Association of polymorphisms in promoter region of TNF-α -238 and -308 with clinical outcomes in patients with immune-mediated inflammatory diseases on anti-TNF therapy.

The hypothesis of the study was that polymorphisms in promoter regions -238 and -308 of TNF-α could be associated with different clinical outcomes in inflammatory bowel diseases (IBD) and immune-mediated rheumatic diseases (IMRD). The aim was to examine the possible association of both polymorphisms with concentration of C-reactive protein (CRP) and fecal calprotectin (fCAL), onset of the remission and development of the ADA in patients on therapy with anti-TNF inhibitors. The prospective study was done in patients with IBD and IMRD on infliximab (IFX) or adalimumab (ADM). Patients were genotyped for TNF-α -238 and -308 polymorphisms. The concentration of CRP, fCAL, IFX or ADM and antibodies to drugs were measured according to manufacturer's instructions and followed-up for 6 or 12 months. Out of all patients (N = 112), number of patients in remission did not differ according to genotypes (for IBD patients P = 0.509 vs 0.223; for IMRD patients P = 0.541 vs 0.132 for TNF-α -238 and -308, respectively). Initial CRP concentration was higher in IBD patients with TNF-α -308 GG than GA/AA genotypes in patients who failed to achieve remission [11.8 (4.4-39.6) vs 3.1 (1.5-6.5), P = 0.033]. In IBD patients with remission, fCAL concentration after at least 6 months of therapy was higher in TNF-α-308 GG than in GA genotype [52 (25-552) vs 20 (20-20) µg/g, P = 0.041]. Our results showed the association of TNF-α -308 GG genotype with a higher concentration of CRP and fecal calprotectin in patients with inflammatory bowel diseases on IFX or ADM therapy. Clinical remission and development of antibodies to anti-TNF drugs were not associated with TNF-α -238 and -308 polymorphisms.

Effect of extract from Boswellia serrata gum resin on decrease of GAD65 autoantibodies in a patient with Latent Autoimmune Diabetes in Adults.

BACKGROUND: Extracts from Boswellia serrata gum resin have anti-inflammatory effect and are used for treatment of a variety of chronic inflammatory diseases. It was previously demonstrated that the treatment with Boswellia serrata gum resin of LADA (Latent Autoimmune Diabetes in Adults) patients decreased blood levels of IA2 antibodies, one of the markers associated with LADA autoimmune diabetes. PRIMARY STUDY OBJECTIVE: The purpose of this study was to test whether Boswellia serrata gum resin also influences GAD65 autoantibodies as the other marker associated with LADA. METHODS/DESIGN: We report a case study of male patient diagnosed with LADA with positive GAD65 autoantibodies who was treated with extract from Boswellia serrata gum resin, during 9 months. Blood levels of GAD65 autoantibodies, fasting blood glucose levels and HbA1c were measured before the treatment and periodically during the treatment. RESULTS: Over the observed period, the blood levels of GAD65 autoantibodies linearly decreased about 25%. CONCLUSION: The study confirms that extract of Boswellia serrata gum resin seems to prevent insulitis in patients with LADA, as indicated by its action on both markers of autoimmune diabetes, i.e., GAD65 and IA2 autoantibodies. The possibility that the treatment with boswellic acids of LADA patients with positive autoantibodies could be beneficial on the course of the disease, calls for further investigation and a clinical study.

Lower concentration of vitamin D is associated with lower DAS28 and VAS-pain scores in patients with inflammatory rheumatic diseases treated with infliximab: a pilot study.

Vitamin D is beneficial in patients with immune-mediated rheumatic diseases as it has been shown that it lowers the incidence risk and the level of inflammation. To examine the association between clinical outcomes and initial 25-hydroxyvitamin D [25(OH)D] concentrations in patients with the immune-mediated rheumatic diseases treated with infliximab for 9 months. This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions.This study was performed in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with infliximab for at least 38 weeks. Disease activity was assessed using Disease Activity Score (DAS28) for RA and PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, while the global assessment was performed using the Visual Analogue Scale (VAS). Patients were divided into 2 groups according to 25(OH)D concentration which was classified as deficient or non-deficient (below and above 50 nmol/L, respectively). Concentrations of infliximab (IFX) and C-reactive protein (CRP) were measured according to the manufacturer's instructions. The study included 23 patients (14 with RA, 6 with AS and 3 with PsA), median age 54 years, 15 females. Vitamin D deficient and non-deficient groups had median initial concentrations of 38 and 61 nmol/L, respectively. DAS28 and pain on VAS calculated at the 2nd and 38th week showed a statistically significant decrease only in RA and PsA patients with vitamin D deficiency (P = 0.02 and 0.06, respectively). Lower initial concentration of 25(OH)D in patients treated with infliximab was associated with better improvement of clinical measures (DAS28 and VAS) of disease after 9 months of therapy.

CHOLESTEROL AND CHLORIDE IN ACUTE HEART FAILURE.

Detecting predictors of poor outcome is crucial for understanding the underlying pathophysiology of heart failure (HF) and thus creating new therapeutic concepts. It is well established that low serum lipid levels are associated with unfavorable outcomes in HF patients. Several studies examined the association between serum lipids and established predictors of mortality in HF patients. The aim of the present study was to examine the association of serum lipid and chloride concentrations, as well as their impact on survival in acute heart failure (AHF). The present study was performed as a prospective, single-centre, observational research. The study included 152 patients with AHF. Spearman's correlation coefficient revealed a significant positive correlation of serum chloride levels with serum levels of total cholesterol (ρ 0.221, p=0.006), low-density lipoprotein cholesterol (LDL-c) (ρ 0.187, p=0.015) and high-density lipoprotein-cholesterol (HDL-c) (ρ 0.169, p=0.038). Binary logistic regression revealed a significant association of chloride, total cholesterol and LDL-c serum levels measured at admission with hospital survival (OR 1.077, CI 1.01-1.154, p=0.034), (OR 1.731, CI 1.090-2.748, p=0.020) and (OR 1.839, CI 1.033-3.274, p=0.038), respectively, as well as with 3-month survival (OR 1.065, CI 1.002-1.131, p=0.042), (OR 1.625, CI 1.147-2.303, p=0.006) and (OR 1.711, CI 1.117-2.622, p=0.014), respectively. In conclusion, positive statistical association between serum cholesterol (total cholesterol, LDL-c and HDL-c) and chloride levels may suggest their similar modulation by AHF pathophysiology. Serum levels of total cholesterol, LDL-c and chloride contribute to patient survival.

Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset.

OBJECTIVE: The objective of the research was to evaluate diagnostic and predictive value for determination of KFLC in cerebrospinal fluid (CSF) compared to the qualitative procedure of OCB determination in patients with CIS who converted to MS during a two-year period. PATIENTS AND METHODS: KFLC, total immunoglobulin G (IgG), serum albumin and CSF albumin were determined with an immunonephelometric method in 151 patients with suspected MS who were admitted to the Neurology Clinic while CSF/serum quotients (QKFLC, QIgG and QAlb) and indexes were calculated with regards to albumin (QCSF/Qserum). Presence of OCBs was determined by isoelectric focusing with immunofixation. Based on their clinical, OCB and magnetic resonance imaging (MRI) findings, 50 patients were classified as other neurological disorder patients (OND), and 101 patients were classified as CIS, 50 of which converted to MS during the two-year period. ROC analysis, ROC curve comparisons and comparison of median KFLC parameters were used to find optimal cut-off with regards to CIS diagnosis and conversion to MS. RESULTS: CSF KFLC median was 2,01 mg/L in MS group contrary to 0,68 mg/L and 0,17 mg/L in CIS and OND group, and KFLC index was 33,52 mg/L contrary to 9,68 mg/L and 3,71 mg/L (p < 0,0001). ROC analysis for accuracy of detection of intrathecal synthesis for QKFLC and KFLC index showed an AUC of 0,891 and 0,839 and the cut-off of 0,027 and 8,82, respectively (sensitivity 73,2% and 71,3%; specificity 96,0% and 98,0%; +PV 97,4% and 98,6%). The diagnostic accuracy of KFLC index for conversion from CIS to MS showed AUC of 0,840 and a cut-off of 9,092 (sensitivity 90,0%; specificity 73,3%; -PV 93,7%). Life age correlates significantly with serum KFLC (r = 0,34; p < 0,0001) and through aging process lower KFLC indexes can be expected, i.e. likelihood of false negative diagnoses. CONCLUSION: KFLC index showed diagnostic value, although it is not more specific and more sensitive than OCB. Application of KFLC might serve as a screening method while OCB could be used in uninterpretted cases only. Patients who converted to MS have significantly higher KFLC which can contribute to an early diagnosis and prompt therapy with its predictive role.

Comparison of Enzymatic Assay for HBA1C Measurement (Abbott Architect) With Capillary Electrophoresis (Sebia Minicap Flex Piercing Analyser).

OBJECTIVE: To compare the analytical performances of the enzymatic method (EM) and capillary electrophoresis (CE) for hemoglobin A1c (HbA1c) measurement. METHODS: Imprecision, carryover, stability, linearity, method comparison, and interferences were evaluated for HbA1c via EM (Abbott Laboratories, Inc) and CE (Sebia). RESULTS: Both methods have shown overall within-laboratory imprecision of less than 3% for International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (<2% National Glycohemoglobin Standardization Program [NGSP] units). Carryover effects were within acceptable criteria. The linearity of both methods has proven to be excellent (R2 = 0.999). Significant proportional and constant difference were found for EM, compared with CE, but were not clinically relevant (<5 mmol/mol; NGSP <0.5%). At the clinically relevant HbA1c concentration, stability observed with both methods was acceptable (bias, <3%). Triglyceride levels of 8.11 mmol per L or greater showed to interfere with EM and fetal hemoglobin (HbF) of 10.6% or greater with CE. CONCLUSION: The enzymatic method proved to be comparable to the CE method in analytical performances; however, certain interferences can influence the measurements of each method.

Ascorbic acid-A black hole of urine chemistry screening.

BACKGROUND: Study was performed in order: (i) to assess the comparability of glucose, bilirubin, hemoglobin, leukocyte esterase, and protein; (ii) to assess accuracy of glucose, bilirubin, hemoglobin, leukocyte esterase, and protein; and (iii) to evaluate interference of ascorbic acid on the glucose, bilirubin, hemoglobin, and nitrite determination using 2 different dipsticks: iChem Velocity, Iris Diagnostics and Combur-10M, Roche Diagnostics. METHODS: Random urine specimens were included in the study. Comparability, accuracy, and ascorbic acid interference testing were performed. RESULTS: Obtained results have shown almost perfect agreement for all parameters between 2 dipsticks in samples with negative ascorbic acid. Agreement in samples with positive ascorbic acid was not acceptable for bilirubin, protein, nitrite, and hemoglobin. Accuracy was not acceptable for hemoglobin and leukocyte esterase on both dipsticks. Ascorbic acid interference examination has shown that intensity of interference differs between dipsticks. Ascorbic acid interferes with glucose, hemoglobin, nitrite, and bilirubin at different concentrations causing false-negative results. CONCLUSION: Obtained results indicate that it is necessary to determine diagnostic accuracy of used dipstick in order to define purpose of urinalysis. It is very important to choose dipstick with ascorbic acid indicator and to examine ascorbic acid impact on dipstick analytes independently of manufacturer claims.

Kappa Free Light Chains in Cerebrospinal Fluid of Patients with Identified Oligoclonal Immunoglobulin G.

BACKGROUND: Production of kappa free light chains (KFLC) represents a part of humoral immune response, along with the synthesis of intrathecal immunoglobulins. Increased concentrations of immunoglobulin G light chains, kappa and lambda chains, were identified through research of numerous diseases of central nervous system. The qualitative method of isoelectric focusing (IEF) followed by immunofixation currently represents the accepted standard in identifying oligoclonal bands (OCB), but establishing a sensitive immunonephelometric method for quantification of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) has paved a way for new diagnostic possibilities. Andersson classified the pattern types of OCB, ranging from type 1 to type 5, wherein types 2 and 3 indicate intrathecal synthesis. Our aim was to determine KFLC in CSF of patients with clinically isolated syndrome (CIS) who had presented with type 2 and type 3 OCB, to determine if there is a difference in concentrations between those two groups and to establish a borderline value of KFLC which would enable differential diagnostics. SUBJECTS AND METHODS: 70 patients, who underwent lumbar punction for CSF analysis and had their blood sampled through the cubital vein, participated in the study. Patients were classified according to Andersson as type 2 or type 3, which besides adulthood, represented the inclusion criteria. The average age of patients classified as type 2 was 36 years, and those classified as type 3 was 39 years, where it is evident that there was not a statistically significant difference (p=0.0685). We used a qualitative electrophoretic technique of IEF with agarose gel followed by immunofixation, and a quantitative immunonephelometric method. All results were interpreted on a level of statistic significance of p<0.05. RESULTS: CSF KFLC concentrations in type 3 were statistically and significantly elevated with regard to type 2 (Mann-Whitney test, p=0.0430). The median for KFLC in type 2 was 0.9 mg/L, while the median for KFLC in type 3 was 2.71 mg/L, and the detection limit for both types was 0.18 mg/L. We used a statistical ROC curve to determine that KFLC concentration can be used for differential diagnostics, meaning it can discriminate type 2 from type 3 with clinical sensitivity of 61% and clinical specificity of 71% (AUC=0.641) (p=0.037). CONCLUSION: Despite the obtained statistically significant differences in concentrations of KFLC between types of OCBs and ROC analysis results, determination of KFLC by a nephelometric method, insufficiently strong clinical sensitivity and specificity does not justify abandonment of IEF method followed by immunofixation.

Hypochloraemia as a predictor of developing hyponatraemia and poor outcome in acute heart failure patients.

AIMS: Heart failure (HF) is a major public health issue currently affecting more than 23 million patients worldwide. Hyponatraemia has been shown to be a predictor of poor outcome in patients with acute and chronic HF. Therefore, we aimed at finding a marker for early detection of patients at risk for developing hyponatraemia. To this end, the present study investigated the relationship between initial serum chloride and follow-up sodium levels in acute heart failure (AHF) patients. METHODS AND RESULTS: The present study was performed as a prospective, single-centre, observational research with a total of 152 hospitalised AHF patients. Compared to patients with initial normochloraemia, patients with initial hypochloraemia had a statistically significantly higher incidence of hyponatraemia after a 3-month follow-up [P<0.001; odds ratio (OR)=27.08, CI: 4.3-170.7]. A similar finding was obtained upon exclusion of patients with initial hyponatraemia with Fishers test [P=0.034; odds ratio (OR)=15.5, CI:1.7-140.6]. Binary logistic regression revealed a significantly increased in-hospital mortality in the hypochloraemic/normonatriaemic (OR=4.08, CI 1.08-15.43, P=0.039), but not in the hypochloraemic/hyponatraemic, normochloraemic/hyponatraemic or normonatriaemic/normochloraemic patients. Ejection fraction (EF) at admission was significantly higher in hypochloraemic/normonatriaemic, compared to normonatriaemic/normochloraemic patients, but similar to EF in both hypochloraemic/hyponatraemic and normochloraemic/hyponatraemic patients. The N-terminal precursor Brain Natriuretic Peptide (Nt-proBNP) levels at admission were significantly lower in hypochloraemic/normonatriaemic compared to hypochloraemic/hyponatraemic and normonatriaemic/normochloraemic patients, respectively. CONCLUSION: The data show that initial low serum chloride concentration is predictive of developing hyponatraemia and associated with increased in-hospital mortality in AHF patients.

Increased calcium-independent lipoprotein phospholipase A2 but not protein S100 in patients with schizophrenia.

BACKGROUND: The aim of this paper was to investigate serum concentrations of calcium-independent lipoprotein phospholipase A2 (PLA2) and protein S100 in schizophrenia patients in comparison to healthy controls and correlate them with the clinical severity, duration, and number of schizophrenia relapses. SUBJECTS AND METHODS: This study included 65 schizophrenia patients and 70 controls. Schizophrenia was diagnosed according to DSM-IV-TR criteria. Clinical severity was determined by PANSS. PLA2 and protein S100 concentration were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: PLA2 concentrations were higher in patients with schizophrenia, whereas protein S100 concentrations were not. Higher concentrations of PLA2 were positively correlated with the duration of illness and number of episodes, as determined by multivariate analysis. CONCLUSION: PLA2 might be considered a possible biochemical trait marker for schizophrenia. Further research with larger and more homogeneous clinical samples is required.

Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats.

BACKGROUND: We investigated the possible non-lipid effects of simvastatin (SIMV) on paraoxonase 1 (PON1) and butyrylcholinesterase (BuChE) activity, as well as on malondialdehyde (MDA) levels in normolipidemic rats. METHODS: Two experimental groups of Wistar rats (10mg/kg/day of SIMV) and two control groups (saline) underwent a 21-day treatment period (TP). On the 22nd day one experimental and one control group of rats were sacrificed. Remaining groups of animals were sacrificied on the 32nd day of the study (10-day after-treatment period (AT)). Blood samples and slices of liver, heart, kidney, and brain tissue were obtained for the measurement of PON1 and BuChE activity and levels of MDA. Data were analyzed by means of t-test for independent samples. p values≤0.05 were considered as statistically significant. RESULTS: SIMV caused a significant decrease of serum and liver PON1 activity (18-24%, p≤0.05) and MDA concentrations in the plasma, heart, liver, kidney, and brain (9-40%, p≤0.05), while plasma and liver BuChE activity increased by 29% (p≤0.05) and 18%, respectively. All effects of SIMV were largely diminished following AT. The exception was MDA, which remained significantly decreased in plasma and all tissues analyzed. CONCLUSION: SIMV significantly decreased PON1 activity and MDA levels and increased BuChE activity. We suggest that the decrease of MDA levels is a beneficial therapeutic effect of SIMV, for example in cardiovascular disorders, while the increase of BuChE activity, especially in brain, may be a potential adverse effect in patients with Alzheimer disease.

Effect of Extra Virgin Olive Oil on Biomarkers of Inflammation in HIV-Infected Patients: A Randomized, Crossover, Controlled Clinical Trial.

BACKGROUND: Premature atherosclerosis in HIV-infected patients is associated with chronic infection by itself and adverse effects of antiretroviral treatment (ART). Extra virgin olive oil (EVOO) has a beneficial effect on the cardiovascular system because of its anti-inflammatory properties. The objective of this study was to determine whether the consumption of EVOO improves inflammation and atherosclerosis biomarkers in HIV-infected patients receiving ART. MATERIAL AND METHODS: This randomized, crossover, controlled trial included 39 HIV-positive male participants who consumed 50 mL of EVOO or refined olive oil (ROO) daily. Four participants dropped out of the study. Leukocyte count, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde, glutathione-peroxidase, superoxide dismutase, oxidized LDL and von Willebrand factor were determined before the first and after each of the 2 intervention periods. Intervention and washout periods lasted for 20 and 14 days, respectively. RESULTS: In participants with >90% compliance (N=30), hsCRP concentrations were lower after EVOO intervention (geometric mean [GM], 1.70 mg/L; 95% confidence interval [CI], 1.15-2.52) compared to ROO administration (GM, 2.92 mg/L; 95% CI, 1.95-4.37) (p=0.035). In participants using lopinavir/ritonavir, ESR and hsCRP concentrations decreased 62% and 151%, respectively, after EVOO administration. In the whole study population (N=35) we found no difference in analyzed biomarkers after EVOO administration. CONCLUSIONS: Our exploratory study suggests that EVOO consumption could lower hsCRP in patients on ART.

Folic acid and vitamin B(12) supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized, double-blind, placebo-controlled trial.

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B(12). The aim of this study was to determine whether there is an impact of folic acid and vitamin B(12) supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B(12) will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 µmol/L. Participants were randomly assigned to receive either a daily folic acid (800 µg) and vitamin B(12) (1000 µg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 µmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B(12) as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.

Diagnostic accuracy of serum brain derived neurotrophic factor concentration in antidepressant naïve patients with first major depression episode.

Diagnosing major depressive disorder (MDD) continues to be based on meeting phenomenological and descriptive criteria. As of yet, there is still no non-invasive, peripheral biomarker that would allow for a certain diagnosis of MDD. The objective of this paper is to use the receiver operating characteristic (ROC) analysis to test the diagnostic value of serum concentrations of brain derived neurotrophic factor (BDNF) in diagnosing the first episode of MDD. Among 1014 patients admitted for an initial psychiatric evaluation, antidepressant naïve patients diagnosed with first episode MDD were separated into the test group. Only patients signing an informed consent form were included in the study. Using DSM-IV-TR diagnostic criteria, those patients meeting the MDD criteria (N = 122) and patients not meeting MDD or other psychiatric disorder criteria (N = 142) were differentiated. Subjects with repeated episode MDD (N = 121) and other psychiatric comorbid illnesses (N = 138) in the MDD group were excluded from the study. In the group without MDD or other psychiatric illnesses, patients with physical comorbidities (N = 59) were excluded. The serum concentration of BDNF was determined in all patients using the ELISA assay. Subjects with first episode MDD showed differences in serum BDNF concentrations (ng/mL) in comparison to the control group of patients not meeting the criteria for first episode MDD (mean ± SD; 37.5 ± 13.3 vs. 56.8 ± 6.3; t = 1.372; df = 262; p < 0.01). The ROC analysis established a discriminant diagnostic value of serum BDNF in diagnosing MDD. The area under the curve (AUC) was 0.892 with a 95% confidence level (0.826-0.939), which was statistically significant at p < 0.01. The serum BDNF had a high diagnostic sensitivity of 83.9% and a specificity of 93%. Serum BDNF concentrations appear to be a promising tool in discriminating subjects with MDD from those without MDD.

Impact of admission anemia, C-reactive protein and mean platelet volume on short term mortality in patients with acute ST-elevation myocardial infarction treated with primary angioplasty.

OBJECTIVES: To investigate admission anemia, C-reactive protein (CRP) and mean platelet volume (MPV) together as prognostic markers in ST-elevation myocardial infarction (STEMI). DESIGN AND METHODS: Baseline hemoglobin, CRP and MPV were determined in 543 patients with acute STEMI to whom primary angioplasty was performed and evaluated for short term mortality (30 days). RESULTS: After multivariate analysis anemia (odds ratio 2.69, 95% confidence interval 1.24-5.86) and CRP (odds ratio 3.40, 95% confidence interval 1.13-10.22) remained significant independent predictors of short-term mortality. Addition of anemia and CRP to PAMI risk score improved prediction of short-term outcome; area under ROC curve rose from 0.76 to 0.87 (p<0.001). CONCLUSION: Better ability to determine 30-day mortality was obtained when anemia and CRP were incorporated into the PAMI risk score.

Reference intervals for reproductive hormones in prepubertal children on the automated Roche cobas e 411 analyzer.

OBJECTIVES: To establish reference intervals for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), total and free testosterone (T) and sex-hormone binding globulin (SHBG) in prepubertal children and to assess age- and gender-related differences. DESIGN AND METHODS: A total of 948 subjects, 480 girls and 468 boys, between 1 and 11 years of age, were included in this study. All assays were performed on a Roche cobas e 411 immunoassay analyzer. Reference intervals have been evaluated according to the most recent CLSI guidelines. RESULTS: Median values of LH, FSH and T were significantly higher in subgroups ranging from ≥ 8 to < 11 years, for both genders. In girls of that age, reference values of E2 were significantly higher than in younger ones, and in boys of the corresponding age. CONCLUSION: Established reference intervals are applicable to other laboratories that use the same instrumentation.

Serum concentrations of CRP, IL-6, TNF-α and cortisol in major depressive disorder with melancholic or atypical features.

The aim of the present study was to explore possible differences between serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and cortisol concentration in patients with major depressive disorder (MDD) with melancholic features, and MDD with atypical features. As secondary aim, we investigated possible associations with clinical features such as suicidal ideation, number of episodes, duration of depression and symptomatology severity. We included 55 MDD patients (32 with melancholic features and 23 with atypical features) and 18 healthy controls. When compared to healthy controls, MDD with melancholic or atypical features showed higher CRP and IL-6, but not TNF-α. Cortisol concentration was higher in MDD with melancholic type, in comparison to the atypical type of MDD or controls. A positive correlation was found between the severity of depressive symptoms, concentrations of IL-6 and cortisol in the MDD group with melancholic features, while a negative correlation was observed between IL-6 and CRP in the MDD group with atypical feature. Also, in the MDD group with atypical features, there was a correlation between the severity of anxiety symptoms based on the Hamilton Rating Scale for Anxiety (HARS), concentration of CRP, and the duration of symptoms. In conclusion, we observed several differences in serum CRP, IL-6, and cortisol concentrations in MDD patients considering clinical features as well.

[Compensated creatinine method and glomerular filtration rate estimation in a heterogeneous population of patients]. / Kompenzirana metoda za odredivanje kreatinina i procjena glomerularne filtracije u heterogenoj populaciji bolesnika.

Creatinine is a metabolite excreted mainly by glomerular filtration, which makes it an important endogenous indicator of kidney function. Creatinine clearance is defined as the ratio of the concentration of creatinine in serum and urine. It assesses glomerular filtration. Creatinine and creatinine clearance have the leading role in the early diagnosis, monitoring and classification of chronic kidney disease. The routine method for determining the concentration of creatinine is the Jaffé photometric method. A newer version is the compensated method. Furthermore, the recommended equation for the estimation of glomerular filtration rate (GFR) is the one based on the MDRD study (eGFR) intended for people over 18 years. The aim of the study was to evaluate how the introduction of the compensated method would affect the clinical use and influence the assessment of GFR in the interpretation of findings and treatment monitoring for people over 20 years. The study group included 130 men and 142 women whose requested laboratory test was creatinine clearance. Data were collected over 20 days at Sestre milosrdnice University Hospital. Serum creatinine concentration and eGFR were determined by the compensated and uncompensated Jaffé method. In conclusion, the compensated creatinine method is not statistically comparable with the uncompensated method, but is clinically fully applicable to the general population above the age of 20, given that the reference intervals are changed. Comparison of eGFR as estimated by the compensated and uncompensated methods to determine creatinine concentration showed the same results as the comparison of clearance. Using the compensated method yielded statistically incomparable results in GFR estimation. However, in clinical practice, patient classification according to stages of chronic kidney disease (CKD) was comparable in the male group according to clearance and eGFR (pi=0.922 and pi=0.230, respectively), while the female group was classified significantly different according to clearance and eGFR (pi<0.016 and pi<0.001, respectively). Switching to the compensated creatinine method while simultaneously applying the eGFR formula was shown to be valid, as patient classification according to CKD stages was comparable (pi=0.921); thus, the methods are reliable for use instead of creatinine clearance in the general population with various diagnoses, which can be noted in all laboratories and which is, although inhomogeneous, routinely used to measure daily creatinine clearance.

Serum Brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression.

INTRODUCTION: The aim of this study was to compare the concentration of serum Brain-derived neurotrophic factor (BDNF) in patients suffering from major depressive disorder (MDD) considering the severity of MDD episode defined by the Hamilton rating scale for depression (HAMD-17). The other aim was to research the connection between serum BDNF and the symptomatic dimensions of MDD. SUBJECTS AND METHODS: The study includes 139 participants with major depressive disorder (MDD). Diagnosis of MDD was set by DSM-IV-TR criteria. The severity of MDD was estimated with HAM-D-17 in the manner that mild episode was diagnosed if the score on HAMD-17 was up to 18, moderately severe 18-25 and severe over 25. Concentration of BDNF was determined by the ELISA method. RESULTS: This research could not find a difference in BDNF concentration considering the severity of the depressive disorder in groups suffering from mild, moderately severe and severe episodes of MDD (F=1.816; p=0.169). Factor analysis of HAMD-17 extracted four dimensions of depressive symptoms. None of the symptomatic dimensions was significantly related to BDNF concentration. CONCLUSION: Results of this study indicate that serum BDNF levels are not related to the severity of depression and its specific symptomatic dimensions. These findings support the idea of a complex relationship between BDNF concentration at the periphery and in the CNS.

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis.