Ultrastructural Damage in Vascular Endothelium in Rats Treated with Paclitaxel and Doxorubicin

Endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in the cancer therapy. Paclitaxel and doxorubicin are frequently used anticancer drugs and their cardiac side effects are well observed in clinical setting. Their side effects on the endothelium are still not clear enough. There are few investigations assessing the damages elicited by the combination use of chemotherapy agents in animal experimental models. The purpose of this study was to examine and compare the side effects of doxorubicin and paclitaxel on endothelium in vivo. The drugs were administered weekly to rats via intraperitoneal injections singly or in combinations. Lastly, aorta endothelium was examined. The most familiar parts of the aorta endothelium are the nucleus, free ribosomes, Weibel-Palada granules, plasmalemmal vesicles, and clear basement membrane. Examination of the endothelium and the related structures revealed some clear degenerative findings. Notably, administration of a paclitaxel and doxorubicin combinations caused the most dramatic change in ultrastructure, which may disrupt many functions of the endothelium.     

Characterization of adrenal lesions on chemical shift MRI: comparison of 1.5 T and 3 T MRI

Purpose

To compare three chemical shift MRI techniques [two-dimensional (2D) dual gradient echo (dGRE), 3D VIBE, and 3D VIBE-Dixon] at 3 T and 2D dGRE technique at 1.5 T to assess their ability of detecting microscopic fat in adrenal adenomas and differentiating between adenomas and non-adenomas.

Methods

Seventy-eight patients with 97 lesions (78 adenomas, 19 non-adenomas) underwent both 1.5 T and 3 T chemical shift MRI. The Wilcoxon signed-ranked test was used to determine if there was significant difference between the signal intensity index (SII) values of each technique to assess their ability to detect microscopic fat in adrenal adenomas. ROC analysis was performed for the SII values of each technique, the adrenal-to-spleen SI ratio of 2D dGRE technique at 3 T, and the fat fraction values of the 3D VIBE-Dixon technique to identify the optimal threshold for differentiation of adrenal adenomas from non-adenomas.

Results

For detection of microscopic fat, the mean SII value of 2D dGRE technique at 1.5 T was significantly higher than that of the chemical shift imaging techniques at 3 T (p = 0.001). For discrimination of adenomas from non-adenomas, the area under the curve (AUC) and 95% confidence interval values of 2D dGRE technique at 1.5 T and 2D dGRE, 3D VIBE, 3D VIBE-Dixon techniques at 3 T were calculated as 1.00 (1.00–1.00), 0.991 (0.978–1.00), 0.999 (0.995–1.00), 0.993 (0.979–1.00), respectively, for the SII.

Conclusion

Chemical shift MRI at 1.5 T using the 2D dGRE technique provided the most accurate differentiation between adenomas and non-adenomas. However, there was no statistically significant difference between chemical shift imaging techniques at 1.5 T and 3 T.

     

Malignant peripheral nerve sheath tumor of the vulva,an unusual differential diagnosis for vulvar mass

INTRODUCTION

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, up to one half of the MPNSTs occur in patients with neurofibromatosis type-1 (NF-1), while the rest are sporadic. Here, we present a 52-year-old woman with MPNST of the vulva without NF-1. We will discuss basics of the disease, treatment options and follow-up strategies.

PRESENTATION OF CASE

52-year-old female admitted to our hospital with complaint of abnormal uterine bleeding and rapidly growing vulvar mass. Excisional biopsy of the mass showed MPNST of the vulva. Afterwards, the patient underwent radical vulvectomy with inguinofemoral lymph node dissection. Short after the surgery, multiple lung metastasis were shown and responded to chemotherapy, but rapid local recurrence occurred short after the completion of the chemotherapy.

DISCUSSION

The primary treatment option in MPNSTs is surgical excision with or without adjuvant therapy. There is not enough data about the role of systemic chemotherapy in the management of MPNSTs and it still remains controversial.

CONCLUSION

In general, radiation therapy has not been demonstrated to improve overall survival. Complete surgical resection of the primary tumor is the mainstay of the treatment.     

Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum

It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.     

Effects of ethanol on the properties of platelets and endothelial cells in model experiments

AIM: To investigate effects of ethanol on activity markers of atherosclerosis in an in vitro endothelial cell model. METHODS: After 24 h incubation with ethanol (0.0095%), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide, and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), urokinase plasminogen activator receptor (uPAR), and membrane-type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. RESULTS: The increased expression of VCAM-1 and uPAR on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through pre-incubation with ethanol (P<0.05). Furthermore, platelets in direct contact with ethanol and with endothelial cells pre-incubated in ethanol showed a significant reduction in their CD40L expression (P<0.05). Ethanol had no significant effect on ICAM-1 and MT1-MMP expression on endothelial cells. CONCLUSION: Ethanol directly attenuates platelet activation and has significant endothelial cell-mediated effects on selected markers of atherosclerosis in vitro . These findings underline possible protective effects of ethanol on atherosclerosis.     

Effect of chronic restraint stress and alpha-lipoic acid on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs.

OBJECTIVES: The aim of this study was to evaluate the effect of chronic restraint stress and alpha-lipoic acid (LA) administration on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs. METHODS: Forty male wistar rats, aged 3 months were randomized to one of the following groups: control, restraint stress, LA treated and restraint stress+LA treated. Chronic restraint stress was applied for 21 days (1h/day) and LA (100 mg/kg/day) was administered intraperitoneally for the same period. RESULTS: Restraint stress had no statistically significant effect on lipid peroxidation, copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in rat liver and heart, when compared to the control group. Lipid peroxidation, determined by measuring malondialdehyde (MDA) levels, was found to be increased in the kidney of restraint stress treated rats, compared to controls. Restraint stress-induced lipid peroxidation in the kidney was significantly decreased via LA treatment. Administration of LA also enhanced GPx and decreased Cu/Zn SOD activity in rat kidney, liver and heart, compared to the control group. CONCLUSIONS: The presented data shows that LA is a protective agent against restraint stress--the inducer of lipid peroxidation in the kidney. These findings also suggest that LA-induced changes in antioxidant enzyme activities in rat peripheral organs may contribute to their versatile effects observed in vivo.