The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in ...the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (
= 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein,
= 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein,
< 0.0001 vs. C (1.467 ± 0.501 U/mg protein),
= 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and
= 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein,
< 0.0001 vs. C (6.738 ± 0.339 U/mg protein),
< 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and
< 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein,
= 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752-10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562-5.299) mU/mg protein,
= 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels.
Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated ...by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).
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•Antidepressants alleviated pain hypersensitivity in rats with osteoarthritis (OA).•Duloxetine, unlike vortioxetine, depressed burrowing behavior in OA rats.•Vortioxetine improved cognitive performance in male and female OA rats.•Duloxetine improved cognitive performance only in female OA rats.•Duloxetine induced cardiac oxidative damage in female OA rats.
Metallophilic macrophages (MMs) are a distinct cell type of the rodent thymus. Our previous research has focused on the morphological characteristics of MMs, as well as on the molecular mechanisms ...involved in the development and tissue positioning of these cells. However, the postnatal development of MMs has not been sufficiently studied. In the present study, we investigated the positioning of MMs in the rat thymus between postnatal day 0 (P0) and P30. On P0, MMs were evenly distributed all over the thymic tissue—that is, the cortex, cortico‐medullary zone and medulla. From P0 to P15, the number of MMs in the thymic cortex significantly decreased, and after P15, this number did not change. Thus, the present study shows that on P15, MMs almost completely disappear from the thymic cortex and show their adult position in the cortico‐medullary zone and in the medulla.
Magnesium (Mg), is not only a modulator of the glutamatergic NMDA receptors' affinity, it also prevents HPA axis hyperactivity, thus possibly being implicated in neurobiological features of mood ...disorders. Further uncovering of molecular mechanisms underlying magnesium's proposed effects is needed due to the recent shift in research of treatment resistant depression (TRD) towards glutamatergic pathways. Here, we applied Mg via drinking water for 28 days (50 mg/kg/day), in ACTH-treated rats, an established animal model of depression resistant to tricyclic antidepressants. Using this model in male rats we measured (1) changes in hippocampal neurogenesis and behavioral alterations, (2) adrenal hormones response to acute stress challenge and (3) levels of biometals involved in regulation of monoamines turnover in rat prefrontal cortex. Our results support beneficial behavioral impact of Mg in TRD model together with increased hippocampal neurogenesis and BDNF expression. Furthermore, Mg prevented ACTH-induced disruption in HPA axis function, by normalizing the levels of plasma ACTH, corticosterone and interleukin-6, and by increasing the peripheral release of adrenaline, noradrenaline and serotonin after the acute stress challenge. Finally, the influence on copper/zinc ratio suggested probable magnesium's involvement in monoamine turnover in PFC. Our findings provide further insights into the possible pathways implicated in the behavioral modulation effects of Mg, as well as its central and peripheral effects in ACTH-induced TRD model. Thus, further investigation of molecular signaling related to the glutamatergic transmission and role of Mg, could reveal prospects to novel treatment strategies that could be of particular importance for patients suffering from TRD.
•In ACTH model of treatment-resistant depression Mg alleviates behavioral changes.•HPA axis hyperactivity induced by ACTH was attenuated in Mg-administered rats.•Study suggests involvement of Mg in central and peripheral turnover of monoamines.•In ACTH model of treatment-resistant depression Mg increases neurodevelopment.
Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that ...those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.
Introduction. Angiosarcomas (ASs) arising from vascular tissue, account for 3.3% of all sarcomas and have a poor prognosis. Radiation-induced AS is a rare late complication of radiotherapy (RT) ...treatment and is characterized by a gene expression profile such as amplification of the MYC oncogene, by which we can distinguish primary from secondary induced tumor. Case report. For a 77-year-old female patient with early-stage endometrial adenocarcinoma, a radical hysterectomy with bilateral salpingo-oophorectomy was initially done. According to pathological risk factors, the postoperative external beam conformal RT (CRT) of the pelvis was administered with concomitant brachytherapy. Six years after the treatment, on the anterior abdominal wall, in the region of the postoperative irradiation field and surgical scar, an infiltrative AS of the skin and subcutaneous adipose tissue was histologically confirmed. The patient received six cycles of mono-adriamycin chemotherapy with verified partial regression. Additional immunohistochemical analysis (IHC) of c-MYC, Ki67, and CD34 expression showed a high proliferative index (Ki67 around 60%) and c-MYC positivity indicating the molecular pattern of radiation-induced AS. Furthermore, the high proliferative index could explain the positive response to chemotherapy. Conclusion. The novel postoperative RT techniques provide better survival and local control in risk-endometrial cancer groups with a decrease in irradiation complications. These patients with longer survival are at a higher risk of developing radiation-induced tumors as late side-effects of RT. When assessing the probability of radiation-induced AS, IHC analysis of c-MYC expression could distinguish secondary from other AS if Cahan?s criteria are fulfilled.
Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to ...associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered.
Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA.
Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the setting of Regression analysis, statistically significant differences among grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves analysis, threshold values for different grades were recognized. Grade 2 is identified in patients with AscA > 3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1.
Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR.
Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and ...cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e.,
l
-cysteine (Cys) and
N
-aceyl-
l
-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1–0.2 mL/day) (
n
= 10) (K); (b)
dl
-methionine (0.8 mmol/kg/bw/day) (
n
= 10) (M); (c)
dl
-methionine (0.8 mmol/kg/bw/day) +
l
-cysteine (7 mg/kg/bw/day) (
n
= 8) (C); (d)
dl
-methionine (0.8 mmol/ kg/bw/day) +
N
-acetyl-
l
-cysteine (50 mg/kg/bw/day) (
n
= 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.
Changes in the methionine metabolism can cause a state called hyperhomocysteinemia, inducing oxidative stress in the gut. The production of free radicals is important in the colon damage caused by ...methionine. This study aimed at evaluating the effect of the use of
l
-cysteine and
N
-acetyl-
l
-cysteine on the colon morphometry of young rats treated with methionine. A total number of 32 male rats were distributed in a randomized experimental design in 4 groups: control group treated with saline; methionine group; cysteine + methionine group, and
N
-acetyl-
l
-cysteine + methionine group. After 21 days of treatment, rats were sacrificed and the colon samples were taken for histological and biochemical analysis. Methionine load increased depth of crypts, the lamina muscularis mucosae thickness, the mucosal height, and the number of cells in lamina propria (
p
< 0.01). Combination of methionine with
l
-cysteine (
C
group) and with
N
-acetyl-
l
-cysteine (
N
group) reversed methionine effects. Methionine treatment increased the GPx activity and MDA concentration, while
l
-cysteine and
N
-acetyl-
l
-cysteine increased the catalase activity compared to methionine group. It was concluded that the use of
l
-cysteine and
N
-acetyl-
l
-cysteine was beneficial to decrease intestinal mucosal height and oxidative damage when methionine was used in combination with them.
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