Sevdegül Mungan

Prognostic importance of Claudin-1 and Claudin-4 expression in colon carcinomas

In this study, we analyzed Claudin-1 and Claudin-4 expressions in colon carcinomas. We investigated the relationship between the expression of these tight junction proteins and clinicopathologic parameters. Claudin-1 and 4 expressions were determined by immunohistochemical methods, and the rate of cells expressing these tight junction proteins were calculated with stereologic methods. Fifty-nine colon cancer cases were enrolled in the study group. Claudin-1 and 4 expressions were found to be significantly lower in cases with lymph node metastasis. Mean staining rates of Claudin-1 and 4 in lymph node (+) cases were 36.1±20.1 and 58±28.9, while in lymph node (-) cases, these were 63.8±25.9 and 72.3±25.6, respectively (p=0.0005 for Claudin-1, p=0.049 for Claudin-4). The mean staining rate for Claudin-1 in adenomatous polyps was significantly higher than incarcinomas (77.13±23.4 and 50.6±26.93, respectively) (p=0.003), while it was quite similar for Claudin-4 (65.4±26.9 and 65.3±27.9, respectively). In this study, we demonstrated Claudin-1 and 4 expressions in colon cancer cases. Claudin-1 expression seems to be more prominent in adenomatous polyps as compared with cancer cases. Expression of Claudin-1 decreases significantly in the presence of lymph node metastasis and diminishes in mucinous carcinoma cases, indicating a negative correlation between Claudin-1 expression and neoplastic progression.

How Does Colistin-Induced Nephropathy Develop and Can It Be Treated?

ABSTRACT Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

Comparison of the protective effect of dipyridamole and acetylsalicylic acid on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury☆

PURPOSE Ischemia reperfusion injury arising from testicular torsion results in a loss of spermatogenesis and a significant increase in germ cell apoptosis. We investigated the effects of dipyridamole and acetylsalicylic acid (ASA), 2 well-known platelet inhibitors, on testicular ischemia reperfusion injury. METHODS Thirty adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6 for each group): control, sham-operated, torsion/detorsion (T/D), T/D + dipyridamole, and T/D + ASA. Testicular ischemia was achieved by rotating the left testis 720° clockwise for 2 hours. Thirty minutes before torsion, 10 mg/kg dipyridamole was injected transperitoneally in the T/D + dipyridamole group, and 100 mg/kg ASA was injected transperitoneally in the T/D + ASA group. Sixty days after the initial surgical procedure, ipsilateral orchiectomies were performed for histopathologic examination to determine Johnsens mean testicular biopsy score (MTBS), mean seminiferous tubular diameter (MSTD), and apoptotic index (AI) in all groups. RESULTS Unilateral testicular torsion-detorsion led to a significant decrease in Johnsens MTBS and MSTD values in the ipsilateral testis and a significant increase in AI values of the T/D group. There were no significant differences between the T/D + dipyridamole and control groups in terms of MSTD and MTBS values. Although an amount of improvement exits in T/D + ASA group, there were significant differences between the T/D + ASA and control group MSTD and MTBS values. There was no significant difference between the T/D + dipyridamole and control groups in terms of AI values (P > .05), but the differences between the T/D + ASA and control groups were significant despite a slight decline in AI values of the T/D + ASA group. CONCLUSIONS Our findings show that the use of dipyridamole before testicular reperfusion has a potentially protective effect against long-term injury in testicular ischemia reperfusion injury.

The Significance Of Galectin-3 Expression in the Immunocytochemical Evaluation of Thyroid Fine Needle Aspiration Cytology

The aim of this study is to evaluate the significance of immunohistochemical expression of Galectin-3 in the differential diagnosis of benign and malignant thyroid nodules. We studied the fine needle aspiration specimens of 38 patients who had evaluated for nodular goiter and undergone a thyroid surgery between 2004–2005. Slides had been stained immunocytochemically with Galectin-3. The cytoplasmic staining of Galectin-3 was analyzed. Three cases of five follicular carcinomas had positive staining for Galectin-3, while two had not. Two cases with follicular adenomas were negative for Galectin-3. Five cases of six papillary carcinomas had positive staining for Galectin-3, while one case (the case with a papillary microcarcinoma) had not. The single cases with medullary and anaplastic carcinomas were negative for Galectin-3. None of the cases with a benign thyroid pathology had positive staining for Galectin-3. Galectin-3 immunocytochemical staining, had a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 83.3% for thyroid malignancies. For the evaluation of follicular neoplasm, Galectin-3 immunocytochemical staining had a sensitivity of 60%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Galectin-3 expression in thyrocytes is a strong indicator of a malignant proliferative lesion especially for papillary and to an extent in follicular thyroid neoplasms. Galectin-3 could be used as a supplementary marker for cytological diagnosis.

Juvenile hyaline fibromatosis: a case report

Juvenile hyaline fibromatosis ( JHF ) is a rare autosomal recessive disease characterized by papulonodular skin lesions, gingival hyperplasia, joint contractures, and bone lesions. The skin lesions may consist of multiple large tumors, commonly on the scalp and around the neck, and small pearly, pink papules and plaques on the trunk, chin, ears, and around the nostrils. Here, we report a 2‐year‐old boy with characteristic stiffness of the knees and elbows and pink confluent papules on the paranasal folds, and periauricular and perianal regions. He also had hard nodules all over the scalp and around the mouth, and severe gingival hyperplasia. The lesions were totally excised and clinicopathological diagnosis was JHF.

GSPE is superior to NAC in the prevention of contrast-induced nephropathy: Might this superiority be related to caspase 1 and calpain 1?

AIMS Our study was intended to evaluate the role of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), caspases 1 and 3 and calpain 1 in the pathogenesis of contrast-induced nephropathy (CIN) and to compare the protective effects of N acetyl cysteine (NAC) and grape seed proanthocyanidin extract (GSPE) against the development of CIN. MAIN METHODS 32 rats were divided into four groups; control, contrast media (CM), CM+NAC and CM+GSPE. CIN was induced by administration of 7 ml/kg diatrizoate. The experiment was discontinued on the ninth day. Blood was collected for blood urea nitrogen (BUN) and creatinine measurement. Rat kidney tissues were removed for histopathological evaluation and the investigation of caspases 1 and 3, iNOS, eNOS, TUNEL and calpain 1. KEY FINDINGS A significant increase in BUN, creatinine, renal histopathological injury, TUNEL, caspases 1, 3, calpain 1, iNOS and eNOS was observed in the CM group compared to the control group. There was amelioration in all these parameters in the CM+GSPE group, while there was no significant amelioration in BUN, creatinine and renal histopathological injury in the CM+NAC group. In addition, calpain 1 staining and creatinine were significantly lower in the CM+GSPE group compared to the CM+NAC group. SIGNIFICANCE Our study showed, for the first time in the literature, that GSPE has a greater renoprotective effect compared with NAC and that this effective protection may be related to decrease in calpain 1 levels.

Cotyledonoid leiomyoma of uterus: a case report.

The diagnosis of uterine smooth muscle tumors is usually not difficult. Occasionally, benign tumors with an unusual growth pattern may cause some diagnostic confusion for pathologists who had not experienced such a tumor before. A fifty-one year old female patient had admitted to our gynecology outpatient clinics with abnormal uterine bleeding (menorrhagia) and undergone a surgery with a diagnosis of pelvic mass. A neoplasm consisting of spindle cell nodules with prominent hydropic degeneration was observed at pathological examination. Tumor cells were positive for vimentin, desmin and smooth muscle actin at immunohistochemical evaluation. Cotyledonoid leiomyomas are rare benign smooth muscle tumors of uterus which are recently defined in the literature. In this article we report a case of cotyledonoid leiomyoma of uterus with an exophytic growth pattern in the serosa and did not contain an intramural dissecting component.

Neurocytoma Arising in an Adrenal Gland Mature Teratoma

Mature teratoma of adrenal gland is a rare entity. Neurocytoma is a low grade neuronal tumor even rarely seen among central nervous system tumors. Nervous system tumors arising in teratomas are frequently originated from glial or primitive neuroectodermal cells. Here we report a neurocytoma arising in mature cystic teratoma in the right adrenal gland of an 8 years old boy. Histological examination revealed a tumor composed of solid sheets in fibrillar basis with small uniform cells in the neuroglial tissue in teratoma. This is only the second case demonstrating a neurocytoma arising in a mature cystic teratoma in the literature.

A case of recurrent episodes of acute renal allograft failure caused by renal pedicle tortion.

Background: Acute allograft failure which occur intermittently after renal transplantation caused by graft tortion is a very rare entity. We here report highly unusual case of recurrent episodes of acute allograft dysfunction two years after kidney transplantation secondary to ischemic tubular necrosis caused by tortion of renal pedicle due to rotation of the allograft with body movements. Case Presentation: A 55 year-old male patient with living unrelated kidney transplantation for chronic renal failure caused by autosomal dominant polycystic kidney disease had presented recurrent acute deteriorations in renal functions. All laboratory values were within normal limits except elevated serum creatinine levels, acute tubular necrosis in graft biopsy, and detection of pelvic dilatation in renal ultrasonography from time to time. Changes in axis of graft in nuclear medicine scans taken at different times during the same study made us bring to mind the diagnosis of renal pedicle tortion. Renal blood flow measurements with Doppler ultrasonography in different body positions helped to reach the final diagnosis of mobile kidney right on time. The patient is now well after prompt surgical treatment with nephropexy. Discussion: Unfortunately, tortion of allograft once occurred is associated with very high rate of graft loss due to arterial compromise and infarction and it is very difficult to diagnose without high level of suspicion. We discuss the causes of renal allograft tortion and the measures to prevent its occurrence and the methods to diagnose.

Perspective on Rhabdomyolysis-Induced Acute Kidney Injury and New Treatment Options

Aim: The purpose of this study was to assess the role of caspase-dependent apoptosis, caspase 1, calpain 1, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) and the protective effect of grape seed proanthocyanidin extract (GSPE) in the development of rhabdomyolysis-induced acute kidney injury (AKI). Materials and Methods: Twenty-one rats were divided into 3 groups - control, rhabdomyolysis and rhabdomyolysis + GSPE. Rhabdomyolysis was induced in the rhabdomyolysis and rhabdomyolysis + GSPE groups with the injection into both hind limbs of 10 ml/kg hypertonic (50%) glycerol following 24-hour dehydration on the 6th day. The rhabdomyolysis + GSPE group was given GSPE at 100 mg/kg by gavage for 7 days. The experiment was concluded 48 h after glycerol injection. Blood specimens were collected, and kidney tissues were extracted for histopathological examination. Results: We identified an increase in blood urea nitrogen, creatinine, histopathological score, iNOS, caspase 3, caspase 1 and calpain 1 expression in the rhabdomyolysis group compared to the controls and a decrease in eNOS expression. In the rhabdomyolysis + GSPE group, however, there was a decrease in these mediators, together with an increase in eNOS expression. Conclusion: This study shows for the first time in the literature that calpain 1 is involved in the pathogenesis of rhabdomyolysis-induced AKI, and that GSPE may have a renoprotective effect.