This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status ...of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants (O.sup.-.sub.2, H.sub.2O.sub.2, NO.sup.-.sub.2, and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the crosssectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.
Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor-binding peptides such as
Y- and
Lu-DOTATOC. The objective of this work was to ...develop a biokinetics model of
Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor.
A multi-compartment model described by two sets of differential equations, one set for the actual 30-min infusion and the other set for the post-infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter-compartment transfer coefficients, λ
, were varied to yield the best fit of the calculated to the measured time-activity data and the
Y-DOTATOC time-activity data in the five-compartments comprising the human body were thus determined. The resulting time-activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self-dose
Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses.
Transfer coefficients λ
, were determined for five-compartments for all patients. Time- activity curves of
Y-DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73-2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05-42.31 mGy/MBq).
Analytical solution of a biokinetic model for
Y-DOTATOC therapy enabled determination of the transfer coefficients and derivation of time-activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.
Dosimetric studies in Nuclear Medicine are very important, especially with new therapeutic methods, the number of which has increased significantly with the Theranostic approach (determining ...diagnostic-therapeutic pairs where similar molecules are labelled with different isotopes in order to diagnose and treat malignant diseases). Peptide receptor radionuclide therapy (PRRT) has been used successfully for many years to treat neuroendocrine tumors (NET). 90Y-DOTATOC is one of the radiopharmaceuticals used frequently in this type of therapy.
In this work, blood and urine samples from 13 patients treated with 90Y-DOTATOC were measured by a liquid scintillation beta counter (LSC). Calibration of the beta counter for this type of measurement was done and all results are presented in the paper. The presented paper also provides a methodology for determining the measurement uncertainty for this type of measurement.
Immediately after the administration of radiopharmaceuticals, the activity in the blood was different from 6.31% to 88.9% of the applied radioactivity, while 3 h after the termination of the application, the average value of radiopharmaceuticals in the blood was only 3.84%. The activity in the excreted urine depended on the time when the patients urinated after the therapy. It was measured that as much as 58% of the applied radioactivity was excreted in the first urine after the therapy in a patient who urinated 4.5 h after the completed application of the therapy. In most patients, the highest urine activity was in the first 10 h after the application, while the activities after that time were negligibly low.
The described methodology of measuring and evaluating activity in blood and excreted urine can be applied to other radiopharmaceuticals used in nuclear medicine. It could be useful for researchers for dosimetric assessments in clinical application of PRRT.
: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal ...models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress.
: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days.
: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties.
: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.
The aim of this study was to evaluate alterations in depressive-like behaviors in rats following chronic administration of a supraphysiological dose of anabolic androgenic steroids (AASs) as well as ...exposure to a prolonged exercise protocol. The role of hippocampal sex hormones receptors in the modulation of depressive-like behavior was also assessed. A total of 48 male Wistar albino rats were divided into six groups: control, exercise (1 h/day, five consecutive days), nandrolone-decanoate (ND, 20 mg/kg/week, in a single dose), exercise plus ND, testosterone-enanthate (TE, 20 mg/kg/week, in a single dose), and exercise plus TE. After the 6-week protocols were complete, the rats underwent behavioral testing in the tail suspension test (TST). Rats were sacrificed for the collection of blood samples, to determine sex hormones levels, and isolation of the hippocampus, to determine androgen receptors (AR) and estrogen receptors α (ERα) expression. ND and TE treatment induced significant depressive-like behavior, opposing the antidepressant effect of exercise. Chronic TE administration elevated testosterone (T) and dihydrotestosterone (DHT) serum levels, and this was augmented by exercise. In contrast, ND and exercise alone did not alter T or DHT levels. There were no changes in serum estradiol levels in any of the groups. Immunohistochemical analysis showed that exercise reduced AR immunoreactivity in all hippocampal regions and increased the ERα expression in the CA1, dentate gyrus (DG), and total hippocampal sections, but not in the CA2/3 region. AASs administration increased AR expression in all hippocampal regions, although not the total hippocampal section in the TE group and did not significantly decrease ERα. The hippocampal AR/ERα expression index was lowered while parvalbumin (PV)-immunoreactivity was enhanced by exercise. AASs administration increased the AR/ERα index and reduced PV-immunoreactivity in the hippocampus. The number of PV-immunoreactive neurons negatively correlated with the antidepressant effects and the AR/ERα ratio. Our results suggest a potential role of the numerical relationship between two sex hormones receptors (stronger correlation than for each individual receptor) in the regulation of depressive-like behavior
the hippocampal GABAergic system in rats, which allow better understanding of the hippocampal sex hormones receptors role in modulation of depressive-like behavior.
(1) Background: The aim of this study was to show the effects of swimming and nandrolone administration on cardiodynamic and morphometric parameters of the isolated rat heart. (2) The study included ...72 Wistar rats, divided into three groups, scheduled to be sacrificed after the second, third, and fourth week. Each group was divided into four subgroups: control (T-N-), nandrolone (T-N+), swimming training (T+N-), and swimming training plus nandrolone (T+N+) group. The rats from T+N- and T+N+ swam 1 h/day, 5 days/week while ones from T-N+ and T+N+ received weekly nandrolone decanoate (20 mg/kg). The isolated hearts were perfused according to the Langendorff technique and measured parameters: dp/dt max/min, SLVP, DLVP, heart rate, and coronary flow. Hearts were fixed and stained with H/E and Masson trichrome dyes. (3) dp/dt max and dp/dt min were increased in the T-N+ group at higher perfusion pressure compared to the T-N- group. SLVP and DLVP were increased in all groups after the 4th week. Collagen content was increased in T-N+ by 403% and in T+N+ by 357% groups, while it was decreased in T+N- compared to the control after 4th week. (4) Conclusions: Nandrolone alone or combined with swimming had a deleterious effect on myocardial function and perfusion.
Background:Atherosclerosis is a chronic fibroproliferative disease that includes accumulation of cholesterol-rich lipids in the arterial wall. Though numerous studies have investigated ...atherosclerosis, not enough is known about the exact mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall. Therefore, we explored the 125I-LDL transport into the arterial wall under constant perfusion flow and pressure as well as the influence of duration of atherogenic diet on 125I-LDL transport and biomechanical properties of carotid artery.Methods and Results:The isolated segment of rabbit carotid artery was used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg) blood vessel distension, with the possibility to change and precisely calculate shear stress during the experiment. Obtained results indicate the influence of atherogenic diet duration and consequent variation of shear stress on 125I-LDL transport into the blood vessel wall. 125I-LDL transport into the blood vessel wall at low pressure-induced blood vessel distension decreases by the increase of the shear stress and in relation to the atherogenic diet duration. At high pressure-induced blood vessel distension, 125I-LDL transport increases in relation to the atherogenic diet duration and the increase of shear stress.Conclusions:The influence of shear stress is a more dominant parameter on LDL uptake at low pressure-induced blood vessel distension; however, the atherogenic diet duration has more of a dominant influence on LDL uptake at high pressure-induced vessel distension. (Circ J 2015; 79: 1846–1852)
Purpose
Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor‐binding peptides such as 90Y‐ and 177Lu‐DOTATOC. The objective of this work ...was to develop a biokinetics model of 90Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor.
Methods
A multi‐compartment model described by two sets of differential equations, one set for the actual 30‐min infusion and the other set for the post‐infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter‐compartment transfer coefficients, λij, were varied to yield the best fit of the calculated to the measured time‐activity data and the 90Y‐DOTATOC time‐activity data in the five‐compartments comprising the human body were thus determined. The resulting time‐activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self‐dose 90Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses.
Results
Transfer coefficients λij, were determined for five‐compartments for all patients. Time‐ activity curves of 90Y‐DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73–2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05–42.31 mGy/MBq).
Conclusion
Analytical solution of a biokinetic model for 90Y‐DOTATOC therapy enabled determination of the transfer coefficients and derivation of time‐activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.
The aim of this study was to investigate histamine blood concentration in subjects suffering from different types of ischemic heart diseases during the period of eight days. Our results showed that ...the histamine blood level was associated with different types of ischemic heart diseases. The blood histamine level in all investigated patients was significantly higher when compared to control subjects (44.87 ± 1.09 ng mL−1), indicating the increase of histamine release in patients suffering from coronary diseases. In patients suffering from ACS-UA and ACS-STEMI, the second day peak of histamine level occurs (90.85 ± 6.34 ng mL−1 and 121.7 ± 6.34 ng mL−1, resp.) probably as the reperfusion event. Furthermore, our data suggest that histamine can be additional parameter of myocardial ischemia along with cardiac specific enzymes and may prove to be an excellent single prognostic marker for multitude of ischemic heart diseases.
In this work we have described the new mathematical approach, with spectral analysis of the data to evaluate position and motion in the „„open field““ experiments. The aim of this work is to ...introduce several new parameters mathematically derived from experimental data by means of spectral analysis, and to quantitatively estimate the quality of the motion. Two original software packages (TRACKER and POSTPROC) were used for transforming a video data to a log file, suitable for further computational analysis, and to perform analysis from the log file. As an example, results obtained from the experiments with Wistar rats in the „open field“ test are included. The test group of animals was treated with diazepam. Our results demonstrate that all the calculated parameters, such as movement variability, acceleration and deceleration, were significantly lower in the test group compared to the control group. We believe that the application of parameters obtained by spectral analysis could be of great significance in assessing the locomotion impairment in any kind of motion. Projekat Ministarstva nauke Republike Srbije, br. III41007 i br. ON174028
PDF
