Second Primary Tumors in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience.

Background and Objectives: In this study, we investigated the frequency and type of second primary malignant tumors (SPMTs) accompanying gastrointestinal stromal tumors (GISTs), patient and tumor characteristics, and follow-up and survival data. Materials and Methods: We included 20 patients with SPMTs from a total of 103 patients with GISTs in a single center in Turkey. At the time of GIST diagnosis, patient age, sex, presentation symptoms, localization, pathological features of the tumor, stage, recurrence risk scoring for localized disease, treatments received, time of SPMT association, follow-up times, and survival analysis were recorded for each patient. Localization, histopathology, and stage of SPMT accompanying GISTs were also recorded accordingly. Results: SPMT was detected in 19.4% of patients with GISTs. Of the patients, 50% were men and 50% were women. The mean age at the time of diagnosis of GIST was 63.8 ± 10.81 years (range: 39-77 years). Of the GISTs, 60% were localized in the stomach, 25% in the small intestine, and 70% were at low risk. Of the SPMTs, 60% were in the gastrointestinal system. SPMTs were diagnosed as synchronous with GISTs in 50% of the patients. The mean follow-up period of the patients from the diagnosis of GIST was 45.6 (0.43-129.6) months. When the data were finalized, 5% died due to GIST, 35% died due to SPMT, and 15% died due to non-disease-related causes. Conclusions: SPMT was detected in 19.4% of patients with GISTs. GISTs were frequently located in the stomach, and most of them were at low risk. The most common SPMTs were gastrointestinal system tumors, and their coexistence was found to be synchronous. Most patients died due to SPMT during follow-up.

Impact of caffeic acid phenethyl ester treatment on vancomycin-induced pancreatic damage in rats.

This study investigates the preventive effect of caffeic acid phenethyl ester (CAPE) on pancreatic damage induced by vancomycin (VCM) in rats. Rats were equally divided into three groups: group I (control), group II (only VCM-treated group) and group III (VCM + CAPE-treated groups). VCM was intraperitoneally administered at a dose of 200 mg kg(-1)twice daily for 7 days. CAPE was administered orally at 10 µM mL(-1) kg(-1) dose once daily for 7 days. The first dose of CAPE administration was performed 24 h prior to VCM injection. Blood and pancreas tissue samples were removed and collected after the study. Serum alkaline phosphatase (ALP), amylase, γ-glutamyl transferase (GGT) and lipase activities were determined. Pancreas tissue samples were evaluated with the light microscope. Group II significantly increased serum ALP, amylase, GGT and lipase activities when compared with the control group. Group III significantly decreased serum ALP, amylase, GGT and lipase activities when compared with group II. In histopathological examination, it has been observed that there was a significant pancreatic damage in group II. CAPE exerted prominent structural protection against VCM-induced pancreatic damage and this effect was statistically significant. CAPE caused a marked reduction in the extent of pancreatic damage. We have concluded that it may play an important role in the VCM-induced pancreatic damage and reduce the pancreatic damage both at the biochemical and histopathological aspects.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma.

BACKGROUND: Claudin 18.2 (CLDN18.2) is a cell surface protein expressed by gastric cancer cells. The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death. A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma. AIM: To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma. METHODS: This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma. We investigated the effect of CLDN18.2 expression on clinicopathological characteristics (age, sex, histological grade, Lauren classification, family history, metastatic site, HER2 expression) and prognosis for patients with metastatic gastric adenocarcinoma. RESULTS: CLDN18.2 expression was positive in 73.8% (48) of the patients. During the median 17.7-mo follow-up period, 89.2% (58) of the patients died. Median progression-free survival and overall survival (OS) were 6 mo (95% confidence interval: 1.6-10.4) and 12 mo (95% confidence interval: 7.5-16.5). There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients. In univariate and multivariate Cox regression analysis, there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS. CONCLUSION: CLDN18.2 expression was quite high in patients with gastric adenocarcinoma, identifying the proportion of the patients in whom zolbetuximab would be efficacious. There is no statistically significant correlation with clinicopathological characteristics and OS. CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma, although it is predictive.

Evaluation of histopathological results of minor salivary gland biopsies in patients with the diagnosis of Sjögren's syndrome.

Objectives: This study aims to evaluate which of the histomorphological criteria defined in labial salivary gland biopsy are more valuable in diagnosing Sjögren's syndrome (SS) and to examine its correlation with clinical and laboratory findings. Patients and methods: Between January 2005 and January 2019, a total of 927 patients (104 males, 823 females; mean age: 51 years; range, 19 to 85 years) who underwent minor salivary gland biopsies with the suspicion of SS were retrospectively analyzed. The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2016 classification criteria were used for the classification of SS. We evaluated salivary gland biopsies histomorphologically for the presence and number of lymphocytic focus, as well as chronicity findings (acinar atrophy, ductal dilatation, fibrosis), the presence of lymphocytic infiltration, distribution, localization, ectopic germinal center, and mast cell count. The presence of accompanying diseases, clinical and laboratory findings including age, sex, the presence of dry eye and mouth, and autoantibodies for discriminating SS were noted. Histomorphologically, salivary gland biopsy which fulfilled the adequacy criteria for glandular tissue were compared with the other criteria used to diagnose SS. Results: Strong chronicity and diffuse lymphocytic infiltration were significantly higher in the SS group compared to the non-SS group (p<0.001). Lymphocytic focus score >1 was significantly higher in the SS group compared to the non-SS group (p<0.001). Strong chronicity, acinar atrophy, andductal dilatation were significantly higher in the SS group compared to the non-SS group (p<0.001). Conclusion: More than one lymphocytic focus is the most valuable finding in diagnosing SS. However, it should be kept in mind that, in cases of SS, ductal dilatation, acinar atrophy, and chronicity may be present without lymphocytic infiltration.

Correlation of 18F-FDG/PET SUVmax, SUVmean, MTV, and TLG with HIF-1α in Patients with Colorectal Cancer

Objectives: Post-hypoxia hypoxia-inducible factor (HIF)-1α activation plays a vital role in colorectal cancer (CRC) angiogenesis. Although glucose metabolism is induced in some cancer types via HIF-1α, the prognostic significance of HIF-1α in CRC and its correlation with 18fluorinefluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET) remain controversial. This study aims to investigate the association between 18F-FDG/PET parameters and HIF-1α expression in CRC. Methods: Thirty-six histopathologically confirmed patients with CRC who had 18F-FDG/PET scans before surgery were enrolled in the study. The correlations between the maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, HIF-1α overexpression, and histopathological features were evaluated. Results: The tumor location, tumor diameter, perineural invasion, lymphovascular invasion, T and N stage were not significantly correlated with HIF-1α overexpression. In contrast, the tumor differentiation was negatively correlated with HIF-1α expression (r=-0.332, p=0.048). None of the 18F-FDG/PET parameters was significantly correlated with HIF-1α overexpression. A significant relationship was found between tumor differentiation, tumor necrosis percentage, and MTV (p=0.030, p=0.020). Conclusion: The expected association between HIF-1α overexpression and 18F-FDG/PET parameters was not found in this study. However, there was a relationship between MTV, tumor differentiation, and tumor necrosis percentage. Hence, further studies are required to predict the pathological and prognostic courses of CRC using a diagnostic 18F-FDG/PET evaluation.

The protective effect of erdosteine on vancomycin-induced pancreatic damage in rats.

OBJECTIVE: The goal of this study was to investigate whether vancomycin (VCM) has a negative effect on pancreatic tissue and to elucidate the role of erdosteine (ERD), an expectorant and an antioxidant agent, on possible VCM-induced pancreas impairment in rats. MATERIALS AND METHODS: A total of 21 male Wistar albino rats were included in this study. All animals were equally divided into three groups as follows: Controls (n = 7), VCM treated group (200 mg/kg twice daily for 7 days intraperitoneally, n = 7) and VCM (200 mg/kg) + ERD treated group (10 mg/kg day orally ERD, n = 7). The first dose of ERD administration was performed 24 h prior to VCM injection and the study was continued for 7 days. At the end of the study, all animals were sacrificed. Blood and pancreas tissue samples were collected. For biochemical analysis, serum amylase, lipase, alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT) activities were measured. For histopathological examination, pancreas tissue samples were investigated under the light microscope. RESULTS: VCM administration has significantly increased the serum amylase, lipase, ALP, and GGT activities, when compared with the controls. VCM + ERD administration significantly decreased the serum lipase, amylase, and GGT activities. There was no statistically significant difference between the VCM + ERD treated group and only VCM treated group by means of serum ALP levels. It has been observed that there was a prominent pancreatic tissue damage in only VCM given group. However, ERD exhibited structural protection against VCM-induced pancreatic damage and this effect was statistically significant. ERD has also obtained a marked reduction in the extent of pancreatic damage. CONCLUSION: Erdosteine may play an important role in the VCM-induced pancreatic damage and may reduce the pancreatic damage both in biochemical and histopathological aspects.

Iloprost downregulates expression of adhesion molecules and reduces renal injury induced by abdominal aortic ischemia-reperfusion.

The aim of this study was to examine the effect of iloprost in renal injury induced by abdominal aortic ischemia-reperfusion (IR) and how it can modulate the expression of adhesion molecules during this effect. Twenty-four Wistar-Albino rats were randomized into three groups (n=8) as follows: control (sham laparotomy), aortic IR (120 min ischemia and 120 min reperfusion), and aortic IR + iloprost (0.45 microg/kg/hr intravenous infusion during 120 min reperfusion). Blood and renal tissue samples were obtained for biochemical analysis. A histological evaluation with both hematoxylin-eosin staining and immunostaining was also done. Biochemical analyses showed that aortic IR significantly increased (p<0.05 vs. control) whereas iloprost significantly decreased (p<0.05 vs. aortic IR) plasma levels of malondialdehyde, P-selectin, intercellular adhesion molecule-1 (ICAM-I), and tissue levels of malondialdehyde and catalase. Histological evaluation with immunostaining showed that aortic IR significantly increased (p<0.05 vs. control) whereas iloprost significantly decreased (p<0.05 vs. aortic IR) the immunoreactivity of P-selectin, tumor necrosis factor-alpha, CD11b, CD18, and ICAM-1. Hematoxylin-eosin staining showed that iloprost also attenuated the morphological changes associated with aortic IR. The results of this study show that iloprost reduces renal injury induced by aortic IR in rats and downregulates expression of adhesion molecules at both the local and systemic levels after aortic IR during this protective effect.

The development of fetal pylorus during the fetal period.

OBJECTIVE: The objective of this study was to explore the localization of the pylorus, its macroscopic and microscopic development and relationship with neighboring structures. MATERIALS AND METHODS: The study is carried out on 160 human fetuses aged between 9 and 40 weeks of gestation. Abdomen was divided into four quadrants by horizontal and vertical planes passing through the umbilicus. Topographical localization of the pylorus in reference to these quadrants and its distance were determined. Pylorus was divided into pre-pyloric, pyloric, and post-pyloric regions. Starting from the pre-pyloric end, serial sections spanning whole pyloric part were obtained. Wall thickness, the thickness of the muscular coat were measured under light microscope using sections stained with hematoxylin eosin. Sections with the thickest muscular coat were considered as the region where pyloric sphincter was. FINDINGS: Pylorus was located in the right upper quadrant, on the median plane and in the left upper quadrant. There was a significant relation between the thickness of the muscular coat in the stomach, duodenum and the pyloric region and gestational age. In the region of the pyloric sphincter, the rate of increase in the thickness of the muscular coat was higher in the first and the first half of the second trimesters than term fetuses. CONCLUSION: We believe that data obtained in the present study will contribute to the assessment of development of the pyloric region in intra-uterine cases.

Cartilaginous choristomas in tonsillectomy specimen: A prospective analysis.

OBJECTIVE: Cartilaginous Choristomas (CC) are rare benign lesion in the head and neck. In our study, we aimed to share the findings we have observed in CC cases in tonsillectomy specimens in daily practice. MATERIALS AND METHODS: This is a prospective analysis done at Department of Pathology, Süleyman Demirel University Faculty of Medicine between 2002 and 2018. All of the tonsillectomy materials fixed in 10% formaldehyde were followed up by sampling one side of the cross-sections if no macroscopically specific pathology was observed routinely. All the specimens were processed and embedded in paraffin. The paraffin sections are stained with hematoxylin and eosin and examined under microscope. RESULTS: Tonsils of 141 patients among 2355 tonsillectomy patients had CC in their specimens. A total of 155 (3.68%) CC were detected because they were seen in bilaterally in 14 patients. More than one CC was observed in 20 patients. Two of the CC was observed calcification and one have ossification. No salivary gland was observed adjecent to the choristomas in 29 patients. Significant fibrosis was more frequent in patients 15 years of age and older. CONCLUSION: The presence of hyaline cartilage in the tonsil is hamartomatous development. The CC observed in the tonsil is non fibrotic and not related to age. They can be unilateral, multifocal or bilateral in tonsil. None of the cases we have seen with the CC found a primary malignancy associated with tonsillitis. The incidence of ectopic cartilage in tonsillectomy specimen is %5.99.

The protective effect of erythropoietin on renal injury induced by abdominal aortic-ischemia-reperfusion in rats.

BACKGROUND: Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The purpose of this study is to examine the effect of erythropoietin on renal injury induced by aortic IR in rats. MATERIAL AND METHODS: Twenty-four Wistar-Albino rats were randomized into 3 groups (8 per group). The control group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. The aortic IR group underwent clamping of the infrarenal abdominal aorta for 30 min followed by 60 min of reperfusion. The aortic IR + erythropoietin group underwent the same aortic IR periods and was pretreated with 1000 U/kg subcutaneous erythropoietin 5 min before ischemia. In rat kidney specimens, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase were measured. Histological evaluation of the rat kidney tissues was also done. RESULTS: Aortic IR significantly increased the levels of MDA and superoxide dismutase (P < 0.05 versus control). Erythropoietin significantly decreased the levels of MDA, superoxide dismutase, and catalase (P < 0.05 versus aortic IR). Histological evaluation showed that aortic IR significantly increased (P < 0.05 versus control), whereas erythropoietin significantly decreased (P < 0.05 versus aortic IR) the focal glomerular necrosis, dilation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, interstitial inflammatory infiltration, and congestion of blood vessels. CONCLUSIONS: The results indicate that erythropoietin has protective effects on renal injury induced by aortic IR in rats.

Expression of cyclooxygenase-2, matrix metalloproteinase-2 and matrix metalloproteinase-9 in premenopausal and postmenopausal endometrial polyps.

OBJECTIVES: Cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) are influenced by relative levels of estrogen and are involved in promoting cell proliferation and angiogenesis. The present study investigated expression of COX-2, MMP-2 and MMP-9 in endometrial polyps from premenopausal and postmenopausal women. METHODS: Premenopausal (n=18) and postmenopausal (n=22) endometrial polyps were included in the study. None of the women were using non-steroid anti-inflammatory drugs, hormone replacement therapy or any other estrogen containing pills. Immunohistochemical analysis for MMP-2, MMP-9 and COX-2 were performed on formalin fixed, paraffin-embedded tissue using the streptavidin-biotin-peroxidase technique. The cut-off value for positiviy was set to 10% and staining more than 50% was regarded as intense staining. Staining of 10-25% and 25-50% were recorded as mild and moderate, respectively. RESULTS: COX-2, MMP-2 and MMP-9 were stained in epithelial cells and stroma of premenopausal and postmenopausal endometrial polyps. Stromal expression of COX-2, MMP-2 and MMP-9 were found significantly higher in premenopausal polyps compared to postmenopausal polyps (p<0.05). There were no other significant differences in the immunohistochemical expressions in the epithelium of premenopausal and postmenopausal endometrial polyps except MMP-9. CONCLUSION: Polyps from both premenopausal and postmenopausal women express epithelial and stromal COX-2, MMP-2 and MMP-9, however immunohistochemical expression of these markers may be different due to menopausal status. This may suggest a shared pathogenesis for pre- and postmenopausal endometrial polyps.

Postmenopausal complete hydatidiform mole: a case report.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a disease with a course of trophoblastic proliferation, and histologically classified as partial hydatidiform mole, complete mole, invasive and metastatic mole, choriocarcinoma and placental site trophoblastic tumor. Occurrence of GTN in postmenopausal women is rare. CASE: We report the case of a 56-year-old postmenopausal woman with a complete mole. The patient was admitted to gynecology outpatient clinic with abdominal pain, nausea and vomiting for about 1 month. Ultrasound examination revealed enlargement of the uterus with endometrial thickness containing hypo/hyper echogeneous and cystic areas. Serum beta-HCG was tested against the possibility of GTN because of the appearance in sonography and was found >5000. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The serum level of beta-HCG has decreased from initially observed 188,000-0 U/ml in 4th week. The resected uterus contained an endometrial, cystic, grapelike tumor. Microscopic examination demonstrated hydropic degeneration of all the chorionic villi with trophoblastic cell proliferation consistent with a complete hydatidiform mole. CONCLUSION: To our knowledge, our case is the fourth description in the world literature of a benign complete hydatidiform mole in a postmenopausal woman. Although benign gestational trophoblastic disease generally occurs in women of reproductive age and is extremely rare in postmenopausal women, when evaluating patients who are in postmenopausal period the diagnosis of hydatidiform mole must always be considered.

Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy.

Leukemia inhibitory factor (LIF) is essential for implantation of the embryo in the endometrium. It is not clear whether the blastocyst requires expression of LIF for implantation into tissues other than endometrium. Immunohistochemical localization of LIF was performed in the fallopian tube of 20 women with ectopic pregnancies, 7 women with normal pregnancies and 20 healthy non-pregnant women. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and non-pregnant fertile women or at operation for tubal surgery in ectopic pregnancies. Biopsies were assayed by immunohistochemistry. Semi-quantitative immunohistochemical reaction scores (IRS) were used for immunohistochemical analyses. Immunolabeling of LIF was detected in the surface epithelium and stroma of fallopian tubes in all subjects. IRS score in the epithelium and stroma of non-pregnant women and women with intrauterine pregnancy were similar (p>0.05). However, women with ectopic pregnancy had significantly increased labeling of LIF compared to others (p<0.05). Immunohistochemical labeling of LIF in the fallopian tube was found to be increased in ectopic pregnancies compared to non-pregnant and healthy pregnant controls. This may indicate a role of LIF in the ectopic implantation of embryos.

Cyclooxygenase-2 expression in primary and recurrent pterygium.

BACKGROUND: Pterygia are common, benign, fibrovascular, and infiltrative processes of the corneo-conjunctival junction of unknown pathogenesis. Cyclooxygenase-2 (COX-2) mediates the rate-limiting step in arachidonic acid metabolism. Extensive evidence indicates that the COX-2 prostanoid pathway is involved in inflammation. The aim of the study was to document the immunohistochemical expression of COX-2 in primary and recurrent pterygia. MATERIALS AND METHODS: In this study, 21 primary pterygia and 12 recurrent pterygia from subjects undergoing pterygium surgery and six normal corneal-scleral tissue specimens were studied immunohistochemically for COX-2 expression. RESULTS: COX-2 was expressed in primary pterygia and recurrent pterygia specimens. There was a statistically significant difference in COX-2 expressions in fibroblasts between primary and recurrent pterygium cases ( P = 0.001). There were statistically significant differences in COX-2 expressions in surface epithelium ( P = 0.028) and stromal inflammatory cells ( P =0.000) between control tissues and primary pterygia tissues. We also detected statistically significant differences in COX-2 expressions in surface epithelium ( P =0.000), stromal fibroblasts P =0.000 (stromal fibroblasts and inflammatory cells), vessels ( P = 0.027) and inflammatory cells ( P =0.001) between control tissues and recurrent pterygia tissues. CONCLUSIONS: This is the first study to document the expression of COX-2 in primary and recurrent pterygia. In our opinion after excision of pterygia, fibroblastic proliferation continues and this contributes to recurrence.

Serum, salivary, and tissue levels of plasminogen in familial Mediterranean fever, amyloidosis, and chronic periodontitis.

BACKGROUND: There are no published studies regarding the role of the plasminogen (PLG) system in familial Mediterranean fever (FMF), FMF-associated secondary amyloidosis, or chronic periodontitis (CP), although recent limited data have focused on the association between FMF and chronic periodontitis. Therefore, the aim of this study was to evaluate the serum, salivary, and gingival tissue levels of PLG in patients with CP, FMF, and amyloidosis. METHODS: The study population included 122 patients with FMF (only FMF, and FMF and amyloidosis and 128 individuals who were systemically healthy controls. Blood and salivary samples were obtained from the cases and controls, and clinical periodontal parameters were recorded. Serum and salivary PLG levels were assessed. The gingival tissue samples of the case and control groups were analyzed histopathologically and immunohistochemically for amyloid deposition and PLG. RESULTS: The amyloidosis group had significantly more severe clinical periodontal parameters than those of the FMF and systemically healthy groups (P < 0.05). Salivary levels of PLG were significantly higher in the FMF and amyloidosis groups compared with those in the control group (P < 0.001). The FMF with periodontitis and amyloidosis with periodontitis groups had higher salivary PLG levels compared with those in the CP group. Serum and salivary PLG levels were significantly associated with the clinical periodontal parameters in the FMF group. The amyloidosis cases had hyperplasia, severe inflammation, and activation of the gingiva. CONCLUSION: The PLG system could play an important role in inflammatory diseases, such as chronic periodontitis, FMF, and FMF-associated secondary amyloidosis.

Immunohistochemical expression of PTEN in normal, hyperplastic and malignant endometrium and its correlation with hormone receptors, bcl-2, bax, and apoptotic index.

PTEN is a tumor suppressor gene that is frequently mutated in type I endometrioid endometrial carcinomas (EECs), and is involved in the control of cell proliferation, differentiation, and apoptosis. In this study, we aimed to assess the relationship between PTEN expression and estrogen, progesterone receptors (PRs), other apoptosis-related proteins, such as bcl-2 and bax, and apoptotic index (AI) in EEC, its precursor lesion hyperplasia, and cyclical endometrium. We also evaluated the relationship between PTEN expression and clinicopathologic parameters. PTEN, estrogen receptor (ER), PR, and bcl-2 and bax expressions were evaluated immunohistochemically, and AI was evaluated in hematoxylin and eosin (HE)-stained slides in 23 cyclical and 37 hyperplastic endometria and in 35 EECs. PTEN expression was higher in cyclical endometrium than in the carcinomas (p<0.05). The PTEN expression level was significantly higher in non-atypical hyperplasias than in EEC, but there were no differences between atypical complex hyperplasia (ACH) and EEC and between hyperplasias. In the carcinomas, there was a negative correlation between grade and PTEN expression (r=-0.338, p=0.047). In conclusion, we presume that PTEN is involved in the early phases of endometrial tumorigenesis, and it can be speculated that decreased PTEN expression with loss of differentiation in carcinoma can contribute to the emergence of tumors with a more aggressive phenotype.

Protective effect of caffeic acid phenethyl ester (CAPE) on fluoride-induced oxidative stress and apoptosis in rat endometrium.

High fluoride intake may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the tissues, thus leading to oxidative damage. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygen species mediated oxidative stress in ischemia-reperfusion and toxic injuries. Several studies suggest that supplementation with anti-oxidant can influence fluoride induced tissue damage. The aims of this study was to investigate the possible role of malondialdehyde (MDA) levels and activity of superoxide dismutase (SOD) and catalase (CAT), in the pathogenesis of fluoride-induced endometrial damage and to demonstrate the effect of CAPE, the potent antioxidant, in decreasing the toxicity. Twenty-four adult female rats were randomly divided into three experimental groups, as follows: control group, fluoride-treated group (F), and fluoride plus CAPE-treated group (F+CAPE). Fluoride was given orally as 30mg/L NaF solution in spring water daily for 45 days. CAPE was co-administered intraperitoneally (i.p.) with a dose of 10µM/(kgday) for 46 days. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. The activities of antioxidant enzymes such as SOD and CAT as well as the concentration of MDA, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the endometrium. Fluoride administration increased MDA levels (p<0.05), decreased SOD (p<0.05) and CAT (p<0.05) activities. CAPE co-administration with fluoride treatments caused significantly decreased MDA levels (p<0.05), increased SOD (p<0.05) and CAT (p<0.05) activities in endometrial tissue when compared with F alone. Diffuse apoptosis in glandular epithelium and stromal cells was found by TUNEL method in endometrial tissues of rats treated with fluoride. The severity of these lesions was reduced by administration of CAPE. In conclusion, our study demonstrated that MDA may play an important role in the pathogenesis of fluoride-induced oxidative endometrial damage. CAPE may have protective aspects in this process by its antioxidant and anti-inflammatory effect.

Expression of NGF, GDNF and MMP-9 in prostate carcinoma.

The aim of the present study was to investigate the immunohistochemical expression of NGF, GDNF and MMP-9 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse their association with the clinicopathological parameters in PC cases. Immunohistochemistry was performed on the tissue microarray (TMA) sections of 30 BPH, 40 HGPIN and 121 primary PC tissues. There was a significant difference regarding the expression of NGF and GDNF between PC and HGPIN (p<0.0001; p<0.0001), and PC and BPH (p=0.001; p<0.0001), but not between HGPIN and BPH (p>0.05). Furthermore MMP-9 expression was significantly different among all groups (PC vs. HGPIN, p<0.0001; PC vs. BPH, p<0.0001; HGPIN vs. BPH, p=0.001). NGF, GDNF and MMP-9 expression was significantly stronger in cases with high Gleason score (p<0.0001, p=0.004, p<0.0001 respectively) and pT stage (p=0.046, p=0.004, p=0.001, respectively) in PC cases. All these markers were also associated with perineural, lymphovascular and extraprostatic invasion (p <0.05). In addition, a positive correlation was found between NGF and MMP-9 (p<0.0001, r=0.435), NGF and GDNF (p<0.0001, r=0.634), and GDNF and MMP-9 (p<0.0001, r=0.670) in PC cases. According to our results we suggest an interaction between NGF, GDNF and MMP-9 during the transition to malignancy in PC. Also this interaction may involve in regulating PC cell differentiation, tumor invasion, progression, and the agressiveness of PC.

Catastrophic antiphospholipid syndrome treated with rituximab: A case report.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and fatal condition that is characterized by diffuse venous and/or arterial thromboembolism within a short period of time and histopathological confirmation of small-vessel occlusion in at least one organ or tissue in the presence of positive antiphospholipid antibodies. Here we report the case of a 19-year-old woman with CAPS. During the first week of her hospitalization, she was diagnosed with CAPS on the basis of skin necrosis, pulmonary artery thrombosis, cerebral venous sinus thrombosis, and positive lupus anticoagulant. She was treated with corticosteroids, intravenous immunoglobulins, plasmapheresis, and anticoagulants. Forty days after the onset of CAPS, cutaneous lesions were recurred during skin surgery. She required a high dose of corticosteroids, intravenous immunoglobulins, and rituximab. No further thrombotic events occurred. Rituximab may be an effective treatment option for patients with CAPS.