Browsing by Author "Obradovic, Milan (48061421600)"

Context. Prognostic considerations include assessing the risk of liver fibrosis in people with non-alcoholic fatty liver disease (NAFLD). Objectives. This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods. Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results. Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib-4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion. HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether non-obese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis. © 2022, Acta Endocrinologica Foundation. All rights reserved.

Context. Prognostic considerations include assessing the risk of liver fibrosis in people with non-alcoholic fatty liver disease (NAFLD). Objectives. This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods. Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results. Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib-4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion. HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether non-obese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis. © 2022, Acta Endocrinologica Foundation. All rights reserved.

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.

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.

We studied the in vivo effects of estradiol on size and biochemical parameters of cardiomyocytes in pathophysiological conditions such as obesity and insulin resistance. Male Wistar rats were normally fed (controls, n = 7) or fed with high-fat diet (obese, n = 14). Half of the obese rats (obese + estradiol, n = 7) were treated with a single dose of estradiol (40 μg/kg, intraperitoneally) and 24 hours after treatment all the rats were killed. Estradiol in vivo in obese rats resulted in a significant increase in protein kinase B (Akt) activation (P < .05) and decrease in heart mass (P < .05), ratio of the heart mass/body mass (P < .05), transverse diameters of cardiomyocytes (P < .001), concentration of serum high-sensitivity C-reactive protein (P < .001), and total cholesterol (P < .01) compared with obese nontreated rats. Our results suggest that estradiol in obese/IR rats affects the size of cardiomyocytes and its actions lead in vivo to a reduction in obesity-induced cardiac hypertrophy via Akt. © The Author(s) 2013.

Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

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.

Background: Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. Methods: In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-ΚB (NFΚB-p50) in heart was increased by 77% (p<0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signalregulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were shown to be significantly reduced in HF-fed rats. Results and Conclusion: Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFΚB-p50 proteins. Decreased levels of oestradiol and ERΚ protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression. © 2017 Bentham Science Publishers.

Background: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. Methods: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectro-photometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Co-immunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phos-phatidylinositol-3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. Results: Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. Conclusion: Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R. © 2019 Bentham Science Publishers.

Background: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. Methods: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectro-photometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Co-immunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phos-phatidylinositol-3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. Results: Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. Conclusion: Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R. © 2019 Bentham Science Publishers.

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.

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), metabolic syndrome (MetS), and type 2 diabetes (T2DM) are metabolic disorders that belong to a highly prevalent disease cluster with a significant impact on public health worldwide. MetS is a complex condition characterized by metabolism perturbations that include glucose intolerance, insulin resistance, dyslipidaemia, associated pro-inflammatory state, and arterial hypertension. Because the components of MetS commonly co-occur, the management of these disorders cannot be considered separate issues. Thus NAFLD, recognized as a hepatic manifestation of MetS, is frequently associated with T2DM. This review analyses the underlying connections between these diseases and the risks associated with their co-occurrence. The effective management of NAFLD associated with MetS and T2DM involves an early diagnosis and optimal treatment of each condition leading to improvement in glycaemic and lipid regulation, liver steatosis, and arterial hypertension. The net effect of such treatment is the prevention of atherosclerotic cardiovascular diseases and liver fibrosis. © 2022 Termedia & Banach.

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.

Carotid endarterectomy (CEA) is the gold standard for the treatment of symptomatic patients with atherosclerotic carotid disease. However, benefit of the CEA procedure depends on the rate of peri- and postoperative adverse neurological events. Therefore, brain monitoring is important in detecting cerebral ischemia during and after CEA and also allows to prompt appropriate action. Traditional methods of cerebral monitoring are being replaced by novel, easy-to-use techniques that allow continued monitoring of regional cerebral oxygen saturation. In this review, we present the recent literature data related to the mechanism of cerebral oximetry and its practical use during and after CEA. © The Author(s) 2013.

Endovascular surgery represents a minimally invasive procedure for the treatment of occlusive and aneurysmal arterial disease. However, it is followed by inflammatory response, with a rise in specific inflammatory biomarkers, such as C-reactive protein, serum amyloid A and fibrinogen. Shear stress during balloon inflation and vascular injury represents triggering events for the inflammatory process, stimulating the production of proinflammatory molecules and activation of circulating monocytes. The current literature indicates that stent implantation induces more prominent inflammatory reaction. Additionally, it has been shown that muscular arteries of femoropopliteal segment react to a greater extent to stent implantation, compared with elastic carotid or iliac arteries. The endovascular treatment of thoracic and abdominal aortic aneurysm is frequently followed with post-implantation inflammatory syndrome. Most recent findings point out that stent graft material plays a significant role in the inflammatory response, representing a challenge for clinicians. Future studies should consider the pathophysiology of the inflammatory response associated with endovascular procedures as well as predictors and risk factors including preventive strategies and therapeutic algorithms. Although the potential role of anti-inflammatory drugs after endovascular procedures has been observed, it needs to be validated in upcoming trials. The Neutrophil Lymphocyte Ratio, platelet count, Platelet-to-Lymphocyte Ratio and other biomarkers should be considered in future trials to assess the inflammatory response after endovascular procedures. Inflammatory markers may also become therapeutic targets. © 2017 Bentham Science Publishers.