Lower plasma soluble TWEAK concentration in patients with newly diagnosed hypertension.

PURPOSE: To determine circulating levels of the soluble TNF-like weak inducer of apoptosis (sTWEAK)and its association with demographic and biochemical parameters in a young group of patients with newly diagnosed and never treated hypertension. METHODS: A total of 51 patients (mean age 21.7 ±1.4 years, body mass index (BMI) 24.5 ±1.6 kg/m2) with primary untreated hypertension, and 37 age- and BMI-matched healthy controls (mean age 22.5 ± 1.9 years, BMI 24.7 ± 1.5 kg/m2) were studied. Serums TWEAK and plasma asymmetrical dimethyl arginine (ADMA) levels were measured by EIA. RESULTS: In patients and controls, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 149.8±5.65/93.4±3.4 mmHg and 124.2±6.4/78.24±5.5 mmHg, respectively. Serum sTWEAK levels were lower in the patient group (882.6±228.9 µmol/L vs. 1060.2±231.7µmol/L, p=0.001), whereas plasma ADMA levels were higher(0.837±0.34µmol/L vs.0.3176±0.25µmol/L, p < 0.001). sTWEAK serum levels correlated with SBP(r=-0.301; p=0.005) and DBP (r=-0.279; p=0.009). Circulating plasma ADMA levels also correlated with SBP (r=0.734; p < 0.001) and DBP (r=0.733; p < 0.001). CONCLUSION: Young patients with yet untreated primary hypertension have lower circulating serum sTWEAK level compared with healthy controls. Further research for possible associations among serum sTWEAK, endothelial dysfunction and other measures of atherosclerosis may be of benefit in order to better understand the pathophysiology of hypertension and to establish more effective treatment options.

Decreased plasma apelin levels in pubertal obese children.

BACKGROUND: Apelin is a recently defined peptide relevant to the mechanism of obesity-related disorders. There has been no report so far about the levels of plasma apelin in obese children. METHODS: In this study plasma apelin, adiponectin, and high sensitivity C reactive protein levels were investigated in obese (n=32) and nonobese (n=40) children. The effects of pubertal status on the apelin and adiponectin levels were evaluated as well. RESULTS: When compared to nonobese controls, the obese children had significantly lower plasma apelin (p = 0.004), adiponectin and HDL cholesterol levels (p = 0.001 for both), and higher hs-CRP, triglycerides, insulin and Homeostasis Model Assessment (HOMA-IR) indexes (p < 0.001 for all). The difference between the apelin levels was present only in the pubertal period (p = 0.002). CONCLUSIONS: The results of the present study indicate that plasma apelin levels are lower in child obesity and pubertal state is an important determinant of plasma apelin levels.

Mean platelet volume and its relationship with carotid atherosclerosis in subjects with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is an emerging risk factor for atherothrombosis. AIMS: The aim of this study was to investigate the levels of MPV in subjects with NAFLD having no confounding factors for atherosclerosis such as obesity, diabetes mellitus, and hypertension. In addition, the possible relationship between MPV and carotid artery intima media thickness (CIMT), a well known marker of subclinical atherosclerosis, was also studied. METHODS: MPV and CIMT levels were measured in 60 biopsy-proven NAFLD subjects and 54 healthy controls. Age and sex were similar between two groups. RESULTS: Body mass index and waist circumference levels were higher in the NAFLD group when compared to the controls. There were no differences between the two groups regarding LDL cholesterol levels, whereas HDL cholesterol levels were lower in the NAFLD group. MPV and CIMT levels were not different between the two groups. According to the correlation analyses, CIMT levels were positively correlated to age in patients with NAFLD. However, no significant correlation was found between MPV and CIMT levels. CONCLUSIONS: The results of this study do not show any difference in MPV levels between subjects with NAFLD and controls. These finding suggests that in the absence of other metabolic risk factors, MPV might not be involved in the mechanism(s) of increased cardiovascular risk in NAFLD.

The accuracy of home glucose meters in hypoglycemia.

BACKGROUND: Home glucose meters (HGMs) may not be accurate enough to sense hypoglycemia. We evaluated the accuracy and the capillary and venous comparability of five different HGMs (Optium Xceed [Abbott Diabetes Care, Alameda, CA, USA], Contour TS [Bayer Diabetes Care, Basel, Switzerland], Accu-Chek Go [Roche Ltd., Basel, Switzerland], OneTouch Select [Lifescan, Milpitas, CA, USA], and EZ Smart [Tyson Bioresearch Inc., Chu-Nan, Taiwan]) in an adult population. METHODS: The insulin hypoglycemia test was performed to 59 subjects (56 males; 23.6 +/- 3.2 years old). Glucose was measured from forearm venous blood and finger capillary samples both before and after regular insulin (0.1 U/kg) was injected. Venous samples were analyzed in the reference laboratory by the hexokinase method. In vitro tests for method comparison and precision analyses were also performed by spiking the glucose-depleted venous blood. RESULTS: All HGMs failed to sense hypoglycemia to some extend. EZ Smart was significantly inferior in critical error Zone D, and OneTouch Select was significantly inferior in the clinically unimportant error Zone B. Accu-Chek Go, Optium Xceed, and Contour TS had similar performances and were significantly better than the other two HGMs according to error grid analysis or International Organization for Standardization criteria. The in vitro tests were consistent with the above clinical data. The capillary and venous consistencies of Accu-Chek Go and OneTouch Select were better than the other HGMs. CONCLUSIONS: The present results show that not all the HGMs are accurate enough in low blood glucose levels. The patients and the caregivers should be aware of these restrictions of the HGMs and give more credit to the symptoms of hypoglycemia than the values obtained by the HGMs. Finally, these results indicate that there is a need for the revision of the accuracy standards of HGMs in low blood glucose levels.

Cord blood and maternal serum neopterin concentrations in patients with pre-eclampsia.

BACKGROUND: Pre-eclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study was to investigate neopterin concentrations in cord blood and maternal serum in patients with pre-eclampsia and a control group. METHODS: Cord blood and maternal serum neopterin were measured in 21 patients with pre-eclampsia and in 27 control subjects. Neopterin concentrations were measured by high performance liquid chromatography. RESULTS: Cord blood neopterin concentrations were significantly increased in patients with pre-eclampsia compared to controls (54.3+/-16.8 vs. 43.4+/-8.5 nmol/L, p=0.011, respectively). Maternal serum neopterin (257.3+/-36.8 vs. 150.9+/-33.8 nmol/L, p<0.001) was also higher in patients with pre-eclampsia. CONCLUSIONS: Cord blood and maternal serum neopterin concentrations are higher in patients with pre-eclampsia. Maternal serum neopterin concentrations used may be used as a marker for the early diagnosis of pre-eclampsia.

Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates.

Human milk is a complex biological fluid. It contains many nutrients, anti-infectious and biologically active substance. Human milk also contains many angiogenic polypeptides. We have determined four of these: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), insulin-like growth factor- I (IGF-I) and platelet-derived growth factor (PDGF). The aim of this study was to compare the concentrations of VEGF, b-FGF, IGF-I and PDGF in human milk collected from mothers with preterm and term neonates. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (38>weeks) infants at days 3, 7 and 28 postpartum. Milk samples were analyzed for VEGF, b-FGF and PDGF by enzyme-linked immunosorbent assay and IGF-I was measured by radioimmunoassay method. Human milk levels of VEGF, IGF-I and b-FGF were significantly higher (p<0.001). Furthermore, within-preterm group concentrations of VEGF, IGF-I and PDGF significantly differed during postpartum days 3-7-28 (p<0.001, p<0.05, p<0.001, respectively), but did not do so for b-FGF concentrations. In term groups, concentrations of IGF-I and VEGF significantly differed (p<0.05, p<0.001, respectively), but did not do so for concentrations of b-FGF and PDGF. This is the first report of simultaneous measurements of four major angiogenic factors in human milk collected from mothers with preterm and term. Our results suggest that three of four angiogenic factors, VEGF, b-FGF and IGF-I, are higher concentration in human milk which collected from preterm mothers than those of terms.

Serum chitotriosidase enzyme activity in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a public health problem in many countries. Chitotriosidase (ChT) is an enzyme secreted by activated macrophages that catalyzes the hydrolysis of chitin and chitin-like substrates. The goal of this study was to assess the relationship between serum ChT activity and mortality. METHODS: ChT activities on the first day of hospitalization were analyzed in serum from 46 patients with CCHF and 36 healthy controls. Serum ChT activities and other clinical and laboratory parameters for patients with non-fatal and fatal CCHF were compared. RESULTS: The median ChT activity was increased in all patients with CCHF [189.9 (134.8-246.6) nmol/mL/h]. The median ChT activity in the non-fatal CCHF group [220.2 (180.6-290.1) nmol/mL/h] was higher compared with the fatal CCHF group [29.2 (16.5-45.7) nmol/mL/h] (p<0.001). In univariate analysis, platelet count, lactate dehydrogenase (LDH), and activated partial thromboplastin time were associated with mortality. CONCLUSIONS: This is the first study investigating the association of serum ChT enzyme activity with mortality from CCHF. This study suggested that relatively low ChT enzyme activities may be a prognostic marker in patients with CCHF.

The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status.

BACKGROUND: Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. Also, there is growing evidence supporting the role of reactive oxygen species in the pathogenesis of thyroid disorders. The aim of this study was to investigate the influence of hypothyroidism, hyperthyroidism, and their treatments on the metabolic state of oxidative stress, and antioxidant status markers. METHODS: A total of 20 newly diagnosed patients with overt hypothyroidism due to Hashimoto's thyroiditis, 20 patients with overt hyperthyroidism due to Graves' disease, and 20 healthy subjects as the control group were enrolled in the study. Fasting blood samples (12 h), taken at the initiation, after the 30th and 60th day of therapy were analyzed for malondialdehyde, nitrite, vitamin E, vitamin A, beta-carotene, ascorbate, and myeloperoxidase and superoxide dismutase activity. No patient presented additional risk factors for increased reactive oxygen species levels. RESULTS: Malondialdehyde, nitrite, vitamin E, and myeloperoxidase activity increased in patients with hypothyroidism. After 2 months, the levels of nitrite and vitamin E were reduced to control levels by treatment. The patients with hyperthyroidism had increased levels of malondialdehyde and myeloperoxidase activity in comparison with the controls. Treatment with propylthiouracil attenuated these increments after 1 month. CONCLUSIONS: Our results reveal an increased generation of reactive oxygen species and impairment of the antioxidant system in patients with hyperthyroidism, and particularly in patients with hypothyroidism. These findings indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome.

BACKGROUND AND AIM: The association of hyperbilirubinemia in Gilbert's syndrome (GS) with a decrease in prevalence of coronary artery disease is a well-known phenomenon. In this study, the state of low-density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS. METHODS: For this purpose, serum cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, apolipoprotein A and B, bilirubins, thiobarbituric acid-reactive substances, and the sensitivity of LDL oxidation levels, as well as serum alanine aminotransferase, aspartate aminotranserfase, gamma glutamyl transferase, and alkaline phosphatase activities, were determined in 17 patients with Gilbert's syndrome and 15 healthy adults. RESULTS: There was no significant difference between the groups except the indirect bilirubin parameter (P < 0.001). In comparison with the healthy individuals, LDL oxidation levels between 75 and 120 min were significantly lower (P < 0.005) along with prolonged lag-phase in GS patients, indicating a delay in oxidation susceptibility. CONCLUSION: It is suggested that the chronic hyperbilirubinemia leading to a lag-phase prolongation in LDL oxidation and a decrease in LDL oxidation may be reason for the low percentage of coronary artery disease.

Metformin and oral contraceptive treatments reduced circulating asymmetric dimethylarginine (ADMA) levels in patients with polycystic ovary syndrome (PCOS).

There is a little information in literature about circulating asymmetric dimethylarginine (ADMA) concentrations in polycystic ovary syndrome (PCOS) and the results reported are discrepant. In this study, therefore, we aimed (1) to determine the circulating ADMA concentrations in 44 women with PCOS and 22 age- and BMI-matched healthy controls, (2) to evaluate its correlations with insulin resistance, gonadotrophins, and androgen secretion, and (3) to compare effects of metformin and ethinyl estradiol-cyproterone acetate (EE/CPA) treatments on circulating ADMA concentrations. In conclusion, our data indicate that circulating ADMA concentrations in non-obese, non-hypertensive and young women with PCOS are significantly higher than healthy controls and they improved by a 3-month course of metformin and oral contraceptive treatments.

Protective effects of diets supplemented with omega-3 polyunsaturated fatty acids and calcium against colorectal tumor formation.

This study is to evaluate the effect of dietary omega-3 polyunsaturated fatty acid (omega-3 PUFA) and/or calcium supplementation on colon tissue of the carcinogenic N-methyl-N-nitrosurea (NMU)-injected rats and to investigate this effect by the assessment of the oxidative stress. The rats were divided into four groups: those fed with a standard diet, with a diet supplemented by omega-3 PUFA, those fed with a diet with calcium, and those fed with a standard diet with the combination of omega-3 PUFA and calcium. Rats were injected with an intrarectal NMU. After 32 weeks, colon tissue specimens and plasma were taken to histopathologically investigate and analyze tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities and erythrocyte MDA levels. The tumor incidences in supplemented-diet groups II and IV were found to be significantly lower when compared with those of the controls (P < 0.05). Superoxide dismutase and glutathione peroxidase antioxidative enzyme activities in colorectal tissue were increased in the study groups when compared with control rats (P < 0.001) and MDA levels were significantly lower than in the controls (P < 0.001) while the levels in group IV were rather decreased than those in group III (P = 0.011). These results suggest that the dietary supplementation of PUFA and/or calcium may be useful in the prevention of colorectal tumor formation.

Bilberry inhibits angiogenesis in chick chorioallontoic membrane.

Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. Bilberry has been traditionally used as a folk medicine for some countries. The purpose of the present study was to evaluate the effect of bilberry in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, bilberry inhibited angiogenesis in a concentration-dependent manner. Compared with the normal group, bilberry group has significant decreased vessels proliferation. These results provide evidence that bilberry inhibits angiogenesis and may be useful for treating angiogenesis-dependent human diseases.

Chitotriosidase levels in healthy elderly subjects.

Chitotriosidase (CHIT) belongs to the family of glycosylhydrolases and is highly homologous to chitinases from lower organisms. The enzyme CHIT is of interest for clinical reasons, because it is selectively expressed in chronically activated tissue macrophages. In most ethnic groups, approximately 6% of all individuals are homozygous for CHIT deficiency. Pathological tissue macrophages in several disease conditions massively express CHIT. A shared feature of such cells in the different conditions is the accumulation of lipid material in the lysosomal apparatus. Serum CHIT activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker. Our objective is to determine the levels of serum CHIT activity in healthy elderly subjects. Healthy 90 (between 65-94 years old) elderly people and 69 (between 20-44 years old) young people were chosen. Serum CHIT enzymatic activity was determined with the flurometric enzyme activity assay using artificial 4-MU substrate. We found CHIT activity 270 +/- 21 (nmol/mL/h) (values are mean +/- SD) in elderly people and 136 +/- 17 in young people. There are statistical differences between elderly and young subjects.

Age-related paraoxonase activity changes in Turkish population.

Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme capable of hydrolyzing diverse substrates from organophosphate (OP) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified low-density lipoprotein (LDL). The aim of this study was to investigate, with aging, the activity of PON1 associated with HDL and partially responsible for its antiatherogenic activity. The study involved 187 individuals (67 males and 120 females) divided into three groups according to their ages, young (n = 49; 20-44 years, mean age = 30.12 +/- 6.6 years), middle aged (n = 25; 45-64 years, mean age = 52 +/- 5.6 years), and elderly subjects (n = 113; 65-95 years, mean age = 78.94 +/- 6.2 years). Interestingly, serum total cholesterol and LDL-cholesterol levels significantly decreased with age (P < 0.05). The elderly aged group had also significantly lower body mass index than the middle aged group (P < 0.05). Serum paraoxonase activity and HDL cholesterol levels remained unchanged with age. The prevalence of phenotype AA, AB, and BB in our subjects' group was 40.6%, 45.9%, and 13.5%, respectively.

Mitochondrial DNA alterations in aging.

During the aging process, the increase of mitochondrial DNA (mtDNA) alterations has been reported. In this study, we investigated deletions/insertions in the approximately 2.4-kb region (from 14680 to 578 bp) of mtDNA covering D-loop region. A total of 96 individuals (ages between 20 and 94 years) were screened in this study. Genomic DNA was purified from whole blood samples. The 2.4-kb region of mtDNA was amplified with PCR and visualized by agarose gel electrophoresis. The sequence of the amplicon was confirmed in one sample by sequencing. We detected mtDNA deletions in only two cases (ages 26 and 30 years) at this resolution. As a result, there is no increase in the major deletions/insertions in the analyzed mtDNA region with aging. Complete sequencing of this region is needed to detect any age-dependent changes.

Deuteronation and aging.

Deuterium has one proton and one neutron in its atomic nucleus, but hydrogen has only proton. The natural abundance of deuterium is 1 per approximately 6600 hydrogen atoms. Therefore deuterated water (both HOD + D(2)O [heavy water]) abundance is 1 per approximately 3300 water molecules. One dissociation product of deuterated and heavy water is deuteron (proton + neutron, D(+), H(2)OD(+)/D(3)O(+)). Because heavy water has a lower ionization constant than water, the D(+)/H(+) ratio is approximately 1/15,000 in biological fluids. O-D bond length is shorter than O-H, and D-O-D angle is lesser than H-O-H. Once a deuteron exchanges with proton on the water-exposed surface of a macromolecule, it can lead to a conformational change and the reverse exchange will be less likely. Deuteron bonds are stronger than proton bonds. Therefore an increase of deuteronated macromolecules can be expected in due course of time. In order to test this hypothesis, we conducted a pilot study and measured the D/H ratio in the tails of three Sprague-Dawley rats at different ages (4 weeks, 5 weeks, and >1-year old) by elemental analysis coupled with isotope ratio mass spectrometry (EA-IRMS) technique. To prevent the effect of daily water consumption, the homogenized tails were lyophilized before analysis. The results, as mean of several measurements, of 4 weeks, 5 weeks, and >1-year-old rats were per thousand-94 +/- 9.56, per thousand-101.71 +/- 6.89, per thousand-83.68 +/- 3.46 delta((2)H) relative to VSMOW, respectively. Although there is a slight increase in >1-year-old rat, the difference among the animals was not significant. We propose that, before reaching to a final conclusion about the accumulation of deuterium with aging, the measurements should be done not in whole tissue samples but in purified macromolecules from a larger set of animals.

Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism.

BACKGROUND: The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation. METHODS: To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined. RESULTS: Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells. CONCLUSIONS: Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent.

Effects of non-heavy smoking on high-density lipoprotein cholesterol in healthy Turkish young men.

OBJECTIVE: Decreased effects of smoking on serum high-density lipoprotein cholesterol (HDL-c) were demonstrated in subjects smoking more than 20 cigarettes a day. We aimed to evaluate the effects of non-heavy smoking (< or =20 cigarettes a day) on HDL-c in young, healthy men who are similar in terms of age, physical activity and diet. METHODS: A total of 1012 male students between 19 and 25 years old (21.4 +/- 1.5) in a military college who do not smoke or smoking < or =20 cigarettes a day were enrolled. Subjects who were consuming alcohol were excluded. Smoking levels (0: nonsmoker, 1: 1-5 cigarettes, 2: 6-10 cigarettes, 3:11-20 cigarettes a day) and duration were obtained by a questionnaire. Blood samples were taken after an over-night fasting. Blood pressure and anthropometric measurements were reported. RESULTS: HDL-c showed a stepwise decrease as the level of smoking increased (49 +/- 9 mg/dL in level 0, 47 +/- 7 mg/dL in level 1, 46 +/- 8 mg/dL in level 2, 45 +/- 7 mg/dL in level 3, p < 0.001). Total cholesterol, triglycerides and low-density cholesterol were not different among the smoking levels. Body mass index (BMI) and waist/hip ratio were found to be slightly decreased in smokers. In a multivariate regression model including smoking level, duration, BMI, systolic and diastolic blood pressures, smoking level was the only predictor of HDL-c (B = -1.407, p < 0.001). CONCLUSION: Smoking, even in relatively low levels, has a negative stepwise relationship with HDL-c in a homogeneous population of healthy young men in whom other major non-genetic factors that are known to affect HDL-c levels are identical.