Serum leptin levels and GHR-d3/fl gene polymorphism in acromegalic patients with thyroid nodules.

BACKGROUND: Acromegaly is a rare and serious syndrome that is commonly associated with pituitary neoplasms. Thyroid multinodular disease is a common finding in acromegaly. Leptin is a polypeptide hormone, and studies have shown that it can increase cell proliferation and inhibit apoptosis. OBJECTIVES: The aim of the study was to determine the relationship of serum leptin levels with certain blood parameters and determine if growth hormone receptor (GHR)-d3/fl gene polymorphism is associated with thyroid nodules in acromegalic patients. MATERIAL AND METHODS: A total of 24 acromegalic patients with or without thyroid nodules were included in the study. Gene polymorphisms and blood parameters were examined. RESULTS: A marked increase was observed in serum leptin concentration in acromegalic patients with thyroid nodules compared to patients without them (p < 0.05). GH levels were lower in patients without nodules than in patients with nodules (p < 0.05). Blood glucose levels were higher in patients with nodules compared to those without them (p < 0.05), and the presence of thyroid nodules was associated with decreased blood low-density lipoprotein (LDL) levels compared to patients without nodules (p < 0.05). A significant relationship was observed between growth hormone receptor (GHR)-d3/fl gene polymorphism and leptin levels in acromegalic patients with thyroid nodules (p < 0.001). CONCLUSIONS: These data from acromegalic patients indicate that thyroid nodules are associated with increased serum leptin, GH and blood glucose levels and with decreased LDL levels. GHR-d3/fl gene polymorphism status was strongly related to higher leptin levels.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

BACKGROUND: Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. OBJECTIVES: The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. MATERIAL AND METHODS: We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. RESULTS: We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. CONCLUSIONS: Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

Examination of changes in enzyme activities of erythrocyte glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in rats given Naringenin and Lead acetate.

In our study, controlled experimental groups were performed by giving substances Lead acetate, Naringenin and Naringenin + Lead acetate to rats in vivo conditions Changes in the glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzyme activities in erythrocytes of rats in these groups were compared to the Control group. An inhibition significant degree for G6PD enzyme activity was observed in all groups when compared to the Control group (p < 0.001). While inhibition significant degree for 6PGD enzyme activity was observed in Lead acetate groups (p < 0.001), no significant effect was observed in the Naringenin and Naringenin + Lead acetate groups (p > 0.05). In addition, lead levels in the groups of rats were determined using an inductively coupled plasma mass spectrometer (ICP-MS) device. As a result of measurements by the ICP-MS device, lead levels were found as an average of 42.9 ± 2.51, 36.71 ± 1.13, 172.16 ± 9.63, and 95.07 ± 5.87 ppm in the Control, Naringenin, Lead acetate and Naringenin + Lead acetate groups, respectively. Our results were shown that Naringenin has protective effects on the Lead acetate induced oxidative stress erythrocytes in rat.

Purification and characterization of carbonic anhydrase from Agri Balik Lake trout gill (Salmo trutta labrax) and effects of sulfonamides on enzyme activity.

Carbonic anhydrase (CA) was purified from Agri Balik Lake trout gill (fCA) by affinity chromatography on a sepharose 4B-tyrosine-sulfanilamide column. The fCA enzyme was purified with about a 303.9 purification factor, a specific activity 4130.4 EU (mg-protein)(-1), and a yield of 79.3 by using sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The molecular weight determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was found to be about 29.9 kDa. The kinetic parameters, K(M) and V(max) were determined for the 4-nitrophenyl acetate hydrolysis reaction. Some sulfonamides were tested as inhibitors against the purified CA enzymes. The Ki constants for mafenide (1), p-toluenesulfonamide (2), 2-bromo-benzene sulfonamide (3), 4-chlorobenzene sulfonamide (4), 4-amino-6-chloro-1-3 benzenedisulfonamide (5), sulfamethazine (6), sulfaguanidine (7), sulfadiazine (8), and acetozazolamide (9) were in the range of 7.5-108.75 µM.

Dehydroepiandrosterone sulfate levels in Turkish obese patients.

PURPOSE: Obesity is well known to be linked to higher morbidity and mortality. Elevated plasma levels of free dehydroepiandrosterone (DHEA) are associated with reduced obesity and more limited accumulation of abdominal body fat. In contrast, the relationship between the DHEA sulfate ester (DHEAS) and adiposity is inconsistent and contradictory. METHODS: The aim of this study was to compare DHEAS levels in obese Turkish individuals, 37 men and 246 women. A variety of fatness, hormone, and blood parameters were measured. RESULTS: Statistically significant differences were found between male and female individuals with respect to weight, waist circumference, fat %, insulin, and DHEAS levels. CONCLUSIONS: We found that in the Turkish population, while a correlation between obesity parameters and DHEAS levels exists in both female and male individuals, DHEAS levels are significantly higher in obese male individuals than in obese female individuals.

Resistin and leptin levels in acromegaly: lack of correlation with echocardiographic findings.

PURPOSE: To find out how resistin and leptin levels were affected in patients with acromegaly and whether there is a relation between resistin levels and cardiac parameters. We also aimed to investigate whether resistin and leptin may be a link between insulin resistance and cardiac functions as well as these affected cardiac functions in the patients with acromegaly. METHODS: We included 30 subjects (15 men and 15 women) who had a diagnosis of acromegaly and 30 healthy (10 men and 20 women) subjects. Serum glucose, insulin, growth hormone, insulinlike growth factor 1 (IGF-1), resistin, and leptin levels were obtained, and insulin resistance of subjects were calculated. Echocardiographic studies of the subjects were performed. RESULTS: Resistin levels of the patients with acromegaly were found lower than controls. This difference was statistically significant (P = 0.001). Leptin levels were lower in the patients with acromegaly than in the controls, but this difference was not statistically significant. Resistin and leptin levels were not correlated with growth hormone, IGF-1, and with insulin-like growth factor binding protein 3 levels. Homeostasis model assessment of insulin resistance was positively correlated with resistin levels. (P = 0.03; r = 0.531) but not correlated with leptin levels. There was a positive correlation between body mass index and leptin levels in the patients with acromegaly (P = 0.007; r = 0.482). Interventricular septum thickness, posterior wall thickness, left ventricle mass index, peak early mitral inflow velocity-peak late mitral inflow velocity ratio, deceleration time, ejection time, isovolumetric relaxation time, velocity propagation, and left ventricular end-systolic volume values were significantly greater in the patients with acromegaly. Leptin levels in the acromegalic patients were not correlated with any of them. CONCLUSIONS: We found biventricular hypertrophy and impairment of diastolic and systolic function in the patients with acromegaly. We conclude that changes in resistin and leptin levels are unlikely to account for the insulin resistance of acromegaly. They do not also seem to be contributing factors of cardiovascular changes in patients with acromegaly.

Heavy metal ion inhibition studies of human, sheep and fish α-carbonic anhydrases.

Carbonic anhydrases (CAs, EC 4.2.1.1) were purified from sheep kidney (sCA IV), from the liver of the teleost fish Dicentrarchus labrax (dCA) and from human erythrocytes (hCA I and hCA II). The purification procedure consisted of a single step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The kinetic parameters of these enzymes were determined for their esterase activity with 4-nitrophenyl acetate as substrate. The following metal ions, Pb(2+), Co(2+), Hg(2+), Cd(2+), Zn(2+), Se(2+), Cu(2+), Al(3+) and Mn(3+) showed inhibitory effects on these enzymes. The tested metal ions inhibited these CAs competitively in the low milimolar/submillimolar range. The susceptibility to various cations inhibitors differs significantly between these vertebrate α-CAs and is probably due to their binding to His64 or the histidine cluster.

Purification of glutathione S-transferase isoenzymes from tumour and nontumour human stomach and inhibitory effects of some heavy metals on enzymes activities.

In this study, glutathione S-transferase (GST) enzyme was purified from nontumour and tumour human gastric tissue and in vitro effects of heavy metals on the enzyme were examined. GST was purified 3089 fold with a specific activity of 20 U/mg and a yield of 78% from gastric tumour tissue; and 1185 fold with a specific activity of 5.69 U/mg and a yield of 50% from nontumour tissue by using glutathione-agarose affinity column, respectively. Enzyme purity was verified by SDS-PAGE and subunit molecular mass was calculated around 26 kDa. The molecular weight of the enzyme was calculated as 52 kDa by using Sephadex G-75 gel filtration column. Then, inhibitory effects of metal ions on the enzymes were investigated. Mg(2+) and Cd(2+) had inhibitory effect on the enzymes activities. Other kinetic properties of the enzymes were also determined.

Influence of pesticides on the pH regulatory enzyme, carbonic anhydrase, from European Seabass liver and bovine erythrocytes.

The objective of this study was to assess the inhibitory effects of six commonly used pesticides, cyhalothrin, cypermethrin, dichlorvos, methamidophos, chlorpyrifos and methylparathion, on the pH regulatory enzyme carbonic anhydrase (CA) of Dicentrarchus labrax (European Seabass) liver (dCA) and bovine erythrocytes (bCA). Results of the study showed that the pesticides displayed quite variable inhibition profiles with K(I) values ranging from 0.376 to 26.164µM against dCA, and from 1.174 to 53.281µM against bCA. Methylparathion was the most effective inhibitor for both enzymes. Overall data show that all of the tested pesticides inhibit both dCA and bCA at low concentrations indicating that indiscriminate use of these pesticides might cause disruption of acid base regulation resulting in animal deaths. Our results also point out that susceptibility to these pesticides varies among CAs from different organisms.

The growth hormone receptor polymorphism in patients with acromegaly: relationship to BMI and glucose metabolism.

The aim of this study was to investigate association between the frequencies of Growth Hormone receptor (d3GHR) gene polymorphisms and some clinical parameters of acromegalic patients. Total of 35 acromegalic patients were enrolled to study. The d3GHR polymorphism was identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose (FPG), Fasting insulin, HOMA-IR, IGF-I, GH, IGFBP3, triglyceride, HDL and LDL cholesterol concentrations were evaluated. The frequencies of d3GHR genotypes were found as follows; 5 (14.3%) subjects had d3/d3, 11 (31.4%) had d3/fl and 19 (54.3%) had fl/fl in patients. The prevalence of the d3 and fl alleles was 30 and 70%, respectively. Systolic blood pressure, fasting insulin and HOMA-IR was found significantly increased in homozygote d3GHR genotype group compared to d3/fl subjects (P < 0.05). In addition, BMI was observed significantly different among three genotypes (P = 0.007) and in the subjects with d3/d3 genotype, BMI was found significantly higher than d3/fl and fl/fl genotypes groups. As well as, no significant difference was found between the d3 and fl alleles group in terms of the clinical parameters except for BMI (P = 0.002). It can be said that the d3GHR gene polymorphism may affect BMI, systolic blood pressure and insulin regulation. At the same time we can say homozygote d3GHR genotype and d3 allele carriers may have more risk than other genotypes for high BMI.

Purification of carbonic anhydrase-II from sheep liver and inhibitory effects of some heavy metals on enzyme activity.

In this study; sheep carbonic anhydrase-II (SCA-II) (E.C: 4.2.1.1) was purified from sheep liver and in vitro effects of heavy metals on the enzyme was examined. SCA-II isozyme was purified with about 203 purification fold, a specific activity of 2320 EU/mg-protein and a yield of 72 by using Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. Purity of the SCA-II enzyme was verified by SDS-PAGE technique and subunit molecular mass of the enzyme was found as 29 kDa. In addition to this, inhibitory effects of some metal ions on the enzyme were examined. In this study, sheep liver tissue was chosen; because the liver is an organ in which metal wastes of air, water and food are collected and it is easy to obtain the liver tissue. Because of the very important duties of CA enzyme on living beings, the effect of metals on the CA enzyme was investigated.

Purification and characterization of carbonic anhydrase from the teleost fish Dicentrarchus labrax (European seabass) liver and toxicological effects of metals on enzyme activity.

Carbonic anhydrase (EC 4.2.1.1; CA) was purified and characterized from the liver of the teleost fish Dicentrarchus labrax (European seabass) for the first time. The purification procedure consisted of a single step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The enzyme was purified 78.8-fold with a yield of 46%, and a specific activity of 751.72U/mg proteins. It has an optimum pH at 7.5; an optimum temperature at 25°C; an optimum ionic strength at 10mM and a stable pH at 8.5. The kinetic parameters of this enzyme were determined for its esterase activity, with 4-nitrophenyl acetate (NPA) as substrate and the purified enzyme had an apparent K(M) and V(max) values of 0.44 mM and 0.249 µmolxmin(-1), respectively. The following metals, Al(+3), Cu(+2), Pb(+2), Co(+3), Ag(+1), Zn(+2) and Hg(+2) showed inhibitory effects on the enzyme. Al(+3) and Cu(+2) exhibited the strongest inhibitory action. Pb(+2) was moderate inhibitor, whereas other metals showed weaker actions. All tested metals inhibited the enzyme in a competitive manner. Our findings indicate that these metals inhibit the fish enzyme in a similar manner to other α-CAs from mammals investigated earlier, but the susceptibility to various metals differ between the fish and mammalian enzymes. Our results also demonstrate that these metals might be dangerous at low micromolar concentrations for fish CA enzymes.