The paraoxonase 1, 2 and 3 in humans

The paraoxonase gene family in humans includes three members: PON1, PON2 and PON3. The products of those three genes are the following enzymes: paraoxonase 1 (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3). PON1 is mainly associated with a high density lipoprotein (HDL). A small amount of this enzyme is also bound to very low-density lipoprotein (VLDL) and postprandial chylomicrons. PON1 possess organophosphatase, arylesterase and lactonase activity and it hydrolyzes many different substrates. It is also known that PON1 may have antiatherogenic function. Compared to the PON1, PON2 and PON3 are much less studied and described. PON2 is ubiquitously expressed intracellular protein, while PON3 is bound to HDL, like PON1. The both enzymes possess antioxidant properties.     

Hoopfest: Using longitudinal economic impact data to assess the success of a strategic reorientation

The authors report the economic impact of a strategy change for a nonprofit sport association, Hoopfest, over an eight year period. Hoopfest organizes the largest annual 3-on-3 basketball tournament in the world. The study employs an economic impact methodology because the local community expressed a concern with related economic development issues. An initial assessment indicated the two-day tournament had an overall economic impact on the region of about seventeen million dollars. Twenty-two thousand people competed in the tournament and at least another one hundred thousand people watched the event. Hoopfest officials were challenged by a simple question: how could they enhance the economic benefits of this basketball tournament?     

Laboratory use of hepcidin in renal transplant recipients

Hepcidin is a small peptide with a critical role in cellular iron homeostasis, as it regulates utilization of stored iron and antimicrobial defense in inflammation (bacterial and fungal). Since it was isolated in 2000, and especially in the last decade, numerous studies aimed to evaluate the clinical use of plasma and urine hepcidin as a marker of anemia, especially anemia of chronic disease and post-transplant anemia (PTA). Hepcidin regulation is delicately tuned by two inflammatory pathways activated by interleukin-6 (IL-6) and bone morphogenic proteins (BMPs) and iron regulated pathway sensitive to circulating transferin-iron (TR-Fe) complex. BMP-mediated pathway and TR-Fe sensitive pathway seem to be connected by hemojuveline, a BMP co-factor that interacts with transferine receptor 2 (TRF2) in cases of high TR-Fe circulatory concentration. In addition to these regulatory mechanisms other regulators and signaling pathways are being extensively researched.
Hepcidin has been identified as an important contributor to morbidity and mortality in end stage renal disease (ESRD) but no such association has jet been found in case of PTA. However, there is an association between higher doses of erythropoiesis-stimulating agents (ESA) and mortality in the posttransplant period and the assumption that hepcidin might play a role in ESA resistance in PTA. Thus the review’s main goal was to summarize papers published on the association of hepcidin with PTA, give up-to-date information on hepcidin regulation and on potential therapeutics that optimize hepcidin regulation. We also compared the performances of tests for hepcidin determination and reviewed research on immunosuppressants’ (IS) effect on hepcidin concentration.Key words: hepcidin, kidney transplantation, post-transplant anemia, iron homeostasis     

Haemoglobin A1c-based screening for prediabetes and diabetes mellitus: a multi-center study in Croatian adult population

IntroductionBased on the hypothesis that there is a substantial rate of adults with prediabetes and undiagnosed diabetes mellitus (DM), our aim was to perform haemoglobin A1c (HbA_1c)-based screening in a cohort of Croatian adults and estimate the prevalence of prediabetes and undiagnosed DM according to American Diabetes Association criteria.Materials and methodsThis multi-center, cross-sectional study performed in six Croatian hospitals included 5527 patients aged 40 to 70 years admitted to the Emergency Department or undergoing a primary care check-up. Haemoglobin A1c was measured from leftover whole blood samples using the enzymatic method on either Alinity c or Architect c-series analyser (Abbott Laboratories, Chicago, USA). Haemoglobin A1c between 39-47 mmol/mol was classified as prediabetes, while ≥ 48 mmol/mol as undiagnosed DM.ResultsAfter exclusion of 435 patients with known DM, the final cohort included 5092 patients (median age 57; 56% males). A total of 882 (17.3%) patients had HbA_1c values between 39 and 47 mmol/mol. There were 214 (4.2%) patients with HbA_1c ≥ 48 mmol/mol. Prediabetes prevalence ranged from 14.2% to 20.5%, while undiagnosed DM from 3.3% to 7.3%, with statistically significant differences among settings (P < 0.001). Age-stratified analysis showed that prediabetes and undiagnosed DM prevalence increase with age (P < 0.001), being 25.4% and 5.8%, respectively, in patients aged 60 to 70 years.ConclusionUnderlying impairment of glucose metabolism was identified in about one in five adults, with significant number of patients with already overt DM. These results should serve as a starting point for further steps directed towards promotion of preventive measures for DM in Croatia.     

Early markers of gestational diabetes mellitus: what we know and which way forward?

Women’s metabolism during pregnancy undergoes numerous changes that can lead to gestational diabetes mellitus (GDM). The cause and pathogenesis of GDM, a heterogeneous disease, are not completely clear, but GDM is increasing in prevalence and is associated with the modern lifestyle. Most diagnoses of GDM are made via the guidelines from the International Association of Diabetes and Pregnancy Study Groups (IADSPG), which involve an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. Diagnosis in this stage of pregnancy can lead to short- and long-term implications for the mother and child. Therefore, there is an urgent need for earlier GDM markers in order to enable prevention and earlier treatment. Routine GDM biomarkers (plasma glucose, insulin, C-peptide, homeostatic model assessment of insulin resistance, and sex hormone-binding globulin) can differentiate between healthy pregnant women and those with GDM but are not suitable for early GDM diagnosis. In this article, we present an overview of the potential early biomarkers for GDM that have been investigated recently. We also present our view of future developments in the laboratory diagnosis of GDM.     

Laboratory policies and practices for thyroid function tests in Croatia: survey on behalf of Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine

IntroductionLaboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and postanalytical practices and policies in Croatia.Materials and methodsWorking Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions.ResultsFifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer’s declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer’s reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles).ConclusionThis survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.