Nebivolol alleviates liver damage caused by methotrexate via AKT1/Hif1α/eNOS signaling.

Despite the wide clinical indications, methotrexate (MTX) use is limited because of serious side effects including liver toxicity. MTX was shown to cause tissue damage by mainly oxidative stress and also inflammation and apoptosis. Thus, Nebivolol (NEB) which has antioxidant and antiapoptotic properties were thought to be effective against MTX-induced injury. This study aimed to evaluate the effects of NEB on MTX-induced liver toxicity via AKT/Hypoxia-Inducible Factor 1 Alpha (HIF1α)/Endothelial Nitric Oxide Synthase (eNOS) signaling pathways. Rats were divided into three groups as control, MTX, and NEB. A single dose of MTX (20 mg/kg intraperitoneally) was given to the rats on the first day of the experiment and NEB (10 mg/kg, daily by oral gavage) was given to the treatment group for a week. At the end of the experiment, bloods were taken for aspartate transaminase (AST), alanine aminotransferase (ALT), and total bilirubin (T-BIL) analyses. Liver tissues were harvested for biochemical (total oxidant status (TOS) and total antioxidant status (TAS), genetic (PCR analyses for AKT1, eNOS, and HIF1a), and histological (Hemotoxylin-Eosin, Masson Trichome, Periodic Acid Schiff-Asien Blue, reticulin for histological, and CD3 for immunohistochemical staining) analyses. MTX increased the levels of TOS values, AST, ALT, T-BIL levels and decreased the expressions of AKT/HIF1α/eNOS. NEB treatment reversed all these changes markedly via decreasing inflammation by nitric oxid (NO) production. In conclusion, NEB treatment significantly preserves the liver by decreasing oxidant levels and inflammatory parameters through HIF1α/eNOS signaling. Due to the antioxidant properties of NEB, it can be used in other liver injury models sharing the same pathway.

Investigating the effectiveness of different tea types from various thyme kinds (Origanum onites, Thymbra spicata and Satureja cuneifolia) on anemia and anticholesterolemic activity.

In a study on villagers settled on the outskirts of the Taurus Mountains and whose source of living is thyme, it was revealed that the villagers excessively consumed thyme by adding it to their tea and many of their foods; high incidences of anemia was found among these villagers. In this study, 42 male adult Wistar albino rats weighing 200-250 g were used. The rats were divided to six equal groups as follows: control, cholesterol (Chol), 80 mg/kg Origanum onites Labiatae (OOL), 80 mg/kg Thymbra spicata Labiatae (TSL), 80 mg/kg Satureja cuneifolia Labiatae (SCL), and 160 mg/kg TSL, and each group consisted of seven rats. The control group was fed with normal pellet feed. The Chol group and all the other groups, except for the control group, were fed with 2% cholesterol-containing pellet feed. Physiological serum of 4 ml was given to the control and Chol group, wheile 80 mg/kg of thymes tea was given to the OOL group, TSL group, and SCL group, and 160 mg/kg of thymes tea was given to the TSL group by means of a gavage for 30 days. In the blood samples, the hematologic parameters and the biochemical parameters of serum glucose, blood urea nitrogen, creatinine, total protein, albumin, iron (I), total iron-binding capacity, aminotransferase aspartate, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglyceride, and oxidized LDL levels were examined. The kidney and liver tissues were examined histopathologically. The results of the study showed that different types of thymes had an antihypercholesterolemic effect. In addition to the anemic effect detected in group TSL and the mild granular degeneration found in the liver of 80 mg/kg SCL group, distinct granular degeneration was observed in 160 mg/kg TSL group.

Submandibular hemangioma with multiple phleboliths mimicking sialolithiasis: the first pediatric case.

Hemangiomas are the most common masses of the major salivary glands in parotid glands in childhood particularly. They occur more frequently in the parotid gland and rarely the submandibular gland. Changes in blood flow dynamics within hemangiomas may induce thrombus formation and phleboliths. Cavernous hemangioma may lead to thrombophlebitis in major salivary glands in adults. To our knowledge, cavernous hemangioma of submandibular glands containing phleboliths in childhood has not been described so far in the literature. In this article, we report the first pediatric case of a cavernous hemangioma containing multiple phleboliths in the submandibular gland mimicking submandibular sialolithiasis in a seven-year-old boy.

Diagnostic and prognostic value of Stanniocalcin 1 expression in papillary thyroid cancer.

PURPOSE: To evaluate the potential role of immunohistochemical changes in stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) expressions in papillary thyroid cancer (PTC) tissues in the disease's diagnosis and to investigate their relationship with classical clinicopathological prognostic factors. METHODS: The study included 100 patients with PTC. Normal thyroid tissue adjacent to the tumor was taken as the control group. Clinicopathological prognostic features at the time of diagnosis of patients were recorded. STC1 and STC2 expressions of tumor tissue and adjacent normal tissue were determined immunohistochemically. RESULTS: The sensitivity of STC1 in the diagnosis of PTC was 93%, the specificity was 94%, positive predictive value (PPV) 93.9%, and negative predictive value (NPV) 93.1%. It was determined that the STC1 staining score in tumor tissue was positively correlated with the disease TNM stage score (r = 0.259, p = 0.009) and the increase in STC1 staining score were independent risk factors that increased the risk of lymph node metastasis (R2 = 0.398, p < 0.001). While 21% of the tumor tissues were stained with STC2, none of the normal thyroid tissues adjacent to the tumor tissue showed any staining with STC2. No correlation was found between STC2 immunohistochemical staining of tumor tissue and clinicopathological risk factors for the disease. CONCLUSION: Increased STC1 expression in thyroid lesions may be helpful in diagnosing PTC. In addition, since increased STC1 expression in PTC tissues is associated with the risk of lymph node metastasis, it may be an efficient marker for predicting the prognosis of the disease.

The investigation of gingival iron accumulation in thalassemia major patients.

BACKGROUND: Thalassemia major (TM) is an autosomal-recessive genetic blood disorder. Regular blood transfusions to improve chronic anemia caused by ineffective erythropoiesis and hemolysis lead to iron overload in many organs in TM patients. The aim of this study was to investigate the periodontal status and the iron accumulation in gingival tissues of TM patients and assess whether iron deposition in gingival biopsies could be an alternative method for the diagnosis of body iron overload in TM patients. MATERIALS AND METHODS: This study was conducted on 22 TM patients and 20 healthy matched controls. Plaque index, gingival index, and probing pocket depth were measured and gingival biopsies were obtained in all subjects. Venous blood samplings and liver biopsies were carried out only in patients with thalassemia. Gingiva and liver tissue samples were evaluated histopathologically for inflammation, iron accumulation, and fibrosis. RESULTS: There was no difference between the groups regarding periodontal health, and all patients had mild gingivitis. Gingival iron accumulation was observed only in the TM group. The iron accumulation was detected in the liver of all the patients with thalassemia. The gingival iron accumulation was correlated with neither serum ferritin levels nor hepatic iron accumulations. CONCLUSIONS: The periodontal tissues are affected by iron accumulation as well as hepatic, cardiac, and endocrine tissues in TM patients. Further studies investigating the usage of the gingival biopsy for prediagnosis of body iron overload in TM patients are needed.

The Role of Metabolic Volumetric Parameters in Predicting Malignancy in Incidental Thyroid Nodules Detected in 18F-FDG PET/CT Scans

Objectives: The metabolic activities of tumors can be calculated volumetrically during positron emission tomography/computed tomography (PET/CT) imaging using metabolic tumor volume (MTV) and total lesion glycolysis (TLG). This study aimed to evaluate the roles of MTV and TLG in predicting the malignancy risk of incidental thyroid nodules detected by PET/CT imaging. Methods: Active metabolic areas of each section were manually drawn by region of interest to calculate the MTV of nodules, and all obtained values were then summed. TLG, the product of mean standardized uptake value and MTV, was calculated by multiplying two values. All participants underwent thyroid ultrasonography imaging. All nodules were divided into risk classes according to the European Thyroid Image Reporting and Data System (EU-TIRADS) that was developed by the European Thyroid Association. The American Thyroid Association Guidelines were used to determine which thyroid nodules would undergo thyroid fine-needle biopsy (FNAB). Results were classified according to the Bethesda scoring system. Results: TLG levels were significantly higher in malignant or malignant-suspicious nodules than in benign nodules (p=0.013). Although MTV levels were high in malignant or malignant-suspicious nodules than in benign and non-diagnostic nodules, it was statistically insignificant at limit values (p=0.079). Areas under curve (AUC) were 0.726 (p=0.005) and AUC: 0.668 (p=0.039) for TLG and MTV, respectively. The 2.3 g cut-off value of TLG has a sensitivity of 85.7% and specificity of 59.0%. The 1.7 mL cut-off value of MTV has a sensitivity of 78.6% and specificity of 60.4%. Conclusion: We believe that TLG evaluation will be useful in predicting high-risk malignancy or malignancy suspicion based on EU-TIRADS risk classification of incidental thyroid nodules detected in PET/CT images. We believe that unnecessary thyroid FNABs can be avoided for thyroid incidental nodules if such relation and cut-off values are determined and that it will be useful in hastening the operation of the necessary patients.

Adenomyomatosis of the gallbladder resembling honeycomb in a child.

Adenomyomatosis of the gallbladder is believed to be an uncommon pathologic condition of the gallbladder in childhood. Only three pediatric cases have been described in the literature up to now. Honeycomb gallbladder has been described in two adult patients; no patients have been reported in childhood until now. To the best of our knowledge, we report here the first case of adenomyomatosis of the gallbladder which resembled honeycomb, in a 9-year-old girl presented with recurrent abdominal pain. The diagnosis was made by ultrasound, and confirmed by magnetic resonance cholangiopancreatography and finally cholecystectomy. In conclusion, ultrasound scanning performed more generally in children presenting with recurrent abdominal pain might lead to accurate diagnosis of adenomyomotosis of the gallbladder during childhood.

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.

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.

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.

Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor.

Malignant melanoma of the parotid gland is often metastatic and mainly originates from malignant melanomas in the head and neck. Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously. The investigation of a patient's old photographs may help in the detection of preexisting and regressed pigmented lesions in the facial and neck regions.

Amyloid Goiter Secondary to Ulcerative Colitis.

Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis.

In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: protection by erdosteine.

The aims of this study were to examine vancomycin (VCM)-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM-induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i.p.) with 200mgkg(-1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM-induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels.

Squamous cell metaplasia of the nasopharyngeal epithelium and its association with adult-onset otitis media with effusion.

CONCLUSION: The common association between adult-onset otitis media with effusion (AO-OME) and squamous cell metaplasia (SCM) of the epithelium of Rosenmüller's fossa, which is near the Eustachian tube orifice, implies the predictive role of metaplasia, which probably compromises the drainage function of the middle ear. OBJECTIVE: To determine the effects of nasopharyngeal epithelial changes (SCM) on AO-OME. AO-OME is a multifactorial and insidious disease that may necessitate detailed investigation, i.e. biopsy of the nasopharynx, because of possible underlying nasopharyngeal malignancy. MATERIAL AND METHODS: Fifty-two patients with AO-OME (study group) and 29 with a unilateral neck mass in the posterior triangle without AO-OME (control group) were enrolled. Nasopharyngeal biopsies taken from all subjects were evaluated with regard to surface epithelial changes of the nasopharynx. RESULTS: Nasopharyngeal biopsies revealed SCM in 34/52 patients (65%) in the study group and 9/29 (31%) in the control group (p<0.05). During the follow-up period, recurrence of effusion occurred in 56% of the group with SCM and 22% of the group without it.

Basal cell carcinoma with halo phenomenon in a young female: significance of dermatoscopy in early diagnosis.

Halo phenomenon of nevus may be observed as a circular reaction, although it is unusual around tumors. A 29-year-old woman presented with a pigmented lesion on the cheek since three years. She noted whitening of the skin around the lesion almost after a year following its appearance. Dermatologic examination revealed a pigmented nodular lesion with a hypopigmented halo on the left infraorbital region. The clinical impression was halo nevus, whereas basal cell carcinoma (BCC) was considered in dermatoscopic differential diagnosis. The diagnosis was infiltrative-type BCC histopathologically. The persistence of a perilesional halo around an enlarging pigmented lesion should be carefully examined with accompanying dermatoscopic findings even in young patients for early diagnosis of tumoral lesions.

Neuroendocrine differentiated carcinomas of the breast: a distinct entity.

UNLABELLED: Some primary carcinomas of the breast have been classified as neuroendocrine. In this paper we report on 12 cases of neuroendocrine carcinoma of the breast displaying common and uncommon histological features. MATERIALS AND METHODS: All patients were aged from 43 to 79 (median 66.5) years. The tumors were unilateral and ranged from 0.8 to 7 cm (median 2.35 cm) in diameter. Four tumors were classified as solid cohesive, two as solid papillary, one as Merkel cell-like, two as cellular mucinous, two as cellular mucinous with micropapillary features and one as cellular mucinous with prominent signet ring cells. The tissues were fixed in formalin and routinely processed. All materials were stained with PAS, Alcian blue and also hematoxylin and eosin. Immunohistochemical examination was carried out by the avidin-biotin method using the following antibodies: estrogen receptor protein, progesterone receptor protein, p53, cerbB-2, Ki67, neuron-specific enolase, chromogranin, and synaptophysin. RESULTS: In all cases the tumor cells were stained positively with NSE. Synaptophysin and chromogranin positivity was detected in 11 and five cases, respectively. The prominent histological features were: extensive intraductal growth, pseudorosettes and palisades, low-grade cytologic atypia, plasmacytoid appearance of the tumor cells, and intracellular and extracellular mucin. CONCLUSION: Neuroendocrine-differentiated carcinoma of the breast is a rare and distinct category with different histological subtypes.

Intestinal obstruction due to a mesenteric cyst.

Mesenteric cysts are rarely thought of, may be difficult to diagnose, and are usually asymptomatic except when complicated. Intestinal obstruction is a rarely reported complication of these cysts. A case of mesenteric cyst that was causing obstruction of the large bowel is presented, along with a review of the literature.

Fine-needle aspiration biopsy of invasive micropapillary carcinoma of the breast: a report of five cases.

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine-needle aspiration cytology (FNAC). There are only a few reported cases in the literature. Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases. Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undertaking further studies.

Cytokine levels and histopathology in chronic hepatitis B and chronic hepatitis C.

The changes in balance of cytokine profile may result in either recovery or persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. This study aims to reveal a possible correlation between cytokine levels, ie, tumor necrosis factor (TNF)-α; interferon-gamma (IFN-γ); interleukin (IL)-10, IL-18, and transforming growth factor-beta (TGF-ß); and Ishak score or fibrosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). Fifty patients with CHB (n=25), CHC (n=25), and the control group of subjects with negative hepatitis B and C serology (n=30) were included in the study. Patients who did not agree to participate in the study were excluded. Serum cytokine levels were measured by ELISA. Liver biopsies from the patients were also taken for pathological analyses by the same pathologist. The serum levels of TNF-α, IL-10, and IL-18 in the hepatitis C group were significantly high compared with those of the control group (P=0.017, P=0.001, and P=0.004 respectively), but, only IL-10 levels in the hepatitis B group were significantly high (P=0.001). These groups did not show any significant difference with respect to IFN-γ or TGF-ß levels. In patients with CHB or CHC, there was a significant correlation (P=0.000) between TNF-α and Ishak score or fibrosis; but no such correlation was found with IFN-γ, IL-10, IL-18, or TGF-ß. Result of the current study indicated that cytokine activities were important indicators of clinical severity and progression of HBV- and HCV infections. Further investigations on possible effects of cytokines on hepatocellular damage and fibrosis should be done to arrange new immunopathological approaches to viral hepatitis.