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Lockdown measures to control disease transmission were implemented at the start of the COVID-19 era, worsening the already existing sedentary lifestyle. Reduced physical activity (PA) and unhealthy eating habits have a negative impact on mental health in chronically ill patients, including diabetes patients. Mental illness, on the other hand, encourages a sedentary lifestyle, exacerbating all components of metabolic syndrome. While well-controlled diabetic patients with an HbA1c of less than 7% had a less severe clinical presentation and COVID-19 mortality rates, the favorable effect of PA on immunomodulation and immunoregulation should not be neglected. Given recent data indicating that a sedentary lifestyle is the third independent risk factor for COVID-19 complications and death (after advanced age and organ transplant), including regular PA has never been more vital. Since PA has a major impact on both glycemic control and mental health, implementing structured home-based activity programs could improve glycemic control and psychological well-being, hence positively impacting COVID-19 outcomes.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of drugs that have primarily been used in the treatment of type 2 diabetes. However, as new findings from clinical trials have become available, their indication has been expanded to include treatment of heart failure and chronic kidney disease without the presence of diabetes. The pathophysiological mechanisms of extraglycemic effects of SGLT2i are still being unraveled, but one of the most prominent consequences is a decrease in blood pressure, which has implications for hemodynamics and arterial stiffness. Recent findings indicate that this class of drugs has a beneficial effect on lowering nocturnal blood pressure (BP), with special importance in type 2 diabetes (DMT2), since unregulated nocturnal hypertension is associated with an increased incidence of cardiovascular (CV) events. In this mini-review, we have summarized current knowledge about the effects of SGLT2i on blood pressure, including office, home, and ambulatory BP, and potential implications for treatment of hypertension in diabetic and non-diabetic individuals, with positive effects on cardiorenal outcomes.

Metabolically associated fatty liver disease (MAFLD) is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to cirrhosis. Up to date, there are no approved pharmacotherapies for the treatment of MAFLD, so management focused on lifestyle interventions to encourage weight loss, and treatment of coexisting conditions is the only available option. Unfortunately, the aforementioned is often not potent enough to offer reversal or slow down hepatic inflammation and fibrosis. Glucagon-like peptide-1 receptor agonists have a favorable effect on glycemic management and weight loss of patients with type 2 diabetes mellitus and recently published data suggest their potential in MAFLD treatment. In addition, some of the agents have proven cardiovascular and renal benefits in dedicated cardiovascular outcome trials, making them an interesting therapeutic option. In this opinion review, we discuss the role of semaglutide in MAFLD.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of drugs that have primarily been used in the treatment of type 2 diabetes. However, as new findings from clinical trials have become available, their indication has been expanded to include treatment of heart failure and chronic kidney disease without the presence of diabetes. The pathophysiological mechanisms of extraglycemic effects of SGLT2i are still being unraveled, but one of the most prominent consequences is a decrease in blood pressure, which has implications for hemodynamics and arterial stiffness. Recent findings indicate that this class of drugs has a beneficial effect on lowering nocturnal blood pressure (BP), with special importance in type 2 diabetes (DMT2), since unregulated nocturnal hypertension is associated with an increased incidence of cardiovascular (CV) events. In this minireview, we have summarized current knowledge about the effects of SGLT2i on blood pressure, including office, home, and ambulatory BP, and potential implications for treatment of hypertension in diabetic and non-diabetic individuals, with positive effects on cardiorenal outcomes.

Diabetic nephropathy (DN) is a major cause of chronic kidney disease and endstage renal failure. In this study, the effects of empagliflozin (SGLT2i) on cell viability and oxidative stress were investigated in the LLC-PK1 model of DN. Materials and methods: Cells were exposed to high glucose (HG30 mM) followed by 0.5 mM H2O2 and a combination of glucose and H2O2 for 24 hours. Cells were treated with various combinations of glucose and empagliflozin (100 and 500 nM) and combinations of glucose, H2O2, and empagliflozin. Colorimetric MTT assay was used to determine cell viability. Glutathione (tGSH) and TGF-β1 concentrations were measured using a spectrophotometric/microplate assay and an ELISA kit, respectively. Results: After initial exposure of cells to glucose and oxidative stress, addition of both concentrations improved cell viability and also increased the accumulation of GSH concentration (p < 0.001, p < 0.05). In addition, empagliflozin treatment caused a decrease in TGF- β1 levels in both concentrations of injured cells (p < 0.001). Conclusions: Cellular viability indicates that empagliflozin has a protective effect on renal injury. The renoprotective effect of empagliflozin is mainly mediated by the reduction of antioxidant stress and the antifibrotic properties of the drug.

Diabetic nephropathy (DN) is a chronic complication of diabetes mellitus, both type I and type II, which can lead to end-stage renal kidney failure. This research aimed to assess the effects of empagliflozin (SGLT2i) on cell viability and F- actin distribution in the LLC-PK1 model of DN. To mimic DN, cells were exposed to high glucose (HG30 mM) followed by 0, 5 mM H2O2 and a combination of glucose and H2O2 for 24 hours. The cells were treated with different combinations of glucose and empagliflozin (100 and 500 nM) and combinations of glucose, H2O2, and empagliflozin. MTT colorimetric assay and Erythrosin B color exclusion test were used to determine cell viability. F-actin cytoskeleton was visualized with Phalloidin stain and subsequently quantified. MTT results revealed a significant reduction in cell viability when treated with the HG30/H2O2 combination (p

Introduction: Nonalcoholic fatty liver disease (NAFLD) has become one of the global health problems. Drugs, such as tamoxifen, may trigger or exacerbate pre-existing NAFLD. The aim of our study was to establish a reliable cell culture model of tamoxifen-induced steatosis (TIS) and to investigate a possible antisteatotic effect of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide in this model. Materials and methods: The cell culture model of drug-induced hepatic steatosis was established by incubating Huh7 cells, a human liver cell line expressing the GLP- 1 receptor, with 2 μM tamoxifen for 24 hours. Cells were co-treated with 5 nM to 20 nM liraglutide. Cell survival was measured by the erythrosin B staining exclusion assay, and changes in cell shape and the extent of hepatosteatosis were assessed by fluorescence microscopy with Oil- Red-O (ORO) and DAPI staining, respectively. The expression of various lipogenic genes and signals was assessed by RT-PCR. Results: Tamoxifen significantly decreased cell survival in the TIS model (p < 0, 05), and concurrent treatment with liraglutide had no significant effect. A 5-fold increase in lipid accumulation was observed by ORO staining in the TIS model (p < 0, 001), which was due to the significant increase in the number of lipid droplets. However, liraglutide reversed this effect and significantly decreased the number of lipid droplets (p < 0, 05). Liraglutide co- treatment significantly ameliorated the lipogenic ACSL1 and SREBP-1c gene expression signaling pathways, which were increased in the TIS model (p < 0, 001). Conclusions: Liraglutide ameliorates microsteatotic changes observed in TIS model by downregulation of ACSL1 and SREBP-1c gene pathways.

Corticosteroids are widely used drugs, with many known side effects, such as impairment of glycemic control. This adverse effect is seen both in patients with preexisting diabetes and in normoglycemic ones potentially leading to steroid-induced diabetes mellitus. Corticosteroids are largely used in oncology, both as a curative treatment and as a symptom control in supportive care for patients with various malignancies. Case report: We present a 55-year-old woman who was diagnosed with diabetes mellitus type two six years ago. Diabetes was regulated by an endocrinologist who included gliclazide and metformin/sitagliptin in therapy. She was also treated by an oncologist due to a diagnosis of invasive metastasizing breast cancer. As chemotherapy and dexamethasone treatment was introduced by the oncologist, a significant rise in glycemia (15-20 mmol/l) occurred. Following that, she was prescribed postprandial pre-mixed lispro/NPH and gliclazide was discontinued. This approach maintained glycemia in the normal range. However, in days when chemotherapy and dexamethasone was administered, there was an increase in glucose plasma level. Therefore, in addition to current therapy, it was necessary to administer higher doses of insulin on the day of chemotherapy. The last application of dexamethasone was in October 2020. Diabetic therapy remained the same and HbA1c was 7.1%. Conclusion: Hyperglycemia usually occurs in the first 48 hours after administration of high doses of glucocorticoid therapy. Considering that, close monitoring of glucose profiles should be performed. Oncology patients should have their baseline HbA1c and venous plasma glucose when starting steroid therapy.

Graves’ disease is an autoimmune disease characterized by excessive thyroid hormone production. One of the consequences of that state can be a decrease in bone mineral density (BMD). Graves’ disease is often treated with antithyroid drugs (ATD) as first line therapy, which can lead to disease remission. Moreover, recent data show that improvement in BMD can be expected. However, vitamin D deficiency can coexist along with Graves’ disease, which is also involved in the process of bone remodeling. It is still not known whether lower values of vitamin D can contribute to onset of Graves’ disease and if its supplementation might be helpful in therapy for hyperthyroidism. In the past couple of decades, osteopenia and osteoporosis have become a major health burden not only in post-menopausal women but also as a result of other diseases, leading to extensive research into various pathophysiological mechanisms responsible for bone remodeling. The Wnt (wingless integrated) signaling pathway is a very important factor in bone homeostasis, especially the canonical pathway. Present data indicate that stimulation of the Wnt pathway leads to bone mass increase and, in contrast, its inhibition leads to bone mass decrease. Hence, inhibitors of the canonical Wnt pathway became the focus of interest, in particular sclerostin and dickkopf 1 (DKK1). Hyperthyroidism and osteopenia/osteoporosis are quite common today and can coexist together or as separate entities. In this article, we aimed to give an overview of possible associations and potential mutual pathophysiological mechanisms., Gravesova bolest je autoimuna bolest karakterizirana prevelikom proizvodnjom hormona štitnjače. Jedna od posljedica toga stanja može biti sniženje mineralne gustoće kosti. Liječi se antitireoidnim lijekovima kao prvim izborom čime se može postići remisija bolesti. Postizanjem remisije, može se očekivati i poboljšanje mineralne gustoće kosti. No, uz Gravesovu bolest, može postojati i snižena vrijednost vitamina D koji je također važana za procese pregradnje kosti. Još je uvijek otvoreno pitanje mou li snižene vrijednosti vitamina D pridonijeti nastanku Gravesove bolesti i da li bi njegova supstitucija mogla pomoći u liječenju hipertireoze. Kako je smanjena mineralna gustoća kosti danas rasprostranjena širom svijeta, u prošlim desetljećima počeo se istraživati Wnt put. Ovaj put vrlo je važan za homeostazu kosti, osobito njegov dio koji se naziva kanonički put u kojem sudjeluju i sklerostin i dickkopf 1 kao inhibitori. Svi spomenuti čimbenici, odnosno stanja, danas su učestala i mogu postojati zajedno i odvojeno. Ovim člankom pokušali smo dati pregled moguće veze između njih.

Transforming growth factor-beta (TGF-β) has recently been associated with diabetic nephropathy (DN) development. It causes cell apoptosis induced by oxidative stress and cell proliferation and migration triggered by hyperglycemia and inflammation. Liraglutide is an antihyperglycemic agent that has a direct renoprotective effect. This study aimed to evaluate the effects of liraglutide on cell viability and TGF-β expression in the LLC-PK1 model of DN. Cell viability was determined by colorimetric MTT assay and erythrosine B color exclusion assay. The expression of mRNA TGF- β1 was measured by RT-PCR and β-actin was used as an internal control. LLC- PK1 cell culture was treated with different concentrations of glucose (1.5, 30 mM) and the combination of glucose and H2O2 (0.5 mM) for 24 hours. To study the renal effect of liraglutide, cells were treated for 24 hours with different combinations of glucose and liraglutide (10, 20 nM) and combinations of glucose, H2O2, and liraglutide. A significant decrease in MTT levels compared to control (p < 0.01 ; p < 0.001) was observed after treatment with a combination of HG30/ H2O2 and HG30 alone. Cell viability was improved by the addition of liraglutide (10 nM) to cells treated with HG30, while 20 nM had no effect. There was no significant difference in cell survival with the addition of HG30 and HG30/ H2O2 compared to control. The addition of liraglutide at both concentrations to cells treated with HG30 and HG30/H2O2 improved cell survival, although significance was only numerical, not reaching statistical significance. TGF-β1 expression levels were significantly increased in cells treated with HG30 (p < 0.001). Liraglutide inhibited TGF-β1 expression except in HG30/H2O2 treated cells. Our results support a protective role of liraglutide in LLC-PK1 cells, mediated by inhibition of TGF-β1, thus reducing oxidative stress damage.

Pituitary incidentalomas represent previously unsuspected pituitary lesions, divided into microincidentalomas and macroincidentlomas. They are commonly found by CT or MRI scans indicated for unrealted, non-pituitary disease. Although pathohistological mechanisms and etiology is unclear, 90% of pituitary incidentalomas include benign adenomas. Case report: We present two patients with different diagnosis and treatment of pituitary incidentaloma. First patient is a 25 year-old woman with non-specific headaches, but without clinical signs of endocrinopathy. She has regular menstrual cycles without galactorrhea. Magnetic resonance imaging (MRI) showed microadenoma 5-6 millimeters in size. Initial tests included analysis for hormone hypersecretion and hypopituitarism. Laboratory results revealed increased prolactin. According to the findings, the diagnosis was non secretory microadenoma. No therapy was prescribed, only regular check-ups. Second patient is a 70-year-old woman with frequent headaches, but also without clinical signs of endocrinopathy. MRI showed deformed sella turcica due to an expansive formation extending craniocaudal, more likely corresponding to macroadenoma. Laboratory exams discovered decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH), while prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxine (fT4) were increased. Examination by ophthalmologist revealed severe pale left optic nerve and bitemporal hemianopia. Surgery was recommended. Conclusion: To conclude, decision about appropriate course of treatment and follow up is based on the results of MRI, computed tomography (CT), visual field examination and basal dynamic hormonal or assessments. Not all incidentalomas require neurosurgical intervention. If not treated surgically, patients are treated conservatively, with regular check-ups, imaging studies and hormonal assessments.

Stoljećima ljuta crvena paprika predstavlja jedan od glavnih začina u tradicionalnoj hrvatskoj kuhinji. Osim kao začin tijekom pripremanja jela, crvena paprika pripada nezaobilaznim sastojcima u pripremi suhomesnatih proizvoda. Iako dugo prisutna u prehrani čovjeka, tek unazad desetak godina dobiva status namirnice s izrazito povoljnim učinkom na zdravlje čovjeka. Upravo ljuta paprika odnosno kapsaicin, alkaloid odgovoran za ljutinu biljke, prepoznat je kao glavni čimbenik odgovoran za ljekovita svojstva paprike. Naime, pokazano je da redovito konzumiranje ljute paprike smanjuje rizik za razvoj srčanog i moždanog udara, a time smanjuje i ukupnu kardiovaskularnu smrtnost. Nadalje, poznat je povoljan učinak kapsaicina na značajne kardiovaskularne rizične faktore kao što su hipertenzija te metabolički sindrom. In vivo studije pokazale su povoljan učinak kapsaicina na metabolizam glukoze s posljedičnim smanjenjem inzulinske rezistencije. Također, na životinjskom modelu pokazano je da kapsaicin smanjuje koncentraciju triglicerida u plazmi te dovodi do smanjenja masnog tkiva što rezultira redukcijom tjelesne težine. Uzevši u obzir iznešene dokaze ljuta paprika definitivno zaslužuje centralno mjesto na svakoj polici sa začinima, ako ne zbog zdravstvenih blagodati onda bar zbog vitke linije.

Introduction: Breast cancer (BC) is the most common malignant disease in females taking 26 % of all cancer sites. Third generation aromatase inhibitors like anastrozole are becoming more important in treating BC because of their efficacy and better overall safety in the adjuvant treatment. Single nucleotide polymorphism (SNP) in genes encoding drug metabolizing enzymes could have an important role in individual responses to anastrozole therapy including drug efficacy and side effects. Aim: To explore rates of three SNPs (CYP3A4*1B, CYP3A5*3, UGT1A4*2) important in anastrozole metabolism in population of Croatian BC patients, and its possible correlation to anastrozole induced side effects. Materials and methods: 126 BC patients were included in the study of which 82 were postmenopausal patients with ER positive BC treated with anastrozole and 44 were postmenopausal ER positive patients before hormonal adjuvant therapy. DNA for SNPs was genotyped by TaqMan RT-PCR and BMD was measured by DXA. Results: Homozygotes for the wild type A allele of CYP3A5*3 were not detected, moreover mutant G allele homozygotes were predominant with 88%. Wild type homozygotes of CYP3A4*1B were predominant with 94%, and mutant homozygotes were not detected. CYP3A4*1B and CYP3A5*3 SNPs were in 84.3% linkage disequilibrium and 95.1% in group treated with anastrozol and without treatment. Possible association of BMD changes induced by anastrozole therapy with prevalence of the three explored SNPs was not demonstrated. Conclusion: Even though the mutant CYP3A5*3 SNP was predominant, which may result in poor anastrozole metabolism, no significant differences in BMD between the groups were confirmed.

Breast cancer (BC) is the most prevalent cancer in women worlwide. Nowadays, anastrazole is the first choice treatment in postmeopausal women with hormon-dependent BC (HR-BC). Single nucleotide polymorphism (SNP) in genes encoding drug-metabolizing enzymes (DME) could have a critical role in individual responses to anastrozole.

Introduction: Urolithiasis is a common disease characterized by formation of solid deposits in the urinary tract. Most of the stones generated inside urinary tract are predominantly composed of calcium oxalate which can produced free radicals. Aim: To study the effects of caffeine on formation of crystals and it’s antioxidative effects in an in vitro model of urolithiasis. Materials and methods: LLC-PK1 cells were used as in vitro model of urolithiasis. Oxidative stress was induced by exposing cells to crystals of calcium oxalate. Cells were treated with different concentrations of caffeine. Effects of caffeine on crystallization and oxidative stress was estimated by crystals counts and total glutathione concentrations, respectively. Results: Increasing the concentration proportionally, caffeine stops the crystallization of calcium oxalate in in vitro model of proximal kidney tubules urolithiasis. Number of calcium oxalate crystals was decreasing in correlation with increasing concentrations of caffeine up to 60% and with the length of treatment with caffeine. Concentrations of total glutathione change up to 1, 8% when caffeine is added to cells treated with calcium oxalate crystals suggesting amelioration of oxidative stress. Conclusion: Results suggest that caffeine can lower crystallization and has a positive effect by lowering oxidative stress in our in vitro models of urolithiasis. More studies are needed to further evaluate caffeine’s role in formation of kidney stones.

Caffeine is a naturally occurring central nervous system stimulant and it is found in around sixty plant species. Most common sources are the beans of Coffea arabica and Coffea canephora. Recently it has been shown that caffeine possesses antioxidant properties as well. Further, urolithiasis is a disease defined by formation of solid deposits and most of the stones inside the urinary tract are predominantly composed of calcium oxalate monohydrate (COM) which can produce free radicals. The used cell culture as in vitro model of urolithiasis was the Lilly Laboratories Cell Porcine Kidney (LLC-PK type I). Oxidative stress was caused by exposing cells to COM crystals. Cells were treated with various concentrations of caffeine. Effects of caffeine on crystallization and oxidative stress was evaluated by COM crystallization assay and total glutathione assay, respectively. Caffeine treatment blocked the crystallization of COM in in vitro model of proximal kidney tubules urolithiasis. Total number of COM crystals was decreasing in correlation with increasing concentrations of caffeine up to 60% and with the duration of treatment with caffeine. However, concentrations of total glutathione altered up to 1, 8% only after caffeine treatment. Caffeine inhibits crystallization of COM, however its antioxidant potential in the cellular model of oxalate urolithiasis of proximal kidney tubules LLC-PK type I remains elusive.

High breast density (HBD) reduces the sensitivity of mammography (Figure 1., examples c and d) and is a moderately independent risk factor for breast cancer. However, there is no legislation to notify the patient about HBD in Croatia. Aim was to examine whether the disclosure of BD information among women without breast cancer impacts their knowledge about breast cancer risk factors

Metabolički sindrom (MS) sastavljen je od niza poremećaja koji se manifestiraju centralnom pretilosti, arterijskom hipertenzijom, hiperglikemijom i dislipidemijom, a usko je povezan s rizikom od razvoja šećerne bolesti, kardiovaskularnih bolesti, steatozom jetre, zloćudnih bolesti i demencijom, odnosno pridonosi povećanju mortaliteta. Nažalost, njegova je incidencija u stalnom porastu i u odrasloj i u dječjoj populaciji, a navedeno je u direktnoj vezi sa sedentarnim načinom života i visokokaloričnom prehranom. U prevenciji i liječenju MS-a važnu ulogu ima tjelesna aktivnost jer utječe na patofiziološke mehanizme u podlozi MS-a, prije svega na inzulinsku rezistenciju (IR). Dodatno, tjelesna aktivnost pogoduje poboljšanju lipidograma i sniženju arterijskoga krvnog tlaka te pridonosi redukciji tjelesne mase. Preporučuje se minimalno 150 minuta aerobne tjelesne aktivnosti umjerenog intenziteta uz provođenje vježba snage 2 – 3 puta na tjedan. Također, već od dječje dobi bitno je skratiti vrijeme provedeno u sedentarnom načinu života., Metabolic Syndrome (MS) encompasses several disorders including abdominal obesity, arterial hypertension, hyperglycaemia and dyslipidaemia, and is closely related to the risk of developing type 2 diabetes, cardiovascular diseases, liver steatosis, malignant diseases and dementia, which lead to higher mortality. Unfortunately, incidence of MS is continually increasing, not only in adults but also in children, which is in direct correlation with the sedentary lifestyle and high-calorie diet. Physical activity plays an important role in both prevention and treatment of MS as it affects underlying pathophysiological mechanisms of MS, especially insulin resistance (IR). Additionally, physical activity improves lipid profile, reduces arterial blood pressure and helps lose weight. Guidelines suggest at least 150 minutes of moderate-intensity aerobic exercise combined with strength training 2 − 3 times per week. Moreover, it is important to reduce sedentary time in early childhood.

Introduction: The aim of this study was to assess knowledge about BC risk factors and attitudes about BC chemoprevention among women without diagnosed BC and to investigate whether the accuracy of self-percieved BC risk affects the willingness to the BC chemoprevention. Materials and Methods: A random sample of 164 women without BC who were referred to an ultrasound or mammographic examination at the Health Center Osijek were included in the study. An anonymous questionnaire about BC risk factors and chemoprevention was administered. Participants reported self-perceived 5-year and lifelong risk of BC using a 5-point Likert scale. Participants' BC risk was objectively estimated using The Breast Cancer Risk Assessment Tool (BCRAT). Results: Participants were divided into 3 groups based on the accuracy of their 5-year risk self-assessment ; 110 participants have accurately stimated their risk, 37 underestimated and 13 overestimated the risk. There was no significant difference (χ2 test) between the groups in knowledge about BC risk factors. The best known risk factor in all groups was having a 1st degree relative diagnosed with BC (χ2 test, P>0, 99). Participants in an overestimated risk group have more relatives with BC, except 1st degree relative with BC (χ2 test, P=0, 006). Participants in the underestimated risk group were older (Kruskal Wallis test, P

Introduction: Drug prescription represents one of the most common activities in the daily work of primary care physician (PCP). Various data showed that outpatient drug consumption in Croatia makes up to 62.5% of total drug consumption, making PCP's role even more important. The Goal: The aim of this study was to assess the attitudes and practices of PCPs regarding the pharmacotherapy control habits. Materials and Methods: The study was conducted as a cross-sectional study involving 195 licensed PCP's in Croatia. The self-assessment survey questionnaire evaluated attitudes of PCP's regarding side effects, drug interactions and their ability to decide toward rational pharmacotherapy habits. Mann-Whitney-U or Kruskal-Wallis tests were used. P-values of