The prognostic value of first-trimester cystatin C levels for gestational complications.

AIMS: This study is designed to evaluate predictive value of first-trimester cystatin C levels for long-term pregnancy complications. METHODS: The cross-sectional study population consisted of patients who admitted to outpatient clinic of a Maternity Hospital between September 2013 and December 2014. Among the 203 participants who accepted to participate in the study, 174 subjects who continued antenatal follow-up in the same clinic were included in the final analyses. Cystatin C, blood urea nitrogen, Creatinine levels and estimated glomerular filtration rates were evaluated in the first-trimester routine antenatal visit. Mode of delivery and gestational complications were noted. RESULTS: First-trimester cystatin C levels were significantly higher in cases complicated with preterm delivery and premature rupture of membrane (PROM) compared to uncomplicated ones (0.58±0.07 vs. 0.55±0.07, P=0.041, and 0.58±0.07 vs. 0.55±0.07, P=0.036). With a cutoff value of 0.505 mg/L, sensitivity of cystatin C for preterm delivery and PROM was 91.9% and specificity was 27.7% with a negative predictive value of 92.3% and a positive predictive value of 26.6%. CONCLUSION: Detection of cystatin C levels in the first trimester of pregnancy for the prediction of preterm/PROM seems as a promising preliminary data. The relatively higher first-trimester cystatin C levels in complicated pregnancies are conspicuous. The results imply that in pregnancy cystatin C might be more than a marker for renal function.

The association of osteocalcin and adiponectin with glucose metabolism in nondiabetic postmenopausal women.

BACKGROUND/AIM: This study was designed to determine if osteocalcin is associated with insulin resistance, metabolic risk factors and adiponectin levels in nondiabetic postmenopausal women. METHODS: A total of 87 menopausal nondiabetic subjects were enrolled into the study. Levels of fasting plasma glucose (FPG), insulin and serum lipids were determined. To estimate insulin sensitivity, homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were used. Serum total osteocalcin and adiponectin levels were measured and the features of metabolic syndrome were identified. RESULTS: The mean age of the patients was 54.7 years. Among the participants, 28.7% were obese (body mass index, BMI, ≥30). Insulin resistance was detected by HOMA-IR in 42.5% and by the QUICKI index in 63.2% of the cases. Metabolic syndrome was present in 29.8% of the patients. Neither the baseline characteristics nor the metabolic risk factors were correlated with osteocalcin or adiponectin levels (p > 0.05). When the patients were analyzed regarding BMI, osteocalcin levels were significantly lower in overweight women. Serum adiponectin levels were significantly lower in women with metabolic syndrome. CONCLUSION: No correlation between total osteocalcin and FPG, fasting insulin and insulin resistance parameters was found in nondiabetic postmenopausal women. Serum levels of adiponectin were associated with metabolic syndrome.

The impact of route of anesthesia on maternal and fetal ischemia modified albumin levels at cesarean section: a prospective randomized study.

OBJECTIVE: Ischemia modified albumin has been shown to increase in ischemic situations, and has also been shown to increase in fetal cord blood in deliveries by cesarean section. The aim of this study is to reveal whether anesthesia has an impact on maternal and fetal cord ischemia modified albumin levels. METHODS: Seventy two women with uncomplicated term pregnancies were randomized to spinal (n=37) or general anesthesia (n=35) groups. The blood pressure, oxygen saturation, and pulse rate of the patients were recorded during the procedure. Maternal blood samples of ischemia modified albumin (IMA) were taken 10 min from the start of the procedure. The fetal cord blood samples of IMA were taken immediately after birth. RESULTS: Maternal (0.99 ± 0.19 vs. 0.80 ± 0.27) and fetal (1.00 ± 0.21 vs. 0.70 ± 0.26) IMA levels were significantly higher in the general anesthesia group. Fetal IMA levels were positively correlated with maternal gravidity (r=0.31; P=0.008), parity (r=0.25; P=0.028), and fetal birth weight (r=0.23, P=0.045). Also, as time from incision to delivery lengthens, fetal IMA levels increase (r=0.29, P=0.012). CONCLUSION: Fetal cord ischemia modified albumin levels were higher in the general anesthesia group, therefore, it is proposed that regional anesthesia should be the preferred route of anesthesia for an elective cesarean section, at least until the impact of high fetal cord IMA levels are manifested.

Anti-Mullerian hormone and insulin resistance in classic phenotype lean PCOS.

PURPOSE: This study is designed to explore the correlation between AMH levels and IR in normal weight PCOS women. MATERIALS AND METHODS: This prospective study was conducted on 55 patients, who were admitted to obstetrics and gynecology department of a university clinic. Study group was consisted of 34 patients diagnosed as polycystic ovary syndrome (PCOS) according to the Rotterdam Criteria, whereas control group was consisted of 21 healthy volunteers without any features of clinical or biochemical hyperandrogenism, who had regular menstrual cycles. BMI ≥ 25 kg/m(2) were considered overweight and obese and excluded. Blood samples were obtained during days 2-3 after spontaneous menses or progesterone-induced withdrawal bleeding after overnight fasting for at least 12 h. The weight, height, hip and waist circumferences of the patients were measured. Fasting insulin and glucose (FPG) levels were used for calculating different insulin resistance indexes (Homeostatic Model Assessment (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)). RESULTS: No significant difference was found between PCOS and control groups regarding the mean age, BMI, waist to hip ratio (WHR), mean values of FPG, FPG/insulin ratio and HOMA B (p > 0.05). AMH values were significantly higher in PCOS cases when compared with controls (4.7 vs. 3.4 ng/mL) (p < 0.05).The mean values of HOMA-IR and QUICKI indexes were significantly higher among PCOS cases when compared with controls. E2 levels were significantly lower and Total-T were significantly higher in PCOS patients. When PCOS cases are categorized according to the existence of IR, no difference in Total-T and AMH levels between both groups. Although not statistically significant, a negative correlation of AMH with HOMA-IR and a positive correlation with QUICKI index were found. Among the hormone parameters, AMH was found to be positively correlated with Total-T (r = 0.332, p = 0.013). CONCLUSION: Although the relation between AMH and androgen production is supported by current evidence, the mechanism underlying the relation between AMH and insulin resistance is not clear yet.

Sex-hormone-binding globulin early in pregnancy for the prediction of severe gestational diabetes mellitus and related complications.

AIMS: The aim of this study was to evaluate the predictive value of sex-hormone-binding globulin (SHBG) for the diagnosis of gestational diabetes mellitus (GDM), and to clarify the association between SHBG levels and GDM complications/medication requirements. MATERIAL AND METHODS: Among the participants (n = 93) who provided blood samples between 13 and 16 weeks' gestation, 30 cases subsequently developed GDM. Complications and medical interventions were noted. The best cut-off point of SHBG and diagnostic performance were calculated. RESULTS: The mean age was 28.45 ± 5.0 years. SHBG levels were lower in the GDM group (n = 30) when compared with non-GDM (n = 63) cases (<0.01). Among the GDM women, SHBG was lower in the insulin therapy group (n = 15) compared with medical nutritional therapy alone (n = 15) (P < 0.01). A good predictive accuracy of SHBG was found for GDM requiring insulin therapy (area under the curve: 0.866, 95% confidence interval: 0.773-0.959). An SHBG threshold for 97.47 nmol/L had a sensitivity of 80.0%, specificity 84.6%, positive predictive value 50.0% and negative predictive value 95.7%. The calculated odds ratio for SHBG < 97.47 nmol/L was 12.346 (95% confidence interval: 1.786-83.33). CONCLUSIONS: SHBG is valuable for screening women early in pregnancy for GDM risk; however, a standard assay for analyses and a threshold level of serum SHBG for a constant gestational week has to be determined.

The value of copper and zinc levels in hernia formation.

BACKGROUND: A defect in collagen metabolism is suspected to be one of the factors responsible for hernia formation. Lysyl oxidase is a copper-dependent enzyme in the process that provides for the structural integrity of collagen molecules, while zinc is essential for tissue maintenance. MATERIALS AND METHODS: In a prospective fashion, copper and zinc levels were measured in plasma and tissue specimens obtained from indirect (n=23), direct (n=20) and incisional hernia patients (n=19) and from healthy controls (laparoscopic cholecystectomy patients, n=15) by enzymatic colorimetric analysis. RESULTS: Groups were similar in age, comorbid diseases and body mass index. Whereas plasma levels of Cu and Zn in hernia and control patients were similar, and tissue levels were significantly lower in all hernia groups (especially the incisional hernia group) compared to controls (P<0·001). The incisional hernia group had significantly lower tissue copper levels than direct hernia patients and lower zinc levels than indirect hernia patients. CONCLUSIONS: Patients with all types of hernia, especially those with incisional hernias, have significantly lower tissue copper and zinc levels than control patients, despite having similar plasma levels. This finding might reflect excessive consumption or dysfunction of lysyl oxidase as playing a role in the aetiology of hernias.

The effect of treatment with montelukast on levels of serum interleukin-10, eosinophil cationic protein, blood eosinophil counts, and clinical parameters in children with asthma.

Interleukin (IL)-10 is an important immunoregulatory and anti-inflammatory cytokine. IL-10 levels are reduced in asthmatic airways. A regulatory mechanism involving IL-4 induced allergen-specific IL-10 production may be defective in allergic subjects, and this defect potentially contributes to more intense inflammation. The aim of this study was to define the effect of treatment with montelukast on serum levels of IL-10, eosinophil cationic protein (ECP), blood eosinophil counts, and clinical parameters (symptom score and lung function tests) in children with mild and moderate persistent asthma. Twenty-five children with mild-to-moderate persistent asthma and 25 nonatopic healthy children as controls were enrolled in the study. Patients were treated with montelukast for four weeks. Lung function tests for forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and forced expiratory flow between 25% and 75% (FEF25-75) were performed before and after treatment. Serum IL-10, ECP levels, and blood eosinophil counts were determined in both the control group and asthmatic children before and after treatment. The mean serum IL-10 levels were significantly lower before treatment than after treatment (1.75 +/- 0.9 pg/ml and 5.49 +/- 3.6 pg/ml; p < 0.001) and in control subjects (5.6 +/- 2.8 pg/ml). After four weeks of treatment with montelukast, the mean blood eosinophil count value (608 +/- 73/mm3 and 469 +/- 57/mm3; p < 0.05) but not the ECP value (33.98 +/- 24.3 microg/L and 29.03 +/- 19.2 microg/L; p > 0.05) was significantly decreased. After treatment with montelukast, all clinical parameters and lung function tests improved. We found no statistical correlations between the serum level of IL-10 and the serum level of ECP, eosinophil count, lung function tests, or clinical scores after treatment with montelukast. Montelukast caused a statistically significant increase in serum IL-10 levels and decrease in peripheral blood eosinophil counts over the four-week treatment period. Our study indicates that montelukast provides clinical benefits for children with chronic asthma and produces an anti-inflammatory response by increasing serum IL-10 levels,

The correlation between birth weight and insulin-like growth factor-binding protein-1 (IGFBP-1), kisspeptin-1 (KISS-1), and three-dimensional fetal volume.

PURPOSE: This study aimed to determine the relationship between birth weight, and maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on three-dimensional ultrasonography. MATERIALS AND METHODS: The study included 142 pregnant women at gestational week 11°-136. All fetuses were imaged ultrasonographically by the same physician. Maternal blood samples were collected at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1 levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal weights were recorded at birth. Birth weight ≤10th and the >90th percentiles was defined as small and large for gestational age (SGA and LGA), respectively. RESULTS: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS-1 levels were 58.2 mm (35.3-79.2 mm), 16.3 cm3 (3.8-34.4 cm3), 68.1 ng mL-1 (3.8-377.9 mL-1), and 99.7 ng L-1 (42.1-965.3 ng L-1), respectively. First-trimester IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p < .05). There was a significant positive correlation between CRL and FV, and between the IGFBP-1 and KISS-1 levels. IGFBP-1 levels and maternal weight at delivery were negatively correlated with neonatal birth weight. There was no correlation between CRL or FV and maternal IGFBP-1 or KISS1 levels (p > .05). The maternal IGFBP-1 level during the first trimester was a significant independent factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005-1.018, p < .001; and OR: 1.297, 95%CI: 1.074-1.566, p = .007, respectively). There was no significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level. CONCLUSIONS: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level during the first trimester might be a better biomarker of fetal growth. Additional larger scale studies are needed to further delineate the utility of IGFBP-1 as a marker of abnormal birth weight.

The evaluation of cystatin C, IL-1beta, and TNF-alpha levels in total saliva and gingival crevicular fluid from 11- to 16-year-old children.

BACKGROUND: The aim of this study was to evaluate the levels of cystatin C, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in the total saliva and gingival crevicular fluid (GCF) of periodontally healthy children (PHC) and children with gingivitis (CG) who were between 11 and 16 years old. METHODS: The study was carried out with 10 PHC and 25 CG. Unstimulated total saliva and GCF samples were obtained. Clinical parameters, including probing depth (PD), clinical attachment loss (CAL), plaque index (PI), gingival index (GI), and gingival bleeding index (GBI), were assessed. GCF samples were collected from four maxillary upper incisors. After sampling, biochemical analyses were performed using latex particle-enhanced turbidimetric immunoassay for cystatin C and enzyme-linked immunosorbent assay for IL-1beta and TNF-alpha. The multivariate analysis of variance test was used for statistical evaluation. RESULTS: In total saliva, cystatin C and TNF-alpha levels were higher in PHC, and IL-1beta levels were higher in CG, but the differences were not statistically significant. In GCF, cystatin C levels were higher in PHC (P >0.05), whereas TNF-alpha and IL-1beta levels were higher in CG (P >0.05). In the CG group, there were positive correlations between the GCF cystatin C level and the PI of the sampled site (r = 0.488; P <0.05); also, GCF IL-1beta (r = 0.603; P <0.05) and TNF-alpha (r = 0.456; P <0.05) levels were positively correlated with PD and CAL. For the whole mouth and the sampled sites, PI, GI, GBI, PD, and CAL values were higher in CG (P <0.05), but no significant differences were detected between GCF volumes of the two groups. CONCLUSIONS: To the best of our knowledge, this study represents the first evaluation of cystatin C in the gingival disease mechanism in children. Our results showed that total saliva and GCF cystatin C levels were higher in PHC (P >0.05), but there was no correlation between cystatin C levels and IL-1beta or TNF-alpha levels in total saliva or GCF.

Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells.

The antidiabetic agent metformin was shown to further possess chemopreventive and chemotherapeutic effects against cancer. Despite the advances, the underlying molecular mechanisms involved in decreasing tumor formation are still unclear. The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. We investigated the effects of metformin in HepG2 and H2009 cells, verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system. Our results showed metformin induced oxidative stress and reduced antioxidant capacity. Also, metformin treatment with hydrogen peroxide (H2O2) enhanced these effects. Although DNA BER enzyme activities were not changed accordantly together by metformin as a single agent or in combination with H2O2, activated p53 was decreased with increased oxidative stress in H2009 cells. Our study on the relationship between metformin/reactive oxygen species and DNA BER system in cancer cells would be helpful to understand the anticancer effects of metformin through cellular signal transduction pathways. These findings can be a model of the changes on oxidative stress that reflects p53's regulatory role on DNA repair systems in cancer for the future studies.

Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes.

Metformin is used to reduce hyperglycemia that induces energetic stress and leads to reduction in gluconeogenesis. Also, metformin inhibits complex I in oxidative phosphorylation, thereby decreasing cellular ATP levels. Activation of AMPK by the reduced ATP levels can induce inhibition of reactive oxygen species (ROS) production and activate p53-mediated DNA repair. DNA polymerase-ß and XRCC1 function to repair DNA damages in the BER (base excision repair) system. In type 2 diabetes patients, metformin can enhance AMPK activation therefore suppress oxidative stress. The changes on oxidative stress may alter p53's function and effect many cellular pathways such as; DNA repair. In our project we aim to understand the effects of metformin on p53 and DNA-BER system based on the oxidative status in type 2 diabetes patients. Oxidative and antioxidative capacity, catalase, SOD, GPx activities and, DNA pol beta, XRCC1 and p53 levels were measured in metformin using or non-using type 2 diabetes patients and controls. Metformin enhanced SOD and GPx activities in type 2 diabetes patients but the reflection of this increase to the total antioxidant capacity was not significant. Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients. Our study reinforces the potential benefit of metformin in antioxidative capacity to protect cells from diabetic oxidative stress and in regulation of DNA BER system.

Ischemia modified albumin in perinatology.

Ischemia modified albumin is a novel marker of ischemia generated due to hypooxygenation and increased hydroxyl free radicals in low pH. The molecule has been licenced for clinical use as an early marker for acute coronary syndrome in cardiology. Since presence of ischemia might have serious and sometimes devastating effects in perinatology, various researches have evaluated its value in different clinical conditions. This narrative review aims to summarize the literature concerning the value of IMA in perinatology and guide for further research.

Serum cardiovascular risk factors in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients have increased cardiovascular morbidity and mortality. The cardiovascular markers associated with OSA are currently not defined. OBJECTIVES: The aims of this study were to determine whether OSA is associated with serum cardiac risk markers and to investigate the relationship between them. METHODS: Sixty-two male patients were classified into two groups with respect to apnea-hypopnea index (AHI): group 1, sleep apnea (n = 30), with AHI > 5; and group 2 (n = 32), with AHI < 5. We compared cardiovascular risk factors in both groups with control subjects (n = 30) without OSA (AHI < 1). Serum cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I, apolipoprotein B, lipoprotein (a), C-reactive protein (CRP), and homocysteine were measured. Statistical significance was assessed with analysis of variance at p < 0.05. In correlation analysis, Pearson correlation was used. RESULTS: There was no significant difference between group 1 and group 2 in total cholesterol, LDL-C, HDL-C, triglyceride, apolipoprotein A-I, apolipoprotein B, and lipoprotein (a). All of the M-mode echocardiographic parameters were in the normal reference range. Serum homocysteine and CRP levels were significantly increased in group 1 compared to group 2 (p < 0.05). Serum CRP values were increased in both group 1 and group 2 when compared with control subjects (p < 0.05). Serum homocysteine values were higher in group 1 than in control subjects (p < 0.05). CONCLUSIONS: Our results show that OSA syndrome is associated not only with slight hyperhomocysteinemia but also with increased CRP concentrations. Increased plasma concentrations of homocysteine and CRP can be useful in clinical practice to be predictor of long-term prognosis for cardiovascular disease and the treatment of OSA.

Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia.

OBJECTIVE: The aim of this study was to evaluate the influence of malignancy and the impact of nephrotoxic drugs used in bone marrow transplantation (BMT) on the circulating levels of cystatin C in leukemia. METHODS: We studied nineteen patients (eleven men and eight women; mean age 30.1 +/- 11.2, 27.9 +/- 7.1 years) with acute lymphoblastic leukemia, acute myeloid leukemia and chronic myeloid leukemia. Cystatin C, urea, creatinine and creatinine clearance (CrCl) were measured 24 h before BMT, 1 week after BMT, 2 weeks after BMT and 3 weeks after BMT. The control group consisted of twenty healthy adults, and the mean age was 29.1 +/- 8.9. RESULTS: At the pretransplantation period, values of cystatin C were significantly higher than in the control group (P < 0.05). Urea, creatinine and CrCl values were not statistically different from the controls. One week after BMT, the level of cystatin C was significantly low as compared to the levels measured 24 h before BMT, but was still significantly higher than the controls (P < 0.05), whereas the levels of urea, creatinine and CrCl were in accordance with the levels of the controls. Two and three weeks after BMT, cystatin C values maintained the significant increase (P < 0.05), whereas the values of urea, creatinine and CrCl still corresponded with those of the controls in both group. CONCLUSIONS: Our preliminary data expose that cystatin C is not a reliable GFR marker in patients during leukemia or for monitoring nephrotoxic drugs used in BMT, but we can not reach definitive conclusion due to no gold standard for comparing the diagnostic accuracy of cystatin C. Further study is needed to elucidate the precise mechanism underlying this observation.

Comparison of angiotensin-converting enzyme, malonaldehyde, zinc, and copper levels in preeclampsia.

Preeclampsia is a syndrome of unknown etiopathogenesis. Recent studies carried out on preeclampsia have focused on the increase in free radicals in the feto-placental unit with poor perfusion. It is believed that the renin-angiotensin system (RAS) has a role in the poor perfusion of the placenta. It is uncertain whether there is a pre-existing impairment in RAS in pre-eclamptic pregnant women or not. In the present study, we measured angiotensin-converting enzyme (ACE), malonaldehyde (MDA), zinc, and copper levels in the placental tissue of 16 pre-eclamptic pregnant women and compared them with those in 20 healthy pregnant women. Whereas ACE activity and MDA were found to be high in the placentas of pre-eclamptic patients, zinc and copper levels were low and there was a negative correlation between ACE activity and zinc concentration. These findings suggest that high ACE activity might play a role in the increase in tissue hypoxia and consequent lipid peroxidation through vasoconstriction; zinc deficiency in the placental tissue might cause insufficiency of superoxide dismutase, an antioxidant enzyme. Furthermore, deficiency in placental zinc also plays a role in the biosynthesis of connective tissue, maintaining its integrity, which might have an impact on the structure of the spiral arteries.

The association between ischemia modified albumin and placental histopathology in uncomplicated term deliveries.

Ischemia modified albumin (IMA) is a marker of ischemia elevated in different clinical conditions and its use for hypoxia in perinatology is of current interest. We aimed to investigate the association between maternal and cord blood IMA levels and placental histopathological findings in uncomplicated term deliveries. In this study, placental histopathological evaluation in uncomplicated deliveries that ended with healthy newborns revealed 80.6% vasculopathy. The results support the hypothesis that hypoxia exceeding the placental reserve ends with fetal compromise. Moreover, the presence of maternal vasculopathy in placenta is not correlated with maternal and fetal IMA levels.

CRP at early follicular phase of menstrual cycle can cause misinterpretation for cardiovascular risk assessment.

OBJECTIVE: C-reactive protein (CRP) is a well-known marker of inflammation and infection in clinical practice. This study is designed to evaluate CRP levels in different phases of menstrual cycle, which might end up with misleading conclusions especially when used for cardiovascular risk assessment. METHODS: Twenty-seven women were eligible for the cross-sectional study. Venous blood samples from each participant were collected twice during the menstrual cycle. The first sampling was held at 2nd to 5th days of the menstrual cycle for FSH, estradiol, CRP, and sedimentation, and the second was done at 21st to 24th days of the menstrual cycle for measurement of progesterone, CRP, and sedimentation values. RESULTS: CRP values were significantly higher in the early follicular phase compared to luteal phase (1.8 mg/L [0.3-7.67] vs. 0.7 mg/L [0.1-8.3], p < 0.001, respectively). In both phases of the menstrual cycle, sedimentation rate was similar (12.1 ± 6.7 vs. 12.3 ± 7.7; p = 0.717, respectively). CONCLUSIONS: CRP levels in early follicular phase of the menstrual cycle (menstruation) are significantly higher than CRP levels in luteal phase of the same cycle. In reproductive age women, detection of CRP for cardiovascular risk assessment during menstruation might not be appropriate.

Ischemia-modified albumin levels in patients with acute decompensated heart failure treated with dobutamine or levosimendan: IMA-HF study.

OBJECTIVE: Ischemia-modified albumin (IMA) is a sensitive biomarker of myocardial ischemia. However, data on IMA levels in acute heart failure (HF) are still lacking. In this study, we aimed to evaluate serum IMA levels in acute decompensated HF and the effects of dobutamine and levosimendan treatments on IMA levels. METHODS: This was a prospective, multicenter study that included 70 patients hospitalized with acute decompensated HF and left ventricular ejection fraction < 35%. Blood samples for IMA measurements were obtained on admission and 24-48 h after the initiation of HF therapy. Twenty-nine patients were treated with standard HF therapy, 18 received levosimendan, and 23 received dobutamine in addition to standard of care. A single serum specimen was also collected from 32 healthy individuals each. IMA concentrations were measured by the albumin cobalt binding colorimetric assay, and the results were given in absorbance units (AU). Independent and paired sample t-tests, Mann-Whitney U test, and Wilcoxon signed-rank test were used for the analysis. RESULTS: In patients with acute decompensated HF, the serum concentration of IMA was significantly higher than those of healthy subjects (0.894 ± 0.23 AU vs. 0.379 ± 0.08 AU, p < 0.001). Overall, the IMA levels significantly decreased after 24-48 h of HF therapy (0.894 ± 0.23 AU and 0.832 ± 0.18 AU, p = 0.013). Furthermore, the IMA levels were also found to significantly decrease with standard HF therapy (1.041 ± 0.28 vs. 0.884 ± 0.15 AU, p = 0.041), with levosimendan (0.771 ± 0.18 vs. 0.728 ± 0.18 AU, p = 0.046) and also with dobutamine (0.892 ± 0.18 vs. 0.820 ± 0.13 AU, p = 0.035). CONCLUSION: Patients with acute decompensated HF had elevated IMA levels, and appropriate HF therapy significantly reduced the serum IMA levels. Dobutamine or levosimendan did not increase the IMA levels, suggesting a lower potential in inducing myocardial ischemia when used in recommended doses.

C-type lectin domain family 12, member A: A common denominator in Behçet's syndrome and acute gouty arthritis.

C-type lectin domain family 12, member A (CLEC12A) is a C-type lectin-like pattern recognition receptor capable of recognizing monosodium urate crystals. Monosodium urate crystals, the causative agents of gout are also among the danger-associated molecular patterns reflecting cellular injury/cell death. In response to monosodium urate crystals, CLEC12A effectively inhibits granulocyte and monocyte/macrophage functions and hence acts as a negative regulator of inflammation. Behçet's syndrome and gout are autoinflammatory disorders sharing certain pathological (neutrophilic inflammation), clinical (exaggerated response to monosodium urate crystals) and therapeutic (colchicine) features. We propose the hypothesis that decreased expression of CLEC12A is a common denominator in the hyperinflammatory responses observed in Behçet's syndrome and gout. Major lines of evidence supporting this hypothesis are: (1) Downregulation/deficiency of CLEC12A is associated with hyperinflammatory responses. (2) CLEC12A polymorphisms with functional and clinical implications have been documented in other inflammatory diseases. (3) Colchicine, a fundamental therapeutic agent used both in Behçet's syndrome and gout is shown to oppose the downregulation of CLEC12A. (4) Behçet's syndrome and gout are characterized by a hyperinflammatory response to monosodium urate crystals and other than gout, Behçet's syndrome is the only inflammatory condition exhibiting this exaggerated response. (5) Genomewide linkage and association studies of Behçet's syndrome collectively point to 12p12-13, the chromosomal region harboring CLEC12A. (6) Patients with severe forms of Behçet's syndrome underexpress CLEC12A with respect to patients with mild forms of the disease. If supported by well-designed, rigorous experiments, the forementioned hypothesis pertinent to CLEC12A will carry important implications for therapy, designing experimental models, and uncovering immunopathogenic mechanisms in Behçet's syndrome and gout.