Sebahat Turgut

Effects of cadmium and zinc on plasma levels of growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding protein 3

Humans are constantly exposed to cadmium (Cd) as a result of the increase in air pollution and cigaret use. Zinc (Zn), which is an essential element for the metabolism of and the constituent of many enzymes, causes growth retardation in the deficiency status so at present it is often added to the diet without measuring blood levels of this element. We also aimed to observe the effects of both Cd and Zn on the plasma levels of growth hormone (GH), insulin-like growth factor I(IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3) in this study. For this purpose, 27 young Wistar albino male rats were divided into three groups. The first group was given 50 mg/L of CdCl2, the second group received 500 mg/L of ZnSO4, and the third group, as a control, received only drinking water for 1 mo. At the end of this period, plasma GH, IGF-I, and IGFBP-3 of the animals were analyzed in the blood obtained. The significance between groups was evaluated with the Mann-Whitney U-test. According to our results, levels of IGF-I and IGFBP-3 in the Cd-administered group were significantly lower than those of controls (p<0.05 and p<0.01 respectively). No statistically significant difference was observed between Zn administered and control groups in terms of all three parameters. These results show that although the addition of Zn to the diet of healthy rats had no effect on the levels of GH, IGF-I, and IGFBP-3, Cd addition lowered the levels of IGF-I and IGFBP-3 but did not change the levels of GH compared to controls.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.

Angiotensin-Converting Enzyme Gene Polymorphism Is Associated with Anemia in Non–Small-Cell Lung Cancer

The angiotensin-converting enzyme (ACE) plays an important role not only in the regulation of vascular homeostasis but also in stimulation of hematopoiesis. We aimed to evaluate the association between insertion/deletion (I/D) polymorphism of the ACE gene and anemia at the time of the diagnosis. We enrolled 75 patients with non–small-cell lung cancer (NSCLC) and 85 age- and sex-matched healthy control participants. The I/D polymorphism of ACE was identified by using polymerase chain reaction from peripheral blood samples. Statistical analyses were performed with SPSS for Windows. The distributions of the ACE genotypes and alleles are similar in patients and in healthy participants (P = 0.29 and P = 0.08, respectively). In patients with NSCLC, 34 (45.3%) had anemia; of whom 3 (8.8%) had genotype II, 24 (70.6%) had genotype ID, and 7 (20.6%) had genotype DD (P = 0.001). The patients with the II and ID genotypes had more frequent anemia at the time of the diagnosis (odds ratio = 6.02; P = 0.001). Our findings suggest that I/D polymorphism of the ACE gene may influence the development of anemia in patients with NSCLC.

IGF(CA)19 and IGFBP-3-202A/C gene polymorphism in patients with acromegaly

OBJECTIVE We aimed to investigate IGF-1 and IGFBP-3 gene polymorphisms in patients with acromegaly. DESIGN We included 34 patients with acromegaly and 37 healthy subjects to study. At baseline examinations, antropometric measurements were done. Genomic DNA from the patients and controls were prepared. Serum, glucose, insulin, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, growth hormone (GH), Insulin-like growth factor I (IGF-I) and IGFBP-3 levels of subjects were analyzed. RESULTS The frequency of genotype IGF-1(CA)19 and IGFBP3-202 A/C gene was significantly different between control and patients. In acromegalic patients, a significant difference in the serum IGF-1 levels and LDL cholesterol levels among the three IGF(CA)19 genotype. LDL levels were positively correlated with IGF-1. Subjects having >194 bp genotype had higher IGF-1 and LDL cholesterol levels. We observed that the patients with 194 bp genotype have more invasive and bigger tumors and they require adjunctive therapies. Clinical characteristics among the three IGFBP3-202 A/C genotype, AA, AC and CC, did not display any significant difference. CONCLUSIONS In our study, 194 bp allele (20 CA repeats) of the IGF-I promoter have higher circulating IGF-I levels than others. We have found that the patients with 194 bp genotype are the resistant patients with active disease and they required high dose medication. We think this study may help to define the patients, who are resistant to drug therapy, and possible cardiovascular disease.

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction

OBJECTIVE Our aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function. DESIGN AND METHODS The study included 51 patients (mean age 42.2+/-1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3+/-2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range. MAIN OUTCOME Baseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment. CONCLUSIONS In this study, it was shown that GH-IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH-IGF axis in patients with subclinical hypothyroidism.

Orexins increase penicillin-induced epileptic activity.

Orexins have been implicated with physiological function including sleep-wake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on excitability are controversial. We investigated the effects of intracortical injections of orexin A (100 pmol) and B (100 pmol) on the electrophysiological manifestation of epileptic seizures induced by cortical penicillin application in adult male rats. In comparison to saline, orexin A and B enhanced significantly the spike number, spike amplitude and spectral power values induced by cortical penicillin. Our findings indicates that orexins enhances the hyperexcitable and hypersyncronic cortical epileptic activity induced by focal application of penicillin-G.

Angiotensin-Converting Enzyme I/D Polymorphism in Behçet’s Disease

Objective: To investigate a potential relationship between I/D polymorphism within intron 16 of the angiotensin-converting enzyme (ACE) gene located on human chromosome 17 and Behçet’s disease. Materials and Methods: Genomic DNA was obtained from 35 Turkish patients diagnosed with Behçet’s disease according to the International Study Group criteria and 150 healthy individuals. Polymerase chain reaction was used to detect the presence of I and D (insertion and deletion) alleles in intron 16 of the ACE gene in these DNA samples. Results: We found differences in ACE I/D polymorphism between Behçet’s disease and healthy controls (χ2 = 4.61, d.f. = 1, p = 0.044). In Behçet’s disease patients, the D allele frequency was 84.3% and I allele frequency 15.7%. Conclusion: An association between Behçet’s disease and ACE polymorphism may provide a useful basis for future molecular studies and therapeutic approaches in this complex disease.

Orexins cause epileptic activity.

Orexins have been implicated in the regulation of sleep-wake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on epileptic activity are controversial. We investigated whether intracortical injections of orexin A (100 pmol) and B (100 pmol) cause epileptic activity in rats. We observed epileptic seizure findings on these two groups rats. Orexin A and B also significantly increased total EEG power spectrum. Our findings indicate that orexins cause epileptic activity.

Effects of Angiotensin-Converting Enzyme Polymorphism on Aortic Elastic Parameters in Athletes

Background: Physiologic adaptations in an athlete’s heart include increased left and right ventricular chamber size, left ventricular wall thickness and mass. Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to identifya deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. Therefore, the ACE genes, which have been shown to be polymorphic, could be candidate genes for large-artery stiffness. Methods: 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic examination, and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic valve. Aortic systolic diameter was measured at the time of full opening of the aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic strain, stiffness index and distensibility were calculated. Results: Left ventricular mass index and left ventricular ejection fraction were significantly higher in athletes than controls (p < 0.001). The aortic distensibility index and strain were significantly greater in athletes compared with controls (respectively: 5.8 ± 2.7 vs. 4.7 ± 1.8 cm–2 dyn–1 10–6, p = 0.017; 12.3 ± 2.4 vs. 9.3 ± 3.1, p < 0.001). The aortic stiffness index was significantly lower in athletes than in controls (4.8 ± 1.9 vs. 6.1 ± 2.1, p < 0.001). The aortic distensibility index and strain were statistically different in ACE DD vs. DI groups and DD vs. II groups of athletes. The aortic stiffness index was statistically different in ACE DD vs. II groups of athletes. Aortic parameters were similar according to ACE genotypes in controls. Conclusion: The results of this study indicate that aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes.

Angiotensin-converting enzyme gene polymorphism in overweight and obese Turkish patients with insulin resistance.

The aim of this study was to analyze the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in obese Turkish patients with insulin resistance (IR). Sixty-two obese Turkish patients with IR were enrolled in this study. One hundred healthy people without IR were recruited as the control group. ACE amplification was performed by polymerase chain reaction. The frequency of the DD genotype was significantly higher in obese patients with IR than in control subjects. Of sixty-two patients, 1 (1.6%) had an II genotype, 22 (35.5%) had an ID genotype, and 39 (62.9%) had a DD genotype. The frequency of the I allele in the patient group was significantly lower than in controls. We found that the frequency of the DD genotype was higher in obese Turkish patients with IR. ACE gene I/D polymorphism may be associated with obesity in the Turkish population.