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Biomedical subjects

M Alevizaki

Publications and source records attributed to M Alevizaki.

At least 19 recordsLinked to original sources

Association of dehydroepiandrosterone-sulfate with endothelial function in young women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to assess non-invasively endothelial function of young women with polycystic ovary syndrome (PCOS) in comparison with healthy age-matched women and a group of young women with idiopathic hirsutism (IH). The possible role of metabolic and hormonal parameters on endothelial function was also examined. DESIGN: Descriptive clinical trial. METHODS: Fifty-six women, 27 with PCOS, 16 with IH and 13 healthy age-matched women were studied. Endothelial function of resistance arteries was assessed by venous occlusion plethysmography. Metabolic and hormonal parameters were estimated in this study population. RESULTS: The duration of reactive hyperemia (durRH) was shorter in PCOS group when compared with normal controls (63.75 +/- 13.33 s vs 113.18 +/- 20.92 s, P = 0.036). A similar finding was observed when PCOS were compared with IH group (63.75 +/- 13.33 s vs 105 +/- 17.20 s, P = 0.05). The durRH did not differ between IH and control group (105 +/- 17.20 s vs 113.18 +/- 20.92 s, ns). A significant positive linear correlation was found between the durRH and dehydroepiandrosterone-sulfate (DHEA-S) levels (r = +0.48, P = 0.04) in the PCOS group. The basal insulin resistance index (HOMA) differed significantly between PCOS, IH and control groups. There was no significant correlation between durRH and HOMA index or testosterone levels in the PCOS group. CONCLUSIONS: Endothelial dysfunction may be an early sign of cardiovascular system abnormalities in young PCOS women. It is possible that increased DHEA-S levels may offer a cardioprotective advantage that attenuates the effects of cardiovascular risk factors that accompany PCOS.

Adult↗

Lack of suppression of plasma glucagon levels in late pregnancy persists postpartum only in women with previous gestational diabetes mellitus.

The aim of the present study was to examine fasting (0') and postglucose glucagon levels in normal and gestational diabetes mellitus (GDM) pregnancy, as available data are somewhat conflicting. To this end we studied 18 women with GDM at 26-32 weeks of pregnancy and compared these with 26 normal pregnant women matched for age and BMI. We also examined glucagon suppressibility postpartum (2-4 months) in the same ex-GDM women, in whom normal glucose tolerance was confirmed (WHO criteria) and compared these with 17 controls matched for age and BMI. Glucose, insulin and glucagon levels were measured during a 100 or 75 g oral glucose tolerance test (OGTT) respectively. In pregnant women, baseline and 3 h after glucose ingestion, plasma glucagon levels were significantly higher (p < 0.05) in women with GDM compared to normal women. Interestingly, in normal pregnancy a significant increase (p < 0.01) of postglucose plasma glucagon levels at 1 and 2 h compared to baseline levels was observed, while there was no change in GDM pregnancy. In postpartum euglycaemic women, there was no difference in basal glucagon levels between the two groups. A differential glucagon response during OGTT was observed: in control women there was a significant glucagon suppression (p < 0.01) at 2 h, while there was a significant glucagon increase (p < 0.01) 1 h after glucose ingestion, in ex-GDM women. We conclude that (a) absence of the suppressibility of glucagon in ex-GDM women with normal OGTT may indicate insulin resistance and might be involved in the natural history towards glucose intolerance; and (b) nonsuppression of glucagon in normal late pregnancy as well as in pregnancy complicated by GDM may be due to "physiological" insulin resistance of the alpha cells during this period.

Adult↗

Thyroid hormone excess increases basal and insulin-stimulated recruitment of GLUT3 glucose transporters on cell surface.

BACKGROUND: In hyperthyroidism, tissue glucose disposal is increased to adapt to high energy demand. Our aim was to examine the glucose transporter isoforms involved in this process and their regulation through insulin in monocytes from subjects with hyperthyroidism. METHODS: Blood (20 ml) was withdrawn from 12 healthy and 12 hyperthyroid subjects. The abundance of glucose transporter isoforms (GLUT) on the monocyte surface membrane was determined in the absence and presence of insulin (10-100 mU/l) using flow cytometry. Anti-CD14-PE monoclonal antibody was used for monocyte gating. GLUT isoforms were determined after staining the cells with specific antisera to GLUT1, GLUT3 and GLUT4. RESULTS: Hyperthyroidism increased basal monocyte-surface GLUT1, GLUT3 and GLUT4 transporters. In these cells, insulin had a marginal effect on GLUT4 translocation (25 %, p < 0.02) and a more significant effect on GLUT3 translocation (45 %, p < 0.001) on plasma membrane. CONCLUSIONS: In the hyperthyroid state, (1) basal abundance of GLUT1, GLUT3 and GLUT4 transporters on the cell surface is increased; (2) insulin mainly increases the recruitment of GLUT3 and, to a lesser extent, GLUT4 glucose transporters on the plasma membrane. These findings may provide a mechanism to explain the increment of glucose disposal in peripheral tissues in hyperthyroidism.

Adult↗

The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men.

OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.

Aged↗

Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects.

Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19/87 patients with SLE and in four of the healthy controls(P = 0.0057). SLE patients with MVP were younger (33.6 +/- 12.4 years) than those without MVP (41. +/- 12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11/19) compared with SLE patients without prolapse (15/68, P = 0.04). This association was independent of age. The aCL-lgG levels were significantly higher in SLE patients with MVP (32.37 +/- 43.26) compared with SLE patients without MVP (22.24 +/- 29.95, P = 0.04). Thyroid autoantibodies tended to be more common in S LE patients with MVP. Th e prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodies in SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.

Adult↗

HLA DQA1*0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease.

Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA1*0501 and DRB1*0301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disease and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA1*0501 and DRB1*0301 genomic regions were amplified by PCR and characterized by hybridization with sequence specific oligonucleotides (SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA1*0501 and DRB1*0301 antigens were significantly increased in patients compared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respectively). Neither of these two antigens was an independent risk factor for Graves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especially in females (RR/F=27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data suggest that HLA DQA1*0501 and DRB1*0301 antigens are not independent risk factors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the development of Graves' disease in the Greek population, particularly in females.

Female↗

High plasma amylin/islet amyloid polypeptide levels in patients with residual medullary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: We have previously reported that amylin/islet amyloid polypeptide (IAPP) mRNA is detected in a substantial subset of medullary carcinomas of the thyroid (MTCs). The aim of this study was to determine if the amylin/IAPP gene is expressed as the IAPP peptide in MTC tissues. DESIGN AND METHODS: In 10 patients with a histological diagnosis of MTC and with persisting or recurrent disease (basal calcitonin levels >250 pg/ml), the fasting serum insulin and plasma glucose, IAPP and calcitonin levels were measured and compared with those of 18 normal control subjects matched for age and body mass index. IAPP expression was studied by immunohistochemistry in MTCs and lymph-node metastasis tissues. RESULTS: Seven of ten MTC patients had abnormally elevated IAPP levels. Plasma IAPP and serum insulin levels were correlated in both patients and controls, but the slope of the regression line was significantly higher for MTC patients. IAPP staining was detected in four out of 12 random MTC samples and in two out of five lymph-node metastases, using immunohistochemistry. CONCLUSIONS: These results indicate that MTC cells express IAPP at the peptide level and that this raises the peripheral plasma levels. Further studies may reveal whether this is a feature of malignant disease.

Amyloid↗

The effect of iodine administration on the development of thyroid autoimmunity in patients with nontoxic goiter.

OBJECTIVE: Previous studies, mostly performed in iodine-deficient areas, have suggested that the administration of iodine to patients with endemic goiter may be associated with the development of thyroid autoantibodies (ThAbs); however, this has not been a consistent finding. In this study, we evaluated the effect of iodine on thyroid function and on the development of indices of autoimmunity (ThAbs and lymphocytic infiltration) in an iodine replete area. METHODS: Iodized oil (1 mL) was administered intramuscularly to 40 euthyroid patients with nontoxic goiter, adequate iodine intake, and absent or normal levels of ThAbs. Blood and urinary samples were taken at time 0, 3, 6, and 12 months after iodine administration. Thyroid volume was evaluated and fine-needle aspiration (FNA) was performed at 0, 6, and 12 months. RESULTS: Seven patients developed abnormal levels of ThAbs at some time between 3 and 12 months after iodine administration (p = 0.017). Mean anti-thyroglobulin (Tg) antibody levels increased at 6 months without reaching abnormal levels, but did not reach statistical significance (p = 0.062). Lymphocytic infiltration was detected in FNA smears in 10 cases before and in 27 cases after treatment (p = 0.0003). Triiodothyronine (T3) decreased at 12 months of follow-up, while thyroxine (T4) and thyrotropin (TSH) levels did not change significantly. A decrease in the mean levels of thyroglobulin as well as a small reduction in goiter size was observed at 6 and 12 months. CONCLUSION: The administration of iodized oil to patients with small nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of ThAbs in some cases and by an increase in thyroid lymphocytic infiltration.

Adult↗

Hormonal parameters in gestational diabetes mellitus during the third trimester: high glucagon levels.

Hormonal parameters during the last trimester of pregnancy contribute to a natural increase of insulin resistance. It is not known whether any of these are further involved in the manifestation of gestational diabetes mellitus (GDM) in affected individuals. Basal levels of adrenocorticotropic hormone, cortisol, growth hormone, insulin-like growth factor-I, prolactin, glucagon, estradiol, progesterone, human placental lactogen and human chorionic gonadotropin were investigated in 15 nonobese women with GDM and 26 matched normal pregnant women (N). A linear discriminant analysis was performed to further compare the predictive value of the basal hormone levels. Plasma glucagon levels were significantly higher in the GDM group (p = 0.014); this difference was even higher (p = 0.007) when the number of women was increased (GDM = 33, N = 62). No significant differences were found in the levels of any of the other hormones. It is not clear whether elevated glucagon levels have any involvement in the pathogenesis of GDM or simply reflect the relative insulin deficiency of these women.

Adult↗

Three mRNA transcripts of the proopiomelanocortin gene in human placenta at term.

The proopiomelanocortin (POMC) gene whose normal pituitary specific mRNA product is 1200 bases (b) is also expressed in placenta and its peptide derivatives such as ACTH and beta-endorphin may play an important role in the initiation of labor. So far, two mRNA transcripts, one small (800b) and one large (1380b) have been reported in placenta by Northern blot analysis, similar to other endocrine tissues and various extrapituitary tumors; however, it is questionable whether both of these transcripts are effectively translated to a functional protein. We examined by Northern blot analysis the size and the differential expression of placental POMC gene transcripts in pregnant women with different modes of delivery. Placental tissues were collected from two groups of pregnant women, six with vaginal delivery (VD) and five with cesarean section (CS). In both groups of placentae three POMC gene transcripts were detected of 800, 1200 and 1380 bases; the 1200b pituitary specific species often predominated and was always present. The 800b transcript was also always present, while the large transcript (1380b) was expressed in 3/6 VD and 2/5 CS placental tissues. No differences in the relative levels of any of these mRNA species showing effect of the mode of delivery were observed. We conclude that POMC gene transcription in placental tissue at term gives rise to three mRNA transcripts, thus resembling extrapituitary tumors. The reported changes in the levels of the derivative peptides according to the mode of delivery do not reflect changes in POMC mRNA levels and could be attributed to a post-translational effect.

Blotting, Northern↗

Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek women with gestational diabetes.

OBJECTIVE: This study assessed whether the Trp(64)Arg polymorphism of the beta3-adrenergic receptor (beta3-AR), which has been associated with obesity, insulin resistance, weight gain, and earlier onset of type 2 diabetes, is more frequent in women who develop gestational diabetes mellitus (GDM) or whether it is associated with weight gain during pregnancy RESEARCH DESIGN AND METHODS: A total of 311 Greek pregnant women (180 with GDM and 131 without GDM [control]) who underwent a 100-g oral glucose tolerance test (OGTT) in the third trimester of pregnancy were genotyped for the beta3-AR Arg(64) polymorphism. Insulin levels were also determined during the OGTT. RESULTS: The frequency of Trp(64)Arg heterozygotes in this population was approximately 7% and was similar in the GDM and control groups (6.7 vs. 6.9%) as well as in the obese (BMI > or =27 kg/m2) and the nonobese (6.3 vs. 6.8%) subgroups. In the GDM group, BMI, fasting insulin resistance index, and diastolic blood pressure were significantly higher in Trp(64)Arg carriers; these differences were no longer observed when obesity was considered. In the 4 subgroups (control Trp(64)Trp and Trp(64)Arg and GDM Trp(64)Trp and Trp(64)Arg), a highly significant trend was evident of an increase in the percentage of subjects with shorter height. CONCLUSIONS: The frequency of the Arg(64) allele in Greek pregnant women is relatively rare compared with other ethnic groups and is probably not related to the development of GDM or obesity The observed tendency for shorter body height in Arg(64) carriers merits further evaluation in larger population samples.

Adult↗

Mitral valve prolapse in autoimmune thyroid disease: an index of systemic autoimmunity?

A coexistence of mitral valve prolapse (MVP) with autoimmune thyroid disease (AITD) has been described, but there are not sufficient data to explain this association. The aim of the present study was to investigate the prevalence of MVP in patients with AITD and to evaluate whether any correlation between MVP and certain immunological parameters exists. M-mode, two-dimensional Doppler echocardiography was performed in 29 patients with Graves' disease (GD), 35 with Hashimoto's thyroiditis (HT), 20 with nonautoimmune goiter, and 30 normal controls. Serum samples were examined for antinuclear antibodies (ANA), antibodies against extractable nuclear antigen (ENA), antiphospholipid antibodies (aCL), rheumatoid factor (RF), thyroid autoantibodies (TAAb), immunoglobulins and C3, C4. Eight of 29 GD patients and 8 of 35 HT patients had MVP, while none of the control group and 2 of 20 of the simple goiter group had MVP (p < 0.05). ANA were detected at low titers in 5 of 8 in MVP(+) GD versus 3 of 21 in MVP(-) GD (p < 0.05). In the HT group the MVP(+) patients had a significantly higher incidence of ANA and ENA, 5 of 8 and 2 of 8 versus 5 of 27 and 0 of 27 of MVP(-) patients, respectively, p < 0.05. A statistically significant higher incidence of aCL was found in HT MVP(+) patients. (3/8) versus HT MVP(-) 1/27, p < 0.05. RF levels (immunoglobulin A [IgA]) were significantly higher in MVP(+) patients. The association of MVP with nonorgan-specific autoantibodies indicates that MVP may also be an autoimmune disease. It is possible that patients with AITD who also have MVP may be at an increased risk to develop systemic autoimmunity.

Adult↗

The predominant form of non-toxic goiter in Greece is now autoimmune thyroiditis.

Endemic non-toxic goiter (NTG) in Greece has been attributed primarily to iodine deficiency. Thirty years ago about 60% of the prepubertal boys and girls examined in endemic goiter regions presented with NTG and among them thyroid autoimmunity was rarely detected. Although iodine supplementation has corrected this deficiency during the past 30 years, new cases of NTG still appear. To evaluate the prevalence and type of NTG and the effect of iodine supplementation on them in Greece at present, we performed two cross-sectional clinical studies and a retrospective pathology one: (i) thyroid gland volume and urinary iodine excretion (UIE) were assessed in a representative sample of 1213 schoolchildren from previously endemic and non-endemic regions; (ii) serum thyroxine, tri-iodothyronine, TSH, thyroid autoantibodies (AAB) (anti-thyroid peroxidase and anti-thyroglobulin antibodies) and UIE (in 60 patients) were measured in 300 consecutive patients with NTG from Athens and Heraklion; and (iii) we compared the prevalence of autoimmunity among fine needle aspiration smears of benign thyroid pathologies performed by the same pathologist between 1985 and 1986 (975 cases) and between 1994 and 1995 (2702 cases). We found that 12. 5% of the schoolchildren examined in regions with a previous history of endemic goiter had NTG, whereas this percentage was only 1.7% in areas without such a history. In Athens (61.6%) and Heraklion (58. 5%) a substantial number of NTG patients were AAB positive and biochemically hypothyroid. UIE in Athens did not differ between patients with autoimmune goiter (ATG) and simple goiter. The prevalence of autoimmune stigmata in pathology smears has increased from 5.94% (years 1985-1986) to 13.91% (years 1994-1995) (P<0.05). We conclude that: (i) the persistence of endemic goiter in regional foci despite iodine deficiency correction suggests a possible role for a naturally occurring goitrogen; (ii) ATG is the predominant form of NTG in Greece nowadays; and (iii) the five-fold decrease in the prevalence of NTG during the past 30 years followed by the increase of ATG may support the relative character of the latter.

Autoantibodies↗

Decreased stature in gestational diabetes mellitus.

Short stature has been associated with various degrees of abnormal glucose tolerance in middle-aged people, where the effects of age and metabolic control would be difficult to exclude. We chose to examine body stature in women with gestational diabetes mellitus (GDM), a prediabetic state affecting a young group of people. A sample of 2772 Greek pregnant women, referred for GDM screening was examined. After a 100-g oral glucose tolerance test, 1787 women were classified as normal (N), 300 women were found with one abnormal glucose value (OAV) and 685 women with GDM. Basal insulin resistance was calculated in 640 women by homeostasis model assessment. In addition, 51 pregnant women with pre-existing Type II (non-insulin-dependent) diabetes mellitus and 109 with pre-existing Type I (insulin-dependent) diabetes mellitus were included in the study. There was a gradual decrease in mean height (cm) as glucose intolerance became more severe: N: 161.0 +/- 6.2, OAV:160.2 +/- 6.1, GDM:158.7 +/- 6.3, Type II diabetes 158.2 +/- 7.0 (p < 0.001, analysis of variance]. Height in Type I diabetes (160.1 +/- 5.9) did not differ from the normal group. The difference in height between the normal and GDM groups remained (p < 0.001) when body weight, age, birth before or after 1960 and educational status were also taken into account. An independent correlation was also found between height and insulin resistance (n = 640) adjusted for the above mentioned variables. In conclusion, short stature appears to be associated with glucose intolerance as an independent variable, even when this intolerance is both mild and temporary. The previously unrecognised independent association of stature with basal insulin resistance merits further investigation.

Adult↗