Effect of hypothyroidism in the thyroidectomized rats on immunophenotypic characteristics and differentiation capacity of adipose tissue derived stem cells.

INTRODUCTION: Thyroid hormones influence multiple physiological functions, like growth, differentiation, protein synthesis and metabolic rate. The hypothyroid state is a complex hormonal dysfunction rather than a single hormonal defect. The relation between hypothyroidism after thyroidectomy and stem cells is not clear. AIM: This study was designed to investigate the effect of thyroidectomy on the proliferation, telomerase enzyme activities, immunophenotypic properties and differentiation potentials of adipose tissue-derived (AT-) stem cells (SCs). MATERIALS AND METHODS: AT-SCs after 60 and 120 days of thyroidectomized (Tx) rats were compared to normal rats by flow cytometry and immunocytochemistry analyses, and their telomerase activities were estimated. RESULTS: The telomerase activity was found to be positive for AT-SCs of Tx rats of both 60 and 120 days used in this study, but a decrease was noticed in the cells with the long-term exposure to hypothyroidism. This might indicate the decrease in the regenerative ability of the AT-SCs after 120 days of Tx compared to cells after 60 days of Tx. Both cell lines were induced to differentiate into adipogenic, osteogenic and neurogenic cell lineages, but osteogenic marker expression was not detected in the undifferentiated AT-SCs of the Tx rats. Osteogenic differentiation was also failed in stem cells derived from Tx rats, shown by Alizarin red S staining and alkaline phosphates enzyme assays. DISCUSSION: These results suggest that hypothyroidism affected SCs, altered stem cell characteristics, like telomerase activity and loss of in vitro bone formation, but not adipogenic or neurogenic differentiation ability. CONCLUSIONS: Hypothyroidism after Tx affects the osteogenic differentiation capacity of stem cells, which might be one of the factors of bone loss due to postnatal hypothyroidism.

Correlation between c-erbB2 expression, lymphovascular invasion and other biological and clinical prognostic factors and preoperative tumor markers in patients with early-stage and locally advanced breast cancer.

PURPOSE: To evaluate the correlation between c-erbB2 expression, lymphovascular invasion and other biological and clinical prognostic variables and preoperative CA 15-3 and CEA levels in patients with early-stage and locally advanced breast cancer. METHODS: Preoperative serum concentrations of CA 15- 3 and CEA were measured in 123 patients undergoing surgical treatment for stage I-III breast cancer and the association between these markers and clinical and biological variables were evaluated. RESULTS: With cut-off values of 45 U/ml (CA 15-3) and 2.5 ng/ml (CEA), the sensitivity for CA 15-3 and CEA was 10% and 24% and their mean values were 23 U/ml and 2.32 ng/ml, respectively. A significant correlation between preoperative levels of CA 15-3 and CEA was noticed (p=0.023). Preoperative CA 15-3 levels were significantly higher in patients with tumors > 5 cm (p<0.0001), with positive axillary lymph nodes (p=0.04), with increasing nodal burden (p= 0.025) and in patients with stage III disease (p=0.003). Tumor size >5 cm (p=0.002), increasing axillary nodal burden (p=0.02) and stage III disease (p<0.0001) were also significantly correlated with CEA values above the cut-off level. There were no correlations between CA 15-3 and CEA levels and other variables including c-erbB2 expression, age, grade, hormone receptor status, and lymphovascular invasion. CONCLUSION: Preoperative CA 15-3 and CEA levels are significantly correlated with tumor size, axillary nodal status and stage in patients with non-metastatic breast carcinoma. No correlation between preoperative values of CA15-3/CEA and c-erbB2 status, lymphovascular invasion and other prognostic factors was detected.

Effects of experimental obstructive jaundice on contractile responses of dog isolated blood vessels: role of endothelium and duration of bile duct ligation.

1. We examined the effects of experimental obstructive jaundice caused by bile duct ligation (BDL) on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording responses to noradrenaline (NA), 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) in canine isolated renal arteries and to NA in isolated mesenteric arteries in vitro. All studies were performed 7 days after the onset of BDL in renal arteries and 3, 7 and 15 days after the onset of BDL in mesenteric arteries. 2. The maximum contraction evoked by both NA and 5-HT was significantly attenuated with no change in agonist potency (pD2 value) in renal arteries with endothelium obtained from 7 day BDL dogs when compared with those from sham-operated controls (SO). However, the reduction almost disappeared when the endothelium was removed. In contrast, no change in the responsiveness of renal arteries to KCl could be detected at 7 day BDL. Endothelium-dependent relaxations produced by ACh were significantly increased in renal artery rings from 7 day BDL dogs, but the endothelium-independent relaxations produced by papaverine in BDL preparations were not changed when compared with SO controls. 3. At 7 and 15 days after BDL, the Emax values of the mesenteric ring of BDL dogs to NA were significantly lower than that of SO controls, whereas 3 days after surgery there was no significant difference. The pD2 values in arteries obtained from 15 day BDL animals were significantly lower than those obtained from SO control animals. However, no significant changes in pD2 values were seen 3 and 7 days after the onset of BDL. 4. In conclusion, it is suggested that enhanced production and/or release of nitric oxide, mainly of endothelial origin, is associated with reduced vascular responses to contractile agents in experimental obstructive jaundice and that this effect is related to the duration of obstructive jaundice. These results may explain, at least in part, a cause of hypotension that leads to renal failure in patients with obstructive jaundice.

Experimental study on the role of mast cells in peritoneal adhesion formation.

OBJECTIVE: To investigate the potential role of mast cell stabilisation in the prevention of post-operative adhesions. DESIGN: Laboratory animal experiment. SETTING: University hospital, Turkey. SUBJECTS: Ninety Wistar albino rats. INTERVENTION: Under anaesthesia, a lower midline laparotomy was performed, the caecum exposed and grasped until haemorrhage occurred. The rats were divided into three groups. Group 1, 2 and 3 were intra-peritoneally administered 1 ml of saline, disodium cromoglycate 5 mg/kg in 1 ml of saline and 10 mg/kg in 1 ml of saline, respectively thirty minutes prior to laparotomy and immediately subsequent to abdominal closure. They were later sacrificed, laparotomy repeated and the presence and extent of intraabdominal adhesions evaluated. RESULTS: Adhesion scores were best in the high disodium cromoglycate dose group of rats (p < 0.05) and the number of degranulated mast cells was significantly low in this group (p < 0.05). CONCLUSION: Disodium cromoglycate may be an effective agent for attenuating adhesion formation when administered in suitable doses.