Circulating fetuin-A in patients with pancreatic cancer: a hospital-based case-control study.

CONTEXT: A proteomic analysis has proposed fetuin-A (alpha-2-HS-glycoprotein) as a new potential marker for pancreatic cancer (PC). OBJECTIVE: Circulating fetuin-A levels in patients with PC. METHODS: Serum fetuin-A was measured in 81 cases with PC and 81 matched controls before the initiation of any treatment. RESULTS: Serum fetuin-A was not independently associated with the presence of PC. Although there was a trend with higher fetuin-A levels across PC stages, comparisons of fetuin-A in patients within different PC prognostic stages revealed no differences. CONCLUSIONS: Circulating fetuin-A was similar between patients and controls and was not associated with the disease severity.

Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome.

OBJECTIVE: Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.

Serum levels of ischemia modified albumin in overweight/obese postmenopausal women: a potential biomarker of atherosclerotic burden associated with oxidative stress.

OBJECTIVE: Menopause is associated with weight gain and an increase of cardiovascular risk. The aim of the present study was to estimate serum ischemia-modified albumin (IMA) levels in postmenopausal women and evaluate their association with body mass index (BMI) and coronary artery disease (CAD). METHODS: The study included 130 non-smoker postmenopausal women aged 43-80: 40 with BMI 26-32 kg/m(2) (Group A), 60 with BMI 21-25 kg/m(2) (Group B), and 30 with documented CAD and BMI 23-29 kg/m(2) (Group C). Serum IMA, albumin, hsCRP and NT-proBNP, glucose and insulin were measured. Homeostasis assessment model score (HOMA) and Quantitative insulin sensitivity index (QUICKI) were co-estimated. RESULTS: Serum IMA and IMA to albumin ratio were significantly elevated in Group A as compared to Group B (p<0.001) and similar to those of Group C. hsCRP and NT-proBNP did not differ between Groups A and B while they were lower in comparison to Group C (p<0.001). Glucose, insulin and HOMA were elevated in Group A compared to Group B (p<0.001) while QUICKI was lower (p<0.001). In Group A, IMA was positively correlated with BMI, hsCRP, insulin, HOMA and negatively with QUICKI. In postmenopausal women, multivariable regression analysis revealed that obesity was the strongest significant determinant of circulating IMA levels (p<0.001) contributing, therefore, to the elevated serum IMA concentration. CONCLUSIONS: Postmenopausal obesity is associated with elevated serum IMA possibly due to obesity associated oxidative stress. IMA measurement could provide an assessment of atherosclerotic burden in postmenopausal women. Further clinical evaluation is under investigation.

Platelet markers correlate with glycemic indices in diabetic, but not diabetic-myelodysplastic patients with normal platelet count.

BACKGROUND: Altered thrombocyte morphology and function have been reported in patients with diabetes mellitus (DM) type 2. The aim of the present study was to determine the associations between platelet morphology markers and hemoglobin A1C (HbA(1c)), fasting glucose (FG), hypertension and coronary heart disease (CHD) in patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in controls. METHODS: This cross-sectional study included 30 cases with primary MDS with normal platelet count and non-insulin dependent diabetes, 30 non-insulin dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age and gender. RESULTS: After adjusting for body mass index, platelet number, CHD and hypertension, HbA(1c) and FG were significant predictors of mean platelet volume (MPV) and platelet distribution width (PDW) in diabetic patients. There was no correlation between platelet parameters and HbA(1c) or FG in diabetic MDS patients. In controls, FG and hypertension predicted significant differences in platelet morphology. Platelet count correlated with platelet morphology in diabetic MDS and control groups, but not in diabetics. CONCLUSIONS: MPV and PDW are associated with glycemic indices in diabetic patients but not in diabetic MDS patients with normal platelet counts. Non-diabetic controls also exhibit FG related changes in platelet morphology. This suggests other factors inherent to bone marrow dysplasia, platelet turnover and biochemistry, or vascular environment affect platelet morphology in diabetic MDS patients even with normal platelet count. Platelet morphology in this population may be an early marker for myelodysplasia. These findings also support platelet morphology change as a marker for elevated macrovascular disease risk.

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case-control study in Greece.

AIM: Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. METHODS: Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined. RESULTS: Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01-0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls. CONCLUSION: Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

Ischemia modified albumin, high-sensitivity c-reactive protein and natriuretic peptide in patients with coronary atherosclerosis.

BACKGROUND: Ischemia modified albumin (IMA), is a new biomarker of oxidative processes involved with coronary artery disease (CAD). We determined serum IMA, high-sensitivity C-reactive protein (hsCRP), and natriuretic peptide (NT-proBNP), and evaluated their correlation with severity of coronary atherosclerosis in patients undergoing coronary angiography (CA). Cardiac troponin T (cTnT), CK-MB mass, albumin and Total Antioxidant Status (TAS) were also evaluated. METHODS: The study included 114 patients (88 men and 30 women) aged 43-80 years with documented CAD without evidence of acute coronary syndrome undergoing CA and 163 controls (131 men and 32 women) similarly aged. RESULTS: IMA, hsCRP and NT-proBNP were higher (p<0.001 and p=0.008 for NT-proBNP) while TAS was lower (p<0.001) in patients than in controls. IMA and TAS were negatively correlated in all subjects (p<0.01). Among patients, there was no correlation between IMA and the number of diseased vessels. For CAD diagnosis the best cut-off point for IMA was 101.5 KU/L with a sensitivity and a specificity of 87.7% and a negative predictive value of 83.3%. IMA was associated with an increased risk for CAD (OR=1.23, 95% CI: 1.16-1.31; p<0.001). CONCLUSIONS: IMA determination may provide earlier information of CAD presence before hsCRP or NT-proBNP elevation, contributing to early assessment of overall patient risk.

Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study.

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case-control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.

Adiponectin and resistin are associated with risk for myelodysplastic syndrome, independently from the insulin-like growth factor-I (IGF-I) system.

AIM: Obesity has been implicated in the aetiology of myelogenous leukaemia and myelodysplasia (MDS). We hypothesised that altered secretion of adiponectin and resistin may underlie this association. We thus investigated the role of both total and high molecular weight (HMW) adiponectin and resistin in MDS. METHODS: In a case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age between 2004 and 2007. Total and HMW adiponectin, resistin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein (IGFBP-3) were determined. RESULTS: Lower serum total or HMW adiponectin and/or resistin levels were independently associated with higher risk of MDS controlling for age, gender, BMI and serum levels of leptin, IGF-I and IGFBP-3 (p<0.002). Although total and HMW adiponectin were both significantly inversely associated with MDS when modelled either in quartiles or continuously, HMW did not offer any substantial additional predictive value over total adiponectin (Odds ratio (OR)=0.91 versus 0.93 for a 1 microg/ml change, respectively). IGF-I was positively associated with MDS by bivariate analysis and both IGF-I and IGFBP-3 were higher in advanced MDS and higher risk stages, but were not significantly and independently associated with MDS. CONCLUSION: Total and HMW adiponectin may have a protective role in MDS, whereas resistin levels may be decreased via a compensatory mechanism.

Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight/obese postmenopausal women.

OBJECTIVE: In obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. METHODS: Thirty in total, overweight/obese postmenopausal women, were included in the study: 15 with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30 min intervals, leptin, sOB-R, adiponectin and resistin at 60 min intervals during the 120 min OGTT. RESULTS: In fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. CONCLUSION: In overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.

Serum oxidizability, total antioxidant status and albumin serum levels in patients with aneurysmal or arterial occlusive disease.

OBJECTIVES: Oxidative stress is involved in the pathophysiology of atherosclerosis. The aim of the present study was to estimate the extent of oxidative stress in patients with aneurysmal and arterial occlusive disease (AAOD) by analyzing the magnitude of serum oxidizability, total antioxidant status and serum antioxidants and to evaluate their potential clinical significance. DESIGN AND METHODS: The study was conducted on 47 patients with AAOD and 49 healthy individuals. Oxidative stress was assessed by: a) copper-induced lipid oxidation described in terms of "lag-time" (t(LAG)) and "maximal rate of accumulation of absorbing products" (RA) and b) the measurement of serum total antioxidant status (TAS) and hydrophilic serum antioxidants (albumin, uric acid, transferrin, bilirubin). LDL-cholesterol and HDL-cholesterol were also estimated. RESULTS: A decrease of t(LAG) and albumin levels in patients as compared to controls was observed. t(LAG) was negatively correlated with RA in both patients and controls. RA and LDL-cholesterol did not differ between the two groups. HDL-cholesterol was decreased in patients in comparison to controls. There is statistically significant evidence that low albumin serum levels are associated with increased risk of AAOD. CONCLUSIONS: The results support the involvement of oxidative stress in AAOD. Significant alterations in serum oxidizability were found in patients with AAOD and low albumin serum levels were correlated with the disease. Clinical evaluation of both findings needs further investigation.

Is thyroid autoimmunity a risk factor for developing primary myelodysplastic syndrome?

OBJECTIVE: Thyroid disease has been associated with leukemia and lymphoma. No previous study using clinical and laboratory data has explored whether thyroid disease and especially autoimmune thyroid disease (ATD) is associated with myelodysplastic syndrome (MDS) risk. In this case-control study, we investigated the association of ATD with MDS. METHODS: Our study included 101 cases with incident primary MDS confirmed by histology and cytogenetics, and 101 controls matched on gender and age, admitted for non-neoplastic and non-infectious diseases. All subjects were submitted to clinical, ultrasound thyroid evaluation and serum free T3, free T4, TSH, thyroglobulin, and thyroperoxidase antibodies determination. RESULTS: Adjusting for age, gender, and body mass index, there was statistically significant evidence that ATD is associated with increased risk of MDS (OR = 2.58, 95% CI 1.29-5.16). Interestingly, ATD starting from the remote past (more than 10 years from MDS onset) was positively associated with MDS risk (OR = 5.73. 95% CI 2.03-16.16). Mean serum levels of fT3, fT4, and thyroid antibodies were significantly higher in MDS patients and mean TSH serum levels were significantly lower in MDS patients than in controls (p < 0.05). CONCLUSION: Biological plausibility and empirical evidence highlights the importance of ATD in MDS etiopathogenesis. Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with leukemogenesis.

Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer.

OBJECTIVES: The aim of this study was to evaluate the extent of oxidative stress in patients with breast or ovarian cancer by analyzing the magnitude of serum oxidizability and the involvement of oxidized low-density lipoproteins (oxLDL) in the disease. DESIGN AND METHODS: The study was conducted on 32 patients diagnosed with breast or ovarian cancer but who had not undergone any kind of treatment and 30 healthy individuals of similar age. The evaluation of oxidative stress was assessed by: (a) the ex-vivo susceptibility of serum lipids to oxidation and (b) the detection of oxLDL and anti-oxLDL autoantibodies. Total cholesterol, LDL-cholesterol and HDL-cholesterol were co-estimated. RESULTS: The results indicated that the levels of oxLDL were increased among both breast and ovarian cancer patients as compared to the control subjects. Additionally in patients with breast cancer, serum total cholesterol, LDL-cholesterol, anti-oxLDL antibodies and the maximal rate of diene formation (RA), the index of oxidizable components load, were increased in comparison to controls. There is statistically significant evidence that serum oxLDL levels are associated with increased risk of breast and ovarian cancer. CONCLUSIONS: The findings exhibit a correlation between oxLDL and malignancy, supporting the contribution of oxidative stress to carcinogenesis and the possible involvement of oxLDL in the process of malignancy. The clinical evaluation of the oxLDL measurement is under investigation.

Correlation of nm23-H1 gene expression with clinical outcome in patients with advanced breast cancer.

BACKGROUND: Conflicting results exist regarding the significance of the metastasis suppressor gene nm23-H1 in cancer patients. Initial results from a study done by our group were more indicative of its negative prognostic role in breast cancer. Our aim was to examine further its significance in patients with metastatic breast cancer. PATIENTS AND METHODS: With the semi-quantitative Reverse Transcripted-Polymerase Chain Reaction (RT-PCR) method, solid tumor specimens or samples from malignant effusions in breast cancer patients were examined for the nm23-H1 gene. Clinical data were collected retrospectively and gene expression was correlated with survival. RESULTS: Fourteen patients were included in the current analysis. The gene was detected in 7 patients. No statistically significant differences were observed in the comparison done for prognostic factors between nm23-H1-positive and nm23-H1-negative patients. Women in whom the gene was not detected had longer median survival (49 vs. 6 months, p=0.09). CONCLUSION: In advanced breast cancer, nm23-H1, as detected by RT-PCR, seems to be a predictor of bad prognosis.

Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a case-control study.

OBJECTIVE: Adiponectin plays a protective role in several malignancies, including myeloblastic leukemia, whereas leptin may increase the proliferation of progenitor cells and may stimulate leukemic cell growth in vitro. We investigated the role of adiponectin and leptin levels in the etiopathogenesis of myelodysplastic syndromes (MDS), a preleukemic condition with increasing incidence which has recently been associated with obesity. METHODS: In a case-control study, 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age were studied between 2004 and 2007, and blood samples were collected. RESULTS: Higher serum adiponectin levels were associated with lower risk of MDS by bivariate analysis and after adjusting for age, gender, body mass index and serum levels of leptin (p < 0.001). Subjects in the third quartile for leptin levels had a lower risk of MDS than controls, and low leptin concentrations were observed in low-risk MDS patients with normal or good prognostic karyotype after adjusting for age, gender and body mass index. CONCLUSIONS: Circulating adiponectin and leptin may play an important role in MDS etiopathogenesis. Future studies are needed to confirm these associations and to explore underlying mechanisms.

Clinical study on the serum carcinoembryonic antigen, CA 19-9, CA 50 and alpha-fetoprotein levels in patients with myelodysplastic syndromes.

The present study aimed to determine the serum carcinoembryonic antigen (CEA), CA 19-9, CA 50 and alpha-fetoprotein (alpha-FP) levels between patients with myelodysplastic syndromes (MDS) at diagnosis and controls to clarify their potential clinical significance. A case-control investigation was conducted over a three year period, covering 95 MDS cases and 95 age- and gender-matched controls. Mean serum CEA levels were significantly higher (P = 0.0002) in MDS patients at diagnosis than in hospital controls. Adjusting for age, gender, tobacco consumption, serum CA 19-9, CA 50 and alpha-FP levels, there is statistically significant evidence that serum CEA values are associated with increased risk of MDS (odds ratio = 2.33, 95% confidence interval = 1.56 - 3.49). Six patients with MDS developed malignancies 4-9 months after the diagnosis of myelodysplasia. Serum CEA could be used as marker together with other important diagnostic tools for evaluating an underlying or developing malignancy in patients suffering from MDS.

Presence of high-risk human papillomavirus sequences in breast cancer tissues and association with histopathological characteristics.

OBJECTIVE: To examine the presence of human papillomavirus (HPV) in breast cancer tissues. DESIGN AND METHODS: Four different PCR methods for detection and verification of genital HPVs were applied in frozen breast cancer specimens. Tumors were also evaluated for various histopathological parameters. RESULTS: Seventeen samples out of 107 tested positive (15.9%). HPV RFLP typing identified a total of 21 high-risk viruses: fourteen HPV 16 (67% of all detected HPV types), three HPV 59, two HPV 58, one HPV 73 and one HPV 82 (one sample with double infection and two samples with triple infection). Breast cancer patients harboring high-risk HPV DNA sequences in their tumor were younger than the rest of the patients. Furthermore, they were less estrogen-receptor-positive and more proliferative as observed in the corresponding indices: Ki-67 staining, S-phase/proliferative fractions and percentage of cells with DNA content over 5C. CONCLUSION: The presence of high-risk HPV DNA sequences in the breast cancer tissues studied was verified, and a possible association with acceleration of malignancy was examined.

Circulating oxidized low density lipoprotein, autoantibodies against them and homocysteine serum levels in diagnosis and estimation of severity of coronary artery disease.

The oxidative hypothesis of atherosclerosis proposes that oxidative modification of low density lipoprotein (LDL) plays a critical role in atherogenesis. The evaluation of LDL oxidation in vivo is therefore very important. However, data concerning the evaluation of the above biochemical marker is very limited in clinical practice. This study was conducted to test the hypothesis that plasma levels of ox-LDL reflect atherosclerosis and determine the clinical significance in the measurement of circulating ox-LDL and autoantibodies against them as well as their correlation with homocysteine and lipid parameters in the diagnosis and severity of coronary heart disease. A total of 273 individuals were examined: 41 suffering from unstable angina pectoris (UAP), 62 from stable angina pectoris (SAP) and 170 healthy control subjects. We used a sensitive method for detecting ox-LDL that is based on a direct sandwich technique (ELISA) in which two monoclonal antibodies are directed against separate antigenic determinants on the oxidized apolipoprotein-B molecule along with another enzyme immunoassay designed to determine human antibodies to oxidized LDL (anti-oxLDL) directly in serum. Total homocysteine (HCY) was evaluated by means of a fully automated fluorescence polarization immunoassay. Patients with UAP exhibited marked elevations in oxLDL levels as compared to patients with SAP (161.2 +/- 28.4 vs. 119.2 +/- 26.6, p < 0.001) and the control subjects (67 +/- 18.8, p < 0.001). The difference in oxLDL levels between patients with SAP and the control group was also statistically significant. Similarly, patients with UAP showed marked elevations in anti-oxLDL antibodies compared to both patients with SAP (602.2 +/- 62.2 vs. 510.8 +/- 50.3,p < 0.001) and control subjects (368 +/- 79.6, p < 0.001). The difference in anti-oxLDL levels between patients with SAP and the controls was also statistically significant. OxLDL levels were not correlated with age in any of the groups studied. Triglycerides, LDL-cholesterol and total cholesterol were elevated in patients with UAP as opposed to patients with SAP and the control subjects, while HDL levels were elevated in the control subjects when compared to patients with SAP and UAP. Homocysteine levels were elevated in patients suffering from UAP and SAP when compared to healthy subjects. Patients with UAP or SAP did not differ on homocysteine levels. Our findings demonstrate the presence of oxLDL in vivo, its strong association with coronary artery disease as well as with the severity of the clinical presentation.

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P < 0.001) and abdominal adiposity; higher levels of androgens, insulin, homeostasis model assessment score of insulin sensitivity, and total and low-density lipoprotein-cholesterol; and significantly lower levels of SHBG and high-density lipoprotein-cholesterol. In the studied population (n = 130), PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

The significance of oxidant/antioxidant balance for the pathogenesis of experimental sepsis by multidrug-resistant Pseudomonas aeruginosa.

OBJECTIVE: The significance of lipid peroxidation as an independent factor leading to sepsis by multidrug-resistant Pseudomonas aeruginosa. Design experimental study. METHODS: Twenty-six rabbits were applied. They were divided into two groups; A (n=6) comprising controls, and B (n=20) comprising animals infected by the injection of 1x10(8) cfu/kg inoculum of the test pathogen into the left inner jugular vein. Six rabbits of group B were followed-up to estimate survival; all of the remaining were sacrificed. Blood was sampled for the determination of serum malondialdehyde (MDA) by the thiobarbiturate assay, total antioxidant status (TAS) by a chromogenic assay, tumor necrosis factor alpha by a bioassay on fibrosarcoma L929 cell line, and endotoxins (LPS) by the QCL-1000 LAL assay. RESULTS: Mean survival of group B was 60.0+/-15.8 h. MDA was significantly higher in group B compared to group A at 30, 60, 120 and 150 min. TAS was statistically decreased in group B compared to group A at 30 and 60 min. Increases of MDA in group B were followed by reciprocal decreases of TAS (P of correlation <0.001). Hemodynamic instability was recorded in group B compared to group A 160 min after bacterial challenge. CONCLUSIONS: Early alterations of oxidant/antioxidant balance occur in experimental sepsis by multidrug-resistant P. aeruginosa followed by hemodynamic instability. Results highlight the perspective of the administration of antioxidants as immunomodulatory treatment of sepsis in animal studies.