Heart Tissue Concentrations Research Articles

The systematic investigation of the role of adulterants into the postmortem redistribution of heroin

We aimed to investigate systematically the impact of adulterants on postmortem in vivo pharmacokinetic of heroin and its metabolites by determining the postmortem redistribution (PMR) of heroin in this study. Heroin (1 mg/kg) was administered intravenously to the rats. The rats were euthanized 1 hour after drug administrations, followed by placed in the supine position at room temperature. Femoral (right and left), subclavian, cardiac blood samples and liver, lung, kidney, myocardium and brain samples were collected at the time of death, postmortem 1st, 4th and 24th hour. Heroin (1 mg/kg) containing adulterants (1 mg/kg paracetamol, dextromethorphan and caffeine) was administered intravenously to the same number of rat groups, and the same procedures were repeated. All blood and organ tissue samples were analysed with validated liquid-liquid extraction methods using a liquid chromatography tandem-mass spectrometer. The changes in the levels of heroin metabolites during the postmortem interval were determined in different blood and tissue samples included in our study. Accordingly, apart from the minimal statistical differences in morphine concentrations in the left femoral blood, significant differences in each matrix throughout the postmortem interval, especially in heart blood, lung and kidney tissue were observed. In contrast to morphine, there are minimal differences in morphine-3-glucurinide concentrations in heart tissue and other matrices. Graphical differences were observed between morphine concentrations in heart blood, liver, myocardium and lung of animal groups in the presence of adulterants and animal groups in which heroin was administered alone. The findings obtained in this study may play an important role in elucidating heroin-related death cases by forensic toxicologists or pathologists.

Tragus Nerve Stimulation Suppresses Post-Infarction Ventricular Arrhythmia by Modulating Autonomic Activity and Heterogeneities of Cardiac Receptor Distribution.

BackgroundImbalanced cardiac autonomic control and cardiac receptors redistribution contribute to the arrhythmogenic substrate under the myocardial infarction (MI) condition. Stimulating the auricular branch of vagus nerve (AB-VNS) has been proven to reduce post-infarction ventricular arrhythmia (VAs), but its potential mechanisms were largely unknown.This study aimed to investigate whether long-term intermittent low-intensity AB-VNS could produce a protective effect on modulating autonomic activities and abnormal redistribution of autonomic nerve efferent receptors in a MI canine model.Material/MethodsTwelve healthy beagle dogs underwent ligation of the left anterior descending coronary artery to establish a MI model and were randomized into 2 groups: an AB-VNS group, (AB-VNS for 4 weeks) and a control group (sham stimulation for 4 weeks). Dynamic electrocardiogram recording, neural recording, catecholamine concentration, and histological studies were conducted subsequently.ResultsCompared to the control group, the AB-VNS group had significantly suppressed post-infarction VAs, reduced low frequency (LF) power and increased high frequency (HF) power. In the AB-VNS group, with the progression of reduced cardiac sympathetic activities and augmented cardiac parasympathetic activities, the catecholamine concentration in heart tissue declined in the peripheral infarction area and right ventricle (RV); tyrosine hydroxylase (TH)-positive neurons decreased in the inferior cardiac sympathetic nerve, and choline acetyltransferase (ChAT)-positive neurons increased in the cervical vagus nerve. Expression of TrkA and P75NGFR were reduced in the peripheral MI (peri-MI) and non-MI area with AB-VNS. The mRNA expression of adrenergic and nicotinic receptors (β1-AR, β3-AR, and CHRNA7) significantly declined in the peri-MI and non-MI area of the AB-VNS group.ConclusionsChronic intermittent low-intensity AB-VNS effectively suppressed post-infarction VAs by potentially rebalancing extracardiac intrathoracic autonomic activities, reducing excessive cardiac sympathetic denervation, and attenuating the heterogeneities of cardiac efferent nerve receptors distribution.

CardiacPBPK: A tool for the prediction and visualization of time-concentration profiles of drugs in heart tissue

Background and objectivePrediction of drug concentration in heart tissue is important in terms of drug safety and efficacy. This work presents the Open-Source CardiacPBPK platform for the prediction of the time-concentration profile of drugs, which could potentially reduce the risk of drug development failure due to cardiotoxicity. The objective of the CardiacPBPK development is to accelerate and simplify the in-silico toxicological assessment of new drugs, and to provide supportive material for the research community to use. MethodsThe CardiacPBPK software provides a modular implementation of the PBPK model of heart tissue. It can be easily accessed via the Internet or installed locally. The graphical user interface and tabular design are easy to configure and use. ResultsCardiacPBPK is a tool designed to predict and visualize the time-concentration profiles of a parent compound, and one metabolite, in venous plasma and heart tissue after oral or intravenous drug administration. CardiacPBPK is built on the R-environment framework and supports shiny application features such as interactive visualization of the results, and web applications interface by default. A shiny application refers to a computer program created with the use of shiny package in R. The application is freely available at https://github.com/jszlek/CardiacPBPK and https://sourceforge.net/projects/cardiacpbpk/. This open-source application runs on all platforms supporting R-environment (Linux, Windows, Mac OS X, Solaris). ConclusionsWe demonstrate the application of CardiacPBPK by simulating the study of amitriptyline intoxication in the case of CYP2D6 genetic polymorphism.

Utilizing postmortem drug concentrations in mechanistic modeling and simulation of cardiac effects: a proof of concept study with methadone

Methadone-related poisoning has been found to be the leading and increasing cause of death among intoxication cases in several countries. Aside from respiratory depression, methadone is known to cause QT-prolongation, which may lead to sudden cardiac death. Concentrations in heart tissue should be more accurate for estimating cardiotoxic effects. The aim of this study was to investigate whether the effect of methadone on the QT-interval could be simulated and whether the concentrations in heart tissues allowed for better prediction of the Bazett corrected QT-interval (QTcB). A predictive performance study was conducted using the simulation platform Cardiac Safety Simulator to mimic five literature studies using their described study conditions. Both free and total plasma and heart concentrations were investigated using two different in silico models: the O’Hara-Rudy (ORD) model and the 10 Tusscher (TNNP) model. The results showed that the QTcB of methadone was best predicted either with total plasma using the TNNP model or with free plasma using the ORD model. The ORD model was highly sensitive to the total heart concentrations, resulting in overprediction of the QTcB. The TNNP model also overpredicted the QTcB, but to a lesser degree than the ORD model. Furthermore, due to a low baseline QTcB, the ORD model underpredicted the QTcB for both the free plasma and free heart concentrations. In conclusion, it is possible to simulate the cardiac effects of methadone, yet several elements influence the approach uncertainty including but not limited to biophysically details model of cardiac electrophysiology, exposure data, and input parameters.

Effects of increased myocardial tissue concentration of myristic, palmitic and palmitoleic acids on the course of cardiac atrophy of the failing heart unloaded by heterotopic transplantation.

The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HT(x)) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HT(x) was determined on days 7, 14, 21 and 28 after HT(x) in recipients of either healthy or failing hearts. HT(x) of healthy hearts resulted in 23+/-3, 46+/-3, 48+/-4 and 46+/-4 % HW loss at the four time-points. HT(x) of the failing heart resulted in even greater HW losses, of 46+/-4, 58+/-3, 66+/-2 and 68+/-4 %, respectively (P<0.05). Activation of "fetal gene cardiac program" (e.g. beta myosin heavy chain gene expression) and "genes reflecting cardiac remodeling" (e.g. atrial natriuretic peptide gene expression) after HT(x) was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HT(x) failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.

Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats

BackgroundObesity is associated with numerous metabolic and inflammatory disorders. The current study was aimed to evaluate the effects of vitamin D administration on the markers of oxidative stress and inflammation in the cardiac tissue of high-fat diet induced obese rats.MethodsIn the beginning of the study, 40 male Wistar rats were divided into two groups: normal diet (ND) and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: ND, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α concentration and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) concentrations in the cardiac tissue and serum concentrations of lipids in rats were determined using ELISA kits and spectrophotometry methods respectively.ResultsAccording to our results, GPx activity in ND and ND + vitamin D group was significantly higher compared with HFD group. Similarly, SOD activity was also significantly increased in ND + vitamin D group compared with ND and HFD groups. Moreover, vitamin D administration, significantly reduced catalase activity in ND + vitamin D and HFD + vitamin D groups (P < 0.05). TNF-α concentration in heart tissue in ND + vitamin D group significantly reduced compared with ND group. Cardiac tissue MDA concentration in baseline or after vitamin D administration did not changed significantly.ConclusionVitamin D improved cardiac oxidative stress and inflammatory markers in HFD induced obese rats. Further studies in human models are needed to further confirm the use of this nutrient in daily clinical practice.

A four-compartment PBPK heart model accounting for cardiac metabolism - model development and application

In the field of cardiac drug efficacy and safety assessment, information on drug concentration in heart tissue is desirable. Because measuring drug concentrations in human cardiac tissue is challenging in healthy volunteers, mathematical models are used to cope with such limitations. With a goal of predicting drug concentration in cardiac tissue, we have developed a whole-body PBPK model consisting of seventeen perfusion-limited compartments. The proposed PBPK heart model consisted of four compartments: the epicardium, midmyocardium, endocardium, and pericardial fluid, and accounted for cardiac metabolism using CYP450. The model was written in R. The plasma:tissues partition coefficients (Kp) were calculated in Simcyp Simulator. The model was fitted to the concentrations of amitriptyline in plasma and the heart. The estimated parameters were as follows: 0.80 for the absorption rate [h−1], 52.6 for Kprest, 0.01 for the blood flow through the pericardial fluid [L/h], and 0.78 for the P-parameter describing the diffusion between the pericardial fluid and epicardium [L/h]. The total cardiac clearance of amitriptyline was calculated as 0.316 L/h. Although the model needs further improvement, the results support its feasibility, and it is a first attempt to provide an active drug concentration in various locations within heart tissue using a PBPK approach.

Abstract 11804: GsMTx4-D is a Cardioprotectant Against Myocardial Infarction During Ischemia and Reperfusion

Introduction: GsMTx4 is a selective inhibitor of cationic mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. Inhomogeneous local mechanical stresses due to hypercontracture and swelling, likely induce elevated MSC activity that can contribute to the cation imbalance observed during ischemic reperfusion injury. This study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant during ischemia and reperfusion and to evaluate its effects on cation influx and inflammatory kinases that are regulated by this influx. Hypothesis: GsMTx4 protects heart from ischemic insults through inhibiting the cationic mechanosensitive ion channels. Methods: Ischemia and reperfusion in the mouse heart involved ligating a coronary artery followed by release of the ligature. Results: GsMTx4-D was administered by acute intravenous injection during the ischemic event. Based on pharmacokinetic studies, GsMTx4-D dosage was set to achieve expected plasma concentrations between 50-5000 nM and heart tissue concentrations between 1-200 nM. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by ~40% for acute and pretreated animals, and for both 20 and 45 min ischemic challenges. Many indicators of cardiac output were indistinguishable from sham-treated control hearts after GsMTx4-D treatment and most showed improvement at both 4 and 48 hrs post ischemia. Premature ventricular beats immediately following reperfusion were also significantly reduced by intravenous injections of GsMTx4-D. Myocytes cultured under hypoxic conditions treated with 10 μM GsMTx4-D showed improved contractility and near normal contraction-related Ca 2+ influx. GsMTx4-D inhibited indicators of ischemic damage such as the apoptotic signaling system JNK/c-Jun, but also inhibited the energy response signaling system Akt kinase. Conclusions: GsMTx4-D is a potent cardioprotectant that decreases infarct area, increases cardiac output and decreases arrhythmias that are caused by ischemia and reperfusion. GsMTx4-D improved cardiomyocyte function and suppresses apoptosis, making it potentially useful in multidrug strategies to treat ischemic heart disease.

Abstract P633: Resistance Training Counteracts The Systemic Catecholaminergic Hyperactivation Associated With Experimental Diabetes, But Not Normalize Cardiac Sympathetic Outflow

Previous studies from our laboratory have demonstrated that chronic diabetes in rats results in cardiomyopathy, associated with sympathetic nervous system (SNS) hyperactivity. On the other hand, it is well known that the beneficial cardiovascular effects of exercise training in diabetes are due in part to normalization of the sympathetic outflow and improvement in the responsiveness of the myocardium to autonomic stimulation. Recently, resistance training (RT) has been recognized as a useful therapeutic tool for the treatment of chronic diseases and similar to aerobic exercise, has been reported to improve metabolic profile and body composition. Therefore, the aim of this study was to evaluate the effect of moderate-intensity RT on circulating and cardiac catecholamines concentration, to understand whether this type of exercise is also associated with cardiovascular protection. Wistar rats (3 months old) were randomized into: control (C), diabetic (D), diabetic + RPT (DR) and diabetic + APT (DA). Animals were made diabetic with a single tail injection of streptozotocin (STZ, 50 mg/Kg). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load, and moderate aerobic training was performed on a treadmill (5 days/week, 8 weeks). Diabetes significantly increased plasma concentration of adrenaline (D: 5.3 ± 1.0 vs. C: 4.1 ± 0.6 ng/mL) and noradrenaline (D: 14.5 ± 0.2 vs. C: 3.1± 0.8 ng/mL), and both exercise modalities induced a significant reduction of them: adrenaline (DR: 1.1 ± 0.3; DA: 0.7 ± 0.16 vs. D: 5.3 ± 1.0 ng/mL) and noradrenaline (DR: 1.0 ± 0.2; DA: 0.7 ± 0.1 vs. D: 14.5 ± 0.2 ng/mL). Cardiac concentration of noradrenaline was also increased in diabetic group (D: 62 ± 7 vs. CS: 34 ± 6 pg/g) and only aerobic exercise was capable to reduce its concentration in heart tissue (DA: 30 ± 6 vs. D: 62 ± 7; DR: 55 ± 7 pg/g). The results from the present study show for the first time additional beneficial effects of RT on modulating SNS activity in diabetes. Moreover, considering that RT does not modulate cardiac catecholaminergic secretion, it also highlights the importance of aerobic training in diabetes treatment. Financial Support: FAPESP, CAPES, CNPq

GsMTx4-D is a cardioprotectant against myocardial infarction during ischemia and reperfusion

GsMTx4 is a selective inhibitor of cationic mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. Inhomogeneous local mechanical stresses due to hypercontracture and swelling during ischemic reperfusion injury (IRI) likely induce elevated MSC activity that can contribute to cation imbalance. The aim of this study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant in a mouse IRI model. Ischemia and reperfusion involved ligating a coronary artery followed by release of the ligature. GsMTx4-D was tested by either acute intravenous injection during the ischemic event or by two day pretreatment by intraperitoneal injection, both methods achieving similar results. Based on pharmacokinetic studies, GsMTx4-D dosage was set to achieve expected plasma concentrations between 50 and 5000nM and heart tissue concentrations between 1 and 200nM by intravenous injection. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by ~40% for acute and pretreated animals for both 20 and 45min ischemic challenges. Many indicators of cardiac output were indistinguishable from sham-treated control hearts after GsMTx4-D treatment showing improvement at both 4 and 48h post ischemia, and premature ventricular beats immediately following reperfusion were also significantly reduced. To determine if GsMTx4-D cardioprotection could act directly at the level of cardiomyocytes, we tested its effects in vitro on indicators of IRI damage like cation influx and activation of inflammatory kinases in isolated myocytes cultured under hypoxic conditions. Hypoxia challenged cardiomyocytes treated with 10μM GsMTx4-D showed improved contractility and near normal contraction-related Ca2+ influx. GsMTx4-D inhibited indicators of ischemic damage such as the apoptotic signaling system JNK/c-Jun, but also inhibited the energy response signaling system Akt kinase. We conclude that GsMTx4-D is a potent cardioprotectant in vivo that may act directly on cardiomyocytes and potentially be useful in multidrug strategies to treat IRI.

Differences in tissue distribution of iron from various clinically used intravenous iron complexes in fetal avian heart and liver.

Nanomedicines are more complex than most pharmacologically active substances or medicines and have been considered as non-biological complex drugs. For nanomedicines pivotal pharmacokinetic properties cannot be assessed by plasma concentration data from standard bioequivalence studies. Using intravenous iron complexes (IICs) as model we show that fetal avian tissues can be used to study time dependent tissue concentrations in heart and liver. Clear differences were found between equimolar doses of sucrose, gluconate or carboxymaltose coated iron particles. The range in tissue iron concentrations observed with these clinically widely used IICs provides an orientation as to what should be acceptable for any new IICs. Moreover, sensitivity of the experimental model was high enough to detect a 20% difference in tissue iron concentration. For the authorization of generic products under Article 10 (1) of Directive 2001/83/EC a plasma concentration of an active substance in the range of 80%–125% versus the reference product is usually considered acceptable. Based on its high discriminatory sensitivity this method was used to support a positive marketing authorization decision for a generic nanomedicine product.

Biocompatible Microemulsion Modifies the Tissue Distribution of Doxorubicin

The incorporation of doxorubicin (DOX) in a microemulsion (DOX-ME) has shown beneficial consequences by reducing the cardiotoxic effects of DOX. The aim of this study was to determine the distribution of DOX-ME in Ehrlich solid tumor (EST) and the heart, and compare it with that of free DOX. The distribution study was conducted with female Swiss mice with EST (n = 7 per group; 20-25 g). Animals received a single dose (10 mg/kg, i.p.) of DOX or DOX-ME 7 days after tumor inoculation. Fifteen minutes after administration, the animals were sacrificed, and the tumor and heart tissues were taken for immediate analysis by ultra-performance liquid chromatography. No difference was observed in DOX concentration in tumor tissue between DOX and DOX-ME administration. However, the most remarkable result in this study was the statistically significant reduction in DOX concentration in heart tissue of animals given DOX-ME. Mean DOX concentration in heart tissue was 0.92 ± 0.54 ng mg(-1) for DOX-ME and 1.85 ± 0.34 ng mg(-1) for free DOX. In conclusion, DOX-ME provides a better tissue distribution profile, with a lower drug concentration in heart tissue but still comparable tumor drug concentration, which indicates that antitumor activity would not be compromised.

Oxidative parameters and expression of 70kDa heat shock proteins in pig heart tissue after transport and slaughter.

In view of the significant role of Hsp70 in protecting the organism against the destructive effects of stress, and the possibility of using this protein as a marker of the infarction process in the heart, the aim of this study was to conduct an evaluation of the expression of 70kDa heat shock proteins (Hsp70) and the concentration of TBARS (thiobarbituric acid reactive substances) and nitric oxide ions (NO), determined as nitrite ions, as markers of oxidative stress in hearts obtained from healthy pigs following slaughter and pigs which had died during or immediately after transport with symptoms of sudden cardiac death. The material consisted of hearts obtained from 90 pigs following slaughter and from pigs which had died. Oxidative stress was determined in heart lysates based on the concentration of TBARS and nitrite ions. Expression and concentration of Hsp70 were determined using SDS-PAGE, Western blotting, and ELISA. Expression of Hsp70 was observed in hearts lysates obtained from slaughtered pigs and from those which had died with symptoms of sudden death. The strongest reaction in the Western Blotting was noted in hearts lysates from pigs with no pathological changes. The highest TBARS concentration was observed in lysates from hearts in pigs which had died during or immediately after transport. The highest concentration of NO ions, determined as nitrite ions, was noted in hearts from pigs with myocardial infarction lesions. The significant decrease observed in Hsp70 concentration in heart tissue obtained from the pigs which had died in comparison to the hearts from healthy pigs indicates the important role of this protein in protecting the heart muscle against the destructive effects of stress, which limits the occurrence of post-stress cardiomyopathy in pigs following transport.

Vitamin D3 (Cholecalciferol) Boosts Hydrogen Sulfide Tissue Concentrations in Heart and other Mouse Organs

Vitamin D3 is a crucial co-regulator of bone growth and remodeling, neuromuscular function, inflammation, proliferation, differentiation and apoptosis of cells. Intensive research on endogenous sulfur metabolism has revealed that hydrogen sulfide (H2S) is an important modulator of various physiological processes in mammals. Noteworthy, these compounds are perceived as potential agents in the treatment of numerous disorders, including cardiovascular diseases and different types of cancer. The interaction between vitamin D3 and H2S is unknown. The aim of the study is to assess the influence of cholecalciferol (vitamin D3, calcitriol) on H2S tissue concentrations in mouse brain, heart and kidney. Twenty four SJL mice were given intraperitoneal injections of cholecalciferol at 10000 IU/kg body weight (b.w.) per day (group A, n = 8) or 40000 IU/kg b.w. per day (group B, n = 8). The control group (n = 8) received physiological saline. Free H2S tissue concentrations were measured via the SIEGEL spectrophotometric modified method. There was a significant progressive increase in the H2S concentration along with the rising cholecalciferol doses as compared to the control group in the heart (by 29.6% and by 74.1%, respectively). Higher vitamin D3 dose caused H2S accumulation in the brain (by 10.9%) and in the kidney (by 10.1%). Our study has proven that cholecalciferol affects H2S tissue concentration in different mouse organs.

05 The cardioprotective effect of mildronate is associated with decreased CPT I-dependent fatty acid metabolism in mitochondria

Mildronate is a cardioprotective agent whose mechanism of action is based on decrease in L-carnitine concentration in heart tissue and concomitant decrease in fatty acid metabolism. The present study was...

Effects of ethanolic extract from Radix Scrophulariae on ventricular remodeling in rats

PurposeTo explore the effects of ethanolic extract of Radix Scrophulariae (EERS) on ventricular remodeling in rats. MethodsRats with coronary artery ligation (CAL) were randomly assigned to 5 groups: CAL model; CAL plus 40mg/kg captopril; CAL plus 60mg/kg, 120mg/kg, 240mg/kg EERS. Sham operation rats were randomly assigned to 2 groups, sham-operated control and sham-operated plus 120mg/kg EERS. The rats were orally administered with the corresponding drugs or drinking water for 14weeks. The left ventricular weight index (LVWI) and heart weight index (HWI) were determined. Myocardium tissue was stained with hematoxylin and eosin or picric acid/Sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), angiotensin II (Ang II), aldosterone (ALD), endothelin 1 (ET-1), atrial natriuretic peptide (ANP), tumor necrosis factor α (TNF-α) and renin activity (RA) in myocardium or serum were determined. Real-time RT-PCR was used to detect the mRNA expressions of angiotensin converting enzyme (ACE), ET-1 and ANP. ResultsEERS could significantly reduce the LVWI and HWI, decrease heart tissue concentrations of Hyp and collagen deposition, diminish cardiomyocyte cross-section area, reduce the tissue level of Ang II, ET-1, ANP and TNF-α. EERS could also down regulate the mRNA expression of ACE, ET-1 and ANP in myocardium. ConclusionEERS attenuates ventricular remodeling. The mechanisms may be related to restraining the excessive activation of RAAS, TNF-α and modulating some gene expressions associated with cardiac hypertrophy.

Determination of Uranium Concentration in Sheep Organs for Some Iraqiۥs Cities

The aim of this research is to determine the uranium concentration and its distribution in many sheep organs that live in different region of Iraq. The uranium concentration in tissue samples is measured by using fission tracks registration in CR-39 detector that caused by the bombardment of U235 with thermal neutrons from (241Am-Be) neutron source of thermal flux (5x 103 n.cm-2. s-1). The results show that the maximum uranium concentration in bronchiole tissues of the animals was found in Karbala city (3.706ppm) while the minimum concentration (0.127 ppm) was found in Al-Faluja city, also the same result in lung tissue the maximum value was found in Karbala city (2.313ppm) and the minimum concentration in Al Fluja (0.082). Otherwise, the maximum concentration in liver tissue was found in AdDiwaniyah city (1.156ppm) while the minimum concentration in Al Fluja city (0.153ppm). The uranium concentrations in heart tissues were found various than the previous results. The results of average uranium concentration in each animal were ranged from 0.149 to 1.675 ppm, the maximum values were found in the cities in south region of Iraq.

Determination of Uranium Concentration in Sheep Organs for Some Iraqi&amp;#1765;s Cities

The aim of this research is to determine the uranium concentration and its distribution in many sheep organs that live in different region of Iraq. The uranium concentration in tissue samples is measured by using fission tracks registration in CR-39 detector that caused by the bombardment of U235 with thermal neutrons from (241Am-Be) neutron source of thermal flux (5x 103 n.cm-2. s-1). The results show that the maximum uranium concentration in bronchiole tissues of the animals was found in Karbala city (3.706ppm) while the minimum concentration (0.127 ppm) was found in Al-Faluja city, also the same result in lung tissue the maximum value was found in Karbala city (2.313ppm) and the minimum concentration in Al Fluja (0.082). Otherwise, the maximum concentration in liver tissue was found in AdDiwaniyah city (1.156ppm) while the minimum concentration in Al Fluja city (0.153ppm). The uranium concentrations in heart tissues were found various than the previous results. The results of average uranium concentration in each animal were ranged from 0.149 to 1.675 ppm, the maximum values were found in the cities in south region of Iraq.

Effects of Indian herbal formulation Body Revival on human platelet aggregation and myocardial ischemia in rats

To study the effect of Body Revival (BR), a compound traditional Indian herbal medicine, on human platelet aggregation and isoproterenol (IS)-induced myocardial ischemia (MI) damage in male Wistar rats. BR suspension 10, 20 and 30 μg was mixed with platelet-rich plasma and incubated at 37 degrees centigrade for 30 min, respectively. Then, adenosine diphosphate (ADP, 20 mmol/L) or collagen (2 μg) was added in the mixture and the aggregation was observed against platelet-poor plasma mixed with equal volume of suspension of the same test samples. Wistar rats divided into 4 groups were used to investigate BR's effects on IS-induced MI. Levels of serum creatinine kinase (CK), aspartate transaminase (AST) and alanine transaminase (ALT) were estimated by standard commercial biological kits. Serum nitric oxide (NOx) was also measured. The lipid peroxides (LPO) and protein concentrations in heart tissues were measured. BR could inhibit ADP- or collagen-induced human platelet aggregation dose-dependently. Moreover, it could protect MI caused by IS in rats. BR reduced the levels of serum CK, AST, ALT and NOx dose-dependently and also lowered LPO in heart tissues in comparison with the MI control (P<0.01). BR can inhibit human platelet aggregation and protect MI caused by IS in rats.

Therapeutic effects of continuous infusion of brain natriuretic peptides on postmyocardial infarction ventricular remodelling in rats

Previous studies have shown protective effects of brain natriuretic peptide (BNP) against the postmyocardial infarction (MI) remodelling process. The transcription factor NF-κB is known to play an important role after MI. To investigate if NF-κB is involved in the protective effects of BNP against adverse post-MI remodelling. Rats were randomly assigned to five groups: sham-operation; MI by coronary ligation; MI treated with chronic BNP infusion; MI treated with enalapril; MI treated with BNP+enalapril. Rats were closely monitored for survival rate analysis. Rats from each group were sacrificed on days 3, 7 and 28 postoperation. The results showed that chronic continuous BNP infusion achieved similar effects to enalapril therapy, as evidenced by improved survival rate within the 28-day observation period compared with MI group rats; this effect was closely associated with preserved cardiac geometry and performance. The treatment combination did not offer extra benefits in terms of survival rate. Both BNP and enalapril therapy produced higher heart tissue concentrations of cyclic guanosine monophosphate and lower expression levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin-1 and interleukin-6. These benefits were associated with lower phosphorylation levels of NF-κB subunits IκBα, p50 and p65. While enalapril significantly inhibited extracellular matrix remodelling via regulation of the protein expression ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinase and the activity of matrix metalloproteinase, these variables were not affected by BNP, indicating that the two therapies involve different mechanisms. Chronic BNP infusion can provide beneficial effects against adverse post-MI remodelling.