Dynamics of breast tumor incidence, tumor volume and serum metabolic hormones in calorie restricted rats.

Reports of the effects of calorie restriction on tumors after the tumor has developed are uncommon and limited to a few tumor types. We investigated the effects of calorie restriction on tumor growth in breast cancer after tumor growth had progressed. We used the N-nitroso-N-methylurea (NMU) induced breast cancer model in rats. In addition to a healthy control group (C), rats with 10 - 12 mm tumors were divided into three groups: cancer control group (CC), alternate day feeding group (ADF) and calorie restriction group (CR-50%). At the end of the experimental period the volume of tumors was decreased in the CR-50% group compared to the CC group. Serum adiponectin concentrations for the C and ADF groups were higher than for the CC group. All tumors of the CR-50% group were benign. The highest incidence of malignant and invasive tumors occurred in the CC group. A 50% calorie restriction appears to be an effective dietary intervention for advanced tumors.

The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats.

OBJECTIVE: Amifostine (AMI) has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO)-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations. METHODS: Thirty-six rats were divided into six groups (n=6 in each). Control rats were given intraperitoneal (i.p.) serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups. RESULTS: The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA) levels increased in MITO groups compared to controls. Catalase and glutathione (GSH) levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower. CONCLUSION: MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO-induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation.

Effects of Topical Thymoquinone in an Experimental Dry Eye Model

Objectives: To comparatively evaluate the effects of thymoquinone (TQ), the biologically active main component of volatile oil derived from Nigella sativa seeds, in an experimental dry eye model. Materials and Methods: A total of 36 BALB/c mice 10 weeks of age were used in the study. The mice were divided into 6 groups of 6 mice. Two groups were negative and positive controls, and the other 4 groups were treated with balanced salt solution, fluorometholone (FML), TQ, or vehicle (Tween80). After 1 week of treatment, the mice were killed and the eyes removed for histopathologic examination and cytokine analysis. Interleukin (IL)-1α tumor necrosis factor-α, interferon-γ, IL-2, IL-6, IL-10, and lactoferrin levels in the conjunctival tissue were measured by multiplex immunobead assay. The presence of inflammatory cells in ocular tissue samples were investigated by hematoxylin-eosin and periodic acid-Schiff staining. Inflammatory T cells containing CXT receptor in the conjunctiva were determined by flow cytometry. Results: FLML and TQ groups had less inflammatory cell density and more goblet cells compared to the other groups. High levels of IL-1α and IL-2 were found in the TQ group. Conclusion: TQ treatment was associated with reduced inflammation in pathological examination, but did not significant lower cytokine levels.

Mice with diet-induced obesity demonstrate a relative prothrombotic factor profile and a thicker aorta with reduced ex-vivo function.

: Classical risk factors such as cholesterol and lipoproteins are currently not sufficient to explain all physiopathological processes of obesity-related vascular dysfunction as well as atherosclerosis and arteriosclerosis. Therefore, the discovery of potential markers involved in vascular dysfunction in the obese state is still needed. Disturbances in hemostatic factors may be involved in the developmental processes associated with obesity-related cardiovascular disorders. We hypothesized that alterations of several hemostatic factors in the obese state could correlate with the function and morphology of the aorta and it could play an important role in the development of vascular dysfunction. To test this, we fed mice with a high-fat diet for 18 weeks and investigated the relationships between selected hemostatic factors (in either plasma or in the liver), metabolic hormones and morphology, and ex-vivo function of the aorta. Here, we show that 18-week exposure to a high-fat diet results in a higher plasma fibrinogen and prolonged prothrombin time in diet-induced obese mice compared to the controls. In addition, liver levels or activities of FII, FX, activated protein C, AT-III, and protein S are significantly different in diet-induced obese mice as compared to the controls. Curiously, FII, FVIII, FX, activated protein C, PTT, and protein S are correlated with both the aorta histology (aortic thickness and diameter) and ex-vivo aortic function. Notably, ex-vivo studies revealed that diet-induced obese mice show a marked attenuation in the functions of the aorta. Taken together, aforementioned hemostatic factors may be considered as critical markers for obesity-related vascular dysfunction and they could play important roles in diagnosing of the dysfunction.

The expression of matrix metalloproteinases 8 and 9 by neutrophils of Wistar albino rats with severe qualitative and quantitative protein malnutrition.

Neutrophils are the major cellular immune components in response to bacterial infections. Neutrophil enzymes are important in invasion, inflammation, and infection processes. In order to understand the basic effects of protein malnutrition on neutrophils we studied matrix metalloproteinases 8 and 9 (MMP-8 and MMP-9) production in severe quantitative and qualitative protein malnutrition in rats. Wistar rats (2 months old) were divided into four groups each with three subgroups and fed various protein-containing diets (24% protein, 20% gelatin-containing and N-free) for 7, 14, 21, and/or 28 days. Neutrophil enzyme expression was determined by Western blotting. Leukocytes decreased significantly due to malnutrition (p = 0.001 ) whilst the percentage of neutrophils increased (p = 0.02) in protein-deprived groups. Neutrophils of malnourished rats produced lower levels of MMP-8 at early stages of protein deprivation with an increase in the following weeks. MMP-9 production by neutrophils from N-free diet fed animals was highest after one week. Serum MMP-9 levels decreased in the qualitative but not in the quantitative protein malnutrition groups. Results suggest that neutrophils might be important in reuse of body cell proteins during fasting or malnutrition conditions and dietary manipulation might have profound effects on MMP-8 and -9 production in rats.

Strangulated ventral hernia model in rats.

This study was performed to describe a new model of strangulation obstruction mimicking the situations relevant to abdominal hernias. The strangulation obstruction was induced either by intra-abdominal ligation of an ileal segment 2 cm in length (n = 20) or by a pursestring suture around a fascial defect with a strangulated intestinal loop placed subcutaneously (n = 20). Ten animals served as sham operated controls (n = 10). All animals were euthanized at 12 h postoperatively; strangulated ileum segments were collected for histopathological examination. Microscopic injury scores were similar in both strangulation groups, which were significantly different from the control group (p <.001). The model described here seems to be appropriate for use in further experimental studies concerning strangulation obstruction injury and its consequences, with the added advantage of visualization of the strangulated intestinal loop beneath the skin.

The study of expanded tri-lobed flap in a rabbit model: possible flap model in ear reconstruction?

BACKGROUND: Local flaps are widely used in reconstructive surgery. Tri-lobed skin flap is a relatively new flap and there has been no experimental model of this flap. This flap can be used for repair of full thickness defects in the face, ears and alar region. Based on the size of ears in a rabbit, we designed a model of ear reconstruction using expanded tri-lobed flap. Local flaps are more advantageous in that they provide excellent color and texture matching up with those of the face, adequately restore ear contour, place scars in a favorable location and ideally accomplish these goals in a single stage with minimal donor site morbidity. METHODS: Eight adult New Zealand rabbits were divided into two groups. 50 ml round tissue expander were implanted to four rabbits. After completion of the expansion, a superiorly based tri-lobed flap was elevated and a new ear was created from the superior dorsal skin of each rabbit. Scintigraphy with Technetium-99m pertecnetate was performed to evaluate flap viability. RESULTS: Subtotal flap necrosis was seen in all animals in non-expanded group. New ear in dimensions of the original ear was created in expanded group without complication. Perfusion and viability of the flaps were proved by Technetium-99m pertecnetate scintigraphy. CONCLUSION: According to our knowledge this study is the first to demonstrate animal model in tri-lobed flap. Also, our technique is the first application of the trilobed flap to the possible ear reconstruction. We speculated that this flap may be used mastoid based without hair, in human. Also, tri-lobed flap may be an alternative in reconstruction of cylindrical organs such as penis or finger.

The short-term protective effects of lycopene on renal ischemia-reperfusion injury in rats.

OBJECTIVE: Renal ischemia-reperfusion injury may occur due to nephron-sparing surgery in patients with a solitary kidney or restricted renal parenchymas. Prophylactic agents do not always achieve their intended effects and may exhibit side effects. The present study was designed to investigate the possible protective effects of lycopene against hypoxia-induced renal damage. MATERIAL AND METHODS: Twelve Wistar rats were used in the study. Female Wistar rats were divided into two groups of six rats each; the first group served as the control, and the second group was treated for two days with oral lycopene (4 mg/kg per day) before surgery. All Wistar rats were subjected to right nephrectomy and abdominal aorta clamping for 45 minutes to induce ischemia, followed by 24 hours of reperfusion. Blood samples were collected from all rats twice before surgery and 24-hours after surgery for analyses of serum urea, creatinine, sodium, and potassium levels. Left nephrectomies were performed following reperfusion. Then histopathological scores were estimated, and malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels in renal tissue samples were measured, and compared between groups. RESULTS: There were no significant differences between the control, and the lycopene group with respect to postischemic urea, creatinine, or potassium levels. A significant difference between the groups was observed with respect to postischemic sodium levels (p=0.028). Pathological scores were higher in the control group than in the lycopene group (p<0.05). Mean tissue MDA levels in the control group were higher than in the lycopene group (p=0.055). The mean tissue GSH-Px levels were similar in the control, and lycopene groups. The mean GSH levels in the control group were higher than in the lycopene group (p>0.05). The mean tissue SOD levels were similar in the control, and lycopene groups. The mean CAT levels in the control group were higher than in the lycopene group (p>0.05). CONCLUSION: Lycopene may have a protective effect on the short-term biochemical and histopathological parameters following renal ischemia/perfusion injury.

The short-term effects of different doses of dexamethasone on the numbers of some bacteria in the ileum.

Glucocorticoids are known to affect intestinal biota both directly or indirectly. The aim of the study reported here was to determine the short-term effects of different doses of dexamethasone on the numbers of various ileal bacteria populations. Rats were randomly put into groups, and each group was administered a single-dose injection of dexamethasone at either 0.1, 0.5, 1, 2.5, 5, or 10 mg/kg body weight. At 48-h post-injection, the numbers of total aerobe, anaerobe, lactobacilli and coliform bacteria in the ileum were determined. The numbers of total aerobes and lactobacilli were higher in the groups receiving 5 and 10 mg/kg dexamethasone than in the control and other dose groups (P < 0.01 and P < 0.001, respectively). The number of ileal anaerobic bacteria was higher in group receiving 5 mg/kg than in the other groups (P < 0.01). There were more coliform bacteria in the group receiving 0.1 mg/kg than in the groups receiving 0.5, 1 and 10 mg/kg (P < 0.05). In light of these results, the effects of dose-dependent increases in the number of different bacterial groups affecting gut functions have still to be determined in future studies.

Comparison of double vertical incision with various tubularization techniques and its clinical application.

INTRODUCTION: Tubularization is one of the indispensable practices of reconstructive surgery, especially in the repair of hypospadias. In all procedures of forming a tube, the desired diameter should be reached without any complication. MATERIALS AND METHODS: We used as a new technique, 'double vertical incision', in 8 rabbits and compared it with free skin graft, local flap and single vertical incision. We formed 32 tubes randomly around an 8-french catheter using 7/0 PDS suture. Twenty-one days after the operation, the tubes were taken, randomized to staining with hematoxylin and eosin and with Masson's trichrome and then subjected to histopathological examination. Inflammation, fibrosis and lumen diameter were statistically evaluated. RESULTS: Widest lumen diameters were found in the double incision group and this result was statistically different when compared with the results of the other groups (p < 0.001). CONCLUSIONS: Double vertical incision is promising in that it is easier to perform, provides a desired amount of tissue in cases in which the urethral bed is narrow, and causes no scar. Based on the results we obtained, we applied double vertical incision, a modification of tubularized incised plate urethroplasty popularized by Snodgrass, in 4 patients. The tubes were not distended, their long-term follow-up showed no complication and a urethra of the desired diameter was obtained.