The nitrite concentration in the blood in patients with hypothyroidism as a parameter for the introduction of substitution therapy

Uvod: Primarni hipotireoidizam je kliniĉki sindrom uzrokovan nedostatkom ili neadekvatnim efektima tireoidnih hormona. Povećan rizik od nastanka ubrzane ateroskleroze kao i njene ispoljenosti kod obolelih od primarnog hipotireoidizma moţe se objasniti prisustvom dislipidemije, dijastolne hipertenzije, povećane arterijske krutosti, endotelne disfunkcije, kao i stanjem hiperkoagulabilnosti i inflamacije niskog stepena. Kardiovaskularno ispoljavanje ubrzane ateroskleroze kod obolelih od primarne hipotireoze se ogleda kroz povećan rizik od koronarne bolesti i srĉane insuficijencije, koje su opisane kod razliĉitog stepena ispoljenosti hipotireoidizma i starosne dobi, prevashodno kada je nivo TSH >10mIU/ml. Smanjena produkcija azot oksida (NO) se smatra potencijalno reverzibilnim uzrokom endotelne disfunkcije u supkliniĉkom i kliniĉkom hipotireoidizmu. Sve promene u kardiovaskularnom sistemu u stanjima hipotireoidizma se registruju u neleĉenom primarnom hipotireoidizmu, a vraćaju se delimiĉno ili potpuno na prethodno stanje nakon adekvatne supstitucije levotiroksinom. Nakon dijagnostikovanja kliniĉkog primarnog hipotireoidizma, odmah se pristupa tretmanu levotiroksinom, dok je u sluĉajevima supkliniĉkog hipotireoidizma tretman nedvosmislen kod onih kod kojih se oĉekuje korist (mlade osobe, planiranje trudnoće, trudnoća), kao i kod onih sa nivoom TSH >10mIU/ml. Kod obolelih sa nivoom TSH izmeĊu 4 i 10mIU/ml, individualnim pristupom se odreĊuje da li osobu treba tretirati ili ne, privremeno ili trajno. Prisustvo dislipidemije moţe biti jedan od razloga za uvoĊenje terapije levotiroksinom. Cilj ove doktorske disertacije je bio da se ispita da li koncentracija nitrita (NO2), stabilnog i jednostavno merljivog metabolita NO, moţe biti potencijalni dodatni parametar za uvoĊenje terapije levotiroksinom kod hipotireoidnih, prevashodno supkliniĉkih ispitanika. Radna hipoteza ove doktorske disertacije je bila: da li promena u koncentraciji NO2, kao pokazatelja ateroskleroze, moţe biti pouzdan dodatni kriterijum za uvoĊenje supstitucione terapije levotiroksinom kod hipotireoidnih ispitanika. Stoga je u okviru ove doktorske disertacije merena koncentracija NO2 u krvi obolelih od supkliniĉke i kliniĉke hipotireoze, kao i kod eutireoidnih kontrola, a takoĊe je analizirano da li postoji korelacija izmeĊu koncentracija NO2 i nivoa TSH i fT4, nakon ĉega je odreĊivan i uticaj supstitucione terapije kod tretiranih ispitanika sa primarnom hipotireozom na koncentraciju NO2 u krvi..

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus (DM) is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. In 2021, the global prevalence of diabetes is anticipated to be 10.7% (537 million people). Noncoding RNAs (ncRNAs) appear to have an important role in the initiation and progression of DM, according to a growing body of research. The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs. miRNAs are singlestranded, short (17–25 nucleotides), ncRNAs that influence gene expression at the post-transcriptional level. Because DM has reached epidemic proportions worldwide, it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently. miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation. In this review, we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders. We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM. We examine and synthesize recent research that used novel, high-throughput technologies to uncover ncRNAs involved in DM, necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses

Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines

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

Diabetic cardiomyopathy: The role of microRNAs and long non-coding RNAs

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

New insights on the cardiovascular effects of IGF-1

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 healthMethodsWe 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.ResultsIGF-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.DiscussionWe 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

Subacute thyroiditis following COVID-19 vaccination: Case presentation

Background:Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroiddamage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the formof permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated withCOVID-19.Purpose:The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limiteddocumentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of PfizerBioNTech’s COVID-19 mRNA vaccine.Research design and study sample:Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccineagainst SARS-CoV-2 viral infection. The patient deniedever having an autoimmune disease or any other disease.Painful neck palpation and afirm, slightly enlarged thyroid gland with no surrounding lymphadenopathy wereidentified during the exam. The heart rate was 104 beatsper minute. All of the remaining physicalfindings werenormal.Data collection and/or Analysis:Data collected during the disease are integral to the medical record.Results:Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocyticanaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient’sthyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SATrelated to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition

The role of the liver in glucose and lipid metabolism in obesity

Jetra ima važnu ulogu u održavanju metaboličke homeostaze i predstavlja mesto kompleksne regulacije metabolizma supstrata (ugljenih hidrata, lipida i proteina) od strane insulina i drugih hormona. Proteklih decenija ističe se značaj metaboličkih funkcija jetre u brojnim patološkim stanjima. Mehanizmi kojima gojaznost dovodi do poremećaja metaboličkih procesa u jetri su danas predmet mnogobrojnih istraživanja. Metaboličke i hormonske promene koje su posledica prevashodno visceralne gojaznosti, dovode vremenom do nagomilavanja lipida u jetri. Povećana učestalost gojaznosti i razvoj metaboličkog sindroma doprinose pojavi patofizioloških promena u jetri i razvoju nealkoholne bolesti masne jetre (NAFLD), jednoj od najčešćih bolesti jetre u zapadnoevropskim zemljama. U ovom preglednom članku razmotrili smo najnovije literaturne podatke koji se odnose na ulogu jetre u metabolizmu glukoze i lipida u stanju gojaznosti.The liver plays a vital role in metabolic homeostasis and represents a major site for complex regulation of substrates (carbohydrates, lipids, and proteins) by insulin and other hormones. The significance of liver metabolic functions in many pathophysiological conditions is highlighted over the past decades. Mechanisms of obesity-induced metabolic disturbance in the liver are the topic of numerous research studies. Metabolic and hormonal changes which are caused primarily by visceral obesity lead to hepatic lipid accumulation. Increased prevalence of obesity and the development of metabolic syndrome contribute to pathophysiological changes in the liver and development of non-alcoholic fatty liver disease (NAFLD), one of the most common diseases in Western societies. In this review, we discussed most recent literature data related to the role of the liver in glucose and lipid metabolism in obesity

A quality of life assessment and the correlation between generic and disease-specific questionnaires scores in outpatients with chronic liver disease-pilot study

Introduction. Chronic liver diseases (CLD) are an important cause of morbidity and mortality in general population. The aim of this study was to analyze potential differences between patients with CLD and healthy control group, and to estimate the severity of CLD by using simple questionnaires: general health questionnaire (GHQ-12) and chronic liver disease questionnaire (CLDQ). Methods. A cross-sectional pilot study was performed in Zemun Clinical Hospital during years 2014 and 2015. Sixty participants were divided into 4 groups (15 per group): chronic alcoholic hepatitis, other chronic hepatitis, liver cirrhosis, and healthy control group. Entire study population chose one of four offered answers of structured questionnaires GHQ-12 and CLDQ, based on which mean model of end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were calculated. Results. Mean GHQ12 and CLDQ scores were 10.5 and 5.21 +/- 1.11 respectively. Regarding certain CLDQ domain scores, a significant difference between alcoholic and non-alcoholic hepatitis groups in the worry domain was observed. Mean MELD score was 7.42 +/- 2.89 and did not differ between chronic hepatitis groups, while mean CTP score was 5.73 +/- 0.88. A statistically significant correlation was observed between GHQ12 and CLDQ scores (rho = -0.404, p LT 0.01), but not between subjective and objective scores. Conclusions. Mean GHQ12 and CLDQ scores pointed out to general psychological no-distress condition of the studied participants, as well as scarcely expressed CLD-specific complaints. Mean MELD and CTP scores indicated stable chronic liver diseases, with low three-month mortality rates in the cases of chronic hepatitis, as well as determination to Child A group in the case of liver cirrhosis

Management of Non-Classic Congenital Adrenal Hyperplasia in Pregnant Woman - Non-Referral Center Experience- Case Report

Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder with mutations in genes involved in cortisol and aldosterone production. Based on overall 21-OHase activity, CAH is divided into classic (C-CAH) and non-classic (NC-CAH). Females who suffered from NC-CAH have had increased infertility rates and higher miscarriage susceptibility. The treatment of CAH in pregnancy is still debatable. We present 22-years-old pregnant female (seventh week of gestation), who is currently under dexamethasone (DEX) since almost seven years for NC-CAH. At presentation, she is normotensive, non-obese, with no signs of hirsutism and Cushing syndrome. Seven days after the first visit, an endocrinologist makes informative talk with the patient and her mother about NC-CAH, pregnancy, and drugsassociated risks. Current Clinical Practice Guideline for CAH treatment suggests the use of protocols approved by Institutional Review Boards at Centers experienced in CAH treatment. In women with CAH who are planning a pregnancy, a close relationship between endocrinologist, reproductive gynaecologist and molecular biologist is of great interest. Prenatal management with DEX is advised in particular circumstances. In remaining, the switch from DEX to other glucocorticoids that do not penetrate placenta is advise

Inflammation, nutritional status, pufa profile and outcome in hemodialysis patients

Patients with end-stage renal disease (ESRD) include a significant percentage of malnourished patients with other risk factors: dyslipoproteinemia, insulin resistance, increased oxidative stress and inflammation that together impair endothelial function. Abnormal polyunsaturated fatty acids (PUFA) patterns are reported in patients with ESRD. The basic mechanisms of these disorders are connected with changes in cell functions at the membrane level. Vascular smooth muscle cell proliferation plays an important role in the pathogenesis of atherosclerosis. We have examined the association between atherosclerotic risk factors and nutritional status in hemodialysis (HD) patients. Mortality was followed for up to 18 month. Forty-three HD patients were examined (20 males, 23 females, ages 55±12 years). Nutritional and inflammatory markers, including serum concentrations of C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6), were measured. There was significant positive correlation between the plasma albumin level and CRP. Significant correlation was found between plasma the cholesterol level and some PUFA. Increasing inflammation and endothelial dysfunction predict the development of vascular disease. We report on the relationship between inflammatory markers and nutritional parameter, indices of atherosclerosis and other cardiovascular risk factors in patients on hemodialysis