Sarcoid-derived fibroblasts: links between genomic instability, energy metabolism and senescence.

Bovine papillomavirus 1 (BPV-1) is a well recognized etiopathogenetic factor in a cancer-like state in horses, namely equine sarcoid disease. Nevertheless, little is known about BPV-1-mediated cell transforming effects. It was shown that BPV-1 triggers genomic instability through DNA hypomethylation and oxidative stress. In the present study, we further characterized BPV-1-positive fibroblasts derived from sarcoid tumors. The focus was on cancer-like features of sarcoid-derived fibroblasts, including cell cycle perturbation, comprehensive DNA damage analysis, end-replication problem, energy metabolism and oncogene-induced premature senescence. The S phase of the cell cycle, polyploidy events, DNA double strand breaks (DSBs) and DNA single strand breaks (SSBs) were increased in BPV-1-positive cells compared to control fibroblasts. BPV-1-mediated oxidative stress may contribute to telomere dysfunction in sarcoid-derived fibroblasts. Loss of mitochondrial membrane potential and concurrent elevation in intracellular ATP production may be a consequence of changes in energy-supplying pathways in BPV-1-positive cells which is also typical for cancer cells. Shifts in energy metabolism may support rapid proliferation in cells infected by BPV-1. Nevertheless, sarcoid-derived fibroblasts representing a heterogeneous cell fraction vary in some aspects of metabolic phenotype due to a dual role of BPV-1 in cell transformation and oncogene-induced premature senescence. This was shown with increased senescence-associated ß-galactosidase (SA-ß-gal) activity. Taken together, metabolic phenotypes in sarcoid-derived fibroblasts are plastic, which are similar to greater plasticity of cancer tissues than normal tissues.

Diabetes control and pregnancy outcomes in women with type 1 diabetes treated during pregnancy with continuous subcutaneous insulin infusion or multiple daily insulin injections.

OBJECTIVES: The aim of the study was to compare diabetes control and obstetrical outcomes in pregnant women with type 1 diabetes treated during pregnancy with either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDII). PATIENTS AND METHODS: It was a descriptive, retrospective, observational study of 116 Caucasian pregnant women with type 1 diabetes mellitus. Thirty women were treated during pregnancy with continuous subcutaneous insulin infusion (CSII group) and 86 with multiple daily insulin injections (MDII group). RESULTS: Mean age and body mass index did not differ between groups (p >0.05). Duration of diabetes was longer in CSII than in MDII group, 12.7 +/- 7.20 vs. 7.71 +/- 6.13 years, respectively (p = 0.0005). There were no differences between the studied groups in glycated hemoglobin (HbA(1c)) levels in the I, II and III trimesters of pregnancy - in CSII group 7.41 +/- 1.75, 6.57 +/- 1.09 and 6.46 +/- 0.87, respectively, in MDII group - 7.71 +/- 2.37, 6.65 +/- 1.18 and 6.75 +/- 1.21, respectively (p >0.05). There were no severe hypoglycemia and diabetic coma. Mean duration of pregnancy, rate of premature deliveries, newborn birth weight, incidence of SGA and LGA, and the frequency of neonatal hypoglycemia did not differ between groups (p >0.05). The total malformation rate was 5.13%, including 2 terminated pregnancies and the frequency did not differ between groups (p >0.05). The rate of spontaneous abortions was 16.7% in CSII group and 10.3% in MDII (p >0.05). CONCLUSIONS: No apparent relationships between mode of insulin therapy and pregnancy outcome were found in type 1 diabetes patients.

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes.

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.