ACTA ENDOCRINOLOGICA (BUC)

Aims. To investigate the historical changes in survival with diabetes in patients treated with insulin from diagnosis.\r\nMethods. We analyzed 2811 deaths, 51.5% males, registered at ?I. Pavel? Bucharest Diabetes Centre, aged 40-64 years and deceased between 1943 and 2009. We split the analysis in three time periods according to year of death: 1943-1965,\r\n1966-1988 and 1989-2009.\r\nResults. The mean age at diabetes onset was 51.4?6.8 years, with mean disease duration at death of 17.7?11.6 years\r\nand mean age at death of 69.1?11.2 years. The mean survival after diabetes onset was 13.9?9.8 years in 1943-1965, and rose to 17.3?9.6 years (p<0.001) in 1989-2009. There was a significant increase for coronary heart diseases and cancer and a significant decrease for infections and endstage\r\nrenal disease as causes of death.\r\nConclusions. We found no significant changes in age at onset, which combined with an increase in survival with diabetes lead to a significant increase in age at death.\r\nMajor historical events have a strong impact over survival after the onset of diabetes.

Context. Heat Shock Protein 60 (HSP60) is a chaperone protein which is involved in proteins transfer and re-folding of proteins. Objective. Importance of HSP60 in sperm capacitation and facility of sperm-oocyte membrane binding was confirmed, therefore in this study the effect of HSP60 on the rate of in vitro fertilization and the cleavage rate in mouse embryo was investigated. Design. Ten male mice and twenty five female mice were involved to collect sperms and oocytes required for this study. Subjects and Methods. Sperms were collected from the epididymis of male mouse and oocytes were collected from the oviduct of female mouse following ovarian hyperstimulation. Then, capacitated sperms and oocytes were placed together in fertilization medium in four groups in the presence of different concentrations of HSP60 (10, 50 and 100 ng/mL) and in the absence of HSP60. After calculation of the fertilization rate, zygotes were transformed into the other medium for development and the cleavage rate was monitored to blastocyst stage. Results. There was not a significant difference in the rate of fertilization between 10 ng/mL HSP60 group and the control group. The rate of fertilization and two-cell embryo development decreased significantly (P≤0.05) in 100 ng/mL HSP60 compared to other experimental and control groups. Further, the rate of two-cell embryo development increased significantly (P≤0.05) in 10 ng/mL HSP60 compared to other experimental and control groups. Conclusions. The present study demonstrated that HSP60 in low dose had a positive effect on two-cell embryo development, however it did not have any significant effect on the fertilization rate. Conversely, HSP60 had adverse effects on the fertilization and cleavage rates at higher doses.

Objective. Thyroid dysfunction represents common disorder occurring very frequently among women of reproductive age, including pregnancy. The aim of this literature review was to determine in which way thyroid function during pregnancy is associated with GDM. Design. We conducted review of the literature following the basic principles of literature search. Methods. Two researcher independently searched PubMed in the period of last five years (2018-2023) to identify eligible studies regarding thyroid function and GDM. Results. From 51 papers initially found after the inserting key words in PubMed search field 30 were excluded after the title and abstract review. After reading full text of 21 articles, 15 were included in the review. Conclusions. Our review of literature showed not only that two most common disorders during pregnancy were GDM and thyroid dysfunction, but also indicated that they were in positive correlation.

Introduction. The expression of menin in the thyroid gland has long been debated. Animal models with targeted inactivation of menin in the thyroid gland have shown that its inactivation might play a role in the progression to a more aggressive type of cancer. Human studies are conflicting, some have identified mutations in the MEN1 gene in a subtype of oncocytic thyroid carcinomas, while others have not identified a higher prevalence of thyroid cancer in MEN1 patients. Objective. To analyze the immunohistochemical expression of menin in different types of thyroid carcinomas. Materials and methods. 48 thyroid tumours (12 papillary thyroid carcinomas (PTC), 6 anaplastic thyroid carcinomas (ATC), 12 poorly differentiated thyroid carcinomas (PDTC), 5 medullary thyroid carcinomas (MTC), 5 oncocytic follicular carcinomas (OC), 3 oncocytic adenomas (OA) and 5 goiters (G)) were tested for nuclear expression of menin using an anti-menin antibody. The expression was considered positive, negative or decreased. Results. The expression of menin was positive, identical to normal tissue, in 39 cases (81.25%). The expression was decreased (n=8) or absent (n=1) in 9 tumours (18.75% - 2 PTC, 5 PDTC, 2 OC) accounting for 42% (5/12) of the PDTC and 40% (2/5) of the OC. Conclusions. Our results show that the expression of menin is generally preserved in human thyroid carcinomas, but it can be decreased or absent in certain types of thyroid cancer. Further molecular studies are needed to evaluate to potential of menin protein in tumorigenesis.

Thyroid hormones play a crucial role in the regulation of the mitochondrial oxidative\r\nmetabolism. Hyperthyroidism caused by the acceleration of the energy metabolism leads to\r\nthe occurrence of cellular oxidative stress.\r\nThe aim is to evaluate the pro-oxidant / antioxidant balance and the effect of vitamin\r\nE supplementation in damage caused by the excessive administration of thyroid hormones.\r\nMaterials and Methods. White, male Wistar rats were used in the study. Thirty male\r\nWistar rats were divided into three groups (1:control group, 2:animals treated with LThyroxine\r\n10 &#956;g/animal/day for 30 days, 3:L-Thyroxin treated rats protected with vitamin\r\nE 10 mg/animal/day). Malondialdehyde (MDA), the marker of lipid peroxidation, carbonyl\r\nproteins, SH groups, glutathione (GSH) and superoxide dismutase (SOD) were determined\r\nfrom the serum, while MDA, carbonyl proteins, SH groups and GSH were determined from\r\nthe thyroid tissue homogenates.\r\nThe results showed increased levels of carbonyl proteins (1.31?0.33 nmol/mg protein,\r\np=0.0001) in serum in thyrotoxic group versus control, while MDA levels did not differ\r\nsignificantly from the control. Significantly low values of the SH groups, GSH and SOD were\r\nfound (p<0.001) in the plasma of Thyroxin treated rats. Vitamin E supplementation\r\nsignificantly increased plasma MDA levels in the Thyroxin treated group as compared with\r\nthe control group (p=0.01) and with the animals treated only with Thyroxin (p=0.04).\r\nCarbonyl protein levels in plasma of the hyperthyroid supplemented rats were also increased\r\nas compared to controls (p=0.0002). Antioxidant capacity markers in plasma of group 3 were\r\ndecreased compared with group 1. The marker of lipid peroxidation (MDA) significantly\r\ndecreased in thyroid homogenates of the group 2 as compared with group 1 (p=0.004).\r\nSignificantly high levels of the SH groups (p=0.0006) and low levels of GSH (p=0.0001) were\r\nfound in thyroid homogenates of the L-Thyroxin treated group as compared with controls.\r\nThese results suggest that experimental hyperthyroidism is accompanied with\r\nincreased oxidative stress and with the consumption of antioxidant enzymes in induced\r\noxidative aggressions. No protective effects of vitamin E on oxidative stress induced by\r\nexcessive administration of thyroid hormones were detected.

Gastrointestinal complaints are common among diabetic patients. The gastrointestinal tract contains melatonin. The binding sites of melatonin have been identified in all GIT tissues. Melatonin can modify activities of the gut and liver. The aim of this study was to evaluate the possible protective effects of melatonin against gastric motility and secretary responses in Streptozotocin-induced diabetes in rats. Methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. One week after inducing diabetes, Melatonin (5, 10, 20 mg/ kg/day, IP.) was injected for 14 days. Gastric acid and mucus were measured in all animals by chemical methods. Gastric motility was investigated by powerlab system. Results. Streptozotocin induced a significant increase in blood glucose levels (p<0.001) and significant decrease in gastric acid, mucus, motility and body weight in diabetic groups. Treatment of diabetic rats with melatonin significantly reduced blood glucose (p<0.001) and increased gastric mucus (p<0.001) and motility (p<0.01 and p<0.05 in groups 4 and 5 respectively) with no effect on body weight and gastric acid concentration. Conclusion. These data suggested that melatonin treatment has a therapeutic effect on diabetic gastrointestinal disturbances by reduction of serum glucose and increasing gastric motility and gastric mucus levels, but no effect on gastric acid and body weight.

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Background. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD). Aim. We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats. Study Design. We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7). Methods. We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100. Results. Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg vs. 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg versus 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002). Conclusions. Allopurinol has a therapeutic role against the progression of NAFLD of the rats.

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Introduction. KCNJ11 gene activating mutations play a major role in the development of neonatal diabetes mellitus (NDM). KCNJ 11 gene encodes the Kir 6.2 subunit of ATP- sensitive potassium channel which is a critical regulator of pancreatic beta-cell insulin secretion. Aim. To study KCNJ11 gene mutations in infants with NDM and the effect of sulfonylurea treatment on the glycemic control in patients with KCNJ11 gene mutation. Subjects and methods. Thirty infants with NDM were screened for KCNJ11 gene mutations by DNA sequencing, insulin therapy was replaced by sulfonylurea treatment in patients with mutations. Results. R201C heterozygous mutation was found in one patient who was successfully shifted from insulin therapy to sulfonylurea treatment, while E23k, I337V, and S385C polymorphisms were detected in 14 patients. Conclusion. Screening for KCNJ 11 gene mutations could lead to identification of patients with mutations who can be successfully shifted from insulin therapy to sulfonylurea treatment improving their quality of life.