SERUMSKI BIOMARKERI PRETVORBE KOLAGENA I I III. KOD ZATAJENJA SRCA – POTREBA PONOVNE PROCJENE

Cardiac extracellular matrix is a complex structure presented by a network of fi brillar collagen, fi bronectin, laminin, fi brillin, elastin, glycoproteins and proteoglycans. Myocardial fi brillar collagens (collagen type I and type III) are the main proteins responsible for the structural integrity of the bordering cardiomyocytes. Increased accumulation of fi brillar collagen leading to fi brosis has been reported in pathological cardiovascular conditions like heart failure. Amino-terminal and carboxyterminal propeptides of collagen type I and III are the two major collagen types playing a central role in this process. Derived products from their turnover have been determined in serum of patients with heart failure. Collagen type I and III propeptides refl ect collagen synthesis and degradation. Their use as biomarkers with prognostic or diagnostic aim is an area of intensive studies. This review article summarizes the actual available literature data on serum markers of collagen type I and III turnover in heart failure and discusses their potential as circulating indicators of cardiac fi brosis. The use of collagen type I and III peptides for diagnosis, prognosis and monitoring of heart failure is thoroughly discussed too.Ekstracelularni matriks srca je složena struktura koja se prikazuje kao mreža vlaknatog kolagena, fi bronektina, laminina, fi brilina, elastina, glikoproteina i proteoglikana. Vlaknati kolageni miokarda (kolagen tipa I. i tipa III.) su glavni proteini o kojima ovisi strukturni integritet graničnih kardiomiocita. Povećano nakupljanje vlaknatih kolagena koje dovodi do fi broze opisano je u patološkim kardiovaskularnim stanjima kao što je zatajenje srca. Amino-terminalni i karboksi-terminalni propeptidi kolagena tipa I. i III. dva su glavna tipa kolagena koji imaju središnju ulogu u tom procesu. Produkti njihove pretvorbe određivani su u serumu bolesnika sa zatajenjem srca. Propetidi kolagena tipa I. i III. odražavaju sintezu i raspad kolagena. Njihova upotreba kao biomarkera područje je intenzivnih studija sa svrhom prognoze ili dijagnoze. Ovaj pregledni rad sažima danas raspoložive podatke iz literature o biljezima pretvorbe kolagena tipa I. i III. kod zatajenja srca i raspravlja se o njihovom potencijalu kao cirkulirajućim pokazateljima fi broze srca. Raspravlja se i o primjeni peptida kolagena tipa I. i III. za dijagnozu, prognozu i praćenje zatajenja srca

SERUMSKI BIOMARKERI PRETVORBE KOLAGENA I I III. KOD ZATAJENJA SRCA – POTREBA PONOVNE PROCJENE

Cardiac extracellular matrix is a complex structure presented by a network of fi brillar collagen, fi bronectin, laminin, fi brillin, elastin, glycoproteins and proteoglycans. Myocardial fi brillar collagens (collagen type I and type III) are the main proteins responsible for the structural integrity of the bordering cardiomyocytes. Increased accumulation of fi brillar collagen leading to fi brosis has been reported in pathological cardiovascular conditions like heart failure. Amino-terminal and carboxyterminal propeptides of collagen type I and III are the two major collagen types playing a central role in this process. Derived products from their turnover have been determined in serum of patients with heart failure. Collagen type I and III propeptides refl ect collagen synthesis and degradation. Their use as biomarkers with prognostic or diagnostic aim is an area of intensive studies. This review article summarizes the actual available literature data on serum markers of collagen type I and III turnover in heart failure and discusses their potential as circulating indicators of cardiac fi brosis. The use of collagen type I and III peptides for diagnosis, prognosis and monitoring of heart failure is thoroughly discussed too.Ekstracelularni matriks srca je složena struktura koja se prikazuje kao mreža vlaknatog kolagena, fi bronektina, laminina, fi brilina, elastina, glikoproteina i proteoglikana. Vlaknati kolageni miokarda (kolagen tipa I. i tipa III.) su glavni proteini o kojima ovisi strukturni integritet graničnih kardiomiocita. Povećano nakupljanje vlaknatih kolagena koje dovodi do fi broze opisano je u patološkim kardiovaskularnim stanjima kao što je zatajenje srca. Amino-terminalni i karboksi-terminalni propeptidi kolagena tipa I. i III. dva su glavna tipa kolagena koji imaju središnju ulogu u tom procesu. Produkti njihove pretvorbe određivani su u serumu bolesnika sa zatajenjem srca. Propetidi kolagena tipa I. i III. odražavaju sintezu i raspad kolagena. Njihova upotreba kao biomarkera područje je intenzivnih studija sa svrhom prognoze ili dijagnoze. Ovaj pregledni rad sažima danas raspoložive podatke iz literature o biljezima pretvorbe kolagena tipa I. i III. kod zatajenja srca i raspravlja se o njihovom potencijalu kao cirkulirajućim pokazateljima fi broze srca. Raspravlja se i o primjeni peptida kolagena tipa I. i III. za dijagnozu, prognozu i praćenje zatajenja srca

ALLERGIC CONTACT DERMATITIS FROM FORMALDEHYDE EXPOSURE.

Formaldehyde is a ubiquitous chemical agent, a part of our outdoor and indoor working and residential environment. Healthcare workers in difficult occupations are among the most affected by formaldehyde exposure. Formaldehyde is an ingredient of some dental materials. Formaldehyde is well-known mucous membrane irritant and a primary skin sensitizing agent associated with both contact dermatitis (Type IV allergy), and immediate, anaphylactic reactions (Type I allergy). Inhalation exposure to formaldehyde was identified as a potential cause of asthma. Quite a few investigations are available concerning health issues for dental students following formaldehyde exposure. Such studies would be beneficial for early diagnosis of hypersensitivity, adequate prophylactic, risk assessment and management of their work

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Concomitant contact allergy to formaldehyde and methacrylic monomers in students of dental medicine and dental patients

Objectives: A multitude of acrylic monomers is used in dentistry. Formaldehyde is a ubiquitous chemical agent, which is an ingredient of some dental materials and may be released from methacrylate-based composites. The purpose of the study is to evaluate the incidence and the risk of cross-sensitization to some methacrylic monomers (methylmethacrylate – MMA, triethyleneglycol dimethacrylate – TEGDMA, ethyleneglycol dimethacrylate – EGDMA, 2,2-bis-[4-(2-hydroxy-3-metha­crylo-xypropoxy)phenyl]-propane – Bis-GMA, 2-hydroxy-ethyl methacrylate 2-HEMA, and tetrahydrofurfuryl methacry­late) and formaldehyde in students of dentistry, dental professionals and dental patients. Material and Methods: A total of 139 participants were included in the study, i.e., occupationally exposed dental professionals, students of the 3rd, 4th and 6th year of dental medicine, and occupationally unexposed dental patients. They were patch-tested with methacrylic monomers and formaldehyde. The results were subjected to statistical analysis (p < 0.05). Results: From the allergic to formaldehyde students of the 3rd and 4th year of dental medicine, 46.2% were also sensitized to MMA. Among the group of patients, the incidence of cross-sensitization to formaldehyde and methacrylic monomers was as follows: to TEGDMA – 20.6%, to ethyleneglycol dimethacrylate – 20.7%, to 2-HEMA – 20.7% and to tetrahydrofurfuryl methacrylate – 24.1%. Contact allergy to MMA was diagnosed among 22.7%, and to TEGDMA – among 27.1% of the students of the 3rd and 4th year of dental medicine. In the group of occupationally unexposed dental patients the prevalence of contact allergy to ethyleneglycol dimethacrylate was 20.7%, to Bis-GMA – 27.6%, to 2-HEMA – 44.9% and to tetrahydrofurfuryl methacrylate – 38.0%. Conclusions: The students of the 3rd and 4th year of dental medicine could be outlined as a group at risk of sensitization to MMA and TEGDMA and of cross-sensitization to MMA and formaldehyde. Probably, due to the ubiquitous occurrence of formaldehyde and the wide use of composite resins and bonding agents containing TEGDMA, ethyleneglycol dimethacrylate, 2-HEMA and tetrahydrofurfuryl methacrylate in dentistry, the group of dental patients could be at risk of cross-sensitization to formaldehyde and some methacrylic monomers

Povezanost aterogenog indeksa plazme i hipertrofije lijeve klijetke u bolesnika sa zatajivanjem srca s ejekcijskom frakcijom srednjeg raspona

Aim: The aim of the present study was to investigate whether an association between lipid indices- atherogenic index of plasma (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II) and triglyceride index (TGL-index) and the development of left ventricular hypertrophy exists in patients with heart failure with mid-range ejection fraction (HFmrEF). Material and methods: The study involved 56 patients with HFmrEF and normal lipid profile, median age 64 (47-84) and 22 healthy subjects, median age 58 (51-69). The patients were divided in two subgroups: subjects with left ventricular hypertrophy (n=32); (HFmrEF+LVH) and subjects without left ventricular hypertrophy (n=24); (HFmrEF-LVH). The lipid profile was measured by laboratory, while lipid indices were calculated, using the established formulas. Results: There was not statistically significant difference between the lipid indices in patients with heart failure with mid-range ejection fraction compared to healthy controls (p>0.05). HFmrEF+LVH patients showed statistically significantly higher values of atherogenic index of plasma than HFrEF-LVH patients: 0.16 (0.05/0.37) vs. 0.04 (0.01/0.11); (KW=5.80; p=0.02). TC/HDL, LDL/HDL and TG/HDL values were not significantly higher in HFmrHEF+LVH than HFmrEF-LVH patients: 4.8 (3.98/5.75) vs. 4.49 (3.58/5.63); 2.91 (2.1/4.0) vs. 2.9 (2.5/4.25) and 1.36 (1.11/2.08) vs. 1.13 (0.9/1.53), respectively (p>0.05). No significant gender differences between lipid indices were found. Atherogenic index of plasma showed correlation with LVH (r=0.45; p=0.01) and interventricular septum thickness (r=0.55; p=0.002). Conclusion: Our findings show an association between atherogenic index of plasma and LVH in patients with HFmrEF with normal lipid profile. Further studies are warranted to confirm whether determination of AIP may be used for monitoring development and progression of left ventricular hypertrophy in heart failure with mid-range ejection fraction.Cilj: Cilj ove studije bio je istražiti postoji li povezanost između lipidnih indeksa - aterogeni indeks plazme (engl. atherogenic index of plasma; AIP), Castellijev indeks rizika I (engl. Castelli Risk Index I; CRI-I), Castellijev indeks rizika II (engl. Castelli Risk Index II; CRI-II) i trigliceridni indeks (engl. triglyceride index; TGL-index) i razvoj hipertrofije lijeve klijetke postoji u bolesnika sa zatajivanjem srca s umjereno smanjenom ejekcijskom frakcijom (HFmrEF). Materijali i metode: Ispitano je 56 bolesnika s HFmrEF s normalnim lipidnim profilom, prosječne dobi 64 (47 - 84) godine i 22 zdravih ispitanika prosječne dobi 58 (51 - 69). Pacijenti su podijeljeni u dvije podskupine: ispitanici s hipertrofijom lijeve klijetke (n = 32) (HFmrEF+LVH) i ispitanici bez hipertrofije lijeve klijetke (n = 24) (HFmrEF-LVH). Profil lipida mjeren je laboratorijski, dok su indeksi lipida izračunati pomoću ustaljenih formula. Rezultati: Nije bilo statistički značajne razlike između indeksa lipida u bolesnika sa srčanim zatajenjem s izbacivačkom frakcijom srednjeg opsega u usporedbi sa zdravim kontrolama (p > 0,05). Pacijenti s HFmrEF+LVH pokazali su statistički značajno veće vrijednosti aterogenog indeksa plazme od bolesnika s HFmrEF-LVH: 0,16 (0,05 / 0,37) naspram 0,04 (0,01 / 0,11) (KW = 5,80; p = 0,02). Vrijednosti TC/HDL, LDL/ HDL i TG/HDL nisu bile statistički značajno više u bolesnika s HFmrEF+LVH nego u skupini HFmrEF-LVH: 4,8 (3,98 / 5,75) naspram 4,59 (3,58 / 5,63), 2,91 (2,1 / 4.0) naspram 2,9 (2,5 / 4,25), odnosno 1,36 (1,11 / 2,08) naspram 1,13 (0,9 / 1,53) (p > 0,05). Nisu pronađene značajne razlike između indeksa lipida koje bi ovisile o spolu ispitanika. Aterogeni indeks plazme pokazao je korelaciju s LVH (r = 0,45; p = 0,01) i debljinom interventrikularnog septuma (r = 0,55; p = 0,002). Zaključak: Naši nalazi pokazuju povezanost između aterogenog indeksa plazme i LVH u bolesnika s HFrEF s normalnim lipidnim profilom. Daljnja ispitivanja opravdana su kako bi se potvrdilo može li se određivanje AIP koristiti za praćenje razvoja i napredovanja hipertrofije lijeve klijetke u zatajenju srca s izbacivačkom frakcijom srednjeg raspona

Serum Levels of Antibodies to Advanced Glycation End Products in Patients with Type 2 Diabetes Mellitus and Hypertension

Background and Aims: Proteins containing advanced glycation end products are highly immunogenic and anti-advanced glycation end products antibodies (anti-AGEs antibodies) are found in the sera of diabetics.Materials and methods: Enzyme-linked immunosorbent assay (ELISA) was used for measuring levels of anti-advanced glycation end products antibodies in sera of 93 patients with type 2 diabetes mellitus and arterial hypertension (mean age 61.4±11.3 years, diabetes duration 9.88±3.12 years; hypertension duration 9.28±4.98). These values were compared to serum anti-AGEs antibodies in 42 age and sex matched controls. Diabetics were divided in two groups according to presence or absence of microangiopathy, group 1 (n=67) and group 2 (n=26), respectively.Results: Serum levels of anti-AGEs antibodies in patients with type 2 diabetes mellitus and arterial hypertension were statistically significantly higher than those in the control group (1.39±0.39 vs. 1.05±0.32), (p<0.05). Group 1 showed significantly higher levels of anti-AGEs antibodies than those of healthy controls (1.53±0.14 vs. 1.05±0.32), (p<0.01). Anti-AGEs antibodies levels were higher in patients with microvascular complications than these in patients without complications. Anti-AGEs antibodies correlate with diastolic blood pressure (r=0.26, p=0.05) and body mass index (r=0.37, p=0.03). We found significantly higher percentage of positive patients for anti-AGEs antibodies (mean+2SD) in group 1 than in group 2.Conclusion: Determining the levels of serum anti-AGEs antibodies can help physicians make early diagnosis and prognosis of the severity of late diabetic complications in hypertensive patients

PILOT STUDY OF CONTACT SENSITIZATION OF FORMALDEHYDE-RELEASERS, FORMALDEHYDE AND GLUTARALDEHYDE IN DENTAL STUDENTS

Introduction: Occupational allergic contact sensitization is common in dental personnel. Some of the most common occupational allergens in dental practice are some formaldehyde-releasers, formaldehyde and glutaraldehyde. Aim: The aim of the present study was to evaluate the rate of contact sensitization to formaldehyde, quaternium-15, imidazolidinyl urea, diazolidinyl urea, and to glutaraldehyde in students of dental medicine and dental patients. Material and methods: A total of 50 participants were included in the study: 40 students of dental medicine exposed to formaldehyde-releasers, formaldehyde and glutaraldehyde during the course of their education; 10 dental patients without occupational exposure to the latter substances served as a control group. All of them were patch-tested with the studied allergens. Results: The sensitization rate to formaldehyde was significantly higher in the group of dental patients if compared to the one of dental students (χ2=5.37; p=0.021). Positive skin patch test reactions to quaternium-15 and to imidazolidinyl urea were observed only in the group of dental students. A significantly higher rate of sensitization to diazolidinyl urea, if compared to the one to imidazolidinyl urea (χ2=5.4; p=0.02) and to quaternium-15 (χ2=6.76; p=0.009), as well as to glutaraldehyde, if compared to the one to quaternium-15 (χ2=3.96; p=0.04) for the whole studied population was established. For the whole studied population, significantly increased rate of concomitant sensitization to formaldehyde and glutaraldehyde (χ2=6.18 p=0.013), as well as to diazolidinyl urea and to glutaraldehyde was established (χ2=9.12 p=0.003). Conclusions: We consider the importance of exposure to diazolidinyl urea, quaternium-15, imidazolidinyl urea and glutaraldehyde during the course of practical education in dentistry for the onset of sensitization. The exposure to formaldehyde is ubiquitous and is difficult to distinguish the roles of environmental and occupational exposures. The promotion of proper personal protection as well as adequate information on occupational chemical hazards should start as early as during the first years of education in dentistry

Concomitant sensitization to glutaraldehyde and methacrylic monomers among dentists and their patients

Background: A multitude of methacrylic monomers is used in dentistry. Glutaraldehyde (G) is used in dental practice and consumer products as a broad-spectrum antimicrobial agent. The purpose of our study is to evaluate the frequency and the risk of concomitant sensitization to some methacrylic monomers (methyl methacrylate (MMA), triethyleneglycol dimethacrylate (TEGDMA), ethyleneglycol dimethacrylate (EGDMA), 2,2-bis-[4-(2-hydroxy-3-methacrylo-xypropoxy)phenyl]-propane (Bis-GMA), 2-hydroxy-ethyl methacrylate (2-HEMA) and tetrahydrofurfuryl methacrylate (THFMA)) and glutaraldehyde in students of dentistry, students from the dental technician school, dental professionals and dental patients. Material and Methods: A total of 262 participants were included in the study: students of dentistry, students from the dental technician school, dental professionals, and dental patients as a control group. All were patch-tested with methacrylic monomers and glutaraldehyde. The results were subject to the statistical analysis (p < 0.05). Results: Among the group of dental students, the highest frequency of concomitant sensitization was to TEGDMA and G (15.5%). In the group of patients the highest frequency of concomitant sensitization was to EGDMA and G (16.4%). The frequency of concomitant sensitization among dental professionals was much lower, with the highest rate to TEGDMA and G (7.7%), too. We consider the students from the dental technician school, where the exposure to glutaraldehyde is less likely, to be the group at a lesser risk of concomitant sensitization. Conclusions: Dental students and dental patients could be outlined as groups at the risk of concomitant sensitization to glutaraldehyde and methacrylic monomers. For dental professionals, we assumed an increased risk for concomitant sensitization to TEGDMA and aldehydes that are commonly used in dentistry. We consider the students from the dental technician school to be the group at a lesser risk of concomitant sensitization to glutaraldehyde and methacrylic monomers. Med Pr 2016;67(3):311–32