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Amifostine use in radiation-induced kidney damage
(Springer Heidelberg, 2008) Kaldir, Mine; Cosar-Alas, Rusen; Cermik, Tevfik Fikret; Yurut-Caloglu, Vuslat; Saynak, Mert; Altaner, Semsi; Caloglu, Murat
Purpose: To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis. Material and Methods: 30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a Co-60 unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated. Results: After irradiation, the median value of right kidney function was 48% (44-49%) and 50.5% (49%-52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%). Conclusion: Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.
Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats
(W J G Press, 2006) Soylu, Ali Riza; Aydogdu, Nurettin; Basaran, Umit Nusret; Altaner, Semsi; Tarcin, Orhan; Gedik, Nursal; Umit, Hasan
AIM: To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats. METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mu g collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05). CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis. (C) 2006 The WJG Press. All rights reserved.
Blind-ending duplicate ureter with giant cystic dilatation
(Aves, 2009) Kaplan, Mustafa; Alicioglu, Banu; Aktoz, Tevfik; Altaner, Semsi; Inci, Osman
Blind-ending ureter is a rare ureteric duplication anomaly. Most cases are asymptomatic and are detected incidentally. Blind-ending ureter with a huge cystic dilatation is extremely unusual. A 46-year-old man with a complaint of low back pain was referred from the neurosurgery department upon demonstration of a large cystic mass in the retroperitoneum by lumbar magnetic resonance imaging. Ultrasonography showed a large cystic mass filling the right side of the abdomen and the entire pelvis. Intravenous urography showed malrotation and lateral deviation of the right kidney with grade 1 hydronephrosis, severe dilatation of the ureter with proximal kinking, and medial deviation of the ureter. Computed tomography revealed a huge cystic mass beginning at the medial aspect of the upper pole of the right kidney, filling the right half of the abdomen and all the pelvis. The cyst had septations in the pelvis. Cyst aspiration yielded no atypical cells. During surgical exploration, it was noted that the cyst extended to the level of the upper pole of the right kidney and opened into the bladder with an ectopic orifice superior to the right ureter, suggesting the presence of a blind-ending ureter. The normal ureter was dilated and compressed. During resection of the cystic mass, the right ureter was injured and ureteroneocystostomy was performed. Histopathologic identification of the cystic lesion was made as uroepithelial cells. No complication was seen in postoperative period.
Breast cancer, ovarian gonadoblastoma and cervical cancer in a patient with Peutz-Jeghers Syndrome
(Springer Heidelberg, 2008) Kilic-Okman, Tulay; Yardim, Turgut; Gucer, Fatih; Altaner, Semsi; Yuce, M. Ali
Background Peutz-Jeghers Syndrome (PJS) is a rare autosomal dominant disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. Patients with PJS have increased risk for gastrointestinal, breast, and female genital tract cancers. Case Multiple genital tract cancers in a 34-year-old woman with PJS are described. The patient, who was admitted to our department with severe vaginal bleeding, was performed right salpingo-oophorectomy because of pure gonadoblastoma in 1996. In 2003, concomitant to cervical carcinoma, breast cancer was diagnosed. Patient underwent left modified radical mastectomy due to the invasive papillary carcinoma. The patient received six cycles combination chemotherapy and radiation therapy because of stage IIIB cervical cancer. Conclusion(s) This is the first case report presenting PJS associated with multiple genital tract tumors including ovarian gonadoblastoma in literature. The clinical significance of these tumors in PJS patients has been reviewed.
BURNED-OUT TUMOR OF THE TESTIS: CASE REPORT
(Aves, 2008) Kaplan, Mustafa; Karagol, Hakan; Altaner, Semsi; Aktoz, Tevfik; Caloglu, Murat; Inci, Osman
Introduction: Burned-out testicular tumor is a rare entity. The term burned-out tumor of the testis describes a spontaneously and completely regressed testicular tumor which presents by its metastases to retroperitoneum, mediastinum, lymph nodes such as supraclavicular, cervical and axillary. This condition is different and less common from the primary extragonadal germ cell tumors. Many pathologists are not familiar with the findings that support a diagnosis of burned-out primary in a patient with metastatic germ cell tumor. We report 2 cases of burned-out testicular tumors to illustrate the clinical, radiological and histopathological features. Burned-out testicular tumor must be considered in a patient with retroperitoneal lymph node involvement and histology of germ-cell tumor in the absence of palpable testicular tumor. Metastases should be treated according to the histology and clinical stage of the tumor. Radical orchiectomy must be performed because of the high rate of persistent testicular tumor.
Colonic metastasis from carcinoma of the breast that mimicks a primary intestinal cancer
(Yonsei Univ Coll Medicine, 2006) Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem
Although the lung, liver, or bones are the most common location for distant metastases; in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.
The correlation between TTF-1 immunoreactivity and the occurrence of lymph node metastases in patients with lung cancer
(Sage Publications Ltd, 2006) Altaner, Semsi; Yoruk, Yener; Tokatli, Fusun; Kocak, Zafer; Tosun, Birsen; Guresci, Servet; Kutlu, Kemal
Aims and background: Thyroid transcription factor (TTF-1) is a tissue-specific transcription factor expressed in the epithelial cells of thyroid and lung. The aim of this study was to evaluate the relationship between the expression of TTF-1 and clinicopathological parameters in pulmonary adenocarcinoma and adenosquamous carcinoma. Methods: Resection material of pneumonectomies and lobectomles of 39 patients was retrospectively examined. Twenty-eight patients were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors were classified into 3 groups: a strongly positive group (++) with double dagger 50% tumor cells positive for TTF-1; a weakly positive group (+) with 1-49% positive tumor cells; and a negative group (-) with less than 1% or no positive tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank tests. Results: Staining for TTF-1 was negative in 10 cases. There was focal staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of 39, and 15 (75%) of these were adenocarcinomas. There was a statistically significant association between TTF-1 and lymph node metastases (P = 0.029). No relationship was found between TTF-1 positivity and disease-free and overall survival. Conclusions: TTF-1 expression may be a predictor of lymph node metastases. Additional work in a larger group of patients is needed to better assess the utility of this marker.
Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat
(Elsevier Science Inc, 2008) Memis, Dilek; Hekimoglu, Sevtap; Sezer, Atakan; Altaner, Semsi; Sut, Necdet; Usta, Ufuk
Objective: Curcumin has antioxidant, antitumor, and anti-inflammatory properties. However, it remains unknown whether curcumin has any protective effects on sepsis. The purpose of this study was to demonstrate whether curcumin prevents organ dysfunction in animals with sepsis. Methods: Rats were randomized into four groups. The control group (group I, n = 7) did not receive any treatment. The curcumin group (group II. n = 10) only received 1.2 g/kg of curcumin. Escherichia coli were injected into the remaining groups intraperitoneally after general anesthesia. Five hours after injection, 12 rats received placebo (group III), and 10 rats received 1.2 g/kg of curcumin (group IV) for 7 d. All rats were sacrificed on postsepsis day 8 and it midline laparotomy was performed. Livers, kidneys, and small bowels were excised for evaluation of the degree of inflammation and tissue alterations histopathologically. Results: In the liver, widespread hydropic degeneration of hepatocytes were seen in the sepsis group. There was no hydropic degeneration of hepatocytes and no portal inflammation ill the sepsis/curcumin group. With respect to the small bowel, the sepsis group showed edema and prominent intraepithelial infiltration of neutrophil leucocytes and plasma cells. Inflammation and hyperemia in the lamina propria in the sepsis/curcumin group were less than those in the sepsis group, With respect to the kidneys, the sepsis group showed severe acute tubular necrosis that was more restricted in the sepsis/curcumin group than in the sepsis group. Conclusion: curcumin reduced organ dysfunction in rats with experimentally formed sepsis. We propose that curcumin may he useful in the therapy of organ dysfunction due to sepsis, shock, and other diseases associated with local or systemic inflammation. (C) 2008 Elsevier Inc. All rights reserved.
Cutaneous metastasis of epidermoid carcinoma of the larynx: a case report
(Kare Publ, 2006) Ibis, Kamuran; Ibis, Cem; Yurut-Caloglu, Vuslat; Altaner, Semsi; Caloglu, Murat; Karagol, Hakan; Cosar-Alas, Rusen
The frequency of distant metastasis of epidermoid carcinoma of the larynx is between 6.5-7.2%. The common sites of metastasis are lung, liver and bone. Cutaneous metastasis is very rare. A 56-year-old male with locally advanced larynx carcinoma who received curative radiochemotheraphy a year ago was presented to our department with subcutaneous nodular lesions, and fatigue. Physical examination revealed 0.5 cm sized, and 1x1cm sized subcutaneous nodular lesions in the right arm, and in the parasternal area, respectively. Histopathologic examination confirmed the skin metastasis of epidermoid carcinoma of the larynx. The patient has profound anemia, hypercalcemia, hypernatremia, and hyperglicemia with complicated diabetic foot. Although the symptomatic treatment began immediately, the patient died on the third day of hospitalisation. Cutaneous metastasis may be the first sign of local failure, of distant metastasis, or even of the undetected laryngeal carcinoma with poor prognosis.
Dermatofibroma mimicking malignancy on integrated F-18 fluorodeoxyglucose PET-CT
(Turkish Soc Radiology, 2009) Demir, Mustafa Kemal; Ozdemir, Huseyin; Genchallac, Hakan; Altaner, Semsi; Kartal, Oezcan
A 31-year-old female with a history of ovarian cancer underwent an F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) scan. The PET-CT demonstrated focal nodular uptake in the subcutaneous tissue of the back adjacent to the paraspinal muscles. Color Doppler ultrasonography examination demonstrated a vascular solid mass. The patient underwent biopsy followed by excision. The pathologic diagnosis was dermatofibroma. Although benign, dermatofibromas can have intense FDG uptake.
Dermoid cyst of the parotid gland: First pediatric case
(Elsevier Ireland Ltd, 2010) Tas, Abdullah; Yagiz, Recep; Altaner, Semsi; Karasalihoglu, Ahmet R.
A dermoid cyst is the result of inclusion of epithelial cells along the lines of embryonic closure. Dermoid cysts of the head neck are uncommon and account for only 7% of all such cysts. They are most often reported as arising in the floor of the mouth. Dermoid cyst is rarely seen in the parotid gland. To our knowledge, there have been only six previous case reports in the English literature. Dermoid cyst of the parotid gland in pediatric patient has not been previously reported in the literature. This is the first case report concerning a dermoid cyst in a pediatric patient. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Eccrine porocarcinoma: a case report and literature review
(Kare Publ, 2007) Saynak, Mert; Kocak, Zafer; Altaner, Semsi; Ozen, Alaattin; Cosar Alas, Rusen; Yurut Caloglu, Vuslat; Uregen, Burcu
Eccrine porocarcinoma is a rare malignant sweat gland tumor. The lower extremity represents the most common tumor site for this entity. Surgical excision seems to be the best treatment choice. The surgical margins should be free of tumor, otherwise a local recurrence is most likely. Regional lymph node dissection should be performed if there is evidence of lymphadenopathy. Here, we present clinical and pathological findings of a 69 years old woman diagnosed with eccrine porocarcinoma arising from the skin of the trunk.
THE EFFECT OF GENDER ON RADIATION-INDUCED ACUTE LUNG INJURY IN A RAT MODEL
(Lippincott Williams & Wilkins, 2012) Kocak, Zafer; Bilal, Burcu U.; Cosar, Rusen; Altaner, Semsi; Ozen, Alaattin; Cukurcayir, Funda
[Abstract Not Available]
The Effect of N-acetylcysteine on Brain Tissue of Rats Fed with High-Cholesterol Diet
(Walter De Gruyter Gmbh, 2008) Eskiocak, Sevgi; Altaner, Semsi; Bayir, Serpil; Cakir, Erol
Objectives: The effect of N-acetylcysteine in rats fed a high-cholesterol diet on oxidative stress in the plasma and brain tissue of rats was investigated. Methods: The animals were maintained on a basal diet (control, n=10) or a high-cholesterol diet (1 % w/w) for eight weeks. The rats fed high-cholesterol diet were separated to three group; high-cholesterol diet (n=10), low N-acetylcysteine (n=10) and high N-acetylcysteine groups (n=9). Low and high N-acetylcysteine groups received N-acetylcysteine at a dose of 50 and 100 mg/kg/day respectively via intraperitoneally for eight weeks. Malondialdehyde, glutathione, nitric oxide, cholesterol and triglyceride levels were analyzed in the samples. The results were analyzed by Kruskal-Wallis variance analysis and then a Mann-Whitney U test. Results: When N-acetylcysteine was administered at a low dose, lipid peroxidation products in the brain significantly decreased compared with the high-cholesterol group, while glutathione content enhanced. On the other hand, when N-acetylcysteine was administered at a high dose, lipid peroxidation products in the brain and plasma significantly increased compared with the control group. Conclusions: These results suggest that N-acetylcysteine has a dual effect. If the N-acetylcysteine dose was carefully selected, N-acetylcysteine may have a neuroprotective effect against oxidative stress and hypercholesterolemia.
Effect of Topical Dexamethasone for Preventing Experimentally Induced Myringosclerosis
(Galenos Yayincilik, 2017) Uestuendag, Murat; Kocyigit, Murat; Bulut, Erdogan; Altaner, Semsi; Tas, Abdullah; Yagiz, Recep
Objective: We aimed to examine the effect of topical dexamethasone by otomicroscopic and histologic examinations for preventing myringosclerosis induced by myringotomy in rat tympanic membranes. Methods: Twenty-one Sprague Dawley rats (42 ears) were randomly divided into the following three groups after otomicroscopic examinations: experimental surgical group (5 rats), control group (8 rats), and study group (8 rats). The rats of all the groups underwent myringotomy in both tympanic membranes. Other than myringotomy, no additional procedure was performed for the rats in the experimental surgical group. In the control group, 0.9% NaCl was applied to the ears, whereas in the study groups, topical dexamethasone was applied to the ears. These applications in the control and study groups were repeated for nine days. On the 10th day of the study, the rat ears of all groups underwent otomicroscopic and histologic examinations. The prevalence and process of myringosclerosis were evaluated by otomicroscopic examination, whereas inflammation, membrane thickness, and myringosclerosis intensity were evaluated by histologic examination. Results: The growth of myringosclerosis with otomicroscopic examination was lesser in the study group in which topical dexamethasone was applied than the control and experimental surgical groups. Moreover, it was observed that myringosclerosis effected less quadrants in the study group. Histologic examinations revealed that inflammation was significantly lesser in the study group than in the experimental surgical and control groups. The average membrane thickness values were significantly lesser in the study group than in the experimental surgical group. With respect to myringosclerosis growth, no statistically significant difference was observed among all groups, whereas with respect to myringosclerosis intensity, the rat ears in the study group were less severely affected. Conclusion: Thus, our study results suggest that applying topical dexamethasone after myringotomy has positive effects on limiting the intensity and prevalence of myringosclerosis.
The effects of long-term low-dose cyclosporin A treatment on muscles and tendons: an experimental study
(Turkish Assoc Trauma Emergency Surgery, 2009) Aktas, Ranan Guelhan; Aktas, Seref; Yazgan, Oemer; Altaner, Semsi
BACKGROUND Limited studies report that patients receiving immunosuppressive therapy, including cyclosporin A (CsA), face muscle and/or tendon pathologies. The current study aimed (i) to investigate if CsA cause changes in the microscopic structure of striated muscle tissues and tendons after long-term low-dose therapy and (ii) to examine if the vehicle of CsA, Cremophor EL, or steroid administration might cause additional effects. METHODS Twenty-four adult female Sprague-Dawley rats weighing 230300 g were divided at random into four groups. Group 1 served as the control. Groups 2-4 received CsA intraperitoneally for 2.5 months: Group 2 received the oral form of CsA, Group 3 received the intravenous form of CsA, which contains Cremophor EL, and Group 4 received the intravenous form of CsA and prednisolone. Samples from the Achilles tendons and triceps surae muscles were examined at light microscope level. RESULTS Focal necrotic areas, enlargement of connective tissue and increase in mononuclear cells were clear on muscles in the experimental groups. No morphologic effects were observed on tendons. CONCLUSION Long-term low-dose CsA therapy causes focal microscopic changes in muscles but not in tendons. No additional effects were demonstrated with Cremophor EL or steroids. It should be noted that muscle tissue damage after trauma or surgeries in patients receiving CsA might be more dramatic due to the pathologic changes already caused by CsA, as supported by several case reports.
The Effects of Sirolimus on Target Organs During Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model
(Elsevier Science Inc, 2011) Sagiroglu, Tamer; Sezer, Atakan; Altaner, Semsi; Umit, Hasan; Yalta, Tulin; Yagci, Mehmet Ali
BACKGROUND: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant. OBJECTIVE: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model. METHODS: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (+/- 20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis. RESULTS: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 and 2 with regard to degrees of intestinal, hepatic, and renal I/R damage (P = 0.001 for all). CONCLUSION: The findings of the present study demonstrate the attenuating effects of sirolimus on I/R damage in the intestine and remote organs, including the liver and kidney in the setting of MIRS in an experimental rat model. As a therapeutic implication, the utility of sirolimus may be of clinical value in procedures associated with a high likelihood of I/R damage, including major abdominal operations and renal transplantation. However, whether these results apply to humans is unclear. Additional experimental and clinical studies are warranted to confirm the clinical utility of sirolimus in conditions potentially associated with I/R damage. (Curr T her Res Clin Exp. 2011;72:79-93) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.
Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats
(Elsevier Science Inc, 2006) Soylu, Ali Riza; Altaner, Semsi; Aydogdu, Nurettin; Basaran, Umit Nusret; Tarcin, Orhan; Gedik, Nursal; Umit, Hasan
Background: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated. Objective: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease. Methods: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing similar to 200 g were randomly assigned to I of 6 groups: (1) liquid diet + ethanol + vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet + ethanol + vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet + ethanol + vitamin E 15 mg/kg + vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet + ethanol (LDet); (5) liquid diet + isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis. Results: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P < 0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P < 0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P < 0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] mu g collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] mu g collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P < 0.01, P < 0.01, P < 0.05, P < 0.001, and P < 0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P < 0.01, P < 0.05, and P < 0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P < 0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P < 0.05). Conclusions: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study.
Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC
(Humana Press Inc, 2011) Ustun, Funda; Durmus-Altun, Gulay; Altaner, Semsi; Tuncbilek, Nermin; Uzal, Cem; Berkarda, Sakir
Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and Tc-99m-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4 +/- 1.8 vs. 41.8 +/- 1.9, morphine and no-morphine groups, respectively, P < 0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r = 0.52, P < 0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r = 0.40, P < 0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r = 0.51, P < 0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.
Expression of Bcl-2 and Ki-67 in tamoxifen-associated endometrial polyps: Comparison with postmenopausal polyps
(Karger, 2006) Altaner, Semsi; Gucer, Fatih; Tokatli, Fusun; Guresci, Servet; Ozdemir, Cigdem; Puyan, Fulya Oz; Kutlu, Kemal
Background: The aim of this study was to evaluate the expression of Bcl-2 and Ki-67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps. Material and Methods: For this purpose, a retrospective analysis of paraffin-embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM-treated patients, 11 simple endometrial hyperplasia, 10 atypical complex endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included in the study. Hematoxylin/eosin-stained sections were evaluated. Immunohistochemical staining was performed to investigate the expression of Bcl-2 protein and the Ki-67 proliferation index. Results: There was no statistically significant difference between the 5 groups with regard to Bcl-2 staining (p > 0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than in the postmenopausal control group (80%). Positive Ki-67 was highest in the endometrial adenocarcinoma specimens, followed by the atypical complex endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki-67 expression was lower in TAM-associated polyps, but Ki-67 indexes were significantly higher in the TAM-associated group than in the control group (p < 0.0001). Conclusion: Since TAM-associated polyps tend to have higher proliferation indexes and Ki-67 ratios than control groups, we suggest that they are likely to have a higher malignant potential.

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