The “Big Bang” in obese fat: Events initiatingobesity-induced adipose tissue inflammation

Obesity is associated with the accumulation of pro-inflammatory cells in visceral adiposetissue (VAT), which is an important underlying cause of insulin resistance and progres-sion to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokinesin disease development is established, the initiating events leading to immune cell acti-vation remain elusive. Lean adipose tissue is predominantly populated with regulatorycells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissuehomeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13,which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state.Diet-induced obesity is associated with the loss of tissue homeostasis and developmentof type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shiftof ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocytehypertrophy results in upregulated surface expression of stress markers. Adipose stressis detected by local sentinels, such as NK cells and CD8+T cells, which produce IFN-γ,driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VATfollows, leading to inflammation. In this review, we provide an overview of events lead-ing to adipose tissue inflammation, with a special focus on adipose homeostasis and theobesity-induced loss of homeostasis which marks the initiation of VAT inflammation

Effect of Statin Therapy Duration on Bone Turnover Markers in Dyslipidemic Patients

Background and Purpose: Statins are cholesterol-lowering drugs decreasing bone resorption by inhibition of the farnesyl diphosphate synthase step in the mevalonic acid pathway and therefore are believed to have beneficial effects on bone status. The objective was to examine the relationship between statin therapy duration and bone turnover markers in dyslipidemic patients. Patients and Methods: Two hundred and eighty subjects were divided into five groups depending on duration of statin therapy: (controls 0 yrs); (0.1-1.5 yrs); (2-5 yrs); (6-10 yrs); (11-30 yrs). ELISA method was applied on fasting serums using bone formation markers: Osteoprotegerin (pmol/l) and Osteocalcin (ng/ml) and bone resorption markers: sRANKL (pmol/l) and CrossLaps (ng/ml). In statistical analysis, multiple regressions were used. Results: A common influence of studied predictor variables was statistically significant for sRANKL, Serum CrossLaps and osteocalcin (P<0.001), while statistical significance was not found for osteoprotegerin. The largest shares of contributions were recorded in Model 2 for the statin group (40%) and BMI (36%) and in Model 1 for statin group (35%) and total cholesterol (28%). Conclusions: Statins showed favorable influence on osteocalcin and sRANKL, indicating improved bone metabolism in patients with longer duration of statin therapy

Hyponatraemia – diagnostic and therapeutic approach

Hiponatrijemija je najčešći poremećaj metabolizma tjelesnih tekućina i ravnoteže elektrolita u kliničkoj praksi. Prisutna je u oko 15 – 30 % hospitaliziranih pacijenata, a može se očitovati širokim spektrom kliničkih promjena, od vrlo blagih do po život opasnih. Hiponatrijemija je primarno poremećaj ravnoteže vode, obično uz relativni višak tjelesne vode u usporedbi s ukupnim tjelesnim sadržajem natrija i kalija. Hiponatrijemija ovisno o vremenu nastanka može biti akutna (< 48 h) ili kronična (≥ 48 h). S obzirom na vrijednost serumske koncentracije natrija razlikujemo blagu hiponatrijemiju (Na(s) 130 – 135 mmol/l), zatim umjerenu ili srednje tešku (Na(s) 125 – 129 mmol/l) i tešku hiponatrijemiju (Na(s) < 125 mmol/l). U pristupu pacijentu s hiponatrijemijom od životne je važnosti ustanoviti radi li se o akutnim, teškim simptomima hiponatrijemije, kako bi se na vrijeme počelo s terapijskim mjerama koncentriranom 3 % otopinom NaCl. U slučaju izostanka ovih simptoma, dijagnostički algoritam nas usmjerava prema određenim diferencijalno dijagnostičkim entitetima ovisno o vrijednosti urinske osmolalnosti i koncentracije Na u urinu, kako bi terapija bila što točnija i odgovarajuća uzročnom faktoru hiponatrijemije.Hyponatraemia is the most frequent disorder of body fluid and electrolyte balance in clinical practice. It is present in 15–30 % of hospitalized patients and can be manifested with a wide spectrum of clinical symptoms, ranging from very subtle to life threatening. Hyponatraemia is primarily a disbalance in water equilibrium, usually manifested as relative water overload in comparison to total body sodium and potassium concentration. Based on the time of development hyponatraemia can be defined as acute (< 48hrs) or chronic (≥48 hrs). Regarding serum sodium concentration, hyponatraemia can be mild (Na(s) 130–135 mmol/l), moderate (Na(s) 125–129 mmol/l) or profound (Na(s) < 125 mmol/l). When approaching a patient with hyponatraemia it is essential to determine whether hyponatraemia is acute or profound so we could immediately start giving a patient 3 % hypertonic saline. In absence of the above mentioned, the diagnostic algorithm, with emphasis on urine osmolality and urine sodium concentration, is guiding us towards more specific disorders which define proper therapeutic approach

Nonalcoholic fatty liver disease - A multisystem disease?

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physician

Bone Morphogenetic Proteins and Signaling Pathway in Inflammatory Bowel Disease, Inflammatory Bowel Disease - Advances in Pathogenesis and Management

Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract of uncertain origin. Its two main phenotypes are Crohn’s disease (CD) and ulcerative colitis (UC). CD affects any part of the GI tract and is characterized by transmural inflammation, whereas UC is confined to the colon and affects only the mucosal layer. IBD is thought to occur in genetically predisposed individuals that develop an abnormal immune response to enteric bacteria in the intestinal mucosa (Podolsky, 2002; Xavier RJ & Podolsky, 2007). Disease occurs as a result of complex and dynamic interactions between immune and non-immune cells as well as the cross-talk between intestinal epithelium and mesenchyme (Danese, 2011; MacDonald et al., 2011; Strober & Fuss, 2011). Therefore, factors that are able to influence both interactions may be very important for the pathogenesis and treatment of IBD. Bone morphogenetic proteins (BMPs) are a large group of structurally related proteins that belong to the transforming growth factor-β (TGF-β) superfamily. Along with their primarily osteogenic function their importance in development, proliferation and morphogenesis of a variety of cells and tissues has been shown (Hogan, 1996; Vukicevic et al., 1989; 1995; Wozney et al., 1988). In addition, association of BMPs with healing processes of different non-skeletal tissues and organs was also described (Lories et al., 2005; Martinovic et al., 2002; Nguyen et al., 2008; Simic & Vukicevic, 2004; Turk et al., 2009; Vukicevic et al., 1996; Vukicevic & Grgurevic, 2009). Due to their wide-range of effects, they are commonly named “body morphogenetic proteins” (Reddi, 2005). Perturbations in BMP expression and BMP signaling pathway have been associated with the pathological conditions linked to several human diseases such as inflammatory bowel disease (IBD) (Allaire et al., 2011; Burke et al., 2007; Krishnan et al., 2011). In this chapter we will discuss the importance of BMPs in gut development and hereditary diseases as well as their influence on cellular and molecular events that occur in IBD and fibrogenesis, the most common complication of IBD. Furthermore, we will address the therapeutical potential of BMPs, especially BMP7 in treatment of IBD. Finally, we will explore the possibility of BMP pathway components as putative biomarkers of gut tumor development and progression

Hrvatske smjernice za farmakološko liječenje šećerne bolesti tipa 2 [Croatian guidelines for the pharmacotherapy of type 2 diabetes]

Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes