13 results on '"Kramar B"'
Search Results
2. Proviral HIV-1 DNA in Gingival Crevicular Fluid of HIV-1-infected Patients in Various Stages of HIV Disease
- Author
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Matičić, M., primary, Poljak, M., additional, Kramar, B., additional, Tomažić, J., additional, Vidmar, L., additional, Zakotnik, B., additional, and Skalerič, U., additional
- Published
- 2000
- Full Text
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3. C-1 esterase inhibitor prophylaxis for delivery in hereditary angioedema
- Author
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Lovsin, Z. Guzej, M. Vok, I. Kramar, B., primary
- Published
- 1999
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4. Early Intensified Chemotherapy with Autologous Bone Marrow Transplantation in First Line Treatment of Poor Risk Non-Seminomatous Germ Cell Tumours
- Author
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Droz, J.P., primary, Pico, J.L., additional, Biron, P., additional, Kerbrat, P., additional, Cure, H., additional, Héron, J.F., additional, Chevallier, B., additional, Fargeot, P., additional, Kramar, (b), additional, Bouzy, J., additional, and Chevreau, C., additional
- Published
- 1993
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5. Therapeutic Dosage of Antipsychotic Drug Aripiprazole Induces Persistent Mitochondrial Hyperpolarisation, Moderate Oxidative Stress in Liver Cells, and Haemolysis.
- Author
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Pirc Marolt T, Kramar B, Vovk A, Podgornik H, Šuput D, and Milisav I
- Abstract
Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated treatment with aripiprazole affects cell division. Since this process requires a lot of energy, we decided to investigate the impact of aripiprazole on rat liver cells and mitochondria as the main source of cellular energy production by measuring the mitochondrial membrane potential, respiration, adenosine triphosphate (ATP) production, oxidative stress, antioxidative response, and human blood haemolysis. Here, we report that mitochondrial hyperpolarisation from aripiprazole treatment is accompanied by higher reactive oxygen species (ROS) production and increased antioxidative response. Lower mitochondrial and increased glycolytic ATP synthesis demand more glucose through glycolysis for equal ATP production and may change the partition between the glycolysis and pentose phosphate pathway in the liver. The uniform low amounts of the haemolysis of erythrocytes in the presence of aripiprazole in 25 individuals indicate lower quantities of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH+H
+ ), which is in accordance with a decreased activity of glucose 6-phosphate dehydrogenase and the lower dehydrogenase activity upon aripiprazole treatment. The lower activity of glucose 6-phosphate dehydrogenase supports a shift to glycolysis, thus rescuing the decreased mitochondrial ATP synthesis. The putative reduction in NADPH+H+ did not seem to affect the oxidised-to-reduced glutathione ratio, as it remained equal to that in the untreated cells. The effect of aripiprazole on glutathione reduction is likely through direct binding, thus reducing its total amount. As a consequence, the low haemolysis of human erythrocytes was observed. Aripiprazole causes moderate perturbations in metabolism, possibly with one defect rescuing the other. The result of the increased antioxidant enzyme activity upon treatment with aripiprazole is increased resilience to oxidative stress, which makes it an effective drug for schizophrenia in which oxidative stress is constantly present because of disease and treatment.- Published
- 2023
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6. Antipsychotic Drug Aripiprazole Protects Liver Cells from Oxidative Stress.
- Author
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Kramar B, Pirc Marolt T, Monsalve M, Šuput D, and Milisav I
- Subjects
- Antioxidants pharmacology, Aripiprazole pharmacology, Benzodiazepines pharmacology, Benzodiazepines therapeutic use, Hepatocytes, Humans, Hydrogen Peroxide, Olanzapine adverse effects, Oxidative Stress, Antipsychotic Agents pharmacology, Antipsychotic Agents therapeutic use, Chemical and Drug Induced Liver Injury drug therapy
- Abstract
Antipsychotics used to treat schizophrenia can cause drug-induced liver injury (DILI), according to the Roussel Uclaf Causality Assessment Method. The role of oxidative stress in triggering injury in these DILI cases is unknown. We repeatedly administrated two second-generation antipsychotics, aripiprazole and olanzapine, at laboratory alert levels to study underlying mechanisms in stress prevention upon acute oxidative stress. The drugs were administered continuously for up to 8 weeks. For this, hepatoma Fao cells, which are suitable for metabolic studies, were used, as the primary hepatocytes survive in the culture only for about 1 week. Four stress responses-the oxidative stress response, the DNA damage response and the unfolded protein responses in the endoplasmic reticulum and mitochondria-were examined in H
2 O2 -treated cells by antioxidant enzyme activity measurements, gene expression and protein quantification. Oxidant conditions increased the activity of antioxidant enzymes and upregulated genes and proteins associated with oxidative stress response in aripiprazole-treated cells. While the genes associated with DNA damage response, Gadd45 and p21, were upregulated in both aripiprazole- and olanzapine-treated cells, only aripiprazole treatment was associated with upregulation in response to even more H2 O2 , which also coincided with better survival. Endoplasmic reticulum stress-induced Chop was also upregulated; however, neither endoplasmic reticulum nor mitochondrial unfolded protein response was activated. We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo.- Published
- 2022
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7. Differential p16 expression levels in the liver, hepatocytes and hepatocellular cell lines.
- Author
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Kramar B, Šuput D, and Milisav I
- Abstract
Background: One of the most frequently deleted genes in cancer is CDKN2A encoding p16. This protein is often overexpressed in senescent cells, while its suppression can bypass the oncogene-induced senescence to enable transformation and tumorigenesis. The roles of the protein p16 are recently being expanded from the cell cycle progression regulator to the cellular regulator interacting in several different pathways. Yet data on its liver and liver cells' expression are inconclusive., Methods: The expression of the p16 gene in liver and liver cells was determined by RT-qPCR and compared to its protein amounts by western blotting., Results: p16 is expressed at low levels in the liver and rat hepatocytes. Its expression varies from none to the considerable levels in the examined hepatocellular carcinoma cell lines (FaO and HepG2) and in immortalized mouse hepatocytes. Such significant expression differences of an important cellular regulator warrant the need to closely examine the differences in biochemical pathways correlated with the p16 expression when using hepatocytes and hepatoma liver models., Competing Interests: The authors declare that they have no competing interests., (© 2021 Kramar et al.)
- Published
- 2021
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8. Aripiprazole reduces liver cell division.
- Author
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Pirc Marolt T, Kramar B, Bulc Rozman K, Šuput D, and Milisav I
- Subjects
- Animals, Cell Count, Cell Division genetics, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Cell Survival drug effects, Cell Survival genetics, Cellular Senescence drug effects, Gene Expression Regulation drug effects, Rats, Aripiprazole pharmacology, Cell Division drug effects, Liver cytology
- Abstract
Effects of aripiprazole on dopamine regulation are being tested as a treatment for patients with a dual diagnosis of schizophrenia and addictions, often cocaine dependence. Aripiprazole has one of the fewest side-effects among the second-generation antipsychotics. Nevertheless, severe aripiprazole hepatotoxicity was reported in persons with a history of cocaine and alcohol abuse. Here we report that therapeutically relevant aripiprazole concentrations, equal to laboratory alert levels in patients' serum, reduce the rate of hepatocytes' division. This could be an underlying mechanism of severe liver injury development in the patients with a history of alcohol and cocaine abuse, the two hepatotoxic agents that require increased ability of liver self-regeneration. Monitoring liver functions is, therefore, important in the cases when aripiprazole is co-prescribed or used with drugs with potential hepatotoxic effects., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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9. Medical and Dietary Uses of N-Acetylcysteine.
- Author
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Šalamon Š, Kramar B, Marolt TP, Poljšak B, and Milisav I
- Abstract
N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.
- Published
- 2019
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10. Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis.
- Author
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Sustarsic EG, Ma T, Lynes MD, Larsen M, Karavaeva I, Havelund JF, Nielsen CH, Jedrychowski MP, Moreno-Torres M, Lundh M, Plucinska K, Jespersen NZ, Grevengoed TJ, Kramar B, Peics J, Hansen JB, Shamsi F, Forss I, Neess D, Keipert S, Wang J, Stohlmann K, Brandslund I, Christensen C, Jørgensen ME, Linneberg A, Pedersen O, Kiebish MA, Qvortrup K, Han X, Pedersen BK, Jastroch M, Mandrup S, Kjær A, Gygi SP, Hansen T, Gillum MP, Grarup N, Emanuelli B, Nielsen S, Scheele C, Tseng YH, Færgeman NJ, and Gerhart-Hines Z
- Subjects
- Animals, Cells, Cultured, Energy Metabolism, Humans, Membrane Proteins genetics, Mice, Mice, Inbred C57BL, Thermogenesis, Transferases (Other Substituted Phosphate Groups) genetics, Adipocytes metabolism, Adipose Tissue, Beige metabolism, Adipose Tissue, Brown metabolism, Cardiolipins biosynthesis, Membrane Proteins metabolism, Mitochondria metabolism, Transferases (Other Substituted Phosphate Groups) metabolism
- Abstract
Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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11. A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening.
- Author
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van den Berg R, Kooijman S, Noordam R, Ramkisoensing A, Abreu-Vieira G, Tambyrajah LL, Dijk W, Ruppert P, Mol IM, Kramar B, Caputo R, Puig LS, de Ruiter EM, Kroon J, Hoekstra M, van der Sluis RJ, Meijer OC, Willems van Dijk K, van Kerkhof LWM, Christodoulides C, Karpe F, Gerhart-Hines Z, Kersten S, Meijer JH, Coomans CP, van Heemst D, Biermasz NR, and Rensen PCN
- Subjects
- Animals, Circadian Rhythm, Humans, Mice, Wakefulness, Adipose Tissue, Brown metabolism, Fatty Acids metabolism, Lipid Metabolism physiology
- Abstract
Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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12. Detection of hepatitis C virus RNA from gingival crevicular fluid and its relation to virus presence in saliva.
- Author
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Maticic M, Poljak M, Kramar B, Seme K, Brinovec V, Meglic-Volkar J, Zakotnik B, and Skaleric U
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- Adult, Aged, Alanine Transaminase blood, Dental Plaque Index, Female, Genotype, Gingival Crevicular Fluid chemistry, Hepacivirus classification, Hepatitis C, Chronic blood, Hepatitis C, Chronic metabolism, Humans, Male, Middle Aged, Occult Blood, Periodontal Attachment Loss classification, Periodontal Attachment Loss virology, Periodontal Index, Periodontal Pocket classification, Periodontal Pocket virology, Polymerase Chain Reaction, Statistics as Topic, Viremia virology, Virus Shedding physiology, Gingival Crevicular Fluid virology, Hepacivirus genetics, RNA, Viral analysis, Saliva virology
- Abstract
Background: To search for a possible source of hepatitis C virus (HCV) in saliva, the presence and shedding patterns of HCV in gingival crevicular fluid (GCF) and saliva of HCV viremic patients were assessed based on clinical, biochemical, histological, virological, and oral health parameters., Methods: Saliva and GCF samples of 50 HCV viremic patients were collected to detect HCV RNA by a modified commercial polymerase chain reaction (PCR) assay. Clinical oral examination was performed and periodontal status at the collection sites was monitored. The results were correlated to specified parameters., Results: HCV RNA was detected in 59% (29/49) of the GCF specimens and in 35% (17/48) of the saliva specimens. In saliva specimens, HCV RNA was detected only in cases which also had detectable HCV RNA in the GCF samples (P=0.00002) and was significantly related to the presence of blood in saliva (P=0.03). Higher, but not significant, values of oral clinical parameters at the sites of fluid collection were found in GCF specimens harboring HCV RNA. In GCF specimens with no blood detected, HCV RNA was more often present in cases with higher plasma viral load (P=0.05)., Conclusions: The results suggest that besides blood, the other most probable source of HCV in saliva is GCF. Unknown endogenous HCV inhibitory mechanisms in the oral cavity may explain the discrepancies in HCV appearance between saliva and GCF. The results provide a biologic basis for further investigation of the role of HCV in the pathogenesis of periodontal disease.
- Published
- 2001
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13. Changes in TGF-beta 1 levels in gingiva, crevicular fluid and serum associated with periodontal inflammation in humans and dogs.
- Author
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Skaleric U, Kramar B, Petelin M, Pavlica Z, and Wahl SM
- Subjects
- Adult, Aged, Animals, Dental Plaque Index, Disease Models, Animal, Disease Progression, Dogs, Enzyme-Linked Immunosorbent Assay, Female, Gingivitis blood, Gingivitis metabolism, Humans, Male, Middle Aged, Periodontal Attachment Loss metabolism, Periodontal Attachment Loss pathology, Periodontal Index, Periodontal Pocket metabolism, Periodontal Pocket pathology, Periodontitis blood, Transforming Growth Factor beta blood, Gingiva chemistry, Gingival Crevicular Fluid chemistry, Periodontitis metabolism, Transforming Growth Factor beta analysis
- Abstract
Transforming growth factor-beta (TGF-beta) represents a family of polypeptide growth factors, involved in embryogenesis, inflammation, regulation of immune responses and wound healing. To determine whether TGF-beta contributes to the evolution of periodontal disease, we assayed TGF-beta levels in gingiva and crevicular fluid of patients with gingivitis and periodontitis. In parallel, TGF-beta was quantified in gingival fluid and serum of beagles with experimentally-induced periodontitis. Disease was monitored by several clinical parameters including Plaque Index, Gingival Index, probing depth, and epithelial attachment loss. Gingival tissues were obtained from 9 patients at the time of periodontal surgery, and gingival fluid samples were collected from an additional population of 10 periodontal patients. In 14 beagles, experimental periodontitis was induced and gingival fluids collected 6 months later. Fluid was collected by paper strips and volume measured by Periotron. Additionally, sera was collected before and 9 months after the ligature-induced periodontitis in 7 beagles. The levels of TGF-beta 1 were measured by ELISA. In the patients, a significantly higher concentration of TGF-beta 1 was observed both in the gingival tissues and fluid samples obtained from the sites with deeper periodontal pockets than in the less involved sites. In beagles, TGF-beta 1 levels measured in gingival fluid were elevated in moderate disease, declining in fluid samples obtained from the pockets during more advanced experimental periodontitis. Furthermore, with the progression of experimental periodontitis, a decrease in TGF-beta 1 occurred in the sera of the beagle dogs. These data suggest that TGF-beta 1 may play a rôle in the pathogenesis and diagnosis of periodontal disease, and that its actions can be further explored in an animal model.
- Published
- 1997
- Full Text
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