The effects of resveratrol on ovarian hyperstimulation syndrome in a rat model.

OBJECTIVE: The aim of the present study was to investigate effects of resveratrol (RSV) over ovarian hyperstimulation syndrome (OHSS) in rat model. MATERIALS AND METHODS: 24 female Wistar rats (22 days old) were divided into four groups. Group 1 (control group; n = 6) received 0.1 ml intraperitoneal (IP) saline from days 22-26; group 2 (mild-stimulated group; n = 6) received 10 IU pregnant mare serum gonadotropin (PMSG) on day 24 and 10 IU of hCG 48 h later (day 26); group 3 (OHSS group; n = 6) was given 10 IU of PMSG for 4 consecutive days from day 22 and 30 IU hCG on the fifth day to induce OHSS; group 4 (OHSS + RSV group; n = 6) was treated the same as group 3, but received 60 mg/kg RSV 2 h before PMSG injection for 4 consecutive days and 2 h before the hCG injection on the fifth day. RESULTS: Weight gain was highest in the OHSS group. Ovarian weights were lower in the treatment group than OHSS group. Peritoneal fluid VEGF levels were lower for RSV group compared to group 2 and 3. Total VEGF immunoreactivity was higher in OHSS group than group 1, 2 and 4. CONCLUSION: These results indicate that RSV is beneficial for prevention of OHSS by reducing the increases in body and ovarian weight and VEGF activity. These effects may be mediated by anti-inflammatory, anti-oxidant and anti-angiogenic capacity of RSV.

Elevated PAPP-A levels in lean patients with polycystic ovary syndrome.

OBJECTIVES: This study aimed to evaluate the serum concentrations of PAPP-A (pregnancy associated placental protein-A), a biomarker which is associated with cardiovascular disease, in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 62 women with PCOS, and 68 age and body mass index (BMI) matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as PAPP-A levels were assessed in each subject. RESULTS: Women with PCOS and controls yielded similar median serum levels of PAPP-A (1.7 ng/ml versus 1.8 ng/ml, respectively, p = 0.328). However, when patients were compared based on BMI; subgroup analyses found that among women with BMI<27 kg/m2, patients with PCOS exhibited higher PAPP-A levels than controls (2.1 ng/ml versus 1.8 ng/ml, respectively, p = 0.018). When women with PCOS were evaluated in their own based on BMI, lean PCOS women showed higher levels of PAPP-A (2.1 ng/ml versus 1.5 ng/ml, p = 0.002). PAPP-A levels were negatively correlated with age (p = 0.031, r = -0.189), BMI (p = 0.002, r = -0.265) and triglyceride levels (p < 0.001, r = -0.3). CONCLUSION: The data of the present study suggested that PAPP-A might be a clinical indicator in PCOS, in which the risks of metabolic syndrome and cardiovascular event are increased. Especially a group of young patients with BMI <27 kg/m2 might benefit from the cardiovascular risk evaluation using PAPP-A, supplying prognostic information for high risk in the development of cardiovascular disease.

CFH Y402H and VEGF Polymorphisms and Anti-VEGF Treatment Response in Exudative Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to evaluate the prevalence of single nucleotide polymorphisms (SNPs) in complement factor H (CFH) Y402H and VEGF rs2146323 and rs699947 in exudative age-related macular degeneration (AMD) and their relationship with intravitreal anti-VEGF treatment response. METHODS: A total of 109 exudative AMD patients and 70 controls were included. Patients were classified as 'good responders' and 'nonresponders' based on the changes in best corrected visual acuity, central foveal thickness, lesion size, and the persistence of retinal hemorrhage after three dosages of anti-VEGF. We examined CFH, VEGF rs2146323 and rs699947 SNPs, and plasma interleukin-6 (IL-6) levels in both groups. RESULTS: In total, 42 patients (38.5%) and 11 controls (15.7%) had homozygote wild genotype TT (p = 0.002). The variant C allele frequency was 45% in controls and 31.7% in patients (p = 0.011). A and C allele frequencies for VEGF rs699947 and rs2416323 were similar between the control and patient groups (p = 0.947, p = 0.378). Both SNPs were similar in responders and nonresponders. No significant difference was detected between plasma IL-6 levels of the control and AMD groups (p = 0.594), but the levels were higher in good responders than nonresponders (p < 0.001). CONCLUSION: CFH Y402H SNP might be protective for AMD in the Turkish population. VEGF rs2146323 and rs699947 SNPs have no relationship to exudative AMD formation, and none of these seem to have any effect on anti-VEGF response.

Combination of DKK1 and AFP improves diagnostic accuracy of hepatocellular carcinoma compared with either marker alone.

BACKGROUND/AIMS: The Wnt/ß-catenin pathway plays a prominent role in hepatocellular carcinoma (HCC). The Dickkopf (DKK) proteins (DKK1-4) are known Wnt antagonists; the overexpression of DKK1 has been demonstrated in HCC, and increased DKK3 methylation in the HCC tissue is associated with worse prognosis. Thus, the aim of our study was to demonstrate the diagnostic accuracy of serum DKK1 and DKK3 in HCC in comparison with that of serum alpha-fetoprotein (AFP). MATERIALS AND METHODS: We included consecutive 40 HCC patients, 54 cirrhosis patients, and 39 healthy controls. Serum DKK1 and DKK3 levels were measured by an enzyme-linked immunosorbent assay, and serum AFP levels were measured by a chemiluminescence assay. RESULTS: The AFP levels differed in each group and could help differentiate between groups (p < 0.001). The DKK1 levels could help differentiate the HCC group from cirrhosis and control groups (p < 0.001), and the DKK3 levels could help differentiate HCC and cirrhosis groups from the control group (p < 0.001). Combined usage of DKK1 and AFP increased the diagnostic yield, with a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 92.3%, 92.1%, and 87.8%, respectively. CONCLUSION: Although AFP is superior to DKK1 and DKK3 in the diagnosis of HCC, the combination of DKK1 and AFP showed a better diagnostic yield than AFP alone.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Role of serum toll-like receptors 2 and 4 in non-alcoholic steatohepatitis and liver fibrosis.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease is a common cause of chronic liver disease, including non-alcoholic steatohepatitis (NASH). Our aim was to investigate whether serum toll-like receptors 2 and 4 (TLR2 and TLR4) levels are correlated with NASH and able to predict liver fibrosis, as well as to compare these markers with other non-invasive fibrosis scores (aspartate aminotransferase [AST] to alanine aminotransferase ratio, AST to platelet ratio index, fibrosis index, fibrosis 4, and fibrosis cirrhosis index). METHODS: Serum samples were obtained from consecutive biopsy proven NASH patients and healthy controls. Serum TLR2 and TLR4 were measured using ELISA. Stage of fibrosis was evaluated using the Brunt Criteria. The different non-invasive fibrosis scores were compared using areas under the curve. RESULTS: Fifty-seven patients with NASH and 57 healthy individuals were enrolled in the study. Serum TLR2 levels were not significantly different between the healthy controls and NASH patients. The medians were 3.88 ng/mL ± 0.29 versus 3.81 ng/mL ± 0.32, respectively (P = 0.587). In comparing the levels of TLR4 between groups, the medians were 1.05 ng/mL ± 0.13 versus 1.46 ng/mL ± 0.27, respectively (P < 0.001). In NASH patients, the levels of serum TLR4 increased with the stage of fibrosis: TLR4 medians were F0:1.01, F1:1.46, F2:2.14, F3:3.74, F4:5.83 (P < 0.001). TLR4 produced AUCs for ≥ F1, ≥ F2, and ≥ F3 of 0.862, 0.810, and 0.905, respectively (P < 0.001). TLR4 levels were more predictive than other non-invasive fibrosis scores in liver fibrosis. CONCLUSION: Serum TLR4 levels but not TLR2 were elevated in NASH patients in comparison with healthy controls. And in NASH patients, serum TLR4 levels both correlated with and were able to predict liver fibrosis.

Association between Plasma Endothelin-1, Transforming Growth Factor-ß, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-ß, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-ß, and FGF were 81.54 ± 21.62 µmol/mL, 31.82 ± 26.42 µmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-ß, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-ß, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and <70% (P > .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting.

Association of matrix metalloproteinase-1, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, and interleukin-6 with epicardial and myocardial perfusion.

OBJECTIVES: Matrix metalloproteinases (MMPs), which are important regulators of extracellular matrix degradation, are known to induce atherosclerotic plaque rupture because of the degradation of collagen fibers in the fibrous cap. We aimed to investigate the possible association between these enzymes and objective coronary angiographic parameters of epicardial or myocardial perfusion. METHODS: A total of 140 patients with acute coronary syndromes or stable angina pectoris, who were advised to undergo coronary angiography, were included. The correlation between the serum levels of MMP-1, MMP-9, tissue inhibitor of matrix metalloproteinase-1, interleukin-6 (IL-6), and Thrombolysis in Myocardial Infarction frame count (TFC), myocardial blush grade, and the magnitude of change in these parameters after percutaneous intervention was investigated in addition to the association between MMPs and the need for revascularization. RESULTS: TFC and corrected TFC scores were found to be higher in patients with higher MMP-1 levels (R: 0.706, P < 0.001; R: 0.867, P < 0.001). The absolute amount of decrease in TFC/corrected TFC after percutaneous intervention in the patients, who were advised to undergo revascularization, was correlated with higher MMP-1 and MMP-9 levels. MMP-1, MMP-9, and IL-6 were negatively correlated with myocardial blush grade although this association was weaker for MMP-9 and IL-6 compared with MMP-1 (R: -0.574, -0.367, and -0.496, P < 0.001). The mean serum levels of MMP-1, MMP-9, and IL-6 were higher in the patients who were advised to undergo revascularization compared with the patients who did not need revascularization. Odds ratios of MMP-1 and IL-6 for predicting revascularization need were calculated as 1.7 (95% confidence interval: 1.4-2.1; P < 0.001) and 6.5 (95% confidence interval: 2.5-16; P < 0.001), respectively. CONCLUSION: Higher levels of serum MMP-1, MMP-9, and IL-6 can be used to predict worse coronary angiographic findings and may be further targets of active investigation for wide use as risk predictors.

The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis.

Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study, we investigated whether ET-1 has a role in determining the severity of liver fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were enrolled in the study. The patients were categorized into three groups: group 1, patients with elevated transaminase levels who were diagnosed as NASH by liver biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy but having elevated transaminase levels (n=12); and group III, patients with hepatosteatosis observed by ultrasonography, having normal transaminase levels (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all patients. Mean serum ET-1 level was statistically significantly higher in the NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and 5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and 20.40+/-1.40 micromol/L, respectively. None of the patients were identified as grade III fibrosis. It was found that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased in NASH patients (P < 0.05). In conclusion, the serum ET-1 level is higher in NASH patients compared to patients having only steatosis. There appears to be a correlation between severity of fibrosis and serum ET-1 level in NASH patients. It has been found that NASH patients having a twofold increase in their ALT levels had higher ET-1 levels and a more severe grade of fibrosis.

Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis.

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received beta-glucan or beta-glucan + beta-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. beta-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the beta-glucan inhibitor abrogated beta-glucan's survival benefit (50%). After CLP, plasma TNF-alpha, IL-1beta, and IL-6 concentrations were increased in control animals. When beta-glucan was administered, it completely blocked the elevation of TNF-alpha, IL-1beta, and IL-6. Administration of beta-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with beta-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.

Reduced serum acylated ghrelin levels in patients with hyperthyroidism.

BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients.

BACKGROUND: Sleep complaints are common in end-stage renal disease. We aimed to investigate the relationship between sleep-related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels. METHODS: Predialysis serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels in nine patients with sleep complaints were compared with those of nine patients without sleep complaints and nine healthy controls. Patients with sleep complaints underwent polysomnography the night after HD and the following night. RESULTS: Patients with sleep complaints had significantly higher predialysis IL-1beta levels compared with those without and healthy controls (P=0.004 and P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha levels than those without sleep complaints; however, the difference was not significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha and similar mean IL-1beta levels compared with healthy controls (P=0.001, P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was found in six out of nine (66%) patients with sleep complaints. Sleep architecture and cytokine levels did not differ between the two nights. The mean serum IL-1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post-polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF-alpha levels and the apnoea-hypopnoea index. CONCLUSIONS: Proinflammatory cytokines, IL-1beta in particular, might be associated with sleep complaints in HD patients. OSAS is not uncommon in HD patients with sleep-related complaints and sleep architecture does not appear to be effected by the HD procedure itself.

Association between neopterin and carotid intima-media thickness in hemodialysis patients.

BACKGROUND: Atherosclerotic lesions are heavily infiltrated by macrophages. Neopterin can be used as a marker of the activity of macrophages. Serum neopterin levels were elevated in non-renal patients with atherosclerosis. The intima-media thickness (IMT) of the carotid arteries in hemodialysis patients was significantly higher than in control subjects. In this study, we measured serum neopterin levels in hemodialysis patients and evaluated a possible correlation between neopterin levels and carotid IMT. PATIENTS AND METHODS: Thirty-seven hemodialysis patients (26 male/11 female, mean age 47 +/- 15 years) and 12 healthy subjects (8 male/4 female, mean age 43 +/- 10 years) were included in this study. Serum neopterin levels were measured by using a commercial ELISA kit. Carotid IMT of the subjects were measured by high-resolution B-mode ultrasonography. RESULTS: Carotid IMT values were 1.04 +/- 0.29 and 0.77 +/- 0.25 mm in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 110.9 +/- 19.1 and 3.8 +/- 2.3 ng/ml in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 103.2 +/- 21.3 ng/ml in hemodialysis patients with IMT < 1 mm (n = 15), and 116.7 +/- 15.4 ng/ml in hemodialysis patients with IMT > or = 1 mm (n = 22) (p < 0.05). Moreover, there was a significant correlation between serum neopterin levels and carotid IMT (p < 0.05, r = 0.363). CONCLUSION: Our findings suggest that neopterin could be associated with the severity of carotid atherosclerosis in hemodialysis patients.

Influence of locoregional radiation treatment on tumor necrosis factor-alpha and interleukin-6 in the serum of patients with head and neck cancer.

Serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels in the serum of 34 patients with head and neck cancer (HNC) undergoing locoregional radiotherapy (RT) were examined. The aim of the RT was definitive in 19 and postoperative adjuvant in 15 patients. Serum TNF-alpha and IL-6 levels were recorded before RT and after the completion of the fifth week of RT. The mean TNF-alpha levels before and after RT were 28.26 +/- 2.87 and 83.03 +/- 7.47, and the mean IL-6 levels were 61.56 +/- 14.32 and 122.45 +/- 30.66, respectively. The statistical analysis yielded a significant rise in TNF-alpha levels with RT in all patients (p < 0.0001) and also in IL-6 levels in patients treated with postoperative adjuvant RT (p = 0.001). Irradiation is likely to cause an acute phase response, and the cytokines studied may be used to monitor this clinically important response in further trials.

Late cardiac evaluation of children with solid tumors after anthracycline chemotherapy.

BACKGROUND: The therapeutic potential of anthracycline antibiotics is limited by their cardiotoxicity. Electrocardiography, exercise testing, and two-dimensional echocardiography are non-invasive techniques used in the follow-up of children for cardiotoxicity. Plasma B-type natriuretic peptide (BNP) levels are thought to be useful markers in the early detection of AC induced cardiomyopathy. PROCEDURE: We evaluated cardiac status of 34 patients with solid tumors treated with anthracycline antibiotics. All of the patients were asymptomatic and had no evidence of residual malignancy. They were evaluated by electrocardiography, exercise testing, echocardiography, and plasma BNP levels measured before and after the exercise testing. RESULTS: Electrocardiography revealed only minor abnormalities of little clinical significance. All of the patients completed the exercise testing without complication, and the duration of the exercise for each patient was between normal limits. Cardiac output (CO) and wall stress (WS) were significantly increased in patients, than in controls in echocardiographic evaluation of systolic functions (P < 0.001). Diastolic filling patterns showed various abnormalities; M-E, M-A, T-E, T-A, AT, and IVRT were significantly higher than those of controls. Mean plasma BNP levels of the patients (10.56 +/- 10.22 pg/ml) were significantly higher than BNP levels of the healthy controls (4.09 +/- 2.26 pg/ml) (P < 0.016), before exercise testing. The mean plasma BNP levels of the patients (15.70 +/- 14.06 pg/ml) were higher than resting state after exercise testing, but it was not statistically significant (P > 0.05). CONCLUSION: Our findings demonstrated that echocardiographic and biochemical abnormalities could be found even at low cumulative doses of AC antibiotics. The use of serial echocardiographic studies and plasma BNP determinations to identify high-risk patients for cardiotoxicity needs to be verified by additional studies.

Serum leptin levels are associated with tamoxifen-induced hepatic steatosis.

PURPOSE: Tamoxifen, used in breast cancer treatment, may induce hepatic steatosis. It has been suggested that leptin, which has a relationship with body fat stores, may be involved in the pathogenesis of hepatic steatosis. In this study, we compared serum leptin levels in tamoxifen-treated patients with and without hepatic steatosis. METHODS: Thirty-four women with breast cancer receiving tamoxifen were included in the study. Serum samples were obtained from the patients before and 3 months after tamoxifen therapy. RESULTS: Increased hepatic steatosis was detected in 15 of 34 (44%) patients after 3 months of tamoxifen therapy. Serum leptin levels were found to be significantly elevated in patients with increased hepatic steatosis (37.3 +/- 17.7 to 50.5 +/- 22.4 ng/ml, p = 0.023) compared to (48.2 +/- 20.2 to 42.6 +/- 14.9 ng/ml, p > 0.05) after tamoxifen treatment. CONCLUSION: Leptin may play a role in tamoxifen-induced hepatic steatosis. The exact mechanism involved should be investigated in further studies.