Browsing by Author "Gluvic, Zoran (24460256500)"

Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis. © Copyright © 2020 Zaric, Radovanovic, Gluvic, Stewart, Essack, Motwalli, Gojobori and Isenovic.

Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis. © Copyright © 2020 Zaric, Radovanovic, Gluvic, Stewart, Essack, Motwalli, Gojobori and Isenovic.

Thyroid nodules are among highly prevalent thyroid diseases. To make a distinction between benign and malignant thyroid nodules are of cumbersome significance for each endocrinologist. There is no unique and completely accurate diagnostic test, method, or even biomarker that points to a malignant thyroid nodule. Many studies in modern thyroidology are conducted to determine the usefulness of individual biomarkers, which could help clinicians detect thyroid nodules' potential malignant nature. One interesting biomarker with a promising diagnostic potential for the thyroid gland pathological conditions is nitric oxide (NO). Inducible nitric oxide synthase expression is increased in thyroiditis cases and even more in thyroid carcinoma cases, directly connected with increased NO levels in both pathological conditions. We hypothesize that the basal levels of nitrite/nitrate in serum and biopsy washout could indicate nodules' malignant nature. © 2021 Elsevier Ltd

The diabetes pandemic demands solutions for proper glycemic control and prevention of future chronic complications that could result in organ failure or comorbidities. In this regard, we now know that patients diagnosed with diabetes require individual management plans. Thus, new treatment management strategies have been designed to allow clinicians to tailor the most appropriate therapy for diabetes patients individually. These treatment management plans extend beyond defining the appropriate medications for patients; they provide a directive toward some acute and chronic complications that should be screened for, as they are historically known to occur with diabetes. Observing any of the complications or comorbidities requires the patient medication regimen to be adapted accordingly. This chapter describes such modern treatment plans for the two primary forms of diabetes, type 1 and type 2, based on both basic and clinical studies, later incorporated in various diabetes management guidelines and outlines expected future trends. © Springer Nature Switzerland AG 2020.

The diabetes pandemic demands solutions for proper glycemic control and prevention of future chronic complications that could result in organ failure or comorbidities. In this regard, we now know that patients diagnosed with diabetes require individual management plans. Thus, new treatment management strategies have been designed to allow clinicians to tailor the most appropriate therapy for diabetes patients individually. These treatment management plans extend beyond defining the appropriate medications for patients; they provide a directive toward some acute and chronic complications that should be screened for, as they are historically known to occur with diabetes. Observing any of the complications or comorbidities requires the patient medication regimen to be adapted accordingly. This chapter describes such modern treatment plans for the two primary forms of diabetes, type 1 and type 2, based on both basic and clinical studies, later incorporated in various diabetes management guidelines and outlines expected future trends. © Springer Nature Switzerland AG 2020.

Diabetes mellitus (DM) is on the rise, necessitating the development of novel therapeutic and preventive strategies to mitigate the disease’s debilitating effects. Diabetic cardiomyopathy (DCMP) is among the leading causes of morbidity and mortality in diabetic patients globally. DCMP manifests as cardiomyocyte hypertrophy, apoptosis, and myocardial interstitial fibrosis before progressing to heart failure. Evidence suggests that non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), regulate diabetic cardiomyopathy-related processes such as insulin resistance, cardiomyocyte apoptosis and inflammation, emphasizing their heart-protective effects. This paper reviewed the literature data from animal and human studies on the non-trivial roles of miRNAs and lncRNAs in the context of DCMP in diabetes and demonstrated their future potential in DCMP treatment in diabetic patients. Copyright © 2023 Macvanin, Gluvic, Radovanovic, Essack, Gao and Isenovic.

This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p < 0 001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p < 0 01), while serum arginase activity was increased (p < 0 05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser536 (p < 0 05) and decreased level of NFκB-p65 protein (p < 0 001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p < 0 05) and Akt (p < 0 05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB. © 2019 Ivana Resanovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p < 0 001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p < 0 01), while serum arginase activity was increased (p < 0 05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser536 (p < 0 05) and decreased level of NFκB-p65 protein (p < 0 001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p < 0 05) and Akt (p < 0 05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB. © 2019 Ivana Resanovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and subsequent increase in cardiovascular risk. Because of its widespread presence and distribution, invasive diagnostic procedures (i.e., liver biopsy) are reserved for a limited number of subjects. With liver ultrasound, Fatty liver index (FLI) and fibrosis-4 (FIB-4) scores non-invasively assess liver steatosis and fibrosis. We aimed to evaluate the changes in inflammatory markers and FLI/FIB-4 scores in non-obese metformin-treated type 2 diabetes patients (T2DM) with NAFLD. Methods: All subjects underwent abdominal ultrasound aiming for NAFLD stratification (grade 1 to 3 according to its severity). Metabolic parameters (morning glycaemia, HbA1C, lipids, liver function tests), serum inflammatory markers (C-reactive protein, ferritin, and nitric oxide) and FLI/-FIB-4 were calculated. Results: FLI score and ultrasound NAFLD grades were found to correlate (p<0.05). We observed a significant correlation between the levels of ferritin and C-reactive protein (CRP) (p<0.05), and the FLI (p<0.05). Body weight (BW) (p<0.05), waist circumference (WC) (p<0.05), the levels of HbA1c (p<0.05), transferrin (p<0.05), insulin (p<0.05), and FLI score (p<0.05) significantly dif-fered between groups as defined by the severity of NAFLD. Conclusion: This pilot study suggests that the serum inflammatory markers at the average normal values point to the sufficiency of metformin-single therapy in inflammation control in non-obese T2DM patients with NAFLD. © 2022 Bentham Science Publishers.

What is known and objective: The HbA1C marker used in assessing diabetes control quality is not sufficient in diabetes patients with thalassaemia. Case description: A male diabetic patient with thalassaemia was hospitalized due to distal neuropathic pain, right toe trophic ulcer, unacceptable five-point glycaemic profile and recommended HbA1C value. After simultaneously initiated insulin therapy and management of ulcer by hyperbaric oxygen, the patient showed improved glycaemic control and ulcer healing, which led to the patient's discharge. What is new and conclusion: In thalassaemia and haemoglobinopathies, due to discrepancies in the five-point glycaemic profile and HbA1C values, it is necessary to measure HbA1C with a different method or to determine HbA1C and fructosamine simultaneously. © 2019 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.

What is known and objective: The HbA1C marker used in assessing diabetes control quality is not sufficient in diabetes patients with thalassaemia. Case description: A male diabetic patient with thalassaemia was hospitalized due to distal neuropathic pain, right toe trophic ulcer, unacceptable five-point glycaemic profile and recommended HbA1C value. After simultaneously initiated insulin therapy and management of ulcer by hyperbaric oxygen, the patient showed improved glycaemic control and ulcer healing, which led to the patient's discharge. What is new and conclusion: In thalassaemia and haemoglobinopathies, due to discrepancies in the five-point glycaemic profile and HbA1C values, it is necessary to measure HbA1C with a different method or to determine HbA1C and fructosamine simultaneously. © 2019 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.

Objective: This study examined the sensitivity of routine abdominal ultrasound scanning in the detection of colonic malignancy. Patients and Methods: A case control prospective study included 101 patients hospitalized at the Department of Gastroenterology and Liver Diseases of Zemun Clinical Hospital over a four-year period. Since the complaints pointed to colonic malignancy, the patients underwent routine golden standard diagnostic procedures. These patients were referred to an experienced abdominal ultrasound operator who searched for some characteristic signs of colonic malignancy. All of the participants were surgically treated after the completion of relevant procedures for diagnosing colonic malignancy. SPSS for Windows 10.0 was used for data analysis. Results: The sensitivity of an abdominal ultrasound scan in the detection and location of pathological changes pointed to colonic malignancy was different- 76% and 84% respectively. This method was very reliable in detecting right-sided colonic carcinoma (100%). Some specific ultrasonographic signs of colonic carcinoma were observed at the advanced stages of disease. Conclusions: The routine abdominal ultrasonography can be used for the screening of colonic malignancy owing to its high sensitivity, particularly in advanced disease, but solely in conjunction with other methods. Finally, abdominal ultrasonography cannot be a definitive diagnostic tool for colonic carcinoma. © 2008 The Japanese Society of Internal Medicine.

Levothyroxine (LT4) is used to treat frequently encountered endocrinopathies such as thyroid diseases. It is regularly used in clinical (overt) hypothyroidism cases and subclinical (latent) hypothyroidism cases in the last decade. Suppressive LT4 therapy is also part of the medical regimen used to manage thyroid malignancies after a thyroidectomy. LT4 treatment possesses dual effects: substituting new-onset thyroid hormone deficiency and suppressing the local and distant malignancy spreading in cancer. It is the practice to administer LT4 in less-than-high suppressive doses for growth control of thyroid nodules and goiter, even in patients with preserved thyroid function. Despite its approved safety for clinical use, LT4 can sometimes induce side-effects, more often recorded with patients under treatment with LT4 suppressive doses than in unintentionally LT4-overdosed patients. Cardiac arrhythmias and the deterioration of osteoporosis are the most frequently documented side-effects of LT4 therapy. It also lowers the threshold for the onset or aggravation of cardiac arrhythmias for patients with pre-existing heart diseases. To improve the quality of life in LT4-substituted patients, clinicians often prescribe higher doses of LT4 to reach low normal TSH levels to achieve cellular euthyroidism. In such circumstances, the risk of cardiac arrhythmias, particularly atrial fibrillation, increases, and the combined use of LT4 and triiodothyronine further complicates such risk. This review summarizes the relevant available data related to LT4 suppressive treatment and the associated risk of cardiac arrhythmia. © Copyright © 2021 Gluvic, Obradovic, Stewart, Essack, Pitt, Samardzic, Soskic, Gojobori and Isenovic.

Metabolic syndrome (MetS) is a leading public health and clinical challenge worldwide. MetS represents a group of interrelated risk factors that predict cardiovascular diseases (CVD) and diabetes mellitus (DM). Its prevalence ranges between 10 and 84%, depending on the geographic region, urban or rural environment, individual demographic characteristics of the population studied (sex, age, racial and ethnic origin), as well as the criteria used to define MetS. Persons with MetS have higher mortality rate when compared with people without MetS, primarily caused by progressive atherosclerosis, accelerated by pro-inflammatory and pro-coagulation components of MetS. Considering the high prevalence of metabolic disorders (glucose metabolism disorder, hypertension, dyslipidaemia, obesity etc.), preventive healthcare should focus on changing lifestyle in order to reduce obesity and increase physical activity. This narrative review considers the available evidence from clinical and experimental studies dealing with MetS, and current treatment options for patients with insulin resistance and MetS. © 2017 Bentham Science Publishers.

Introduction: Cardiovascular (CV) disorders are steadily increasing, making them the world’s most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV health Methods: We searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years. Results: IGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy. Discussion: We anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs. Copyright © 2023 Macvanin, Gluvic, Radovanovic, Essack, Gao and Isenovic.

Subclinical hypothyroidism (SH) is characterized by a mildly elevated concentration of thyroid stimulating hormone (TSH) despite free thyroxine (FT4) and triiodothyronine (FT3) levels within the reference range. Numerous studies revealed SH to be an independent risk factor for cardiovascular disease (CVD), including atherosclerosis, congestive heart failure, coronary heart disease, ischemic heart disease and the associated mortality. The relationship between SH and CVD is well documented, but the molecular mechanism underlying this correlation remain unknown. Endothelial dysfunction has been recognized as an initial step leading to CVD in patients with SH. Changes in lipid profile, inflammation and/or oxidative stress contribute to the endothelial dysfunction in SH. Moreover, the progression of SH is characterized by significantly decreased nitrite and nitrate levels. Recent animal and clinical studies discussed in this review suggest that nitric oxide (NO) levels could be a reliable biomarker for cardiovascular risk in SH. Understanding the regulation of NO production by thyroid hormone may provide novel and useful knowledge regarding how endothelial dysfunction in SH is linked with CVD and help us to uncover new treatments for SH. We suggest that serum NO level may be an indicator for the introduction and dosage of levothyroxine (LT4) replacement therapy in SH patients. Future studies should focus on understanding the molecular mechanisms underlying the effects of NO in physiological as well as in pathophysiological conditions such as hypothyroidism and their clinical relevance. © 2016 Bentham Science Publishers.

Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD’s possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients. Copyright © 2022 Shandong University, published by Wolters Kluwer, Inc.

Introduction: Patients with Cushing’s syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient’s condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient’s condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients. Copyright © 2022 Popovic, Radovanovic Spurnic, Velickovic, Plavsic, Jecmenica-Lukic, Glisic, Ilic, Jeremic, Vratonjic, Samardzic, Gluvic and Adzic-Vukicevic.

Cardiometabolic diseases (CMD) are a direct consequence of modern living and contribute to the development of multisystem diseases such as cardiovascular diseases and diabetes mellitus (DM). CMD has reached epidemic proportions worldwide. A sodium pump (Na+/K+-ATPase) is found in most eukaryotic cells’ membrane and controls many essential cellular functions directly or indirectly. This ion transporter and its isoforms are important in the pathogenesis of some pathological processes, including CMD. The structure and function of Na+/K+-ATPase, its expression and distribution in tissues, and its interactions with known ligands such as cardiotonic steroids and other suspected endogenous regulators are discussed in this review. In addition, we reviewed recent literature data related to the involvement of Na+/K+-ATPase activity dysfunction in CMD, focusing on the Na+/K+-ATPase as a potential therapeutic target in CMD. Copyright © 2023 Obradovic, Sudar-Milovanovic, Gluvic, Banjac, Rizzo and Isenovic.

An imbalance between pro-oxidative and antioxidative cellular mechanisms is oxidative stress (OxS) which may be systemic or organ-specific. Although OxS is a consequence of normal body and organ physiology, severely impaired oxidative homeostasis results in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells’ function and viability. The thyroid gland is an organ that exhibits both oxidative and antioxidative processes. In terms of OxS severity, the thyroid gland’s response could be physiological (i.e. hormone production and secretion) or pathological (i.e. development of diseases, such as goitre, thyroid cancer, or thyroiditis). Protective nutritional antioxidants may benefit defensive antioxidative systems in resolving pro-oxidative dominance and redox imbalance, preventing or delaying chronic thyroid diseases. This review provides information on nutritional antioxidants and their protective roles against impaired redox homeostasis in various thyroid pathologies. We also review novel findings related to the connection between the thyroid gland and gut microbiome and analyze the effects of probiotics with antioxidant properties on thyroid diseases. Copyright © 2023 Macvanin, Gluvic, Zafirovic, Gao, Essack and Isenovic.