10 results on '"Hrnčić D"'
Search Results
2. Basic characteristics of EEG epileptiform discharges triggered by lindane in a model of experimental prostatitis
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Zubelić Aleksa, Vuletić Jelisaveta, Ašćerić Milivoje, Rašić-Marković Aleksandra, Stanojlović Olivera, Šutulović Nikola, and Hrnčić Dragan
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prostatitis ,lindane ,rats ,seizures ,Medicine - Abstract
Introduction: Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is the most commonly diagnosed non-infectious prostatitis in urology. Studies have shown that CP/CPPS can induce neuroinflammation, which may result in CNS hyperexcitability and a tendency to develop epileptic seizures. Spike salvos are ictal EEG graph elements typical for the experimental model of lindane-induced seizures. There are a number of mathematical models for quantitative analysis of EEG, including the Fast Fourier Transform (FFT). It transforms the signal from time into the frequency domain, providing information on Power Spectral Densities (PSD). Aim: The aim of this study was to investigate the basic characteristics of epileptiform discharges induced by subconvulsive dose of lindane in rats, with experimentally induced CP/CPPS. Material and methods: CP/CPPS was induced by intraprostatic injection of 3% l-carrageenan in male Wistar albino rats. Animals with CP/CPPS were implanted with EEG registration electrodes, and then administered lindane (4 mg/kg, i.p, experimental group, n = 6 per group) or its solvent (DMSO, control group, n = 6 per group). An 8-channel EEG device was used in combination with software developed in the laboratory (NeuroSciLaBG). Ictal EEG epochs were extracted from the original signal and FFT analysis was performed to obtain information taking into account PSD in predefined frequency bands. Results: There was no ictal activity in the EEG of control animals. In experimental animals, ictal activity occurred and the mean duration of the ictal period was 2.06 s. FFT analysis revealed that the Alpha frequency range (7-15 Hz) was markedly dominant during ictal activity. Conclusion: The results of this study showed the characteristics of epileptiform discharges in animals with experimentally induced CP/CPPS. This study and animal model are suitable for future translational studies of the comorbidities of this syndrome.
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- 2022
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3. THE EFFECTS OF ENDOCRINE DISRUPTORS ON FEMALE GONADAL AXIS: AN UPDATE.
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Macut, D., Opalić, M., Popović, B., Ognjanović, S., Bjekić-Macut, J., Livadas, S., Petrović, T., Hrnčić, D., Stanojlović, O., Milutinović, D. Vojnović, Micić, D., and Mastorakos, G.
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ENDOCRINE disruptors , *ENDOCRINE glands , *GENITALIA , *PREMATURE ovarian failure , *POLYCYSTIC ovary syndrome - Abstract
Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison.
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Vesković M, Pejović M, Šutulović N, Hrnčić D, Rašić-Marković A, Stanojlović O, and Mladenović D
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- Humans, Animals, Hepatic Stellate Cells metabolism, Disease Models, Animal, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease etiology, Obesity metabolism, Obesity complications, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Liver Cirrhosis etiology
- Abstract
While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to liver fibrosis even in the absence of metabolic syndrome. This review aims to summarize the current knowledge regarding the mechanisms of liver fibrosis in lean NAFLD. The most commonly used lean NAFLD models include a methionine/choline-deficient (MCD) diet, a high-fat diet with carbon tetrachloride (CCl
4 ), and a high-fructose and high-cholesterol diet. The major pro-fibrogenic mechanisms in lean NAFLD models include increased activation of the extracellular signal-regulated kinase (ERK) pathway, elevated expression of α-smooth muscle actin (α-SMA), collagen type I, and TGF-β, and modulation of fibrogenic markers such as tenascin-X and metalloproteinase inhibitors. Additionally, activation of macrophage signaling pathways promoting hepatic stellate cell (HSC) activation further contributes to fibrosis development. Animal models cannot cover all clinical features that are evident in patients with lean or obese NAFLD, implicating the need for novel models, as well as for deeper comparisons of clinical and experimental studies. Having in mind the prevalence of fibrosis in lean NAFLD patients, by addressing specific pathways, clinical studies can reveal new targeted therapies along with novel biomarkers for early detection and enhancement of clinical management for lean NAFLD patients.- Published
- 2024
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5. Adipose-derived extracellular vesicles - a novel cross-talk mechanism in insulin resistance, non-alcoholic fatty liver disease, and polycystic ovary syndrome.
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Mladenović D, Vesković M, Šutulović N, Hrnčić D, Stanojlović O, Radić L, Macut JB, and Macut D
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- Humans, Female, Animals, Obesity metabolism, Obesity complications, Polycystic Ovary Syndrome metabolism, Insulin Resistance physiology, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Extracellular Vesicles metabolism, Adipose Tissue metabolism, Adipose Tissue pathology
- Abstract
Obesity is the best described risk factor for the development of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) while the major pathogenic mechanism linking these entities is insulin resistance (IR). IR is primarily caused by increased secretion of proinflammatory cytokines, adipokines, and lipids from visceral adipose tissue. Increased fatty acid mobilization results in ectopic fat deposition in the liver which causes endoplasmic reticulum stress, mitochondrial dysfunction, and oxidative stress resulting in increased cytokine production and subsequent inflammation. Similarly, IR with hyperinsulinemia cause hyperandrogenism, the hallmark of PCOS, and inflammation in the ovaries. Proinflammatory cytokines from both liver and ovaries aggravate IR thus providing a complex interaction between adipose tissue, liver, and ovaries in inducing metabolic abnormalities in obese subjects. Although many pathogenic mechanisms of IR, NAFLD/MASLD, and PCOS are known, there is still no effective therapy for these entities suggesting the need for further evaluation of their pathogenesis. Extracellular vesicles (EVs) represent a novel cross-talk mechanism between organs and include membrane-bound vesicles containing proteins, lipids, and nucleic acids that may change the phenotype and function of target cells. Adipose tissue releases EVs that promote IR, the development of all stages of NAFLD/MASLD and PCOS, while mesenchymal stem cell-derived AVs may alleviate metabolic abnormalities and may represent a novel therapeutic device in NAFLD/MASLD, and PCOS. The purpose of this review is to summarize the current knowledge on the role of adipose tissue-derived EVs in the pathogenesis of IR, NAFLD/MASLD, and PCOS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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6. Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover.
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Vasović DD, Ivković S, Živanović A, Major T, Milašin JM, Nikolić NS, Simonović JM, Šutulović N, Hrnčić D, Stanojlović O, Vesković M, Rašić DM, and Mladenović D
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- Animals, Male, Rats, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha genetics, Anti-Inflammatory Agents pharmacology, Aquaporin 4 metabolism, Aquaporin 4 genetics, Retinal Vessels metabolism, Retinal Vessels pathology, Rats, Wistar, Diabetic Retinopathy metabolism, Diabetic Retinopathy pathology, Retina metabolism, Retina pathology, Retina radiation effects, Streptozocin, Cholesterol metabolism, Light, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental complications, Gliosis pathology, Gliosis metabolism
- Abstract
Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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7. The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach.
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Vesković M, Šutulović N, Hrnčić D, Stanojlović O, Macut D, and Mladenović D
- Abstract
The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.
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- 2023
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8. Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats.
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Vasović DD, Vesković M, Šutulović N, Hrnčić D, Takić M, Jerotić Đ, Matić M, Stanojlović O, Ivković S, Jovanović Macura I, and Mladenović D
- Abstract
The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group-control group (C
12/12 ); second group-diabetic group (DM12/12 ; 100 mg/kg STZ); third group-control group exposed to a light/dark cycle 6/18 h (C6/18 ); fourth group-diabetic group exposed to a light/dark cycle 6/18 h (DM6/18 ). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT). Oxidative stress parameters were measured in the cortex, hippocampus and thalamus, while lipid status and fatty acid methyl esters (FAMEs) were measured in the serum. Both EPM and OFT showed a lower degree of anxiety-like behaviour in the DM6/18 vs. DM12/12 group. Lipid peroxidation in the cortex, hippocampus and thalamus was significantly lower in the DM6/18 vs. DM12/12 group ( p < 0.05), associated with an increased level of antioxidant enzymes and protein thiols in the cortex and thalamus. In the DM6/18 group, oleic, vaccenic, dihomo-γ-linolenic and docosahexaenoic acid concentrations were significantly higher in comparison to the DM12/12 group. A shortened daily photoperiod alleviates anxiety-like behaviour in diabetic rats by reduced lipid peroxidation and changes in the serum fatty acids profile.- Published
- 2023
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9. Chronic Prostatitis/Chronic Pelvic Pain Syndrome Induces Depression-Like Behavior and Learning-Memory Impairment: A Possible Link with Decreased Hippocampal Neurogenesis and Astrocyte Activation.
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Šutulović N, Vesković M, Puškaš N, Zubelić A, Jerotić D, Šuvakov S, Despotović S, Grubač Ž, Mladenović D, Macut D, Rašić-Marković A, Simić T, Stanojlović O, and Hrnčić D
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- Humans, Animals, Rats, Male, Astrocytes metabolism, Chronic Disease, Depression complications, Neuroinflammatory Diseases, Rats, Wistar, Pelvic Pain, Hippocampus metabolism, Neurogenesis, Prostatitis complications, Prostatitis metabolism
- Abstract
Pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear since it represents an interplay between immunological, endocrine, and neuropsychiatric factors. Patients suffering from CP/CPPS often develop mental health-related disorders such as anxiety, depression, or cognitive impairment. The aim of this study was to investigate depression-like behavior, learning, and memory processes in a rat model of CP/CPPS and to determine the alterations in hippocampal structure and function. Adult male Wistar albino rats ( n = 6 in each group) from CP/CPPS (single intraprostatic injection of 3% λ -carrageenan, day 0) and Sham (0.9% NaCl) groups were subjected to pain threshold test (days 2, 3, and 7), depression-like behavior, and learning-memory tests (both on day 7). Decreased pain threshold in the scrotal region and histopathological presence of necrosis and inflammatory infiltrate in prostatic tissue confirmed the development of CP/CPPS. The forced swimming test revealed the depression-like behavior evident through increased floating time, while the modified elevated plus maze test revealed learning and memory impairment through prolonged transfer latency in the CP/CPPS group in comparison with Sham ( p < 0.001 and p < 0.001, respectively). Biochemical analysis showed decreased serum levels of testosterone in CP/CPPS group vs. the Sham ( p < 0.001). The CP/CPPS induced a significant upregulation of ICAM-1 in rat cortex ( p < 0.05) and thalamus ( p < 0.01) and increased GFAP expression in the hippocampal astrocytes ( p < 0.01) vs. Sham, suggesting subsequent neuroinflammation and astrocytosis. Moreover, a significantly decreased number of DCX+ and Ki67+ neurons in the hippocampus was observed in the CP/CPPS group ( p < 0.05) vs. Sham, indicating decreased neurogenesis and neuronal proliferation. Taken together, our data indicates that CP/CPPS induces depression-like behavior and cognitive declines that are at least partly mediated by neuroinflammation and decreased neurogenesis accompanied by astrocyte activation., Competing Interests: No conflict of interest was declared by the authors. The corresponding author is an MC member in EU COST Actions 20135 (TEATIME) and 20119 (ANDRONET)., (Copyright © 2023 Nikola Šutulović et al.)
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- 2023
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10. The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.
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Robeva R, Mladenović D, Vesković M, Hrnčić D, Bjekić-Macut J, Stanojlović O, Livadas S, Yildiz BO, and Macut D
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- Female, Humans, Insulin blood, Insulin Resistance, Risk Factors, Dyslipidemias complications, Estrogens therapeutic use, Menopause drug effects, Non-alcoholic Fatty Liver Disease complications
- Abstract
The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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