Chronically Administered Acetaminophen and the Ischemia/Reperfused Myocardium

2003 ◽  
Vol 228 (6) ◽  
pp. 674-682 ◽  
Author(s):  
R. Golfetti ◽  
T. Rork ◽  
G. Merrill

Male and female Hartley strain guinea pigs weighing 280 ± 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion protocol. Our objective was to compare and contrast ventricular function, coronary circulation, and selected biochemical and histological indices in the two treatment groups. Left ventricular developed pressure in the early minutes of reperfusion was significantly greater in the presence of acetaminophen, e.g., at 1 min, 40 ± 4 vs 21 ± 3 mmHg ( P < 0.05). Coronary perfusion pressure was significantly less from 3 to 40 min of reperfusion in the presence of acetaminophen. Creatine kinase release in vehicle-treated hearts rose from 42 ± 14 (baseline) to 78 ± 25 units/liter by the end of ischemia. Corresponding values in acetaminophen-treated hearts were 36 ± 8 and 44 ± 14 units/liter. Acetaminophen significantly ( P < 0.05) attenuated release of creatine kinase. Chemiluminescence, an indicator of the in vitro production of peroxynitrite via the in vivo release of superoxide and nitric oxide, was also significantly attenuated by acetaminophen. Electron microscopy indicated a well-preserved myofibrillar ultrastructure in the postischemic myocardium of acetaminophen-treated hearts relative to vehicle-treated hearts (e.g., few signs of contraction bands, little or no evidence of swollen mitochondria, and well-defined light and dark bands in sarcomeres with acetaminophen; opposite with vehicle). We conclude that chronic administration of acetaminophen provides cardioprotection to the postischemic, reperfused rodent myocardium.

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3471
Author(s):  
Fatima Saqib ◽  
Muhammad Arif Aslam ◽  
Khizra Mujahid ◽  
Luigi Marceanu ◽  
Marius Moga ◽  
...  

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases


2007 ◽  
Vol 19 (1) ◽  
pp. 198
Author(s):  
Y. Hashiyada ◽  
H. Takahashi ◽  
M. Asada ◽  
N. Sakuta ◽  
S. Furuyashiki ◽  
...  

The co-transfer of trophoblastic vesicles (TVs), derived from in vivo-recovered conceptuses, is a well-known method for promoting the successful implantation of embryos through the action of bovine interferon-tau (bIFN-τ) on maternal-fetal recognition. However, the preparation of these TVs is a tedious process. Techniques have progressed for obtaining large numbers of TVs consistently from serially passaged trophoblast cells. The aim of the present study was to compare the function of TVs for co-transfer derived from in vitro production with those derived from in vivo-flushed embryos, and without co-transfer. Production of TVs from serially passaged trophoblast cells was carried out according to the method previously described by Takahashi et al. (2000, Cloned animals and placentation, 147–151, Yokendo: Tokyo, Japan). The in vitro TVs (IVP-TVs), 1–2 mm in diameter, were taken from cells passaged 48th to 52th and 96th. In vivo-derived TVs (vivo-TVs) were prepared from recovered elongating blastocysts 7 days after transfer of frozen–thawed embryos on Day 8 of the estrous cycle. Demi-embryos were produced from fresh embryos of flushed Japanese Black cows by bisection using a micromanipulator. Pairs of demi-embryos, without (control) or with 2 to 4 TVs, were transferred into the uterus ipsilateral of 65 Japanese Short Horn recipients to the functional corpus luteum. Pregnancy diagnoses were performed twice, from Day 30 to 70, by ultrasound scanning. BIFN-τ content of culture media was measured by RIA (Takahashi et al. 2005 Theriogenology 63, 1050–1060). Data were analyzed by chi-square test and Fisher&apos;s exact test. The pregnancy rate in the IVP-TVs group (20.0%, 5/25) had a tendency to be lower than in the vivo-TVs (46.2%, 6/13), although this did not reach statistical significance (P = 0.09). These pregnant animals were transferred TVs from passaged 48th-52nd (5/19). In the control group 33.3% (9/27) of recipients conceived. Twin pregnancy rate was also lower in the IVP-TVs (0/5) than in the other two groups (3/6 and 5/9, P = 0.09 and P = 0.04, respectively). Fetal losses occurred only in the single pregnancies of IVP-TVs (60.0%, 3/5) and vivo-TVs (16.7%, 1/6) up until Day 70. Reproductive efficiency, based on numbers of delivered offspring, was significantly lower in the IVP-TVs (8%, 2/25) compared with the vivo-TVs (61.5%, 8/13) and control (51.9%, 14/27) groups, respectively (P &lt; 0.01). BIFN-τ levels secreted from the TVs derived from passages 46th and 48th were 0.157 ng/mL-1 and 0.113 ng/mL-1, respectively. In conclusion, compared with the in vivo TVs, those from serially passaged trophoblast cells had a negative effect on pregnancy, although the morphology of the two differently derived TVs was similar.


2010 ◽  
Vol 22 (1) ◽  
pp. 217
Author(s):  
H. Stinshoff ◽  
K. Brüning ◽  
A. Hanstedt ◽  
D. Müller ◽  
S. Wilkening ◽  
...  

In vitro production (IVP) of bovine embryos has been greatly improved over the last couple of years. However, only one-third of the total number of embryos transferred worldwide are of in vitro origin. The IVP embryos still show remarkable differences compared with their in vivo-derived counterparts (i.e. bovine embryos produced in vitro are more sensitive to cryopreservation). So far, vitrification seems to be the most promising method to cryopreserve in vitro-produced bovine embryos. The aim of this study was to determine the effect of 2 different cryopreservation methods on the quality of in vitro-produced bovine embryos at the molecular level using a sensitive RT-qPCR assay. Bovine blastocysts were produced using abattoir ovaries and a standard protocol for IVP (Wrenzycki et al. 2001). They were randomly vitrified employing PBS plus ethylene glycol and DMSO or cryopreserved using a programmable freezer and 1.5 M ethylene glycol. After thawing, embryos from both groups were cultured for 48 h. After 24 h of culture re-expansion rates were documented, and after 48 h hatching rates were documented. After hatching, blastocysts were stored at -80°C for subsequent RT-qPCR analysis. The following gene transcripts known to play important roles during preimplantation development were analyzed: HSP70, GLUT-1, GLUT-3, E-CAD, ZO-1, DNMT3a, IFNτ, DCII. Re-expansion rates were 74.7% (68/91) and 75.0% (87/116) for vitrified and conventionally cryopreserved blastocysts, and 57.1% (52/91) and 55.2% (64/116) of re-expanded embryos hatched. The relative abundances of HSP70, GLUT-1, and ZO-1 transcripts were significantly affected in both groups of cryopreservation compared with the control group (hatched blastocysts without cryopreservation). Conventional cryopreservation had a significant effect on the amount of GLUT-3, DNMT3a, and IFNτ mRNA, whereas vitrification significantly affected DCII transcripts. E-CAD mRNA expression was similar in all groups of embryos. These results suggest that not only the cryopreservation process itself but also the method used to freeze the embryos had a significant influence on the mRNA expression of developmentally important genes in hatched bovine blastocysts. The support of the H.W. Schaumann Stiftung (Germany) and Gynemed Medizinprodukte GmbH & Co. KG (Germany) is gratefully acknowledged.


1997 ◽  
Vol 272 (2) ◽  
pp. H613-H617
Author(s):  
T. Meurice ◽  
C. Bauters ◽  
B. Vallet ◽  
D. Corseaux ◽  
E. van Belle ◽  
...  

In animal models, a hypercholesterolemic diet induces areas of deendothelialization and impairs endothelium-dependent vasorelaxation. Angiogenic growth factors increase endothelial cell growth in vivo. This study was thus designed to test the hypothesis that chronic administration of basic fibroblast growth factor (bFGF) in hypercholesterolemic rabbits might restore normal physiological responses to endothelium-dependent agonists. After feeding on a 2% cholesterol diet for 6 wk, 14 New Zealand White rabbits received twice-weekly intravenous boluses of either 2.5 microg bFGF (hypercholesterolemic bFGF group, n = 6) or placebo (hypercholesterolemic control group, n = 8) for 3 wk and were killed for assessment of in vitro vasoreactivity and for histological analysis. Six animals fed with standard rabbit diet were used to assess normal responses. Endothelium-dependent responses to acetylcholine and to the calcium ionophore A-23187 were reduced in the hypercholesterolemic control group compared with normal rabbits. Hypercholesterolemic animals treated with bFGF had significantly better endothelium-dependent responses than hypercholesterolemic rabbits not treated with bFGF. Endothelium-independent responses did not differ significantly among the three groups. A similar degree of plaque formation was observed in control- and bFGF-treated hypercholesterolemic rabbits. These results show that, in this model of atherosclerosis, bFGF has a highly beneficial effect on the functional responses of atherosclerotic vessels and does not have a deleterious effect on the degree of plaque formation.


2002 ◽  
Vol 227 (11) ◽  
pp. 1031-1038 ◽  
Author(s):  
Roseli Golfetti ◽  
Knox VanDyke ◽  
Tyler Rork ◽  
Norell Spiler ◽  
Gary Merrill

Acetaminophen was administered acutely at the onset of reperfusion after 20 min of low-flow, global myocardial ischemia in isolated, perfused guinea pig hearts (Langendorff) to evaluate its influence in the postischemia, reperfused myocardium. Similarly prepared hearts were treated with vehicle or with uric acid (another phenol for comparison). Functionally, acetaminophen-treated hearts (0.35 mM) achieved significantly greater recovery during reperfusion. For example, left ventricular developed pressures at 40 min reperfusion were 38 ± 3, 27 ± 3, and 20 ± 2 in the presence of acetaminophen (P < 0.05, relative to the other two groups), vehicle, and uric acid, respectively. Coronary perfusion pressures and calculated coronary vascular resistances, in the acetaminophen-treated hearts, were significantly lower at the same time (e.g., coronary perfusion pressures in the three groups, respectively, were 40 ± 2 [P < 0.05], 51 ± 3, and 65 ± 12 mm Hg). Under baseline, control conditions, creatine kinase ranged from 12–15 units/liter in the three groups. It increased to 35–40 units/liter (P < 0.05) during ischemia but was significantly reduced by acetaminophen during reperfusion (e.g., 5.3 ± 0.8 units/liter at 40 min). Oxidant-mediated chemiluminescence in all three treatment groups during baseline conditions and ischemia was similar (i.e., approximately 1.5–2.0 min for peak luminescence to reach its half maximal value). It took significantly more time during reperfusion for the oxidation of luminol in the presence of acetaminophen (>20 min, P < 0.05) than in its absence (3–8 min in uric acid- and vehicle-treated hearts). These results suggest that administration of acetaminophen (0.35 mM), at the onset of reperfusion, provides anti-oxidant–mediated cardioprotection in the postischemia, reperfused myocardium.


2017 ◽  
Vol 29 (1) ◽  
pp. 187 ◽  
Author(s):  
C. E. Méndez-Calderón ◽  
C. R. Lazzarotto ◽  
L. H. Aguiar ◽  
F. L. Ongaratto ◽  
K. C. S. Tavares ◽  
...  

Oocyte competence plays a key role in the overall efficiency of reproductive biotechnologies. In cattle, FSH starvation following superovulation (coasting) improves oocyte competence, blastocyst yield and pregnancy outcome when used in ovum pickup-in vitro production programs. The aim of this study was to compare the effect of coasting after exogenous FSH stimulation on goat oocyte quality and competence to support in vitro maturation and in vivo embryo development following cloning procedures in goats. Donor and recipient preparation, cumulus-oocyte complex (COC) retrieval and selection, IVM, cloning by somatic cell nuclear transfer, embryo transfer, and pregnancy diagnosis (Days 23–26) were performed according to our established procedures [Martins et al. 2016 doi: 10.1089/cell.2015.0082]. Cumulus-oocyte complexes were obtained in vivo from 71 cycling FSH-stimulated mature Nubian-crossed goats, combined or not with FSH starvation (coasting period). Donor females were oestrous synchronized with a progesterone intravaginal insert (Day 0). On Day 10, a 0.75-mg D-cloprostenol dose was given IM, with the onset of the superovulation treatment, composed of five 20-mg FSH doses (Folltropin®, Bioniche Animal Health, Pullman, WA, USA), via IM at 12-h intervals. Donors were subjected to laparoscopic ovum pickup either 9 h (control group, n = 36) or 21 h (coasting group, n = 35) after the last FSH dose, respectively. Skin fibroblast cell cultures from a male neonate were co-transfected with a mammary gland expression vector with the human lactoferrin (hLF) coding sequence and with CRISPR/Cas9 system either for the PRNP prion gene or the Rosa26 locus. A bi-allelic hLF-PRNP and a mono-allelic hLF-Rosa26 cell colony were used for cloning. Data were compared by ANOVA or the χ2 test (P < 0.05). No differences were observed between control and coasting for number of follicles (18.7 ± 1.4 v. 21.2 ± 1.7), and retrieved (17.3 ± 1.2 v. 20.7 ± 1.9), viable (15.9 ± 1.1 v. 19.6 ± 1.8), Grade I (1.5 ± 0.3 v. 2.5 ± 0.5), and Grades III+IV (6.0 ± 0.6 v. 5.7 ± 0.7) COC, as well as for COC retrieval (92.4%, 574/621 v. 94.5%, 685/725) and fusion (62.8%, 273/435 v. 61.3%, 311/507) rates, respectively, irrespective of the cell lines. However, the coasting group rendered higher number of Grade II COC (11.3 ± 1.2 v. 8.4 ± 0.7), number and proportion of Grades I+II COC (13.9 ± 1.5 v. 9.9 ± 0.9, 70.8% v. 62.4%), and maturation rate (70.9% v. 65.4%) than the control group, respectively, for a lower proportion of Grades III+IV (29.2% v. 37.6%, respectively). A total of 213 and 233 Day-1 cloned embryos from the control and the coasting groups were transferred to 18 (96/9 hLF-PRNP and 117/9 hLF-Rosa26 cells) and 19 (128/11 hLF-PRNP and 105/8 hLF-Rosa26 cells) female recipients, respectively, resulting in 1/9 (11.1%) and 4/11 (36.4%) pregnancies from the hLF-PRNP cells, and 3/9 (33.3%) and 3/8 (37.5%) from the hLF-Rosa26 cells, for the control (4/18, 22.2%) and coasting (7/19, 36.8%) groups, respectively, for an overall pregnancy rate of 29.7% (11/37). In conclusion, the use of coasting improved oocyte quality and in vitro maturation rate, also appearing to increase pregnancy outcome after goat cloning.


1997 ◽  
Vol 36 (08) ◽  
pp. 259-264
Author(s):  
N. Topuzović

Summary Aim: The purpose of this study was to investigate the changes in blood activity during rest, exercise and recovery, and to assess its influence on left ventricular (LV) volume determination using the count-based method requiring blood sampling. Methods: Forty-four patients underwent rest-stress radionuclide ventriculography; Tc-99m-human serum albumin was used in 13 patients (Group I), red blood cells was labeled using Tc-99m in 17 patients (Group II) in vivo, and in 14 patients (Group III) by modified in vivo/in vitro method. LV volumes were determined by a count-based method using corrected count rate in blood samples obtained during rest, peak exercise and after recovery. Results: In group I at stress, the blood activity decreased by 12.6 ± 5.4%, p <0.05, as compared to the rest level, and increased by 25.1 ± 6.4%, p <0.001, and 12.8 ± 4.5%, p <0.05, above the resting level in group II and III, respectively. This had profound effects on LV volume determinations if only one rest blood aliquot was used: during exercise, the LV volumes significantly decreased by 22.1 ± 9.6%, p <0.05, in group I, whereas in groups II and III it was significantly overestimated by 32.1 ± 10.3%, p <0.001, and 10.7 ± 6.4%, p <0.05, respectively. The changes in blood activity between stress and recovery were not significantly different for any of the groups. Conclusion: The use of only a single blood sample as volume aliquot at rest in rest-stress studies leads to erroneous estimation of cardiac volumes due to significant changes in blood radioactivity during exercise and recovery.


1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.


2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.


2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.


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