The International Journal of Romanian Society of Endocrinology / Registered in 1938

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  • General Endocrinology

    Kassaee SM, Goodarzi MT, Kassaee SN

    Ameliorative Effect Of Trigonella Foenum Graecum L. On Lipid Profile, Liver Histology and Ldl-Receptor Gene Expression in High Cholesterol-Fed Hamsters

    Acta Endo (Buc) 2021 17(1): 7-13 doi: 10.4183/aeb.2021.7

    Background. Trigonella foenum graecum L. (Fenugreek, FG) is used in many countries as a medicinal plant. Evidence has suggested the hypolipidemic effect of Fenugreek; however, its actual mechanism has not been determined yet. Objectives. The purpose of our research was to investigate the effect of Fenugreek on lipid profile, liver histology and LDL receptor gene expression in male hamsters fed with high cholesterol diet. Methods. These animals were given normal diet (ND), high cholesterol diet (HCD: 2% cholesterol and 0.5% cholic acid added to ND), HCD supplemented with 2g and 8g fenugreek per 100g ND (HCD+FG2 and HCD+FG8) respectively for four weeks. At the end of treatment, serum lipids, lipoproteins and liver enzymes were measured. Finally, LDL receptor (LDLR) gene expression was determined in the liver of the studied animals using Real Time-PCR method and liver histological changes were evaluated by H&E staining method. Results. A significant reduction was observed in serum triglyceride (p<0.01), total cholesterol, low and very low density cholesterol, aspartate and alanine transaminases in HCD+FG8 group (p<0.05) compared with HCD group, while serum level of HDL-c (p<0.01) increased. In addition, LDLR gene expression in HCD+FG8 group increased 7.8 folds. The results confirm the protection effect of liver tissue in HCD+FG8 group against pathological changes. There was no significant change in LDLR gene expression in HCD+FG2 group. In conclusion, fenugreek ameliorated dyslipidemia by up-regulation of LDLR gene expression and can be used as a protective agent against hypercholesterolemia.
  • General Endocrinology

    Yildirim AB, Ozdamar S, Kaymak E

    The Effects of Maternal Hypothyroidism on the Immunoreactivity of Cytochrome P450 Aromatase in the Postnatal Rat Testicles

    Acta Endo (Buc) 2017 13(1): 7-16 doi: 10.4183/aeb.2017.7

    Introduction. Abnormal thyroid function affect spermato-genesis and male infertility. For men, the aromatase deficiency can cause infertility. In this study, the aim is to investigate the effect of maternal hypothyroidism on offspring testicular morphology and cytochrome-P450- aromatase (P450arom) immunoreactivity. Materials and Methods. Eighteen Wistar albino pregnant rats were divided into three groups, namely A, B and K groups. Hypothyroidism was induced by adding 0.01% of propyl thiouracil (PTU) in drinking water. Hypothyroid mothers, group A: given PTU for 21 days during pregnancy, group B: given PTU for 21 days prior to pregnancy; control mothers, group K, given only water. Hypothyroid and control group mothers’ pups at postnatal day (PND) 15 and 60 were sacrificed. We determined immunoreactivity intensity of P450arom and mRNA levels by RT-PCR performed in the testis tissues. ELISA method was used for thyroid function tests for T3, T4 and TSH. Structure of seminiferous tubule was evaluated by hematoxylin-eosin staining. Results. It was seen that the aromatase expression in 15-day-old maternal hypothyroid groups was similar to the one in the control group while there was a decline in the aromatase expression of 60-day-old groups. As for mRNA, it was determined that it had a tendency to increase over time in all groups but this increase was not significant. The tubule diameter and Johnsen’s Testicular Biopsy Score diminished in all hypothyroid groups in comparison to the control group. Conclusion. The changes that occur in the early period of testis development due to maternal hypothyroidism negatively affect testis development in the next stages of life. This situation leads to a decline in aromatase expression in the following years.
  • General Endocrinology

    Cadirci K, Turkez H, Ozdemir O

    The In Vitro Cytotoxicity, Genotoxicity and Oxidative Damage Potential of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, on Cultured Human Mononuclear Blood Cells

    Acta Endo (Buc) 2019 15(1): 9-15 doi: 10.4183/aeb.2019.9

    Background. Linagliptin (LNG) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that ameliorates blood glucose control of patients with type 2 diabetes, without developing hypoglycemic risk and weight gain with a good clinical and biological tolerance profile. To the best of our knowledge, its cytotoxic, genotoxic and oxidative effects have never been studied on any cell line. Aim. To evaluate the in vitro cytotoxic, genotoxic damage potential and antioxidant/oxidant activity of LNG in cultured peripheral blood mononuclear cells (PBMC). Material and methods. After exposure to different doses (from 0.5 to 500 mg/L) of LNG, cell viability was measured by the MTT (3,(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) leakage tests. The antioxidant activity was assessed by the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. To evaluate the genotoxic damage potential, chromosomal aberration (CA) frequencies and 8-oxo-2’- deoxyguanosine (8-oxo-dG) levels were determined. Results. Treatment with LNG did not cause statistically significant decreases of cell viability at lower concentrations than 100 mg/L as compared to untreated cultures. However, LNG exhibited cytotoxic action at 250 and 500 mg/L. Also, IC20 and IC50 values of LNG were determined as 8.827 and 70.307 mg/L, respectively. In addition, the oxidative analysis revealed that LNG supported antioxidant capacity at concentrations of 2.5, 5, 10, 25, 50 and 100 mg/L without generating oxidative stress. Besides, the results of CA and 8-oxo-dG assays showed in vitro nongenotoxic feature of LNG. As a conclusion, our findings clearly revealed that LNG had no cytotoxic and genotoxic actions, but exhibited antioxidative activity. In conclusion, therefore it is suggested that LNG use in diabetic patients is safe and provides protection against diabetic vascular and oxidative complications.
  • General Endocrinology

    Chen L, Shen T, Zhang CP, Xu BL, Qiu YY, Xie XY, Wang Q, Lei T

    Quercetin And Isoquercitrin Inhibiting Hepatic Gluconeogenesis Through Lkb1-Ampka Pathway

    Acta Endo (Buc) 2020 16(1): 9-14 doi: 10.4183/aeb.2020.9

    Objective. To observe the impact of quercetin and isoquercitrin on gluconeogenesis in hepatocytes. Methods. Mouse primary hepatocytes were cultured with lactic acid and pyruvic acid. After treatment with quercetin and isoquercitrin for 24 hours, the glucose concentration in the culture supernatant was determined. RT-PCR was used to detect the mRNAs of PEPCK, G6Pase, LKB1, and AMPKα. Protein levels of LKB1, AMPKα, and Thr172 phosphorylation were evaluated by Western blot. Results. The glucose concentration in the gluconeogenesis group (GN) was significantly higher than in the control group (C), but the glucose concentrations in the high level quercetin(group 80Q) and high level isoquercitrin (group 80I) were significantly lower than in the group GN, P<0.01. In the group 80Q, and group 80I, the mRNA levels of PEPCK and LKB1were significantly lower than in the group GN (P<0.01), and the G6Pase mRNA were significantly lower than in the group GN (P<0.05). The protein levels of LKB1 and the phosphorylation of AMPKα Thr172 in the group 80Q, group 40I, and group 80I were higher than in the group GN. The effects of quercetin and isoquercitrin on LKB1 and AMPKα were similar to those of metformin. Conclusions. Quercetin and isoquercitrin inhibit gluconeogenesis in hepatocytes, which may be related to the LKB1 upregulation and phosphorylation of AMPKα.
  • General Endocrinology

    Ursu HI, Podia-Igna C., Delia C.E., Toma G.M., Goran D., Galoiu S., Niculescu D.A., Giurgiu D., Gheorghiu M.L. , Anca IA

    Iodine Status after a Decade of Universal Salt Iodization in Romania: A Bicentric Study in Urban Areas

    Acta Endo (Buc) 2014 10(1): 9-20 doi: 10.4183/aeb.2014.9

    Objective. To assess in a bicentric study the current iodine status of schoolchildren, ten years after implementation of the universal salt iodization (USI) in Romania. Subjects and methods. 102 children from 2 towns, aged between 6 and 11 years, were included in the study group: 66 children from Sibiu, a previously endemic area for iodine deficiency disorders and 36 children from Bucharest, a previously borderline iodine intake area. Body mass index (BMI), total body surface area (BSA), median urinary iodine concentration (UIC) and prevalence of goiter were evaluated. Thyroid volume was measured by ultrasonography. The study was approved by the Local Ethics Committee. An informed consent from the parents was obtained. Results. From the 102 schoolchildren in the study group, 59 were girls and 43 were boys. Median UIC in the total number of samples was 175.2 mcg/L, reflecting a sufficient iodine intake, with statistically significant differences between the two urban regions. The median UIC was 187.35 mcg/L in the Sibiu subgroup and 160.2 mcg/L in the Bucharest subgroup (p < 0.001). The total percentage of goiter in the studied subjects was 5.88%. Percentage of goiter, determined by adjusting ultrasound thyroid volume to sex and BSA, was 1.51% in Sibiu and 13.88% in Bucharest, a statistically significant difference (p = 0.011). None of the subjects showed ultrasonographic pattern suggestive of Hashimoto thyroiditis or macronodules. There was no statistically significant difference between the percentages of overweight or obesity in the two subgroups. Conclusions. Ten years after implementation of USI in Romania, a bicentric study suggests that our country is iodine sufficient in urban areas. In order to prevent recurrence of mild iodine deficiency in schoolchildren, a persistent surveillance, use of sustainable measures and public awareness are required. Recurrence of mild iodine deficiency should be avoided, because even mild iodine deficiency impairs cognition in children.
  • General Endocrinology

    Georgescu C, Georgescu B, Mihu D, Porumb C, Duncea I

    Relationships of Umbilical and Maternal Adiponectin, Resistin and Osteoprotegerin to Maternaland Newborn Anthropometric Characteristics

    Acta Endo (Buc) 2011 7(1): 11-21 doi: 10.4183/aeb.2011.11

    Introduction. Adiponectin, resistin and osteoprotegerin (OPG) are cytokines expressed in the adipose tissue. Pregnancy is associated with gradually increased maternal\r\nlevels of these molecules, also detected in significant amounts in umbilical cord blood serum samples.\r\nAim, patients and methods. To establish the relationships of maternal and umbilical adiponectin, resistin and OPG levels to both maternal and fetal anthropometric measurements and insulin sensitivity, 28 mother-newborn pairs were enrolled in the study. Blood samples were collected in a fasting state, after delivery, and serum insulin, C-peptide, sex hormone-binding globulin, adipocytokines, OPG and bone specific alkaline phosphatase (BAP) were measured.\r\nResults. Compared to maternal values, umbilical serum adiponectin levels were about 3-fold higher; additionally, significantly higher resistin and lower OPG levels were\r\nobserved. Stratification of umbilical and maternal adiponectin levels according to tertiles of birth body weight demonstrated significantly lower maternal adiponectin\r\nlevels by tertiles of neonatal body weight. No relationships were noticed between infant birth weight and maternal or umbilical serum resistin and OPG, respectively. Umbilical resistin was significantly associated to both\r\nmaternal resistin and umbilical adiponectin. Multiple regression analysis showed that maternal BMI, umbilical insulin, C-peptide and resistin explained 71.83% of umbilical serum adiponectin variability. Umbilical resistin was independently predicted by umbilical adiponectin, umbilical C-peptide and maternal BMI, and the model explained 81.49% of umbilical resistin levels.\r\nConclusions. In human, umbilical serum adiponectin and resistin levels are significantly higher compared to adults. These adipokines may mediate the effects of maternal body mass on fetal development. The biology of the\r\nOPG/RANKL cytokine system in fetuses and newborns needs further research.
  • General Endocrinology

    Predoi D, Badiu C, Alexandrescu D, Agarbiceanu C, Stangu C, Ogrezeanu I, Ciubotaru V, Dumitrascu A, Constantinescu AI

    Assessment of compressive optic neuropathy in long standing pituitary adenomas

    Acta Endo (Buc) 2008 4(1): 11-22 doi: 10.4183/aeb.2008.11

    In this study we aimed to evaluate and quantify optic nerve damage caused by long standing compressive pituitary macroadenomas with conventional (ophthalmoscopy) and modern techniques such as fundus camera, confocal scanning laser tomography for quantitative measurements of the thickness of retinal layers as well as visual evoked potentials (VEP) for electrophysiological quantification. Seven patients with large, long standing pituitary macroadenomas were submitted to ophthalmologic evaluation, including a visual field (VF), visual acuity (VA) and eye fundus (F). Heidelberg retinal tomography (HRT) was used for retinal thickness and evaluation of nerve fibers loss, and VEP were measured by pattern reversal and flash stimulus. In addition, all patients underwent tumor imaging (MRI/CT) and specific endocrine evaluation. All cases presented with macroadenomas with suprasellar extension and residual or progressive optic chiasma syndrome; all but one (prolactinoma) were nonfunctioning adenomas, after radical treatment (surgery ? radiotherapy). Adrenal and thyroid substitutive treatment was instituted in all cases due to associated pituitary failure. Evaluation of VF showed 9 eyes with temporal hemianopia, 2 with nasal islands of vision and 1 with nasal hemianopia in a homonymous hemianopia case; another case presented for left 3rd nerve palsy due to a cavernous sinus syndrome, therefore the visual field was not measurable in 2 eyes. Visual acuity was very low (counting fingers) in 4 eyes, while in the rest the VA was between 0.5-0.9. The fundus revealed total atrophy in 2 eyes, band atrophy in 4, temporal pallor in 5 and global pallor in 1. Cup/disk ratio in the case with 3rd nerve palsy was 0.5 (RE) and 0.3 (LE). HRT II stereometric analysis of the optic nerve head showed abnormal values, documenting retinal nerve fiber layer (RNFL) loss that correlated with fundus appearance and visual field defects. Mean RNFL thickness had abnormal values in 8 eyes (from 0.074 to 0.173 &#956;m), correlated with RNFL cross sectional area in 7 eyes (from 0.362 to 0.846 &#956;m2) and 1 eye with low limit values (1000 &#956;m2). In agreement with these data, VEP&#8211;P100 presented increased latency over 120 ms in 8 eyes, borderline (100-120 ms) in 5 and 97.5 ms in only 1 eye. In conclusion, HRT can document the papilla and nerve fiber layer more objective, permitting quantification of the disc&#8217;s alterations due to compressive pituitary macroadenomas. HRT is useful in quantifying RNFL loss in other conditions than glaucoma, when other optic disc imaging tools are not available.
  • General Endocrinology

    Lucan L, Lucan V.C., Tabaran F.A. , Stamatian F


    Acta Endo (Buc) 2013 9(1): 11-21 doi: 10.4183/aeb.2013.11

    Context. The inflammatory disorders of the urinary bladder represent one of the most frequent disorders associated with hormonal unbalances caused by menopause. The involvement of estrogens and mast cells in this complex mechanism mediated by neuro-hormonal pathway is well known, but the pathogenesis through which the hormonal deprivation is affecting the Estrogen Receptor expression and is predisposing to urinary bladder inflammatory changes is still argued. Objective. To determine the structural changes associated with surgically induced menopause, and the effect of estrogen replacement therapy (ERT) in the urinary bladder morphology, mast cell population and Estrogen Receptor (ERα) expression. Subjects and methods. The effect of ovariectomy and ERT was monitored by quantifying the number of mast cells and the structural changes that the urinary bladder suffers. By immunohistochemistry we assessed the changes of the Estrogen Receptor Alpha (ERα) expression in the urothelium and detrusor muscle. The study was carried out on ovariectomised female rats over a period of 42 days. Results. The main alterations associated with the hormonal deprivation were represented by the growth in number of the bladder mast cells, atrophy of the urothelium and amplification of the expression of ERα from the urothelium, but not from the detrusor muscle. ERT significantly decreased the tissue expression for ERα, reduced the severity of bladder atrophy and the number of mast cells. Conclusions. The estrogenic hormonal substitution can diminish the severity of the atrophic, inflammatory and ERα changes in bladder disorders associated with ovarectomy in rat.
  • General Endocrinology

    Kacso A, Goia-Socol M, Hazi G, Tomoaia G, Kacso IM, Georgescu CE

    Effect of Experimental Dysglycemia on Under-Carboxylated Osteocalcin Production in Human Primary Osteoblast-Like Cell Cultures

    Acta Endo (Buc) 2018 14(1): 11-15 doi: 10.4183/aeb.2018.11

    Context. The undercarboxylated form of osteocalcin (ucOC) and osteoprotegerin (OPG) are bonederived molecules involved in the endocrine crosstalk governing the bone, the adipose tissue and the pancreas. In addition, glucocorticoids are major determinants of both insulin resistance and osteoporosis. Objective. We aimed to investigate the response of ucOC and OPG to dysglycemia and/or dexamethasone (DXM) in primary human osteoblastic cell (HOC) cultures. Design and methods. Third-passage sub-confluent primary HOC cultures were treated with glucose: 2.8 mmol/L, 5.6 mmol/L, 11.1 mmol/L and 28 mmol/L, respectively. Alternatively, HOC cultures were subjected to DXM 1 μmol/L. In more complex experiments, HOC cultures were pre-treated with glucose (5.6 mmol/L) with/without insulin (1 pmol/L) followed by DXM (1 μmol/L). 24-hours posttreatment, culture medium ucOC and OPG were measured by ELISA. Results. ucOC production differed significantly (p<0.05) between cell groups, decreasing in a dosedependent manner as glucose concentration in the medium increased. Insulin prevented this effect. OPG levels appeared not to be significantly influenced by the hyperglycemic culture medium and were not related to ucOC concentration (p>0.05). Addition of DXM resulted in significantly lower ucOC concentrations compared to vehicle-treated cells (p<0.05). However, the effect of insulin co-treatment on ucOC was not counteracted by DXM (p<0.05). Conclusions. An obvious alteration of OC production/metabolism was observed as glucose levels changed in the bone microenvironment, to potentially be involved in diabetes-related osteopenia. DXM suppressed ucOC levels however not in insulin-rich environment.
  • General Endocrinology

    Saremi L, Saremi M, Lotfipanah S, Imani S, Zhang TY, Fu J

    Relationship between PPARGC1A Gene Polymorphisms with the Increased Risk of Coronary Artery Disease among Patients with Type 2 Diabetes Mellitus in Iran

    Acta Endo (Buc) 2015 11(1): 13-17 doi: 10.4183/aeb.2015.13

    Type 2 diabetes (T2D) increases the risk of coronary artery disease (CAD) in patients with type 2 diabetes compared with nondiabetic subjects. Several genetic variants are considered as risk factors for CAD, including those implicated in dyslipidaemia and oxidative stress. The PPARGC1A gene is considered as a key regulator of pathophysiological processes contributing to CAD. Aim. We investigated whether the Gly482Ser polymorphism (rs8192678) increased susceptibility to CAD in Iranian population and whether it was associated with clinical and metabolic parameters. Patients and methods. A total of 290 subjects including 149 CAD patients with a history of diabetes and 149 controls were included in our study. The Gly482Ser polymorphism was genotyped using ARMS-PCR method. Based on the type of variables, by the use of SPSS software (Statistical Package for Social Sciences Inc., Chicago, IL, USA) statistical analyses were performed. Results. We found a significant difference in the Gly482Ser substitution between the case and control subjects in Iranian population. However, no significant association was observed between Gly482Ser genotypes and physiologic variables. Conclusion. This gene polymorphism PPARGC1A Gly482Ser may be a potential marker for increased risk of CAD in diabetic patients in clinical treatment and diagnosis in clinical treatment and diagnosis in the Iranian population.