ACTA ENDOCRINOLOGICA (BUC)

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Background. Our study outlines the implication of melatonin in organisms' pain regulatory mechanisms. The literature describes epiphysis opioidergic fibers with µ and d opioid receptors and also pleads for an analgesic dose-dependent effect of melatonin. We analyzed the biologic variability of the analgesic effect of the pineal hormone, based on the psychoneuroendocrine behavior type. In our previous studies we investigated the dinamics of melatonin's analgesic effect within the following psychoneuroendocrine behavioral types: the adrenergic type (hipersensitive to pain), the opioid type (pain hyporeactive) and the intermediate, equilibrated typology (N type). Objectives. Our present research focused on the antinociceptive pharmacologic psychoneuroendocrine variability in the case of co-administration of melatonin (50mg/kgbw, i.p.) with ondansetron (4 mg/kgbw, i.p.), petidine (4mg/kgbw, i.p.) and tramadol (4mg/kgbw, i.p.). Subjects and Methods. Experiments were performed in vivo, using Albino Swiss male mice. Pain sensitivity was assessed using the classical pharmacologic test hot-plate (60°C). Conclusions. Our results showed an amplification of the analgesic effect when petidine was co-administered with melatonin, with best results for the A type of behavior (p<0.02), as follows: 63.41% (melatonin + petidine co-administration) > 54.54% (melatonin + tramadol coadministration) ≈ 52% (melatonin). We also noticed an antagonism between ondansetron and the pineal biomolecule

Phenylketonuria (PKU) is the most frequent inherited amino acid metabolic disorder, and it may also be treated by dietary means. The determination of phenylalanine (Phe) levels in the blood plasma is important not only in early diagnostic, but also in monitoring the treatment of PKU. Purpose. The aim of our work was to develop a simple, sensitive and highly accurate procedure to determine the plasma concentration of Phe. Procedure. The measurement of plasma Phe concentration involves two steps: a) separation of plasma (from the blood taken on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex-50X8 and evaporation of the eluate in vacuum at 40˚C), and b) determination of Phe concentration in the solution of amino acids by HPLC. This analysis was performed using a Dionex Ultimate 3000 instrument equipped with a Ultimate 3000 diode array detector (DAD). The values of Phe concentration in the plasma of several patients were calculated using a calibration curve made with standards of Phe (dilutions of a stock solution of 50 mg/ dL). The measurements in duplicate (plasma Phe) or a greater number of samples from the same concentration of standards of Phe showed extremely small sample to sample differences. Concentrations as low as 0.2 mg/dL could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and highly accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentration of Phe in patients with PKU.

Context. Previous studies have demonstrated a correlation between creatinine and cystatin levels and thyroid disorders. Objective. To further investigate the diagnostic value of serum creatinine to cystatin C ratio in the diagnosis of thyrotoxicosis. Design. One hundred eighty four thyrotoxicosis patients and 406 healthy controls were enrolled. Subjects and Methods. We assessed at baseline characteristics, serum Cr:Cyc in thyrotoxicosis group, control group and subgroups and analyzed the relationship between the indicator and the etiology of thyroid gland toxicity. Results. Subgroup analysis indicated that the Cr:Cyc ratio in the Graves' disease (GD) group was lower than those in the Hashimoto's thyroiditis (HT) and subacute thyroiditis (SAT) groups (P<0.001). Correlation analysis demonstrated that the Cr:Cyc ratio was positively correlated with thyroid stimulating hormone (TSH) and thyrotropin receptor antibody (TRAb) but negatively correlated with free triiodothyronine (FT3) and free thyroxine (FT4) in the GD group. Receiver operating characteristic (ROC) curve analysis indicated that the area under the curve (AUC) value of the Cr:Cyc ratio for the diagnosis of thyrotoxicosis was 0.933 (P<0.001), and the AUC value for the diagnosis of GD was 0.778 (P<0.001). Conclusion. The Cr:Cyc ratio has clinical significance in the diagnosis of thyrotoxicosis and the identification of thyrotoxicosis etiology.

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Testosterone influences cancer development. This in vitro experiment was exerted to determine the association of testosterone with human colorectal cancer(HT29), glioblastoma (A172) and human embryonic kidney(HEK293) cells proliferation. HT-29, A172 and HEK293 cell lines were cultured in standard growth medium, then randomly divided into control group (not exposed to testosterone) and groups exposed to 1, 10, 100 and 1000 μg/mL of testosterone. Cell viability was quantified by MTT assay. Statistical analysis was performed using ANOVA. Viability of HEK293 cells significantly increased in groups exposed to 1 μg/mL and decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.05 and P<0.001, respectively). Viability of HT29 cells significantly increased in groups exposed to 10 and 100 μg/mL of testosterone and significantly decreased when exposed to 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.001 and P<0.001, respectively). Viability of A172 cells significantly decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.001). In conclusion, different doses of testosterone have enhancing or suppressive effects on HEK293, HT29 and A172 cells proliferation; according to which, considering clinical use of testosterone therapy for cancer treatment is a highly controversial issue.

Context. Visceral adipose tissue (VAT) is a strong predictor of carbohydrate metabolism disorders. Abdominal bioelectrical impedance analysis (A-BIA) is a simple method for the measurement of VAT and is a promising tool in screening and follow-up of abdominal obesity. However the role of A-BIA in dieting individuals has not been evaluated adequately in longitudinal followup studies. Objective. The aim of this study is to determine the role of A-BIA in identifying the changes in metabolic predictors after diet and/or exercise therapy. Design. All patients who sought weight loss treatment underwent baseline assessment and were prescribed a program of diet. After a mean follow-up of 3.2 months, data were analyzed. Subjects and Methods. Ultimately, 103 participants who reported adhering to the diet, enrolled to the study. We tested associations between changes in body composition measures and changes in laboratory measures using correlations and multivariate linear regression analysis. Results. Mean loss of body weight was 3.4±2.8 kg. All but waist-to-hip ratio, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels changed significantly (p<0.001). Decreases in body weight, body mass index (BMI), and VAT level significantly correlated with decreases in fasting blood glucose, fasting insulin level, and HOMA-IR score (r=0.230–0.371). In multiple linear regression analysis changes in BMI and VAT significantly correlated with change in HOMA-IR score (F(7.93)=2.283, p=0.034, R2=0.147). Conclusion. Decreases in BMI and VAT, as determined by A-BIA, were predictors of changes in metabolic laboratory measures. A-BIA is useful for followup of patients receiving diet therapy for weight loss.

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Context. Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients. Objectives. It was shown that administration of glucocorticoid receptor antagonist Mifepristone (MIF) leads to variously pronounced changes in the alanine-, aspartate-, tyrosine- aminotransferases (ALT, AST, TAT) activity in the liver of experimental animals. It has been suggested that this selective effect of MIF may be related to differences in the expression of the corresponding genes. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods. Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results. In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions. The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study.