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  • Author: Marijana Dajak x
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Preporuke za Primenu Tumorskih Markera Kod Monoklonskih Gamapatija

Monoklonske gamapatije čine grupu poremećaja koji se karakterišu klonskom proliferacijom plazma ćelija. M protein je tumorski marker specifičan za monoklonske gamapatije jer odražava klonsku produkciju imunoglobulina. Monoklonske gamapatije uključuju: multipli mijelom, Waldenström-ovu makroglobulinemiju (WM), nesekretorni mijelom, prikriveni (smoldering) multipli mijelom, monoklonsku gamapatiju od neodređenog značaja (MGUS, Monoclonal gammopathy of undetermined significance), primarnu sistemsku amiloidozu i bolest teških lanaca. Dijagnoza multiplog mijeloma je zasnovana na detekciji M proteina u serumu i/ili urinu, infiltraciji plazma ćelija u koštanoj srži i litičkim koštanim lezijama na radiografiji skeleta. Prema NACB (National Academy of Clinical Biochemistry) preporukama, tumorski markeri za dijagnozu, screening, identifikaciju klonaliteta, praćenje bolesti i prognostičku evaluaciju kod monoklonskih gamapatija su: elektroforeza proteina u serumu i/ili urinu, imunofiksacija u serumu i/ili urinu, slobodni laki lanci (SLL) u serumu i/ili urinu, viskoznost seruma i β2-mikroglobulin. Imunofiksacija se koristi za identifikaciju klonaliteta (tipa) M proteina primećenog na elektroforezi i kada postoji sumnja bez obzira na normalan proteinski elektroforetogram. Posebno je korisna za prepoznavanje i razlikovanje biklonskih ili triklonskih gamapatija. Viskoznost seruma trebalo bi određivati ako pacijent ima znake i simptome sindroma hiperviskoznosti. WM je najčeŠći uzrok hiperviskoznosti, ali se takođe može pojaviti i kod pacijenata sa velikim nivoima monoklonskog IgA ili IgG. Automatizovana imunoodređivanja SLL u serumu su osetljivija od tradicionalne elektroforetske metode i imunofiksacije za detekciju mijeloma monoklonskih lakih lanaca, nesekretornog mijeloma i AL amiloidoze. Osim toga, odnos SLL u serumu je nezavisan faktor rizika za nastanak maligne progresije kod pacijenata sa MGUS. Određivanje SLL u serumu i elektroforeze proteina seruma kao testova prve linije za razmatranje prisustva mogućih poremećaja B ćelija daje dodatnu dijagnostičku informaciju.

Funkcija Bubrega - Procena Brzine Glomerularne Filtracije

Brzina glomerularne filtracije (GFR) je široko prihvaćena kao najbolja opšta mera funkcije bubrega. Vodiči američke Nacionalne fondacije za bubreg definišu hroničnu bubrežnu bolest (HBB) bilo sa vrednošću GFR koja je manja od 60 mL/min/1,73 m2 ili sa prisustvom oštećenja bubrega, bez obzira na uzrok, u toku 3 ili više meseci i klasifikuju stadijume težine HBB prema GFR. GFR se može meriti kao urinarni ili plazma klirens egzogenih filtracionih markera kao što je inulin. Međutim, zbog teškoća u primeni, troškova i radijacionog izlaganja, ove metode imaju ograničenu upotrebu u rutinskim laboratorijama. Klirens kreatinina može biti korisna alternativa kada egzogeni markeri nisu dostupni, ali sakupljanje urina u vremenskim intervalima nije pogodno za pacijente i osetljivo je na grešku pri sakupljanju. GFR se često procenjuje klinički iz serumskih koncentracija egzogenog kreatinina ili cistatina C. Cistatin C u serumu još uvek nije adekvatno procenjen kao indeks GFR, a na kreatinin u serumu utiču GFR i faktori nezavisni od GFR, uključujući godine, pol, rasu, telesnu veličinu, ishranu, izvesne lekove i laboratorijske analitičke metode. Prema kliničkim vodičima Nacionalne fondacije za bubreg, kliničke laboratorije bi trebalo da izdaju >>procenjenu<< GFR (estimated GFR), izračunatu iz prediktivnih jednačina, kao dodatak izveštavanja vrednosti markera u serumu. Trenutno preporučena jednačina za procenu je razvijena iz MDRD (Modification of Diet in Renal Disease) studije. Ova jednačina koristi godine, pol, rasu (afro-američka prema ne-afro-američkoj) i koncentraciju kreatinina u serumu, a ne zahteva varijablu za telesnu težinu zato što normalizuje GFR za standardnu telesnu površinu od 1,73 m2. Da bi se postigla poboljšana tačnost preračunate GFR sa ovom jednačinom, preporučuje se da komercijalne metode za kreatinin budu kalibrisane prema sertifikovanim referentnim materijalima i sledljive sa IDMS (isotope dilution mass spectrometry) metodologijom. Za MDRD jednačinu je pokazano da je korisna za pacijente sa HBB, ali njena upotreba je još uvek nejasna za ljude sa niskim vrednostima kreatinina u serumu i visokim vrednostima za GFR, uključujući zdrave pojedince, decu i trudnice. Validacione studije su u razvoju kako bi se procenila MDRD jednačina za druge etničke grupe i različita bolesna stanja.

Beta-Trace Protein as a Marker of Renal Dysfunction in Patients with Chronic Kidney Disease: Comparison with Other Renal Markers

Beta-trace protein (BTP), also known as prostaglandin D synthase, is a low-molecular-mass protein which belongs to the lipocalin protein family. It was found to be increased in the serum of patients with renal diseases. The aim of this study was to compare the clinical usefulness of serum levels of beta-trace protein for the detection of renal dysfunction in patients with chronic kidney disease (CKD) with levels of other renal markers: creatinine, cystatin C and β2-microglobulin (B2M). The study included 134 patients with a wide range of renal dysfunction that encompassed all five CKD stages. Obtained data showed that beta-trace protein highly correlated (Spearman test) with creatinine (r = 0.890), cystatin C (r = 0.904) and B2M (r = 0.933) and its levels in serum significantly increased from CKD stage 1 to 5. Furthermore, the values of glomerular filtration rate (GFR) estimated from a BTP-based formula significantly correlated with GFR calculated from creatinine-based and cystatin C-based formulas. ROC analyses showed that BTP had similar diagnostic accuracy for detection of reduced renal function in CKD stages as other renal markers, for estimated GFRs of < 30, < 60 and < 90 mL/min/1.73 m2. The areas under the ROC curves (AUC) for BTP, for these GFR limits, were from 0.983 to 0.917 and they were not significantly different from AUCs for other renal markers. The results of this study showed that BTP may be a useful and reliable serum marker for identifying the magnitude of renal dysfunction in patients with CKD and may have its place beside serum cystatin C and creatinine as an alternative endogenous GFR marker.

N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Hypertensive Heart Disease

Patients with hypertensive heart disease have elevated concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The aim of our study was to evaluate NT-proBNP in patients with long-standing hypertension and in patients with signs of hypertensive cardiomyopathy. The study included three groups of 50 subjects: healthy persons (Control Group), patients with hypertension and normal left ventricular systolic function (Group 1) and patients with longstanding hypertension and signs of hyper tensive cardiomyopathy with impaired left ventricular systolic function (Group 2). Our results show a very good correlation (Pearson's test) between NT-proBNP in Group 1 and Group 2 and C-reactive protein (Group 1: r = 0.8424; Group 2: r = 0.6650), systolic blood pressure (Group 1: r = 0.7213; Group 2: r = 0.4856), diastolic blood pressure (Group 1: r = 0.4282; Group 2: r = 0.3989) and ejection fraction (Group 1: r = -0.7390; Group 2: r = 0.9111). ROC analysis revealed that the AUC between the Control Group and Group 1 for NT-proBNP (0.912) was not significantly different (p>0.05) from the AUC for systolic (0.924) and diastolic pressure (0.937). A cut-off value for NT-proBNP of 5.89 pmol/L can be used to reliably distinguish patients of Group 1 from the Control Group, and a cut-off value of 21.67 pmol/L reliably separates patients from Group 1 and Group 2 (in both cases, the AUC is 1.000). Patients in Group 2 who belonged to the II and III New York Heart Association (NYHA) class had significantly higher levels of NT-proBNP than those in NYHA class I (ANOVA test, p=0.001). These data suggest that NT-proBNP is a useful biomarker for distin guishing patients with long-standing hypertension who are at risk of heart failure, allowing optimization and proper treatment of these patients.

Carbohydrate-Deficient Transferrin - A Contemporary Biomarker in Comparison with Traditional Laboratory Markers of Chronic Alcohol Abuse

Timely identification of excessive alcohol use and its potential complications is a prerequisite for successful treatment. Several routine tests have been used in laboratories that may help in diagnosing alcoholism, such as determination of MCV, AST, ALT, GGT, but it has been shown that they lack specificity and sensitivity. Contemporary bio-markers are increasingly being used today that may due to their unique characteristics help in discovering the onset of chronic alcohol abuse, as well as in abstinence and relapse monitoring. The term carbohydrate-deficient transferrin (CDT) stands for a small group of human transferrin isoforms (asialo, monosialo, and disialotran sferrin) with a lower degree of glycosylation in comparison to the dominant transferrin isoform (tetrasialotransferrin). Persons consuming large quantities of alcohol (≥50-80 g daily) over a period of at least two weeks have increased concentrations of transferrin isoforms lacking one (disialotransferrin) or both (asialotransferrin) carbohydrate chains. In this paper the traditional markers of chronic alcohol abuse (GGT, AST, ALT, and MCV) were determined, as well as the new biomarker CDT, after which diagnostic evaluation was performed and their usability and clinical value in routine laboratory practice were estimated. These markers were also determined in heavy alcoholics on admission into hospital and after two weeks of therapy, with the aim of estimating their diagnostic value for abstinence and relapse monitoring.

Summary

Background: Physical exercise activates the hypothalamo-pituitary-adrenal (HPA) axis and induces the body’s inflammatory response. Due to contemporary dietary habits and increased energy expenditure, athletes are susceptible to depletion of magnesium ions. The aim of our study was to investigate, through assessment of plasma ACTH, serum IL-6, and salivary/serum cortisol levels, if chronic magnesium supplementation might reduce damaging stress effects in amateur rugby players.

Methods: Rugby players (N=23) were randomly assigned to intervention and control group. Basal samples were collected before intervention group started a 4-week-long supplementation with magnesium (500 mg Mg/d). Blood and saliva sampling were done a day before the match (Day-1), on the morning of competition (Game), and during a six-day-long recovery period (Day1, Day3 and Day6). ACTH, serum/salivary cortisol, IL-6 and total/differential leukocytes counts were determined at each time point.

Results: There was a statistically significant increase in ACTH concentration in intervention group compared to control group, while reductions in cortisol concentrations between the two groups were the greatest at Day-1 (p<0.01) and at the day of competition (Game) (p<0.01). Our results revealed that magnesium completely abolished the increase in IL-6 level noted in control group on Day1 and Day3 vs. Day-1 (p<0.01) and also diminished the rise in neutrophil/lymphocyte ratio in intervention group vs. control group (p<0.01).

Conclusions: These results suggest the possibly important influence magnesium supplementation might have on the change of parameters of HPA axis activity and reduction of immune response activation following strenuous physical exercise such as a rugby game.

Abstract

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function.

Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured.

Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p< 0.05), and a trend toward a lymphocyte percentage increase.

Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.