleted after 1 h incubation (>100 μmol/L). In contrast, an increase was measured after 24 h incubation (>0.5 μmol/L). In conclusion, OTA induces oxidative DNA damage at low, not yet cytotoxic concentrations. Oxidative DNA damage might initiate cell transformation eventually in connection with proliferative response following cytotoxic cell death. Both events might represent pivotal factors in the chain of cellular events leading into nephro-carcinogenicity of OTA

Myocardial perfusion SPECT imaging in patients with myocardial bridging

International Nuclear Information System (INIS)

Fang Wei; Qiu Hong; Yang Weixian; Wang Feng; He Zuoxiang

2008-01-01

Objective: Stress myocardial perfusion SPECT imaging was used to assess myocardial ischemia in patients with myocardial bridging. Methods: Ninety-six patients with myocardial bridging of the left anterior descending artery documented by coronary angiography were included in this study. All under- went exercise or pharmacological stress myocardial perfusion SPECT assessing myocardial ischemia. None had prior myocardial infarction. One year follow-up by telephone interview was performed in all patients. Results The mean stenotic severity of systolic phase on angiography was (65 ± 19)%. In the SPECT study, 20 of 96 (20.8%) patients showed abnormal perfusion. This percentage was significantly higher than that of stress electrocardiogram (ECG). The higher positive rate of SPECT perfusion images was showed in the group of patients with severe systolic narrowing (≥75%) than that with mild-to-moderate systolic narrowing (50% vs 6.3%, P<0.001). The prevalence of abnormal image was significantly higher in ELDERLY PEOPLE; patients with STT change on rest ECG than in those with normal rest ECG (54.2% vs 9.7%, P<0.001). During follow-up, one patient with abnormal SPECT perfusion image sustained angina and accepted percutaneous coronary intervention, and no cardiac event occurred in patients with normal images. Conclusions: Stress myocardial perfusion SPECT imaging can be used effectively for assessing myocardial ischemia and has potential prognostic value for patients with myocardial bridging. (authors)

DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

International Nuclear Information System (INIS)

Cogan, Nicola; Baird, Duncan M.; Phillips, Ryan; Crompton, Lucy A.; Caldwell, Maeve A.; Rubio, Miguel A.; Newson, Roger; Lyng, Fiona; Case, C. Patrick

2010-01-01

The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

Energy Technology Data Exchange (ETDEWEB)

Cogan, Nicola [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Baird, Duncan M. [Department of Pathology School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, CF14 4XN (United Kingdom); Phillips, Ryan [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Crompton, Lucy A.; Caldwell, Maeve A. [Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, BS1 3NY (United Kingdom); Rubio, Miguel A. [Center of Regenerative Medicine in Barcelona, CMRB Dr. Aiguader, 88, 7th Floor, 08003 Barcelona (Spain); Newson, Roger [Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Dublin 2 (Ireland); Lyng, Fiona [National Heart and Lung Institute, Imperial College London, London, SW7 2AZ (United Kingdom); Case, C. Patrick, E-mail: c.p.case@bristol.ac.uk [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom)

2010-01-05

The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

Myocardial images in nonacute coronary and noncoronary heart diseases

International Nuclear Information System (INIS)

Poe, N.D.; Eber, L.M.; Norman, A.S.; Selin, C.E.; Terao, E.N.

1977-01-01

To determine the variables that might affect interpretability of myocardial perfusion images in patients with acute myocardial infarctions, images obtained following intravenous administration of potassium-43 or cesium-129 were evaluated in 68 patients with nonacute coronary or noncoronary heart diseases, who were undergoing cardiac catheterization. Severe coronary arterial disease usually produces no distinctive perfusion defects in the resting state. Remote infarcts likewise tend to remain undetectable unless accompanied by wall-motion disturbances that can be detected by ventriculography. Left ventricular hypertrophy or cardiac dilatation can produce perfusion patterns indistinguishable from the ischemic defects of infarction. Right ventricular hypertrophy can cause image alterations that mimic infarcts in the left ventricle. In patients with acute myocardial infarction, sequential imaging studies with perfusion indicators should be of value in determining the effects of various therapeutic maneuvers on regional myocardial perfusion, but variations caused by conditions other than acute vascular occlusion limit the usefulness of perfusion imaging for diagnosing acute infarction. In suspected acute infarction, perfusion imaging will be used most effectively in conjunction with other imaging or nonimaging procedures that show the presence of damaged or necrotic myocardium. The information derived from this study should be generally applicable to the interpretation of imaging results obtained with the newer indicators of myocardial perfusion now in use or under development

Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease

Energy Technology Data Exchange (ETDEWEB)

Virtanen, K.S. [First Dept. of Medicine, Helsinki Univ. Central Hospital (Finland); Nikkinen, P. [Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland); Lindroth, L. [Medix Diacor Lab. Services, Ltd., Espoo (Finland); Kuikka, J.T. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio Univ. Hospital, Univ. of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

2002-06-01

Aim: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. Methods: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of {sup 123}I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. Results: The more reduced post-exercise FFA metabolic rate (-63{+-}18%, mean {+-}1 SD) compared to flow (-36{+-}16%) was related to the severity of myocardial ischemia and wall motion abnormalities. Conclusion: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease. (orig.) [German] Ziel: Bei reversibler und irreversibler Myokardschaedigung infolge Ischaemie sind die Membranfunktionen der Zellen veraendert. Um myokardialen Metabolismus freier Fettsaeuren (FFA) und Durchblutung bei belastungsinduzierter Ischaemie zu vergleichen, untersuchten wir zehn Patienten mit Koronarinsuffizienz, aber ohne vorangegangenen Myokardinfarkt. Methoden: Nach Injektion von {sup 123}I-markierter Heptadekansaeure (HDA) wurde eine Serie von SPECT-Messungen nach Belastung aufgenommen. Die myokardiale Perfusion wurde abgeschaetzt durch die separat durchgefuehrte Thalliumverteilungsstudie nach Belastung. Fettsaeurestoffwechsel, Thallium-Uptake und -Washout wurden fuer die anterioren, posterioren und septalen Segmente berechnet. Ergebnisse: Eine eingeschraenktere FFA-Stoffwechselrate (-63{+-}18%, {+-}1 SD

Mesenchymal Stem Cells : Promising for Myocardial Regeneration?

NARCIS (Netherlands)

Przybyt, Ewa; Harmsen, Martin C.

The pandemic of cardiovascular disease is continuously expanding as the result of changing life styles and diets throughout the Old and New World. Immediate intervention therapy saves the lives of many patients after acute myocardial infarction (MI). However, for many this comes at the price of

Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

Science.gov (United States)

Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

2006-02-15

We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

Sunlight-induced DNA damage in human mononuclear cells

DEFF Research Database (Denmark)

Møller, Peter; Wallin, Hakan; Holst, Erik

2002-01-01

of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individual's background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could......In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single-cell gel electrophoresis. The level of DNA damage was influenced by the average daily influx of sunlight ... to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect...

Local stem cell depletion model for normal tissue damage

International Nuclear Information System (INIS)

Yaes, R.J.; Keland, A.

1987-01-01

The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

Comparison of radiological and morphologic assessments of myocardial bridges.

Science.gov (United States)

Ercakmak, Burcu; Bulut, Elif; Hayran, Mutlu; Kaymaz, Figen; Bilgin, Selma; Hazirolan, Tuncay; Bayramoglu, Alp; Erbil, Mine

2015-09-01

In this study we aimed to compare the findings of coronary dual-source computed tomography angiography of myocardial bridges with cadaveric dissections. Forty-one isolated, non-damaged fresh sheep hearts were used in this study. Myocardial bridges of the anterior interventricular branch of the left coronary artery were demonstrated and analyzed by a coronary dual-source computed tomography angiography. Dissections along the left anterior interventricular branch of the left coronary artery were performed by using Zeiss OPMI pico microscope and the length of the bridges were measured. The depths of the myocardial bridges were measured from the stained sections by using the light microscope (Leica DM 6000B). MBs were found in all 41 hearts (100%) during dissections. Dual-source computed tomography angiography successfully detected 87.8% (36 of the 41 hearts) of the myocardial bridges measured on left anterior interventricular branch of left coronary artery. The lengths of the myocardial bridges were found 5-40 and 8-50 mm with dissection and dual-source computed tomography angiography, respectively. And the depths were found 0.7-4.5 mm by dual-source computed tomography angiography and 0.745-4.632 mm morphologically. Comparison of the mean values of the lengths showed statistically significantly higher values (22.0 ± 8.5, 17.7 ± 7.7 mm, p = 0.003) for the dissections. Radiological assessment also effectively discriminated complete bridges from incomplete ones. Our study showed that coronary computed tomography angiography is reliable in evaluating the presence and depth of myocardial bridges.

Cocaine use may modify HIV/ART-associated myocardial steatosis and hepatic steatosis.

Science.gov (United States)

Lai, Shenghan; Gerstenblith, Gary; Moore, Richard D; Celentano, David D; Bluemke, David A; Treisman, Glenn; Liu, Chia-Ying; Li, Ji; Chen, Shaoguang; Kickler, Thomas; Lai, Hong

2017-08-01

It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52). Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis. Copyright © 2017. Published by Elsevier B.V.

DNA damage by carbonyl stress in human skin cells

International Nuclear Information System (INIS)

Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L.

2003-01-01

Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the α-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N ε -(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress

DNA damage by carbonyl stress in human skin cells

Energy Technology Data Exchange (ETDEWEB)

Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L

2003-01-28

Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the {alpha}-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N{sup {epsilon}}-(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress.

Influence of heavy ions on cell survival, cytogenetic damage and mitochondrial function of human endothelial cells

Science.gov (United States)

Ritter, Sylvia; Helm, Alexander; Lee, Ryonfa; Pollet, Dieter; Durante, Marco

There is increasing evidence that there is an elevated risk of cardiovascular disease among atomic bomb survivors and radiotherapy patients, typically developing with a long latency. However, essentially no information is available on the potential cardiovascular risks associated with space radiation, in particular heavy ions. To address this issue, we have chosen human umbilical vein endothelial cells (HUVEC) as a model system. Cells at an early passage number were irradiated with 0.1 to 4 Gy of either 9.8 MeV/u C-ions (LET=170 keV/µm), 91 MeV/u C-ions (LET=29 keV/µm) or 250 kV X-rays. Cells were regularly subcultured up to 40 days (20 population doublings) post-irradiation. Immediately after exposure cell inactivation was deter-mined by the colony forming assay. Furthermore, at selected time-points cytogenetic damage (formation of micronuclei in binucleated cells) and the mitochondrial membrane potential ΨM (flow cytometric analysis following JC-1 staining) were assessed. Measurement of the directly induced radiation damage showed that 9.8 MeV/u and 91 MeV/u C-ions were more effective than X-rays (i.e. about 3 and 2 times, respectively) with respect to cell inactivation or the in-duction of cytogenetic damage. At the subsequent days in the irradiated cultures the number of cells with micronuclei declined to the control level (3-5Altogether our data indicate that under the applied radiation conditions the integrity of mitochondria which play a significant role in the regulation of cardiovascular cell function is not impaired. With respect to directly induced genetic damage C-ions are more effective than X-rays as observed in other cell systems. If the effectiveness of charged particles for the occurrence of late chromosomal damage in endothelial cells is higher than that of sparsely ionizing radiation needs further clarification. The data obtained up to now indicate that sophisticated cytogenetic techniques have to be applied in order to draw any firm

Oxidative DNA damage and mammary cell proliferation by alcohol-derived salsolinol.

Science.gov (United States)

Murata, Mariko; Midorikawa, Kaoru; Kawanishi, Shosuke

2013-10-21

Drinking alcohol is a risk factor for breast cancer. Salsolinol (SAL) is endogenously formed by a condensation reaction of dopamine with acetaldehyde, a major ethanol metabolite, and SAL is detected in blood and urine after alcohol intake. We investigated the possibility that SAL can participate in tumor initiation and promotion by causing DNA damage and cell proliferation, leading to alcohol-associated mammary carcinogenesis. SAL caused oxidative DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in the presence of transition metal ions, such as Cu(II) and Fe(III)EDTA. Inhibitory effects of scavengers on SAL-induced DNA damage and the electron spin resonance study indicated the involvement of H₂O₂, which is generated via the SAL radical. Experiments on scavengers and site specificity of DNA damage suggested ·OH generation via a Fenton reaction and copper-peroxide complexes in the presence of Fe(III)EDTA and Cu(II), respectively. SAL significantly increased 8-oxodG formation in normal mammary epithelial MCF-10A cells. In addition, SAL induced cell proliferation in estrogen receptor (ER)-negative MCF-10A cells, and the proliferation was inhibited by an antioxidant N-acetylcysteine and an epidermal growth factor receptor (EGFR) inhibitor AG1478, suggesting that reactive oxygen species may participate in the proliferation of MCF-10A cells via EGFR activation. Furthermore, SAL induced proliferation in estrogen-sensitive breast cancer MCF-7 cells, and a surface plasmon resonance sensor revealed that SAL significantly increased the binding activity of ERα to the estrogen response element but not ERβ. In conclusion, SAL-induced DNA damage and cell proliferation may play a role in tumor initiation and promotion of multistage mammary carcinogenesis in relation to drinking alcohol.

Sequential change of cardiomyopathy of Duchenne muscular dystrophy by 201Tl myocardial SPECT

International Nuclear Information System (INIS)

Ono, Seiji; Sugimoto, Seiichirou; Inoue, Kenjirou; Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi.

1989-01-01

201 Tl myocardial SPECT were performed to evaluate of cardiomyopathy in Duchenne type of progressive muscular dystrophy (DMD). Follow up SPECT images of the same patients were also obtained about 1 year after the first scan. Cases subjected to study were 10 DMD. At the first study the hypoperfusion area of the left ventricular muscle were observed in 6 cases (60%) out of 10. At the second study the hypoperfusion areas became wider and lower in 4 out of 6 cases (66.7%). The new hypoperfusion area which was not demonstrated at the first study was observed at the second study in one case of these cases. These results suggested that the positive rate of cardiomyopathy in DMD by 201 Tl myocardial SPECT was high, and 201 Tl myocardial SPECT is a useful examination to detect the change of myocardial damage in DMD. (author)

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

Directory of Open Access Journals (Sweden)

Emerson C Perin

Full Text Available The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18F]FEAU to monitor the long-term (up to 5 months spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

Science.gov (United States)

Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying

2016-01-01

Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Significance Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called “no-option” patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. PMID

Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

Science.gov (United States)

Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

2016-05-01

Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. Copyright © 2016 Elsevier B.V. All rights reserved.

Data on administration of cyclosporine, nicorandil, metoprolol on reperfusion related outcomes in ST-segment Elevation Myocardial Infarction treated with percutaneous coronary intervention

DEFF Research Database (Denmark)

Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo

2017-01-01

Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs direc...

Repair of radiation damage in mammalian cells: its relevance to environmental effects

International Nuclear Information System (INIS)

Han, A.; Elkind, M.M.

1979-01-01

Assessment of the potential biological hazards associated with energy production technologies involves the quantitation of risk on the basis of dose-effect dependencies, from which, it is hoped, some safety guidelines can be developed. Our current knowledge of the biological importance of damage/repair processes stems by and large from radiation studies which clearly demonstrate that cellular response to radiation depends upon the ability of cells to repair the damage. Apparently, the same is true for cellular response to different chemical agents. Drawing upon our experiences from radiation studies, we demonstrate the relevance of ongoing repair processes, as evident in the studies of radiation induced cell killing and neoplastic transformation, to the type of risk estimates that might be associated with the hazards from energy production technologies. The effect of repair on cell survival is considered. It is evident from our studies that in the region of small doses, repair of damage relative to cell lethality is of importance in estimating the magnitude of effect. Aside from the cytotoxic effects in terms of cell killing, one of the greatest concerns associated with energy production is the potential of a given technology, or its effluents, to produce cancer. It is therefore of importance to quantify the risk in this context of damage registration and possible effect of repair on damage expression. It has been generally established that exposure of normal cells in culture to a variety of known carcinogens results in neoplastic transformation. Our observations with C3H/10T1/2 cells in culture lend direct evidence for the hypothesis that reduced tumor incidences at low dose rates of radiation could be due to the repair of induced damage

Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

International Nuclear Information System (INIS)

Venugopal, J.; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

2013-01-01

Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Venugopal, J., E-mail: nnijrv@nus.edu.sg; Rajeswari, R.; Shayanti, M.; Sridhar, R.; Sundarrajan, S.; Balamurugan, R.; Ramakrishna, S.

2013-04-01

Myocardial infarction, a main cause of heart failure, leads to loss of cardiac tissue impairment of left ventricular function. Repair of diseased myocardium with in vitro engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for myocardial infarction. We attempted to solve these problems by in vitro study by selecting a plant based polysaccharides beech wood Xylan for the normal functioning of infarcted myocardium. The present study fabricated Xylan based nanofibrous scaffolds cross-linked with glutaraldehyde (Glu) vapors for 24 h, 48 h and 1% Glu blended fibers for the culture of neonatal rat cardiac cells for myocardial infarction. These nanofibers were characterized by SEM, FT-IR, tensile testing and cell culture studies for the normal expression of cardiac proteins. The observed results showed that the Xylan/polyvinyl alcohol (PVA) 24 h Glu vapor cross-linked nanofibers (427 nm) having mechanical strength of 2.43 MPa and Young modulus of 3.74 MPa are suitable for the culture of cardiac cells. Cardiac cells proliferation increased only by 11% in Xylan/PVA 24 h Glu cross-linked nanofibers compared to control tissue culture plate (TCP). The normal cardiac cell morphology was observed in 24 h cross-linked Xylan/PVA nanofibers but 48 h cross-linked fibers cell morphology was changed to flattened and elongated on the fibrous surfaces. Confocal analysis for cardiac expression proteins actinin, connexin 43 was observed normally in 24 h Glu cross-linked nanofibers compared to all other nanofibrous scaffolds. The fabricated Xylan/PVA nanofibrous scaffold may have good potential for the normal functioning of infarcted myocardium. - Highlights: ► Fabrication of polysaccharides Xylan/PVA nanofibers for cardiac tissue engineering ► Nanofibers characterized by SEM, FT-IR, tensile testing and cell culture studies ► Isolation of cardiac cells and cultured on Xylan/PVA nanofibrous scaffolds ► Cultured cells on 24 h Glu cross

Parametric methods for characterizing myocardial tissue by magnetic resonance imaging (part 2): T2 mapping.

Science.gov (United States)

Perea Palazón, R J; Solé Arqués, M; Prat González, S; de Caralt Robira, T M; Cibeira López, M T; Ortiz Pérez, J T

2015-01-01

Cardiac magnetic resonance imaging is considered the reference technique for characterizing myocardial tissue; for example, T2-weighted sequences make it possible to evaluate areas of edema or myocardial inflammation. However, traditional sequences have many limitations and provide only qualitative information. Moreover, traditional sequences depend on the reference to remote myocardium or skeletal muscle, which limits their ability to detect and quantify diffuse myocardial damage. Recently developed magnetic resonance myocardial mapping techniques enable quantitative assessment of parameters indicative of edema. These techniques have proven better than traditional sequences both in acute cardiomyopathy and in acute ischemic heart disease. This article synthesizes current developments in T2 mapping as well as their clinical applications and limitations. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

The intersection between DNA damage response and cell death pathways.

Science.gov (United States)

Nowsheen, S; Yang, E S

2012-10-01

Apoptosis is a finely regulated process that serves to determine the fate of cells in response to various stresses. One such stress is DNA damage, which not only can signal repair processes but is also intimately involved in regulating cell fate. In this review we examine the relationship between the DNA damage/repair response in cell survival and apoptosis following insults to the DNA. Elucidating these pathways and the crosstalk between them is of great importance, as they eventually contribute to the etiology of human disease such as cancer and may play key roles in determining therapeutic response. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits.

Science.gov (United States)

Xiao, Mingyue; Lu, Xiao; Li, Jianan; Li, Ling; Li, Yongxue

2014-04-01

Ischaemia-induced angiogenesis promises to improve neovascularization by delivery of angiogenic factors or endothelial progenitor cells (EPCs) to cardiac ischaemic areas. In order to avoid the risk of excessive myocardial ischaemia, therefore, we hypothesized that physiological ischaemic training (PIT) of normal skeletal muscle might contribute to myocardial angiogenesis via nitric oxide mediated mobilization of EPCs from the bone marrow in the established rabbit model of controllable myocardial ischaemia. The rabbits were grouped by sham-operation, myocardial ischaemia without PIT, PIT and PIT with pretreatment with the endothelial nitric oxide synthase (eNOS) inhibitor L-nitroarginine methyl ester (L-NAME). Controlled myocardial ischaemia was modelled by a water balloon constrictor implanted on the left ventricular branch in a rabbit. The PIT procedure included three cycles of 3 min of cuff inflation followed by 5 min of deflation on hind limbs of the rabbits for 4 weeks. At the endpoints, circulating EPCs (CD34/Flk-1) were measured by fluorescence-activated cell sorter; capillary density, by immunohistochemistry; blood flow, by a microsphere technique; endothelial nitric oxide synthase (eNOS) mRNA and protein, by real-time reverse transcriptase (RT)-PCR and Western blotting. The mRNA levels of eNOS were significantly higher in the PIT and L-NAME groups than in the sham-operation group (P < 0.05). Phospho-eNOS protein expression was higher in the PIT group than in the sham-operation and myocardial ischaemia without PIT groups (P < 0.05), and the effect was inhibited by L-NAME pretreatment (P < 0.05). Compared with sham-operation and myocardial ischaemia without PIT groups, the PIT group had the highest EPC count (P < 0.001), and the increase of capillary density (P < 0.01) and collateral blood flow (P < 0.05) in the ischaemic myocardium was consistent with the finding of EPC count. These effects were also inhibited by pretreatment with

Genotoxic damage in non-irradiated cells: contribution from the bystander effect

International Nuclear Information System (INIS)

Zhou, H.; Randers-Pherson, G.; Suzuki, M.; Waldren, C.A.; Hei, T.K.

2002-01-01

It has always been accepted dogma that the deleterious effects of ionising radiation such as mutagenesis and carcinogenesis are due mainly to direct damage to DNA. Using the Columbia University charged-particle microbeam and the highly sensitive A L cell mutagenic assay, it is shown here that non-irradiated cells acquire the mutagenic phenotype through direct contact with cells whose nuclei are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a gap junction inhibitor, significantly decreased the mutant yield. Furthermore, when irradiated cells were mixed with control cells in a similar ration as the in situ studies, no enhancement in bystander mutagenesis was detected. Our studies provide clear evidence that genotoxic damage can be induced in non-irradiated cells, and that gap junction mediated cell-cell communication plays a critical role in the bystander phenomenon. (author)

Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model

International Nuclear Information System (INIS)

Stavrev, P; Weldon, M; Warkentin, B; Stavreva, N; Fallone, B G

2005-01-01

The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models

Plasma Concentration of Biomarkers Reflecting Endothelial Cell- and Glycocalyx Damage are Increased in Patients with Suspected St-Elevation Myocardial Infarction Complicated by Cardiogenic Shock

DEFF Research Database (Denmark)

Frydland, Martin; Ostrowski, Sisse Rye; Møller, Jacob Eifer

2018-01-01

BACKGROUND: Mortality in ST-elevation myocardial infarction (STEMI)-patients developing cardiogenic shock (CS) during hospitalization is high. Catecholamines, ischemia, and inflammation (parameters present in CS) affect the endothelium. We hypothesized that plasma level of biomarkers reflecting e...

Cell damage by bilirubin and light

International Nuclear Information System (INIS)

Granli, T.

1993-01-01

Large doses of light are given to newborns during phototherapy for hyperbilirubinemia. Tissues containing concentrations of bilirubin almost in the mM range may be subjected to irradiation. Therefore it is of interest to study cellular effects of light and bilirubin on cells. In order to select the optimal wavelength, possible detrimental effects of light on cells must be taken into consideration among a number of other factors. In this study cellular effects of selected wavelengths of blue-green light are compared. It is not clear whether cullular damage occurs in vivo during phototherapy of newborns. Since a possibility exists that some adverse effects are caused by light, one should choose wavelengths where these effects are minimal without loosing therapeutic efficiency. Todays knowledge of the photochemical mechanisms of phototherapy, indicates that short waved light with wavelengths below 450 nm has a low therapeutic effect. The data in this paper indicate that the cellular damage is most severe at short wavelengths, and these should be reduced to a minimum in the spectra of phototherapy lamps. Further studies of possible side effects of phototherapy should be made. 64 refs., 34 figs., 1 tab

Cell membrane damage by iron nanoparticles: an invitro study

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Gelare Hajsalimi

2016-12-01

Full Text Available Application of nanotechnology in medicinal and biological fields has attracted a great interest in the recent yeras. In this paper the cell membrane leakage induced by iron nanoparticles (Fe-NP against PC12 cell line which is known as a model of nervous system cell line was investigated by the lactate dehydrogenase (LDH test. Therefore, PC12 cells were incubated with different concentration of Fe-NP and test was performed after 48h of incubation of the cells with Fe-NP. The resulting data showed that the Fe-NP induced the damage of PC12 cell membrane in a concentration dependent manner. Hence, it may be concluded that the different cytotoxicty effect of NPs may be referred to the concentration of NPs, type of the NPs and the cells. Indeed, the kind of cytotoxic impacts of NPs on the cells can be reduced by the considering of above-mentioned parameters. The resulting data showed that the Fe-NP induced the damage of PC12 cell membrane in a concentration dependent manner. Hence, it may be concluded that the different cytotoxicty effect of NPs may be referred to the concentration of NPs, type of the NPs and the cells. Indeed, the kind of cytotoxic impacts of NPs on the cells can be reduced by the considering of above-mentioned parameters.

Bone marrow mononuclear cell implantation in myocardial laser channels in the ischemic heart disease surgery. Long-term results

Science.gov (United States)

Chernyavskiy, Alexander; Fomichev, Alexey; Minin, Stanislav; Nikitin, Nikita

2017-10-01

Background: The problem of incomplete myocardial revascularization for diffuse and distal lesions of the myocardium is still relevant. We assessed the clinical and instrumental long-term results of autologous bone marrow cell (BMC) implantation in laser channels in ischemic heart disease with diffuse and distal coronary disease. 35 coronary heart disease (CHD) patients with diffuse and distal coronary disease during coronary artery bypass grafting (CABG) underwent BMC implantation in laser channels. The control group consisted of 29 patients. All patients in this group underwent only CABG. Clinical and instrumental assessment of the method's effect was carried out at two weeks, six months, and six years after surgery. Indirect revascularization showed more significant decreasing of the functional class (FC) New York Heart Association (NYHA), myocardial perfusion and contractility improvement. Autologous BMC implantation in laser channels is an effective method of CHD surgical treatment if it is impossible to perform direct myocardial revascularization. The indirect revascularization effect is formed in the first six months after surgery and remains at the same level for six years.

Cell damage caused by vaginal Candida albicans isolates from women with different symptomatologies.

Science.gov (United States)

Faria, Daniella Renata; Sakita, Karina Mayumi; Akimoto-Gunther, Luciene Setsuko; Kioshima, Érika Seki; Svidzinski, Terezinha Inez Estivalet; Bonfim-Mendonça, Patrícia de Souza

2017-08-01

The present study aimed to characterize cell damage caused by vaginal Candida albicans isolates from women with different symptomatologies. It was evaluated 12 clinical isolates of C. albicans from vaginal samples: 4 from asymptomatic women (AS), 4 from women with a single episode of vulvovaginal candidiasis (VVC) and 4 from women with recurrent vulvovaginal candidiasis (RVVC). We evaluated the ability of C. albicans to adhere to human cervical cancer cells (SiHa), the yeast-SiHa cell interactions and cell damage. All of the clinical isolates presented a high adhesion capacity on SiHa cells. However, clinical isolates from symptomatic women (VVC and RVVC) had higher filamentation after contact (24 h) with SiHa cells and a greater capacity to cause cell damage (>80 %). Clinical isolates from symptomatic women had greater potential to invade SiHa cells, suggesting that they are more pathogenic than AS isolates.

Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

International Nuclear Information System (INIS)

Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

2009-01-01

Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

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Vazhappilly Cijo George

2017-01-01

Full Text Available Scope. Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4 against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. Methods and Results. AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK, NNK acetate (NNK-Ae, methotrexate (MTX, and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage. Furthermore, phosphorylated histone (γ-H2AX and proteins involved in DNA damage (ATM/ATR, Chk1, Chk2, and p53 and repair (DNA-PKcs and Ku80 mechanisms were evaluated by immunofluorescence and western blotting, respectively. The results revealed that AF4-pretreated cells showed lower cytotoxicity, total ROS generation, and DNA fragmentation along with consequent inhibition of DNA tail moment. An increased level of γ-H2AX and DNA damage proteins was observed in carcinogen-treated cells and that was significantly (p≤0.05 inhibited in AF4-pretreated cells, in an ATR-dependent manner. AF4 pretreatment also facilitated the phosphorylation of DNA-PKcs and thus initiation of repair mechanisms. Conclusion. Apple flavonoids can protect in vitro oxidative DNA damage and facilitate repair mechanisms.

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Science.gov (United States)

Davis, Michael E.; Hsieh, Patrick C. H.; Takahashi, Tomosaburo; Song, Qing; Zhang, Shuguang; Kamm, Roger D.; Grodzinsky, Alan J.; Anversa, Piero; Lee, Richard T.

2006-05-01

Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy. engineering | maturation | scaffold

DNA Damage by Radiation in Tradescantia Leaf Cells

International Nuclear Information System (INIS)

Han, Min; Hyun, Kyung Man; Ryu, Tae Ho; Kim, Jin Kyu; Nili, Mohammad

2010-01-01

The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Tradescantia tests are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay. The development of comet assay has enabled investigators to detect DNA damage at the levels of cells. To adapt this assay to plant cells, nuclei were directly obtained from Tradescantia leaf samples. A significant dose-dependent increase in the average tail moment values over the negative control was observed. Recently the adaptation of this technique to plant cells opens new possibilities for studies in variety area. The future applications of the comet assay could impact some other important areas, certainly, one of the limiting factors to its utility is the imagination of the investigator.

DNA Damage by Radiation in Tradescantia Leaf Cells

Energy Technology Data Exchange (ETDEWEB)

Han, Min; Hyun, Kyung Man; Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

2010-04-15

The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Tradescantia tests are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay. The development of comet assay has enabled investigators to detect DNA damage at the levels of cells. To adapt this assay to plant cells, nuclei were directly obtained from Tradescantia leaf samples. A significant dose-dependent increase in the average tail moment values over the negative control was observed. Recently the adaptation of this technique to plant cells opens new possibilities for studies in variety area. The future applications of the comet assay could impact some other important areas, certainly, one of the limiting factors to its utility is the imagination of the investigator.

The repair of damage to DNA in different cell types

International Nuclear Information System (INIS)

Karran, P.

1974-01-01

DNA single strand breaks induced by either X-ray irradiation or by methyl methanesulphonate (MMS) were studied in different lymphoid cell populations directly taken from the animal and maintained in tissue culture merely for the duration of the experiment. The results obtained from these cell populations were compared with those obtained with L5178Y cells maintained in tissue culture. All cell types studied were found to possess at least one class of enzymes required for repair of DNA damage, namely those enzymes involved in the rejoining of X-ray induced by MMS is different in each cell type. Repair replication was at much reduced levels and the endonucleolytic degradation was at much reduced levels and the endonucleolytic degradation was initiated at lower MMS concentration in the lymphoid cells as compared to L5178Y cells. It is suggested that the overall ''repair capacity'' of a population may be related to the number of cells in a cycle which, moreover, might be the only ones to have the ability to repair damage to DNA induced by MMS (G.G.)

Sequential change of cardiomyopathy of Duchenne muscular dystrophy by /sup 201/Tl myocardial SPECT

Energy Technology Data Exchange (ETDEWEB)

Ono, Seiji; Sugimoto, Seiichirou; Inoue, Kenjirou; Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi.

1989-03-01

/sup 201/Tl myocardial SPECT were performed to evaluate of cardiomyopathy in Duchenne type of progressive muscular dystrophy (DMD). Follow up SPECT images of the same patients were also obtained about 1 year after the first scan. Cases subjected to study were 10 DMD. At the first study the hypoperfusion area of the left ventricular muscle were observed in 6 cases (60%) out of 10. At the second study the hypoperfusion areas became wider and lower in 4 out of 6 cases (66.7%). The new hypoperfusion area which was not demonstrated at the first study was observed at the second study in one case of these cases. These results suggested that the positive rate of cardiomyopathy in DMD by /sup 201/Tl myocardial SPECT was high, and /sup 201/Tl myocardial SPECT is a useful examination to detect the change of myocardial damage in DMD. (author).

Cell therapy attenuates cardiac dysfunction post myocardial infarction: effect of timing, routes of injection and a fibrin scaffold.

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Juliana S Nakamuta

Full Text Available BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC post-myocardial infarction (MI and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function. METHODOLOGY/PRINCIPAL FINDINGS: (99mTc-labeled BMC (6 x 10(6 cells were injected by 4 different routes in adult rats: intravenous (IV, left ventricular cavity (LV, left ventricular cavity with temporal aorta occlusion (LV(+ to mimic coronary injection, and intramyocardial (IM. The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by gamma-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%. Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16% vs. 1, 2 or 3 (average of 7% days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%, even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. CONCLUSIONS/SIGNIFICANCE: These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these

Bacterial mutagenicity and mammalian cell DNA damage by several substituted anilines.

Science.gov (United States)

Zimmer, D; Mazurek, J; Petzold, G; Bhuyan, B K

1980-04-01

Several substituted alkyl- and haloanilines were tested for their ability to mutate Salmonella typhimurium and to damage the DNA of mammalian (V79) cells. These results were correlated with their reported carcinogenicity. Of 9 suspected carcinogens, 4 were bacterial mutagens and 4 (out of 7 tested) damaged DNA of V79 cells. The following compounds were weakly mutagenic (less than 150 revertants/mumole): 4-fluoroaniline, 2,3-, 2,4-, 2,5- and 3,4-dimethylaniline, and 2-methyl-4-fluoroaniline. The following compounds were strong mutagens: 2,4,5-trimethylaniline, 2-methyl-4-chloro-, and 2-methyl-4-bromo-, 4-methyl-2-chloro-, 4-methyl-2-bromo- and 2-ethyl-4-chloroaniline. The compounds which damaged DNA in V79 cells were: 2 methyl-4-chloroaniline, 2-methyl-4-bromoaniline, 2,4,5- and 2,4,6-trimethylaniline.

Myocardial thallium-201 kinetics in normal and ischemic myocardium

International Nuclear Information System (INIS)

Grunwald, A.M.; Watson, D.D.; Holzgrefe, H.H. Jr.; Irving, J.F.; Beller, G.A.

1981-01-01

The net myocardial accumulation of thallium-201 after injection depends upon the net balance between continuing myocardial extraction from low levels of recirculating thallium in the blood compartment and the net rate of efflux of thallium from the myocardium into the extracardiac blood pool. These experiments were designed to measure separately the myocardial extraction and intrinsic myocardial efflux of thallium-201 at normal and at reduced rates of myocardial blood flow. The average myocardial extraction fraction at normal blood flow in 10 anesthetized dogs was 82 +/- 6% (+/- SD) at normal coronary arterial perfusion pressures and increased insignificantly, to 85 +/- 7%, at coronary perfusion pressures of 10--35 mm Hg. At normal coronary arterial perfusion pressures in 12 additional dogs, the intrinsic thallium washout in the absence of systemic recirculation had a half-time (T 1/2) of 54 +/- 7 minutes. The intrinsic cellular washout rate began to increase as distal perfusion pressures fell below 60 mm Hg and increased markedly to a T 1/2 of 300 minutes at perfusion pressures of 25--30 mm Hg. A second, more rapid component of intrinsic thallium washout (T 1/2 2.5 minutes) representing approximately 7% of the total initially extracted myocardial thallium was observed. The faster washout component is presumed to be due to washout of interstitial thallium unextracted by myocardial cells, whereas the slower component is presumed due to intracellular washout. The net clearance time of thallium measured after i.v. injection is much longer than the intrinsic myocardial cellular washout rate because of continuous replacement of myocardial thallium from systemic recirculation. Myocardial redistribution of thallium-201 in states of chronically reduced perfusion cannot be the result of increased myocardial extraction efficiency, but rather, is the result of the slower intrinsic cellular washout rate at reduced perfusion levels

Effect of limb ischemic preconditioning on myocardial apoptosis-related proteins in ischemia-reperfusion injury

Science.gov (United States)

GAO, JIANZHI; ZHAO, LINJING; WANG, YONGLING; TENG, QINGLEI; LIANG, LIDONG; ZHANG, JINYING

2013-01-01

The aim of this study was to investigate the effect of limb ischemic preconditioning (LIPC) on myocardial apoptosis in myocardial ischemia-reperfusion injury (MIRI), as well as the regulation of caspase-3 and the B cell lymphoma 2 (Bcl-2) gene in LIPC. A total of 50 rats were divided randomly into 5 groups (n=10). Four rats in each group were drawn out for detection of apoptosis. The sham, MIRI and LIPC groups underwent surgery without additional treatment. In the LY294002 group, LY294002 preconditioning was administered 15 min before reperfusion. In the LY294002+LIPC group, following LIPC, LY294002 was administered 15 min before reperfusion. The relative expression of myocardial Bcl-2 and caspase-3 mRNA and the apoptotic index for each group were determined by reverse transcription-polymerase chain reaction (RT-PCR) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. The ultrastructure of the cardiac muscle tissues was observed by election microscopy. Compared with the sham group, the expression of caspase-3 mRNA in the MIRI group significantly increased (P<0.05) and the expression of Bcl-2 mRNA clearly decreased. Compared with the MIRI group, LIPC reduced the expression of caspase-3 and increased the expression of Bcl-2 mRNA (P<0.05). There were no significant differences between the LY294002+LIPC group and the MIRI group. Compared with the sham group, the apoptotic index of myocardial cells in the MIRI group significantly increased (P<0.05). Compared with the MIRI group, LIPC significantly decreased the apoptotic index of myocardial cells (P<0.05) and LY294002 increased the apoptotic index of myocardial cells. Compared with the LIPC group, LY294002+LIPC significantly increased the apoptotic index of myocardial cells (P<0.05). There were no significant differences between the LY294002+LIPC and MIRI groups. In conclusion, LIPC increased the expression of Bcl-2 and decreased caspase-3 mRNA and

Myocardial infarction

International Nuclear Information System (INIS)

Ando, Jyoji; Yasuda, Hisakazu; Miyamoto, Atsushi; Kobayashi, Tsuyoshi

1980-01-01

sup(99m)Tc-pyrophosphate (PYP) scintigraphy and 201 Tl myocardial scintigraphy were utilized for the diagnoses of the presence, the region, and the extent of myocardial infarction. Exercise 201 Tl myocardial scintigrams and exercise radionuclide ventriculography were utilized for diagnosis of coronary artery lesions in angina pectoris. Radionuclide ventriculography was used to investigate effects of coronary artery lesions on cardiac function and hemodynamics. In order to select adequate treatments for myocardial infarction and estimate the prognosis, it was necessary to detect the presence, the region, and the extent of acute myocardial infarction and to investigate effects of partial infarction on hemodynamics by using radionuclide imaging. Exercise myocardial scintigraphy could be carried out noninvasively and repeatedly for diagnosis of coronal artery disease. Therefore, this method could be applied widely. It was possible to use this method as a screening test of coronary artery diseases for the diagnoses of asymptomatic patients who showed ST changes in ECG, the patients with cardiac neurosis and the patency after a reconstructive surgery of coronary artery. (Tsunoda, M.)

Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

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Jianqin Ye

Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

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Yumei Zhang

Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

Science.gov (United States)

Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

2014-11-01

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science

Design and implementation of the TRACIA: intracoronary autologous transplant of bone marrow-derived stem cells for acute ST elevation myocardial infarction

OpenAIRE

Peña-Duque, Marco A.; Martínez-Ríos, Marco A.; Calderón G, Eva; Mejía, Ana M.; Gómez, Enrique; Martínez-Sánchez, Carlos; Figueroa, Javier; Gaspar, Jorge; González, Héctor; Bialoztosky, David; Meave, Aloha; Uribe-González, Jhonathan; Alexánderson, Erick; Ochoa, Victor; Masso, Felipe

2011-01-01

Objective: To describe the design of a protocol of intracoronary autologous transplant of bone marrow-derived stem cells for acute ST-elevation myocardial infarction (STEMI) and to report the safety of the procedure in the first patients included. Methods: The TRACIA study was implemented following predetermined inclusion and exclusion criteria. The protocol includes procedures such as randomization, bone marrow retrieval, stem cells processing, intracoronary infusion of stem cells in the inf...

Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells.

Science.gov (United States)

Hoshi, Akio; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Akatsuka, Akira; Usui, Yukio; Terachi, Toshiro

2008-06-15

Postoperative damage of the urethral rhabdosphincter (URS) and neurovascular bundle (NVB) is a major operative complication of radical prostatectomy. It is generally recognized to be caused by unavoidable surgical damage to the muscle-nerve-blood vessel units around the urethra. We attempted to treat this damage using skeletal muscle-derived stem cells, which are able to reconstitute muscle-nerve-blood vessel units. Cells were enzymatically extracted and sorted by flow cytometry as CD34/45 (Sk-34) and CD34/45 (Sk-DN) cells from green fluorescent protein transgenic mice and rats. URS-NVB damage was induced by manually removing one-third of the total URS and unilateral invasion of NVB in wild-type Sprague-Dawley and node rats. Freshly isolated Sk-34, Sk-34+Sk-DN cells, and cultured Sk-DN cells were directly transplanted into the damaged portion. At 4 and 12 weeks after transplantation, urethral pressure profile by electrical stimulation through the sacral surface (L6-S1) was evaluated as functional recovery. The recovery ratio in the control and transplanted groups was 37.6% and 72.9%, at 4 weeks, and 41.6% and 78.4% at 12 weeks, respectively (Pcells differentiated into numerous skeletal muscle fibers having neuromuscular junctions (innervation) and nerve bundle-related Schwann cells and perineurium, and blood vessel-related endothelial cells and pericyte around the urethra. Thus, we conclude that transplantation of skeletal muscle-derived multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of postoperative damage of URS and NVB after radical prostatectomy.

Alcohol and the risk of myocardial infarction.

Science.gov (United States)

Flesch, M; Rosenkranz, S; Erdmann, E; Böhm, M

2001-04-01

Epidemiological studies have repeatedly demonstrated a beneficial effect of moderate alcohol consumption on the incidence of coronary heart disease, myocardial infarction and overall mortality. The latter increases with excessive alcohol consumption. Although most epidemiological studies demonstrate a beneficial effect of alcohol consumption independent from the specific kind of alcoholic beverage, there is increasing evidence that wine and in particular red wine might contain pharmacological substances, which prevent atherosclerosis and myocardial infarction independent from the wine ethanol. Pathophysiological mechanisms mediating these beneficial effects include effects of wine phenols and tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial function and smooth muscle cell proliferation. Identification and characterization of the pharmacologically active substances might provide the stage for the development of new substances to be used in the prevention of coronary artery disease and myocardial infarction.

Induction of a monocyte/macrophage phenotype switch by mesenchymal stem cells might contribute to improved infarct healing postacute myocardial infarction

NARCIS (Netherlands)

ter Horst, E. N.; Naaijkens, B. A.; Krijnen, P. A.; van der Laan, A. M.; Piek, J. J.; Niessen, H. W.

2013-01-01

Inadequate healing following acute myocardial infarction (AMI) can lead to the development of heart failure. The ischemic myocardium triggers an inflammatory response that clears cell debris and initiates the onset of scar tissue formation. The duration and intensity of this inflammatory response

Impact of acute hyperglycemia on myocardial infarct size, area at risk and salvage in patients with ST elevation myocardial infarction and the association with exenatide treatment - results from a randomized study

DEFF Research Database (Denmark)

Lønborg, Jacob Thomsen; Vejlstrup, Niels Grove; Kelbæk, Henning Skov

2014-01-01

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage....... In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction...... between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index...

Metformin (dimethyl-biguanide induced DNA damage in mammalian cells

Directory of Open Access Journals (Sweden)

Rubem R. Amador

2012-01-01

Full Text Available Metformin (dimethyl-biguanide is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays and in mice (micronucleus assays. Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

Science.gov (United States)

Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A

2016-01-01

Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

[Study on mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction].

Science.gov (United States)

Yang, Quan; Cao, Yunshan

2017-06-01

To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction. Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0.135 g/kg of Qishen Yiqi dropping pills, and sham operation group and model group were administered the same amount of normal saline, once a day for consecutive 28 days. At the end of treatment, the levels of serum inflammatory factors of leukotriene B4 (LTB4), prostaglandin E 2 (PGE 2 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA); the changes of the indexes of hemodynamic [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of increase/decrease in left ventricular pressure (±dp/dt max)], the ratio of the heart weight/body weight, and the ratio of the left ventricular weight/heart weight (LVW/HW), the myocardial infarction area, myocardial histopathological changes were observed in the three groups; myocardial tissues inflammatory related factors [the mRNA and protein expressions of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX)], and the expression levels of transforming growth factor-β (TGF-β)/Smads signal transduction pathway related protein (TGF-β1, Smad2/3, Collagen I, Collagen III) and cell apoptosis related factors (Bcl-2, Bax) protein were measured. Compared with the sham operation group, levels of serum inflammatory factors, the index of LVEDP, the ratio of the heart weight/body weight, LVW/HW, myocardial infarction area, the mRNA and protein expression levels of inflammatory factors in myocardium, the expression levels of

Assessment of the progressive nature of cell damage in the pilocarpine model of epilepsy

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L. Covolan

2006-07-01

Full Text Available Pilocarpine-induced (320 mg/kg, ip status epilepticus (SE in adult (2-3 months male Wistar rats results in extensive neuronal damage in limbic structures. Here we investigated whether the induction of a second SE (N = 6 would generate damage and cell loss similar to that seen after a first SE (N = 9. Counts of silver-stained (indicative of cell damage cells, using the Gallyas argyrophil III method, revealed a markedly lower neuronal injury in animals submitted to re-induction of SE compared to rats exposed to a single episode of pilocarpine-induced SE. This effect could be explained as follows: 1 the first SE removes the vulnerable cells, leaving behind resistant cells that are not affected by the second SE; 2 the first SE confers increased resistance to the remaining cells, analogous to the process of ischemic tolerance. Counting of Nissl-stained cells was performed to differentiate between these alternative mechanisms. Our data indicate that different neuronal populations react differently to SE induction. For some brain areas most, if not all, of the vulnerable cells are lost after an initial insult leaving only relatively resistant cells and little space for further damage or cell loss. For some other brain areas, in contrast, our data support the hypothesis that surviving cells might be modified by the initial insult which would confer a sort of excitotoxic tolerance. As a consequence of both mechanisms, subsequent insults after an initial insult result in very little damage regardless of their intensity.

Radiation damage in flash memory cells

International Nuclear Information System (INIS)

Claeys, C.; Ohyama, H.; Simoen, E.; Nakabayashi, M.; Kobayashi, K.

2002-01-01

Results are presented of a study on the effects of total ionization dose and displacement damage, induced by high-energy electrons, protons and alphas, on the performance degradation of flash memory cells integrated in a microcomputer. A conventional stacked-gate n-channel flash memory cell using a 0.8 μm n-polysilicon gate technology is employed. Irradiations by 1-MeV electrons and 20-MeV protons and alpha particles were done at room temperature. The impact of the fluence on the input characteristics, threshold voltage shift and drain and gate leakage was investigated. The threshold voltage change for proton and alpha irradiations is about three orders of magnitude larger than that for electrons. The performance degradation is mainly caused by the total ionization dose (TID) damage in the tunnel oxide and in the interpoly dielectric layer and by the creation of interface traps at the Si-SiO 2 interface. The impact of the irradiation temperature on the device degradation was studied for electrons and gammas, pointing out that irradiation at room temperature is mostly the worst case. Finally, attention is given to the impact of isochronal and isothermal annealing on the recovery of the degradation introduced after room temperature proton and electron irradiation

Value of serum tenascin-C in patients with acute myocardial infarction

African Journals Online (AJOL)

Background: Myocardial infarction (MI) is defined as myocardial cell necrosis due to significant and sustained ischemia. TN-C is an extracellular matrix glycoprotein that is expressed in several important steps during the very early stage of cardiogenesis. TN-C is not normally expressed in the adult heart, but transiently ...

Translational findings from cardiovascular stem cell research.

Science.gov (United States)

Mazhari, Ramesh; Hare, Joshua M

2012-01-01

The possibility of using stem cells to regenerate damaged myocardium has been actively investigated since the late 1990s. Consistent with the traditional view that the heart is a "postmitotic" organ that possesses minimal capacity for self-repair, much of the preclinical and clinical work has focused exclusively on introducing stem cells into the heart, with the hope of differentiation of these cells into functioning cardiomyocytes. This approach is ongoing and retains promise but to date has yielded inconsistent successes. More recently, it has become widely appreciated that the heart possesses endogenous repair mechanisms that, if adequately stimulated, might regenerate damaged cardiac tissue from in situ cardiac stem cells. Accordingly, much recent work has focused on engaging and enhancing endogenous cardiac repair mechanisms. This article reviews the literature on stem cell-based myocardial regeneration, placing emphasis on the mutually enriching interaction between basic and clinical research. Copyright © 2012 Elsevier Inc. All rights reserved.

Magnetic resonance imaging of myocardial infarction during prothrombin complex concentrate therapy of hemophilia A

International Nuclear Information System (INIS)

Gruen, D.R.; Winchester, P.H.; Brill, P.W.; Ramirez, E.

1997-01-01

In patients with hemophilia, prothrombin complex concentrates (PCCs) have been successfully used to bypass inhibitors to fctor VIII during bleeding episodes. The use of PCCS, including FEIBA (factor eight inhibitor bypassing activity), has been associated with thromboembolic complications. Myocardial infarction (MI) is a rare but serious complication, reported in 13 previous cases, six in the pediatric age group. In all four patients who died during the acute MI, autopsy revealed extensive myocardial hemorrhage. The hearts of three other patients examined at least 5 months after the acute MI showed no evidence of prior hemorrhage. Magnetic resonance (MR) imaging has been shown to be able to evaluate the sequelae of myocardial infarction in adults with coronary artery disease and in children with Kawasaki syndrome. We report the first case of the used of MR imaging in the evaluation of myocardial damage during the acute stage of a FEIBA-associated MI in a 10-year-old boy. (orig.)

Magnetic resonance imaging of myocardial infarction during prothrombin complex concentrate therapy of hemophilia A

Energy Technology Data Exchange (ETDEWEB)

Gruen, D.R. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Winchester, P.H. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Brill, P.W. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States); Ramirez, E. [Dept. of Radiology, The New York Hospital-Cornell Medical Center, New York, NY (United States)

1997-03-01

In patients with hemophilia, prothrombin complex concentrates (PCCs) have been successfully used to bypass inhibitors to fctor VIII during bleeding episodes. The use of PCCS, including FEIBA (factor eight inhibitor bypassing activity), has been associated with thromboembolic complications. Myocardial infarction (MI) is a rare but serious complication, reported in 13 previous cases, six in the pediatric age group. In all four patients who died during the acute MI, autopsy revealed extensive myocardial hemorrhage. The hearts of three other patients examined at least 5 months after the acute MI showed no evidence of prior hemorrhage. Magnetic resonance (MR) imaging has been shown to be able to evaluate the sequelae of myocardial infarction in adults with coronary artery disease and in children with Kawasaki syndrome. We report the first case of the used of MR imaging in the evaluation of myocardial damage during the acute stage of a FEIBA-associated MI in a 10-year-old boy. (orig.)

The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia

Directory of Open Access Journals (Sweden)

Yuri M. Klyachkin

2014-01-01

Full Text Available Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI and ischemic heart disease (IHD remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM-derived stem/progenitor cells (SPCs. This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD.

In vitro three-dimensional coculturing poly3-hydroxybutyrate-co-3-hydroxyhexanoate with mouse-induced pluripotent stem cells for myocardial patch application.

Science.gov (United States)

Shijun, Xu; Junsheng, Mu; Jianqun, Zhang; Ping, Bo

2016-03-01

Identifying a suitable polymeric biomaterial for myocardial patch repair following myocardial infarction, cerebral infarction, and cartilage injury is essential. This study aimed to investigate the effect of the novel polymer material, poly3-hydroxybutyrate-co-3-hydroxyhexanoate, on the adhesion, proliferation, and differentiation of mouse-induced pluripotent stem cells in vitro. Mouse-induced pluripotent stem cells were isolated, expanded, and cultured on either two-dimensional or three-dimensional poly3-hydroxybutyrate-co-3-hydroxyhexanoate films (membranes were perforated to imitate three-dimensional space). Following attachment onto the films, mouse-induced pluripotent stem cell morphology was visualized using scanning electron microscopy. Cell vitality was detected using the Cell Counting Kit-8 assay and cell proliferation was observed using fluorescent 4',6-diamidino-2-phenylindole (DAPI) staining. Mouse-induced pluripotent stem cells were induced into cardiomyocytes by differentiation medium containing vitamin C. A control group in the absence of an inducer was included. Mouse-induced pluripotent stem cell survival and differentiation were observed using immunofluorescence and flow cytometry, respectively. Mouse-induced pluripotent stem cells growth, proliferation, and differentiation were observed on both two-dimensional and three-dimensional poly3-hydroxybutyrate-co-3-hydroxyhexanoate films. Vitamin C markedly improved the efficiency of mouse-induced pluripotent stem cells differentiation into cardiomyocytes on poly3-hydroxybutyrate-co-3-hydroxyhexanoate films. Three-dimensional culture was better at promoting mouse-induced pluripotent stem cell proliferation and differentiation compared with two-dimensional culture. © The Author(s) 2016.

Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis

International Nuclear Information System (INIS)

Ma, Jiali; Hui, Pingping; Meng, Wenying; Wang, Na; Xiang, Shihao

2017-01-01

The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells. - Highlights: • Ku70 knockdown sensitizes gemcitabine-induced killing of pancreatic cancer cells. • Ku70 knockdown facilitates gemcitabine-induced DNA damage and cell apoptosis. • Ku70 overexpression deceases gemcitabine's sensitivity in pancreatic cancer cells. • Ku70 knockdown sensitizes gemcitabine-induced anti-tumor activity in vivo.

Re-OPCAB vs. Re-CABG for myocardial revascularization.

Science.gov (United States)

Schütz, A; Mair, H; Wildhirt, S M; Gillrath, G; Lamm, P; Kilger, E; Reichart, B

2001-06-01

The present study compared redo coronary artery bypass grafting (Re-OPCAB) techniques with conventional redo coronary artery bypass grafting (Re-CABG) with particular focus on myocardial damage and clinical outcome parameters. Redo OPCAB (Re-OPCAB) was performed on 20 consecutive patients (15 males, mean age 63.2 +/- 9.3 years) using either the anterolateral approach for minimally invasive direct coronary artery bypass (n = 4) or the Octopus technique with regular sternotomy (n = 16). The Re-CABG group consisted of 20 consecutive patients (18 males, mean age 67.1 +/- 6.6 years). Groups did not differ in the number of atherosclerotic risk factors, or left ventricular, renal or liver function. Duration of surgery, number of bypass grafts and amount of transfused red blood cells did not differ significantly between both groups. Requirement of epinephrine (mg/h) within the first 24 h was lower in the Re-OPCAB group (Re-OPCAB: 0.14 +/- 0.22 vs. CABG: 0.88 +/- 0.97; p<0.01). In addition, CKMB levels at 24 h after operation were lower in the Re-OPCAB group (Re-OPCAB: 10.0 +/- 10.1 vs. Re-CABG: 38.7 +/- 28.1 U/l, p<0.001). There were no acute myocardial infarctions or deaths in the perioperative period. In the CABG group, there was a longer time period to extubation (hours) (Re-OPCAB: 9.8 +/- 3.9 vs. Re-CABG: 28.7 +/- 25.5; p<0.001), and the length of ICU stay was significantly prolonged (OPCAB: 1.3 +/- 0.5 versus Re-CABG: 4.4 +/- 8.7; p<0.001). The graft patency rate at follow-up was 95% in the Re-OPCAB group. Re-OPCAB results in decreased cardiac specific enzyme release, reduced requirement of inotropes and comparable clinical outcome in the early postoperative period. It is an appropriate alternative to conventional Re-CABG in selected patients awaiting reoperation for myocardial revascularization. Larger prospective and randomized trials are required to select the appropriate patient who benefits most from one or the other treatment regime.

Changes in nuclear protein acetylation in u. v. -damaged human cells

Energy Technology Data Exchange (ETDEWEB)

Ramanathan, B.; Smerdon, M.J.

1986-07-01

We have investigated the levels of nuclear protein acetylation in u.v.-irradiated human fibroblasts. We measured the levels of acetylation in total acid-soluble nuclear proteins and observed two distinct differences between the irradiated and unirradiated (control) cells. Immediately after irradiation, there is a wave of protein hyperacetylation (i.e. a total acetylation level greater than that of unirradiated cells) that lasts for 2-6 h depending on the experimental conditions. This hyperacetylation phase is then followed by a hypoacetylation phase, lasting for many hours, and the total level of acetylation does not return to that of control cells until 24-72 h after u.v. damage. Both the magnitude and duration of each phase is dependent on the dose of u.v. light used. The wave of hyperacetylation is more pronounced at low u.v. doses (i.e. less than 5 J/m2), while the wave of hypoacetylation is more pronounced at higher u.v. doses (greater than or equal to 8 J/m2). Furthermore, the duration of each phase is prolonged when cells are exposed to 2 mM hydroxyurea. Examination of the acetylation levels of the individual nuclear proteins indicated that acetylation of the core histones follows the same pattern observed for the total acid-soluble protein fractions. Furthermore, these were the only major proteins in the total acid-soluble fraction observed to undergo the early, rapid hyperacetylation immediately following u.v. damage. Acetylation of histone H1 was negligible in both damaged and control cells, while three prominent non-histone proteins were acetylated only after long labeling times (greater than 4 h) in each case, gradually becoming hyperacetylated in the u.v.-damaged cells. These results raise the possibility that a causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells.

Damaging and protective cell signalling in the untargeted effects of ionizing radiation

International Nuclear Information System (INIS)

Coates, Philip J.; Lorimore, Sally A.; Wright, Eric G.

2004-01-01

The major adverse consequences of radiation exposures are attributed to DNA damage in irradiated cells that has not been correctly restored by metabolic repair processes. However, the dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that are the descendants of irradiated cells either directly or via media transfer (radiation-induced genomic instability) or in cells that have communicated with irradiated cells (radiation-induced bystander effects). Radiation-induced genomic instability is characterized by a number of delayed responses including chromosomal abnormalities, gene mutations and cell death. Bystander effects include increases or decreases in damage-inducible and stress-related proteins, increases or decreases in reactive oxygen and nitrogen species, cell death or cell proliferation, cell differentiation, radioadaptation, induction of mutations and chromosome aberrations and chromosomal instability. The phenotypic expression of untargeted effects and the potential consequences of these effects in tissues reflect a balance between the type of bystander signals produced and the responses of cell populations to such signals, both of which may be significantly influenced by cell type and genotype. Thus, in addition to targeted effects of damage induced directly in cells by irradiation, a variety of untargeted effects may also make important short-term and long-term contributions to determining overall outcome after radiation exposures

Evaluation of saw damage using diamond-coated wire in crystalline silicon solar cells by photoluminescence imaging

Science.gov (United States)

Kinoshita, Kosuke; Kojima, Takuto; Suzuki, Ryota; Kawatsu, Tomoyuki; Nakamura, Kyotaro; Ohshita, Yoshio; Ogura, Atsushi

2018-05-01

Si ingots were sliced using a diamond-coated wire, and saw damage was observed even after damage removal etching and texturization. Since invisible microscopic damage was observed only under uncontrolled slice conditions, such damage was identified as saw damage. The wafers with saw damage exhibited the degradation of solar cell conversion efficiency (approximately 1–2% absolute). The results of external quantum efficiency (EQE) measurements showed a slight deterioration of EQE in the short wavelength region. Current–voltage characteristic measurements showed similar results that agreed with the EQE measurement results. In addition, EQE mapping measurements were carried out at various irradiation wavelengths between 350 and 1150 nm. Areas with dark contrasts in EQE mapping correspond to saw damage. In the cells with a low conversion efficiency, both EQE mapping and PL images exhibited dark areas and lines. On the other hand, in the cells with a high conversion efficiency, a uniform distribution of saw damage was observed even with the saw damage in the PL images. We believe that sophisticated control to suppress saw damage during sawing is required to realize higher conversion efficiency solar cells in the future.

Cardiac tissue engineering and regeneration using cell-based therapy

Directory of Open Access Journals (Sweden)

Alrefai MT

2015-05-01

Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

Myocardial Bridging

Directory of Open Access Journals (Sweden)

Shi-Min Yuan

2016-02-01

Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

Inhibition of Matrix Metalloproteinase Activity Prevents Increases in Myocardial Tumor Necrosis Factor-α

Science.gov (United States)

Murray, David B.; Levick, Scott P; Brower, Gregory L.; Janicki, Joseph S.

2010-01-01

Aim TNF-α is known to cause adverse myocardial remodeling. While we have previously shown a role for cardiac mast cells in mediating myocardial TNF-α, matrix metalloproteinases (MMP) activation of TNF-α may also be contributory. We sought to determine the relative roles of MMPs and cardiac mast cells in the activation of TNF-α in the hearts of rats subjected to chronic volume overload. Methods Interventions with the broad spectrum MMP inhibitor, GM6001, or the mast cell stabilizer, nedocromil, were performed in the rat aortocaval fistula (ACF) model of volume overload. Results Myocardial TNF-α levels were significantly increased in the ACF. This increase was prevented by MMP inhibition with GM6001 (p ≤ 0.001 vs. ACF). Conversely, myocardial TNF-α levels were increased in the ACF + nedocromil treated fistula groups (p ≤ 0.001 vs. sham). The degradation of interstitial collagen volume fraction seen in the untreated ACF group was prevented in both the GM6001 and nedocromil treated hearts. Significant increases in LV myocardial ET-1 levels also occurred in the ACF group at 3 days post-fistula. Whereas administration of GM6001 significantly attenuated this increase, mast cell stabilization with nedocromil markedly exacerbated the increase, producing ET-1 levels 6.5 fold and 2 fold greater than that in the sham-operated control and ACF group, respectively. Conclusion The efficacy of the MMP inhibitor, GM6001, to prevent increased levels of myocardial TNF-α is indicative of MMP-mediated cleavage of latent extracellular membrane bound TNF-α protein as the primary source of bioactive TNF-α in the myocardium of the volume-overload heart. PMID:20403361

Un-repairable DNA damage in cell due to irradiation

International Nuclear Information System (INIS)

Yoshii, Giichi

1992-01-01

Radiation-induced cell reproductive deactivation is caused by damage to DNA. In a cell, cellular DNA radical reacts with diffusion controlled rate and generates DNA peroxide radical. The chemical repair of DNA radical with hydrogen donation by thiol competes with the reaction of oxygen with same radicals in the DNA molecules. From the point reaction rates, the prolongation of radical life time is not as great as expected from the reduction in the glutathione content of the cell. This indicates that further reducting compounds (protein bound thiol) are present in the cell. The residual radicals are altered to strand breaks, base damages and so on. The effective lesions for a number of endpoints is un-repaired double strand break, which has been discovered in a cluster. This event gives risk to high LET radiation or to a track end of X-rays. For X- or electron irradiations the strand breaks are frequently induced by the interactions between sublesions on two strands in DNA. A single strand break followed by radical action may be unstable excited state, because of remaining sugar radical action and of having negative charged phosphates, in which strands breaks will be rejoined in a short time to stable state. On the same time, a break in the double helix will be immediately produced if two breaks are on either or approximately opposite locations. The formation of a double strand break in the helix depends on the ion strength of the cell. The potassium ions are largely released from polyanionic strand during irradiation, which results in the induction of denatured region. Double strand break with the denatured region seems to be un-repairable DNA damage. (author)

Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

International Nuclear Information System (INIS)

Maga, J.A.

1983-01-01

The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

ATM-activated autotaxin (ATX) propagates inflammation and DNA damage in lung epithelial cells: a new mode of action for silica-induced DNA damage?

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Zheng, Huiyuan; Högberg, Johan; Stenius, Ulla

2017-12-07

Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16 bronchial epithelial cells (16HBE) lung epithelial cells were exposed to silica particles. Reactive oxygen species (ROS), NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were end points. Low doses of silica induced NLRP3 activation, DNA damage accumulation, and ATM phosphorylation. A novel finding was that ATM induced ATX generation and secretion. Not only silica but also rotenone, camptothecin and H2O2 activated ATX via ATM, suggesting that ATX is part of a generalized ATM response to double-strand breaks (DSBs). Surprisingly, ATX inhibition mitigated DNA damage accumulation at later time points (6-16 h), and ATX transfection caused NLRP3 activation and DNA damage. Furthermore, the product of ATX enzymatic activity, lysophosphatidic acid, recapitulated the effects of ATX transfection. These data indicate an ATM-ATX-dependent loop that propagates inflammation and DSB accumulation, making low doses of silica effective inducers of DSBs in epithelial cells. We conclude that an ATM-ATX axis interconnects DSBs with silica-induced inflammation and propagates these effects in epithelial cells. Further studies of this adverse outcome pathway may give an accurate assessment of the lowest doses of silica that causes cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Flow cytometric determination of radiation-induced chromosome damage and its correlation with cell survival

International Nuclear Information System (INIS)

Welleweerd, J.; Wilder, M.E.; Carpenter, S.G.; Raju, M.R.

1984-01-01

Chinese hamster M3-1 cells were irradiated with several doses of x rays or α particles from 238 Pu. Propidium iodide-stained chromosome suspensions were prepared at different times after irradiation; cells were also assayed for survival. The DNA histograms of these chromosomes showed increased background counts with increased doses of radiation. This increase in background was cell-cycle dependent and was correlated with cell survival. The correlation between radiation-induced chromosome damage and cell survival was the same for X rays and α particles. Data are presented which indicate that flow cytometric analysis of chromosomes of irradiated cell populations can be a useful adjunct to classical cytogenic analysis of irradiation-induced chromosomal damage by virtue of its ability to express and measure chromosomal damage not seen by classical cytogenic methods

Impairment of endothelial-myocardial interaction increases the susceptibility of cardiomyocytes to ischemia/reperfusion injury.

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Thorsten M Leucker

Full Text Available Endothelial-myocardial interactions may be critically important for ischemia/reperfusion injury. Tetrahydrobiopterin (BH4 is a required cofactor for nitric oxide (NO production by endothelial NO synthase (eNOS. Hyperglycemia (HG leads to significant increases in oxidative stress, oxidizing BH4 to enzymatically incompetent dihydrobiopterin. How alterations in endothelial BH4 content impact myocardial ischemia/reperfusion injury remains elusive. The aim of this study was to examine the effect of endothelial-myocardial interaction on ischemia/reperfusion injury, with an emphasis on the role of endothelial BH4 content. Langendorff-perfused mouse hearts were treated by triton X-100 to produce endothelial dysfunction and subsequently subjected to 30 min of ischemia followed by 2 h of reperfusion. The recovery of left ventricular systolic and diastolic function during reperfusion was impaired in triton X-100 treated hearts compared with vehicle-treated hearts. Cardiomyocytes (CMs were co-cultured with endothelial cells (ECs and subsequently subjected to 2 h of hypoxia followed by 2 h of reoxygenation. Addition of ECs to CMs at a ratio of 1∶3 significantly increased NO production and decreased lactate dehydrogenase activity compared with CMs alone. This EC-derived protection was abolished by HG. The addition of 100 µM sepiapterin (a BH4 precursor or overexpression of GTP cyclohydrolase 1 (the rate-limiting enzyme for BH4 biosynthesis in ECs by gene trasfer enhanced endothelial BH4 levels, the ratio of eNOS dimer/monomer, eNOS phosphorylation, and NO production and decreased lactate dehydrogenase activity in the presence of HG. These results demonstrate that increased BH4 content in ECs by either pharmacological or genetic approaches reduces myocardial damage during hypoxia/reoxygenation in the presence of HG. Maintaining sufficient endothelial BH4 is crucial for cardioprotection against hypoxia/reoxygenation injury.

Diagnosis of myocardial ischemia combining multiphase postmortem CT-angiography, histology, and postmortem biochemistry.

Science.gov (United States)

Vanhaebost, Jessica; Ducrot, Kewin; de Froidmont, Sébastien; Scarpelli, Maria Pia; Egger, Coraline; Baumann, Pia; Schmit, Gregory; Grabherr, Silke; Palmiere, Cristian

2017-02-01

The aim of this study was to assess whether the identification of pathological myocardial enhancement at multiphase postmortem computed tomography angiography was correlated with increased levels of troponin T and I in postmortem serum from femoral blood as well as morphological findings of myocardial ischemia. We further aimed to investigate whether autopsy cases characterized by increased troponin T and I concentrations as well as morphological findings of myocardial ischemia were also characterized by pathological myocardial enhancement at multiphase postmortem computed tomography angiography. Two different approaches were used. In one, 40 forensic autopsy cases that had pathological enhancement of the myocardium (mean Hounsfield units ≥95) observed at postmortem angiography were retrospectively selected. In the second approach, 40 forensic autopsy cases that had a cause of death attributed to acute myocardial ischemia were retrospectively selected. The preliminary results seem to indicate that the identification of a pathological enhancement of the myocardium at postmortem angiography is associated with the presence of increased levels of cardiac troponins in postmortem serum and morphological findings of ischemia. Analogously, a pathological enhancement of the myocardium at postmortem angiography can be retrospectively found in the great majority of autopsy cases characterized by increased cardiac troponin levels in postmortem serum and morphological findings of myocardial ischemia. Multiphase postmortem computed tomography angiography is a useful tool in the postmortem setting for investigating ischemically damaged myocardium.

Effect of exogenous apelin-13 on cardiac stem cell mobilization in rats with myocardial infarction

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Nan ZHENG

2013-11-01

0.39±0.08 vs 0.70±0.08, P<0.05; mRNA level: C-kit 2.89±1.89 vs 18.77±14.19, Flk1 2.14±0.95 vs 4.59±0.92, Sca1 4.32±2.44 vs 29.39±11.90, P<0.05, and there was no obvious expression of C-kit, Flk1 or Sca1 protein in sham-operated group. Conclusion　Exogenous apelin-13 protein has protective effect on rats against myocardial infarction, which is closely related to stimulating the proliferation of endogenous cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2013.10.004

Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

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Smith, Michael E; Monroe, J David

2016-01-01

Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

Nexrutine Inhibits Cancer Cell Growth as a Consequence of Mitochondrial Damage and Mitophagy

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Xiang Wu

2015-05-01

Full Text Available Background/Aims: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. Methods: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. Results: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. Conclusion: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.

The Effects of Brazilian Green Propolis against Excessive Light-Induced Cell Damage in Retina and Fibroblast Cells

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Hiromi Murase

2013-01-01

Full Text Available Background. We investigated the effects of Brazilian green propolis and its constituents against white light- or UVA-induced cell damage in mouse retinal cone-cell line 661W or human skin-derived fibroblast cells (NB1-RGB. Methods. Cell damage was induced by 3,000lx white light for 24 h or 4/10 J/cm2 UVA exposure. Cell viability was assessed by Hoechst33342 and propidium iodide staining or by tetrazolium salt (WST-8 cell viability assay. The radical scavenging activity of propolis induced by UVA irradiation in NB1-RGB cells was measured using a reactive-oxygen-species- (ROS- sensitive probe CM-H2DCFDA. Moreover, the effects of propolis on the UVA-induced activation of p38 and extracellular signal-regulated kinase (ERK were examined by immunoblotting. Results. Treatment with propolis and two dicaffeoylquinic acids significantly inhibited the decrease in cell viability induced by white light in 661W. Propolis and its constituents inhibited the decrease in cell viability induced by UVA in NB1-RGB. Moreover, propolis suppressed the intracellular ROS production by UVA irradiation. Propolis also inhibited the levels of phosphorylated-p38 and ERK by UVA irradiation. Conclusion. Brazilian green propolis may become a major therapeutic candidate for the treatment of AMD and skin damage induced by UV irradiation.

Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

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José J. Gaforio

2011-10-01

Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

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Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

2015-01-01

Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

Cell Survival and DNA Damage in Normal Prostate Cells Irradiated Out-of-Field.

LENUS (Irish Health Repository)

Shields, L

2014-10-31

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells are not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci\\/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant

Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing.

Science.gov (United States)

Huber, Bruno C; Fischer, Rebekka; Brunner, Stefan; Groebner, Michael; Rischpler, Christoph; Segeth, Alexander; Zaruba, Marc M; Wollenweber, Tim; Hacker, Marcus; Franz, Wolfgang-Michael

2010-05-01

Mobilization of stem cells by granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI); however, clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularization and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were noninvasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by fluorescence-activated cell sorter (FACS) analysis. Mice (C57BL/6J) were infarcted by left anterior descending artery ligation. PTH (80 mug/kg) and G-CSF (100 mug/kg) were injected for 5 days. Perfusion defects were determined by (99m)Tc-sestamibi SPECT at days 6 and 30 after MI. The number of BMCs characterized by Lin(-)/Sca-1(+)/c-kit(+) cells in peripheral blood and heart was analyzed by FACS. Both G-CSF and PTH treatment resulted in an augmented mobilization of BMCs in the peripheral blood. Contrary to G-CSF and controls, PTH and the combination showed significant migration of BMCs in ischemic myocardium associated with a significant reduction of perfusion defects from day 6 to day 30. A combination of both cytokines had no additional effects on migration and perfusion. In our preclinical model, SPECT analyses revealed the functional potential of PTH reducing size of infarction together with an enhanced homing of BMCs to the myocardium in contrast to G-CSF. A combination of both cytokines did not improve the functional outcome, suggesting clinical applications of PTH in ischemic heart diseases.

Very low temperature rise laser annealing of radiation-damaged solar cells in orbit

International Nuclear Information System (INIS)

Poulek, V.

1988-01-01

Solar cells of all space objects are damaged by radiation in orbit. This damage, however, can be removed by laser annealing. A new in-orbit laser regeneration system for both body- and spin-stabilized space objects is proposed. For successful annealing of solar cells damaged by 10 years' radiation dose in orbit it is necessary for the temperature rise in the incidence point of the laser beam to reach about 400 0 C. By continuous regeneration, however, between two annealing cycles the solar cells are hit by about two orders of magnitude lower radiation dose. This makes it possible to carry out the regeneration at a temperature rise well under 1 0 C! If an optimal laser regeneration system is used, such low temperature rise laser annealing of radiation-damaged solar cells is possible. A semiconductor GaAlAs diode laser with output power up to 10 mW CW was used for annealing. Some results of the very low temperature rise annealing experiment are given in this paper. (author)

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

Science.gov (United States)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.

Science.gov (United States)

Wens, Stephan C A; Schaaf, Gerben J; Michels, Michelle; Kruijshaar, Michelle E; van Gestel, Tom J M; In 't Groen, Stijn; Pijnenburg, Joon; Dekkers, Dick H W; Demmers, Jeroen A A; Verdijk, Lex B; Brusse, Esther; van Schaik, Ron H N; van der Ploeg, Ans T; van Doorn, Pieter A; Pijnappel, W W M Pim

2016-02-01

Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury. In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (Pmass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue. Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions. © 2016 American Heart Association, Inc.

Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

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Lau Chu-Pak

2010-01-01

Full Text Available Abstract Background Recent studies suggested that bone marrow (BM cell implantation in patients with severe chronic coronary artery disease (CAD resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR. Methods and Results We compared the interval changes of left ventricular ejection fraction (LVEF, myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12 injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04 and increase in global LVEF (+9.0%, P = 0.02, the percentage of regional wall thickening (+13.1%, P= 0.04 and MPR (+0.25%, P = 0.03 over the target area at 6-months compared with baseline. Conclusions Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

Excision of x-ray-induced thymine damage in chromatin from heated cells

International Nuclear Information System (INIS)

Warters, R.L.; Roti Roti, J.L.

1979-01-01

Experiments were performed to distinguish between two possible modes of hyperthermia-induced inhibition of thymine base damage excision from the DNA of CHO cells: (1) heat denaturation of excision enzyme(s) or (2) heat-induced alteration of the substrate for damage excision (chromatin). While hyperthermia (45 0 C, 15 min) had no apparent effect on the capacity of the excision enzymes to excise damage from DNA it had a dramatic effect (ca. 80% inhibition) on the ability of chromatin to serve as a substrate for unheated enzymes. These results suggest that hyperthermia-induced radiosensitization of CHO cells may be due primarily to lesions in the cellular chromatin

Surgical myocardial revascularization without extracorporeal circulation

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Salomón Soriano Ordinola Rojas

2003-05-01

Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

Energy Technology Data Exchange (ETDEWEB)

Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2013-04-15

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

International Nuclear Information System (INIS)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

2013-01-01

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ m ). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in

Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin

DEFF Research Database (Denmark)

Kutwin, Marta; Sawosz, Ewa; Jaworski, Sławomir

2014-01-01

of platinum nanoparticles (NP-Pt) and cisplatin with blood compartments are important for future applications. This study investigated structural damage, cell membrane deformation and haemolysis of chicken embryo red blood cells (RBC) after treatment with cisplatin and NP-Pt. Cisplatin (4 μg/ml) and NP-Pt (2......,6 μg/ml), when incubated with chicken embryo RBC, were detrimental to cell structure and induced haemolysis. The level of haemolytic injury was increased after cisplatin and NP-Pt treatments compared to the control group. Treatment with cisplatin caused structural damage to cell membranes...

Microvascular obstruction on delayed enhancement cardiac magnetic resonance imaging after acute myocardial infarction, compared with myocardial {sup 201}Tl and {sup 123}I-BMIPP dual SPECT findings

Energy Technology Data Exchange (ETDEWEB)

Mori, Hiroaki [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Cardiology, Kainan Hospital, Yatomi (Japan); Isobe, Satoshi, E-mail: sisobe@med.nagoya-u.ac.jp [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Sakai, Shinichi [Department of Cardiology, Kainan Hospital, Yatomi (Japan); Yamada, Takashi [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Watanabe, Naoki; Miura, Manabu [Department of Cardiology, Kainan Hospital, Yatomi (Japan); Uchida, Yasuhiro; Kanashiro, Masaaki; Ichimiya, Satoshi [Department of Cardiology, Yokkaichi Municipal Hospital, Yokkaichi (Japan); Okumura, Takahiro; Murohara, Toyoaki [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

2015-08-15

Highlights: • The percentage infarct size (%IS) was significantly greater in the microvascular obstruction (MO) group than in the non-MO group. • The percentage mismatch score (%MMS) on dual scintigraphy significantly correlated with the %IS and the percentage MO. • The %MMS was significantly greater in the non-MO group than in the MO group, and was an independent predictor for MO. - Abstract: Background: The hypo-enhanced regions within the hyper-enhanced infarct areas detected by cardiac magnetic resonance (CMR) imaging reflect microvascular obstruction (MO) after acute myocardial infarction (AMI). The combined myocardial thallium-201 ({sup 201}Tl)/iodine-123-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ({sup 123}I-BMIPP) dual single-photon emission computed tomography (SPECT) is a useful tool for detecting myocardial reversibility after AMI. We evaluated whether MO could be an early predictor of irreversible myocardial damage in comparison with {sup 201}Tl and {sup 123}I-BMIPP dual SPECT findings in AMI patients. Methods: Sixty-two patients with initial AMI who successfully underwent coronary revascularization were enrolled. MO was defined by CMR imaging. Patients were divided into 2 groups as follows: MO group (n = 32) and non-MO group (n = 30). Scintigraphic defect scores were calculated using a 17-segment model with a 5-point scoring system. The mismatch score (MMS) was calculated as follows: the total sum of (Σ) {sup 123}I-BMIPP defect score minus Σ{sup 201}Tl defect score. The percentage mismatch score (%MMS) was calculated as follows: MMS/(Σ{sup 123}I-BMIPP score) × 100 (%). Results: The percentage infarct size (%IS) was significantly greater in the MO group than in the non-MO group (32.2 ± 13.8% vs. 18.3 ± 12.1%, p < 0.001). The %MMS significantly correlated with the %IS and the percentage MO (r = −0.26, p = 0.03; r = −0.45, p < 0.001, respectively). The %MMS was significantly greater in the non-MO group than in the MO group (45.4 �

Hydrocortisone Increases the Vinblastine-Induced Chromosomal Damages in L929 Cells Investigated by the Micronucleus Assay on Cytokinesis-Blocked Binucleated Cells

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Tahere Ebrahimipour

2017-03-01

Full Text Available Background: Stress may cause damages to DNA or/and change the ability of the cells to overcome these damages. It may also cause irregularities in the cell cycle and induce abnormal cell divisions through glucocorticoid-dependent functions. The abnormal cell divisions, in turn, lead to chromosomal mal-segregation and aneuploidy. In this study, the effects of the stress hormone, hydrocortisone (HYD, were investigated on the induced chromosomal abnormalities by vinblastine (VIN during cell cycle in L929 cells. Methods: This work was performed in winter 2013 at Department of Biology, University of Ferdowsi, Mashhad, Iran. Cultured cells were divided into different groups including control, VIN-treated, HYD treated and VIN+HYD co-treated cells. The induced chromosomal damages were investigated by micronucleus assay in cytokinesis-blocked binucleated cells. Results: Although HYD by itself did not increase the micronuclei (Mn frequency, co-treatment of cells with VIN and HYD led to significant increase (P<0.05 in the frequency of Mn in comparison to control and VIN treated groups. Conclusion: Cells treated with stress hormone are more sensitive to damages induced by VIN. Therefore, stress may not directly result in genetic instability, it can increase the harmful effects associated with other genotoxic agents.

Ionizing Radiation-Induced DNA Damage and Its Repair in Human Cells

Energy Technology Data Exchange (ETDEWEB)

Dizdaroglu, Miral

1999-05-12

DNA damage in mammalian chromatin in vitro and in cultured mammalian cells including human cells was studied. In the first phase of these studies, a cell culture laboratory was established. Necessary equipment including an incubator, a sterile laminar flow hood and several centrifuges was purchased. We have successfully grown several cell lines such as murine hybridoma cells, V79 cells and human K562 leukemia cells. This was followed by the establishment of a methodology for the isolation of chromatin from cells. This was a very important step, because a routine and successful isolation of chromatin was a prerequisite for the success of the further studies in this project, the aim of which was the measurement of DNA darnage in mammalian chromatin in vitro and in cultured cells. Chromatin isolation was accomplished using a slightly modified procedure of the one described by Mee & Adelstein (1981). For identification and quantitation of DNA damage in cells, analysis of chromatin was preferred over the analysis of "naked DNA" for the following reasons: i. DNA may not be extracted efficiently from nucleoprotein in exposed cells, due to formation of DNA-protein cross-links, ii. the extractability of DNA is well known to decrease with increasing doses of radiation, iii. portions of DNA may not be extracted due to fragmentation, iv. unextracted DNA may contain a significant portion of damaged DNA bases and DNA-protein cross-links. The technique of gas chromatography/mass spectrometry (GC/MS), which was used in the present project, permits the identification and quantitation of modified DNA bases in chromatin in the presence of proteins without the necessity of first isolating DNA from chromatin. This has been demonstrated previously by the results from our laboratory and by the results obtained during the course of the present project. The quality of isolated chromatin was tested by measurement of its content of DNA, proteins, and RNA, by analysis of its protein

Ionizing Radiation-Induced DNA Damage and Its Repair in Human Cells

International Nuclear Information System (INIS)

Dizdaroglu, Miral

1999-01-01

DNA damage in mammalian chromatin in vitro and in cultured mammalian cells including human cells was studied. In the first phase of these studies, a cell culture laboratory was established. Necessary equipment including an incubator, a sterile laminar flow hood and several centrifuges was purchased. We have successfully grown several cell lines such as murine hybridoma cells, V79 cells and human K562 leukemia cells. This was followed by the establishment of a methodology for the isolation of chromatin from cells. This was a very important step, because a routine and successful isolation of chromatin was a prerequisite for the success of the further studies in this project, the aim of which was the measurement of DNA darnage in mammalian chromatin in vitro and in cultured cells. Chromatin isolation was accomplished using a slightly modified procedure of the one described by Mee ampersand Adelstein (1981). For identification and quantitation of DNA damage in cells, analysis of chromatin was preferred over the analysis of ''naked DNA'' for the following reasons: i. DNA may not be extracted efficiently from nucleoprotein in exposed cells, due to formation of DNA-protein cross-links, ii. the extractability of DNA is well known to decrease with increasing doses of radiation, iii. portions of DNA may not be extracted due to fragmentation, iv. unextracted DNA may contain a significant portion of damaged DNA bases and DNA-protein cross-links. The technique of gas chromatography/mass spectrometry (GC/MS), which was used in the present project, permits the identification and quantitation of modified DNA bases in chromatin in the presence of proteins without the necessity of first isolating DNA from chromatin. This has been demonstrated previously by the results from our laboratory and by the results obtained during the course of the present project. The quality of isolated chromatin was tested by measurement of its content of DNA, proteins, and RNA, by analysis of its protein

Evaluation of cardiomyopathy in Duchenne muscular dystrophy by Tl-201 myocardial SPECT

International Nuclear Information System (INIS)

Jinnouchi, Seishi; Asai, Junko; Inoue, Kenjirou; Hoshi, Hiroaki; Watanabe, Katsushi.

1985-01-01

Clinical evaluation of Tl-201 myocardial SPECT in patients with cardiomyopathy of Duchenne type progressive muscular dystrophy (DMD) was reported. Cases subjected to study were 14 DMD and 8 normal. Using a rotating gamma camera system (ZLC7500 and Scintipac 70A), SPECT data were collected for 16 minutes (32 angles x 30 sec/angle, 180 0 ). The hypoperfusion areas of the left ventricular muscle were observed in 10 patients (71 %), which was in posterior wall (71 %), inferior wall (57 %), lateral and anterior wall (43 %) in the order of frequency. The hypoperfusion area became wider with age and stage, exept for some patients. It was suggested that myocardial degeneration in DMD started in posterior wall and then spread in other areas. For the purpose of quantitative evaluation of myocardial damage, Tl-201 myocardial uptake ratio (MUR) and left ventricular muscle volume (LVMV) were calculated using the results obtained by phantom studies. MUR and LVMV were higher in DMD than those of normal individuals (3.6 +- 1.0 %: 2.7 +- 0.3 %, p < 0.05, 190.2 +- 67.5 ml: 157.8 +- 21.5 ml, n.s., respectively). (author)

Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI Expression in Intestinal Epithelium

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Arjun Balakrishnan

2017-08-01

Full Text Available As the first line of defense against invading pathogen, intestinal epithelium produces various antimicrobial proteins (AMP that help in clearance of pathogen. Bactericidal/permeability-increasing protein (BPI is a 55 kDa AMP that is expressed in intestinal epithelium. Dysregulation of BPI in intestinal epithelium is associated with various inflammatory diseases like Crohn’s Disease, Ulcerative colitis, and Infectious enteritis’s. In this paper, we report a direct correlation between intestinal damage and BPI expression. In Caco-2 cells, we see a significant increase in BPI levels upon membrane damage mediated by S. aureus infection and pore-forming toxins (Streptolysin and Listeriolysin. Cells detect changes in potassium level as a Danger-associated molecular pattern associated with cell damage and induce BPI expression in a p38 dependent manner. These results are further supported by in vivo findings that the BPI expression in murine intestinal epithelium is induced upon infection with bacteria which cause intestinal damage (Salmonella Typhimurium and Shigella flexneri whereas mutants that do not cause intestinal damage (STM ΔfliC and STM ΔinvC did not induce BPI expression. Our results suggest that epithelial damage associated with infection act as a signal to induce BPI expression.

Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

International Nuclear Information System (INIS)

Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

1985-01-01

The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

NARCIS (Netherlands)

Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

Repair of DNA damage induced by ionizing radiation and benzo[a]pyrene in mammalian cells

International Nuclear Information System (INIS)

Cerutti, P.; Shinohara, K.; Remsen, J.

1977-01-01

The biological effects of DNA-damaging agents are codetermined by the structural characteristics of the lesions, the quality and extent of the local distortion of DNA and chromatin structure, and the mode(s) of damage processing used by a given type of cell. Persistent damage (i.e., damage that is not removed before it is reached by DNA replication) may be mostly responsible for mutagenesis and carcinogenesis. To understand the effects of environmental physical and chemical DNA-damaging agents on human health, the mechanisms of damage processing used by human cells have to be elucidated. We report our studies of the excision of gamma-ray products of the 5,6-dihydroxydihydrothymine type (t 0 /sub 2//sup γ/) in normal human fibroblasts and in fibroblasts from patients with the hereditary diseases Fanconi's anemia (FA) and ataxia telangiectasia (AT). Both diseases are characterized by chromosomal instability and increased susceptibility for the development of cancer. Formation and repair of DNA-benzo[a]pyrene adducts were studied in baby hamster kidney cells, secondary mouse embryo cells, and human lymphoma. The relative persistence of DNA-B[a]P may explain the high mutagenicity of the 7,8-dihydroxy-9,10-epoxy-tetrahydrobenzo[a]pyrene metabolites in rodent cells that has been observed by several investigators

Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction.

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Kirsi Alestalo

Full Text Available Acute myocardial infarction (AMI launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI.Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.Twenty-six patients (control group, n = 12; BMMNC group, n = 14 from the previously reported FINCELL study (n = 80 were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall's tau, control 0.6; BMMNC 0.7. At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall's tau, control 0.3; BMMNC 0.7.BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.

Usefulness of multimodality imaging for detection of myocardial infarction in patients with advanced kidney failure: case report

Energy Technology Data Exchange (ETDEWEB)

Veras, Mariana Ferreira; Azevedo, Jader Cunha de; Gamarski, Moisés; Mesquita, Evandro Tinoco; Mesquita, Cláudio Tinoco, E-mail: fvmari@gmail.com [Hospital Procardíaco, Rio de Janeiro, RJ (Brazil); Alves, José Galvão [Centro Universitário de Volta Redonda, RJ (Brazil)

2016-01-15

{sup 99m}Tc-PYP is able to locate hydroxyapatite crystal structures found within the mitochondria of irreversibly damaged myocardial cells. A study conducted in 52 patients undergoing {sup 99m}Tc-PYP imaging, which underwent necropsy after death, showed sensitivity of 89% and specificity of 100% for {sup 99m}Tc-PYP. The positive predictive value of the technique was 100%, and the negative predictive value was 72%. (author)

Stem cell therapy for the treatment of radiation-induced normal tissue damage

International Nuclear Information System (INIS)

Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

2013-01-01

Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

Quantitative measurement of damage caused by 1064-nm wavelength optical trapping of Escherichia coli cells using on-chip single cell cultivation system

International Nuclear Information System (INIS)

Ayano, Satoru; Wakamoto, Yuichi; Yamashita, Shinobu; Yasuda, Kenji

2006-01-01

We quantitatively examined the possible damage to the growth and cell division ability of Escherichia coli caused by 1064-nm optical trapping. Using the synchronous behavior of two sister E. coli cells, the growth and interdivision times between those two cells, one of which was trapped by optical tweezers, the other was not irradiated, were compared using an on-chip single cell cultivation system. Cell growth stopped during the optical trapping period, even with the smallest irradiated power on the trapped cells. Moreover, the damage to the cell's growth and interdivision period was proportional to the total irradiated energy (work) on the cell, i.e., irradiation time multiplied by irradiation power. The division ability was more easily affected by a smaller energy, 0.36 J, which was 30% smaller than the energy that adversely affected growth, 0.54 J. The results indicate that the damage caused by optical trapping can be estimated from the total energy applied to cells, and furthermore, that the use of optical trapping for manipulating cells might cause damage to cell division and growth mechanisms, even at wavelengths under 1064 nm, if the total irradiation energy is excessive

The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

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Razmik Mirzayans

2016-05-01

Full Text Available It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional “repair and survive, or die” hypothesis.

Rhizopus oryzae hyphae are damaged by human natural killer (NK) cells, but suppress NK cell mediated immunity.

Science.gov (United States)

Schmidt, Stanislaw; Tramsen, Lars; Perkhofer, Susanne; Lass-Flörl, Cornelia; Hanisch, Mitra; Röger, Frauke; Klingebiel, Thomas; Koehl, Ulrike; Lehrnbecher, Thomas

2013-07-01

Mucormycosis has a high mortality and is increasingly diagnosed in hematopoietic stem cell transplant (HSCT) recipients. In this setting, there is a growing interest to restore host defense to combat infections by adoptively transferring donor-derived immunocompetent cells. Natural killer (NK) cells exhibit antitumor and antiinfective activity, but the interaction with Mucormycetes is unknown. Our data demonstrate that both unstimulated and IL-2 prestimulated human NK cells damage Rhizopus oryzae hyphae, but do not affect resting conidia. The damage of the fungus is mediated, at least in part, by perforin. R. oryzae hyphae decrease the secretion of immunoregulatory molecules by NK cells, such as IFN-γ and RANTES, indicating an immunosuppressive effect of the fungus. Our data indicate that NK cells exhibit activity against Mucormycetes and future research should evaluate NK cells as a potential tool for adoptive immunotherapy in HSCT. Copyright © 2012 Elsevier GmbH. All rights reserved.

Senescence, apoptosis or autophagy? When a damaged cell must decide its path--a mini-review.

Science.gov (United States)

Vicencio, José Miguel; Galluzzi, Lorenzo; Tajeddine, Nicolas; Ortiz, Carla; Criollo, Alfredo; Tasdemir, Ezgi; Morselli, Eugenia; Ben Younes, Amena; Maiuri, Maria Chiara; Lavandero, Sergio; Kroemer, Guido

2008-01-01

Many features of aging result from the incapacity of cells to adapt to stress conditions. When damage accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Apoptosis (self-killing) is the best-described form of programmed cell death, but autophagy (self-eating), which is a lysosomal degradation pathway essential for homeostasis, reportedly contributes to cell death as well. Unlike mitotic cells, postmitotic cells like neurons or cardiomyocytes cannot become senescent since they are already terminally differentiated. The fate of these cells entirely depends on their ability to cope with stress. Autophagy then operates as a major homeostatic mechanism to eliminate damaged organelles, long-lived or aberrant proteins and superfluous portions of the cytoplasm. In this mini-review, we briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways. (c) 2008 S. Karger AG, Basel.

Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

International Nuclear Information System (INIS)

Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

2010-01-01

Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

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Sudhakar John

2013-01-01

Full Text Available Background. Age-related macular degeneration (AMD is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types. Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged. Results. Thus, for a damage limited to the retinal pigment epithelial (RPE layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried. Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

Assessment of myocardial viability by exercise stress myocardial tomography with 201Tl

International Nuclear Information System (INIS)

Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

1992-01-01

Exercise stress (Ex) and redistribution (RD) myocardial tomography with Tl-201 has been widely used for evaluating myocardial viability. But recent studies have demonstrated that reinjection (ReI) study following RD study is necessary for detecting reversible ischemic myocardium. On the other hand, decreased myocardial washout of Tl-201 after Ex is an indicator of myocardial ischemia. So we have studied the usefulness of myocardial Tl-201 washout rate (WOR) for the evaluation of myocardial viability by comparing it with ReI images. Ex and RD myocardial tomographies were obtained immediately after Ex and 3 hours later. After RD study a small amount of Tl-201 was injected and ReI imaging was repeated. We studied 64 myocardial segments (in 58 patients with coronary artery disease) in which Ex-induced perfusion defects persisted in RD images. According to the changes of perfusion defects between Ex, RD and ReI images, they were classified into 3 types: Type I; perfusion defect on the RD image was identical to ReI image (75%). Type I was divided into 2 subgroups whether perfusion defect at Ex was unchanged (Ia, 42%) or improved (Ib, 33%) on the RD image. Type II; perfusion defect at Ex was reduced on the RD image and it improved furthermore at ReI image (17%). Type III; perfusion defect was the same at Ex and RD but it was reduced on the ReI image (8%). WOR less than 30% was defined as abnormal when Ex heart rate exceeded 120 bpm and lung-myocardial Tl-201 uptake ratio was less than 0.45. The differentiation between Type Ia and Type III is of great importance. History of myocardial infarction, effort angina and Ex induced ST depression could not differentiate these 2 groups. WOR abnormality was observed in all of Type III, but WOR was normal in Type Ia. In conclusion, WOR abnormality in Ex-RD myocardial imaging is useful for evaluating myocardial viability. ReI imaging is necessary for the precise evaluation of viable muscle mass and for inadequate Ex. (author)

Assessment of myocardial perfusion and metabolism for assessment of myocardial viability

International Nuclear Information System (INIS)

Beller, G.

1996-01-01

Identifying preserved myocardial viability in the presence of severe regional left ventricular dysfunction is becoming increasingly more important for clinical decision-making to better select those patients with coronary artery disease who will benefit most from revascularization. 201 Tl remains the most commonly employed radionuclide for detecting both ischemia and viability. A severe persistent defect with 201 Tl uptake compared to peak to improved perfusion and corresponding improved function after revascularisation. Detection of defect reversibility on 201 Tl imaging is enhanced by 'reinjection' of a second 201 Tl dose after acquisition of redistribution images. Initial and 4-hour rest/redistribution imaging has proven most usefull for detection of viability in the resting state in patients with ischemic cardiomyopathy. The greater the extent of preoperative viability, the greater is the improvement in regional and global function after revascularisation. 99 Tc sestamibi has also been demonstrated to be extracted by myocardial cells in proportion to regional blood flow in the presence of viable myocities. Although this agrnt does not redistribute after intravenous injection, its >50% uptake of the tracer implies viablility and predicts improved regional function after revascularisation. Finally positron emission tomography with 18 F fluorodeoxoglucose (FDG) is perhaps the most sensitive noninvasive imaging technique for detection of viability in stunned or hibernating myocardium. A mismatch pattern between regional flow and FDG uptake as approximately an 80-85% positive preicted value for predicting improved function in asynergic myocardial regions after revascualarisation

Pharmacological prevention of reperfusion injury in acute myocardial infarction. A potential role for adenosine as a therapeutic agent.

Science.gov (United States)

Quintana, Miguel; Kahan, Thomas; Hjemdahl, Paul

2004-01-01

The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the

Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents: Implications for Oncolytic Virus Therapy.

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Fox, Candace R; Parks, Griffith D

2018-04-01

A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI - ) is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI - infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI - persistently infected (PI) cells. P/V-CPI - PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and cell death. This increased cisplatin sensitivity correlated with defects in DNA damage signaling pathways such as phosphorylation of Chk1 and translocation of damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced killing of PI cells was sensitive to the inhibition of wild-type (WT) p53-inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage signaling pathways. A similar sensitivity to cisplatin was seen with cells during acute infection with P/V-CPI - as well as during acute infections with WT PIV5 and the related virus human parainfluenza virus type 2 (hPIV2). Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish PI as well as the potential for combining chemotherapy with oncolytic RNA virus vectors. IMPORTANCE There is intense interest in developing oncolytic viral vectors with increased potency against cancer cells, particularly those cancer cells that have gained resistance to chemotherapies. We have found that infection with cytoplasmically replicating parainfluenza virus can result in increases in the killing of cancer cells by agents that induce DNA damage, and this is linked

Current Understanding of the Pathophysiology of Myocardial Fibrosis and Its Quantitative Assessment in Heart Failure

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Tong Liu

2017-04-01

Full Text Available Myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. Myocardial fibrosis results from increased myofibroblast activity and excessive extracellular matrix deposition. Various cells and molecules are involved in this process, providing targets for potential drug therapies. Currently, the main detection methods of myocardial fibrosis rely on serum markers, cardiac magnetic resonance imaging, and endomyocardial biopsy. This review summarizes our current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.

Different Causes of Death in Patients with Myocardial Infarction Type 1, Type 2, and Myocardial Injury.

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Lambrecht, Sascha; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Hosbond, Susanne; Diederichsen, Axel C P; Thygesen, Kristian; Mickley, Hans

2018-05-01

Data outlining the mortality and the causes of death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and those with myocardial injury are limited. During a 1-year period from January 2010 to January 2011, all hospitalized patients who had cardiac troponin I measured on clinical indication were prospectively studied. Patients with at least one cardiac troponin I value >30 ng/L underwent case ascertainment and individual evaluation by an experienced adjudication committee. Patients were classified as having type 1 myocardial infarction, type 2 myocardial infarction, or myocardial injury according to the criteria of the universal definition of myocardial infarction. Follow-up was ensured until December 31, 2014. Data on mortality and causes of death were obtained from the Danish Civil Registration System and the Danish Register of Causes of Death. Overall, 3762 consecutive patients were followed for a mean of 3.2 years (interquartile range 1.3-3.6 years). All-cause mortality differed significantly among categories: Type 1 myocardial infarction 31.7%, type 2 myocardial infarction 62.2%, myocardial injury 58.7%, and 22.2% in patients with nonelevated troponin values (log-rank test; P causes, vs 42.6% in patients with type 2 myocardial infarction (P = .015) and 41.2% in those with myocardial injury (P causes of death did not differ substantially between patients with type 2 myocardial infarction and those with myocardial injury. Patients with type 2 myocardial infarction and myocardial injury exhibit a significantly higher long-term mortality compared with patients with type 1 myocardial infarction . However, most patients with type 1 myocardial infarction die from cardiovascular causes in contrast to patients with type 2 myocardial infarction and myocardial injury, in whom noncardiovascular causes of death predominate. Copyright © 2018 Elsevier Inc. All rights reserved.

[Quantitative changes in the ultrastructure of myocardial cells in Japanese quail during hypergravity, hypodynamia and space flight].

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Bózner, A; Boda, K; Dostál, J; Matĕjková, Z; Devecka, V

1993-03-01

The experimental work aimed at the quantitative ultrastructure of the myocardial cells of the Japanese quail Coturnix coturnix japonica during hypergravitation, hypodynamism and space flight in a Soviet satellite. For the determination of quantitative changes of the myocardial ultrastructure a morphometrical method was used with parameters like the number of mitochondria, average mitochondrial size, relative mitochondrial volume, deficiency of cristae and relative volume of myofibrils. The quails were observed in 3 groups. The absolute control consisted of quails living in normal Earth conditions, in the laboratory group the quails were exposed to conditions of hypergravitation and hypodynamism in a specially constructed centrifuge, and in the flying group the quails were exposed to space flight in a Soviet orbital station MIR. In the group of absolute controls no pathological changes of the myocardial ultrastructure were found. In the flying group there were no significant changes, with the exception of decreased relative volume of myofibrils, which however agrees with the findings on symptoms corresponding to human and animal heart weakness during space flights. In the laboratory group, pathological changes were observed in each of the fractions. The most significant pathological findings were found in the group controls in the center and in hypergravitation combined with hypodynamism. It can be concluded that the laboratories can simulate conditions induced by the start and flight of space ships. (Fig. 2, Ref, 8.)

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

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Pranitha Kamat

Full Text Available Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R injury during myocardial infarction (MI. Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS. We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5 or saline (n = 5 was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE, endothelial cell activation (CD31 and inflammation (IgG, C3b/c, C5b9, MCP-1 were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

Myocardial imaging. Coxsackie myocarditis

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Wells, R.G.; Ruskin, J.A.; Sty, J.R.

1986-09-01

A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

Myocardial imaging. Coxsackie myocarditis

International Nuclear Information System (INIS)

Wells, R.G.; Ruskin, J.A.; Sty, J.R.

1986-01-01

A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1

Radiation-induced DNA damage in halogenated pyrimidine incorporated cells and its correlation with radiosensitivity

International Nuclear Information System (INIS)

Watanabe, R.; Nikjoo, H.

2003-01-01

Cells with DNA containing 5-halogenated pyrimidines in place of thymidine show significant reductions of slope (Do) and shoulder (Dq) of their radiation survival curves. Similar radiosensitization has also been observed in the yield of DNA strand breaks. The purpose of this study is to obtain an insight into the mechanism of cell lethality by examining the relationship between the spectrum of DNA damage and the cell survival. In this study we estimated the enhancement of strand breaks due to incorporation of halogenated pyrimidine, the complexity of DNA damage and the probability of the initial DNA damage leading to cell inactivation. Monte Carlo track structure methods were used to model and simulate the induction of strand breakage by X-rays. The increase of DNA strand break was estimated by assuming the excess strand break was caused by the highly reactive uracil radicals at the halouracil substituted sites. The assumption of the enhancement mechanism of strand breaks was examined and verified by comparison with experimental data for induction of SSB and DSB. The calculated DNA damage spectrum shows the increase in complexity of strand breaks is due to incorporation of halogenated pyrimidines. The increase in the yield of DSB and cell lethality show similar trend at various degrees of halogenated pyrimidine substitution. We asked the question whether this agreement supports the hypothesis that DSB is responsible for cell lethality? The estimated number of lethal damage from the cell survival using a linear-quadratic model is much less than the initial yield of DSB. This work examines the correlation of cell lethality as a function of frequencies of complex form of double strand breaks

Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

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Anthony Skipper

2016-01-01

Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

Dihydropyridines decrease X-ray-induced DNA base damage in mammalian cells

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Wojewodzka, M., E-mail: marylaw@ichtj.waw.pl [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Gradzka, I.; Buraczewska, I.; Brzoska, K.; Sochanowicz, B. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Goncharova, R.; Kuzhir, T. [Institute of Genetics and Cytology, Belarussian National Academy of Sciences, Minsk (Belarus); Szumiel, I. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland)

2009-12-01

Compounds with the structural motif of 1,4-dihydropyridine display a broad spectrum of biological activities, often defined as bioprotective. Among them are L-type calcium channel blockers, however, also derivatives which do not block calcium channels exert various effects at the cellular and organismal levels. We examined the effect of sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate (denoted here as DHP and previously also as AV-153) on X-ray-induced DNA damage and mutation frequency at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in Chinese hamster ovary CHO-K1 cells. Using formamido-pyrimidine glycosylase (FPG) comet assay, we found that 1-h DHP (10 nM) treatment before X-irradiation considerably reduced the initial level of FPG-recognized DNA base damage, which was consistent with decreased 8-oxo-7,8-dihydro-2'-deoxyguanosine content and mutation frequency lowered by about 40%. No effect on single strand break rejoining or on cell survival was observed. Similar base damage-protective effect was observed for two calcium channel blockers: nifedipine (structurally similar to DHP) or verapamil (structurally unrelated). So far, the specificity of the DHP-caused reduction in DNA damage - practically limited to base damage - has no satisfactory explanation.

Sulforaphane enhances irradiation effects in terms of perturbed cell cycle progression and increased DNA damage in pancreatic cancer cells.

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Patrick Naumann

Full Text Available Sulforaphane (SFN, an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT.In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT.Both SFN and RT show a strong and dose dependent survival reduction in clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in γH2AX protein level indicating DNA damage. Effects were more pronounced in combined treatment and both cell cycle perturbation and DNA damage persisted for a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA repair proteins Ku 70, Ku 80 and XRCC4.Our results suggest that combination of SFN and RT exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer.

A protective effect of anthocyanins and xanthophylls on UVB-induced damage in retinal pigment epithelial cells.

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Silván, Jose Manuel; Reguero, Marina; de Pascual-Teresa, Sonia

2016-02-01

Increased exposure to solar ultraviolet B (UVB) radiation causes oxidative damage that may promote age related macular degeneration (AMD) and other ocular pathologies. This study is aimed to demonstrate the protective effects of some anthocyanins and xanthophylls against the UVB-induced oxidative damage to retinal pigment epithelial (RPE) cells. ARPE-19 cells were treated with 5 μM cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, lutein, zeaxanthin or a mixture of cyanidin-3-O-glucoside:zeaxanthin prior to UVB exposure (500 J m(-2)). Cell viability and mitogen-activated protein kinase (MAPK) phosphorylation were determined by MTT assay and western blot analysis, respectively. Oxidative damage was evaluated by measuring the intracellular reactive oxygen species (ROS). The data showed that UVB irradiation reduces the cell viability to 46% with increasing of intracellular ROS levels and phosphorylation of MAPKs. However, pre-treatment (60 min) with 5 μM cyanidin-3-O-glucoside, lutein or zeaxanthin significantly reduced cellular ROS levels and phosphorylation of MAPKs (JNK1/2 and p38) mediated by UVB irradiation and subsequently increased cell viability. Thus, results show that UVB irradiation is able to induce apoptosis in ARPE-19 cells through oxidative stress; however anthocyanins and xanthophylls pre-treatment can attenuate this damage. This suggests that cyanidin-3-O-glucoside, lutein and zeaxanthin are effective in preventing UVB-induced damage in RPE cells and may be suitable as chemoprotective factors for the prevention of ocular damage. The use of natural dietary antioxidants might reduce ocular oxidative damage caused by UVB radiation.

Study progress of cardiac MRI technology in assessment of myocardial viability after myocardial infarction

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Wang Jing; Zhang Hao

2013-01-01

Acute myocardial infarction (AMI) is one of the most common diseases that cause disability and death around the world. Correctly and effectively assessing the myocardial viability after myocardial infarction can reduce the disabled rate and mortality rate. At present, many methods could be used to assess myocardial viability. The cardiac magnetic resonance imaging (CMR) technology has a lot of advantages compared to other methods. In this paper, we reviewed the research progress of CMR in assessment of myocardial viability after myocardial infarction, and compared CMR with other technologies. (authors)

The diagnosis of silent myocardial ischemia. Motion-Frozen (or morphing) myocardial perfusion imaging.

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Chang, Cheng; Ye, Bo; Xie, Wenhui; Zhang, Daoliang; Lei, Bei; Ye, Xiaodan

2016-01-01

Silent myocardial ischemia is typically defined as objective evidence of myocardial ischemia in patients without subjective ischemia symptoms. Currently, coronary artery angiography is the gold standard for diagnosis of asymptomatic coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) can visually demonstrate the morphology, trend and extent of coronary stenosis and is commonly used in clinical screening of CAD. Myocardial perfusion imaging can be used not only to identify whether anatomical stenosis causes myocardial dysfunction, but to also assess the risk stratification and prognosis of myocardial disease (MD). Myocardial perfusion imaging using morphing combined with CTCA can simultaneously show the relationship between CAD and myocardial ischemia from an anatomical and functional aspect. This allows earlier diagnosis of asymptomatic CAD myocardial ischemia, accurate identification of the culprit vessels, and could prevent unnecessary interventional therapy. The 1-day dobutamine stress/resting met-hod is also one of the methods used. The combination of CTCA and the morphing technique can provide anatomical and functional information on coronary arteries at the same time, significantly improving the diagnostic sensitivity, specificity, and accuracy of MD.

Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

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Lin, Hui; Ma, Xuan; Wang, Bai-Chuan; Zhao, Lei; Liu, Jian-Xiang; Pu, Fei-Fei; Hu, Yi-Qiang; Hu, Hong-Zhi; Shao, Zeng-Wu

2017-11-15

Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca 2+ ] i ) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca 2+ ] i . In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening for silent myocardial ischemia caseof diabetics : interest of myocardial perfusion scintigraphy

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Bahri, Haifa

2007-01-01

Silent myocardial ischemia is a major cause of morbidity and mortality in diabetic patients. Its diagnosis by noninvasive means such as myocardial SPECT would improve the management of these patients. The purpose of this study is to assess the frequency of silent myocardial ischemia in asymptomatic diabetics and their evolution. As a result, the myocardial SPECT is a reliable tool for screening for silent myocardial ischemia in diabetic patients. Its prognostic value allows to stratify the cardiac risk and guide therapeutic management. Its integration into a screening strategy in Tunisia seems limited by its low availability and cost. The latter could be reduced by better patient selection.

Vochysia rufa Stem Bark Extract Protects Endothelial Cells against High Glucose Damage

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Neire Moura de Gouveia

2017-02-01

Full Text Available Background: Increased oxidative stress by persistent hyperglycemia is a widely accepted factor in vascular damage responsible for type 2 diabetes complications. The plant Vochysia rufa (Vr has been used in folk medicine in Brazil for the treatment of diabetes. Thus; the protective effect of a Vr stem bark extract against a challenge by a high glucose concentration on EA.hy926 (EA endothelial cells is evaluated. Methods: Vegetal material is extracted with distilled water by maceration and evaporated until dryness under vacuum. Then; it is isolated by capillary electrophoresis–tandem mass spectrometry. Cell viability is evaluated on EA cells treated with 0.5–100 µg/mL of the Vr extract for 24 h. The extract is diluted at concentrations of 5, 10 and 25 µg/mL and maintained for 24 h along with 30 mM of glucose to evaluate its protective effect on reduced glutathione (GSH; glutathione peroxidase (GPx and reductase (GR and protein carbonyl groups. Results: V. rufa stem bark is composed mainly of sugars; such as inositol; galactose; glucose; mannose; sacarose; arabinose and ribose. Treatment with Vr up to 100 µg/mL for 24 h did not affect cell viability. Treatment of EA cells with 30 mM of glucose for 24 h significantly increased the cell damage. EA cells treated with 30 mM of glucose showed a decrease of GSH concentration and increased Radical Oxygen Species (ROS and activity of antioxidant enzymes and protein carbonyl levels; compared to control. Co-treatment of EA with 30 mM glucose plus 1–10 μg/mL Vr significantly reduced cell damage while 5–25 μg/mL Vr evoked a significant protection against the glucose insult; recovering ROS; GSH; antioxidant enzymes and carbonyls to baseline levels. Conclusion: V. rufa extract protects endothelial cells against oxidative damage by modulating ROS; GSH concentration; antioxidant enzyme activity and protein carbonyl levels.

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function