Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Background/aim: The Wnt/ß-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 µg/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/ß-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/ß-catenin pathway. Paricalcitol and the Wnt/ß-catenin pathway are candidates for research in human rheumatoid arthritis.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Adenomatous hyperplasia of the rete testis: Not a true hyperplasia, just proliferation!

There are several tumor-like lesions and miscellaneous neoplasms of the rete testis. We present a case with adenomatous hyperplasia of the rete testis (AHRT). The patient was 24 years old with undescended testis and was referred to our hospital. There were no clinical or endocrine abnormalities. Cryptorchidism was unilateral and the other testis was normal. Right orchiectomy was performed and sent to the pathology laboratory for examination. Morphologic and immunohistochemistry findings confirmed the diagnosis of AHRT in this case. The patient's postoperative course continues uneventfully. AHRT is a rare lesion and can be confused with malignancy. It is incidentally detected in microscopic investigation. It may present as a very small lesion detected in microscopic examination or a solid-cystic mass lesion which is macroscopically evident. Clinical history, localization, histologic features and immunohistochemistry are criteria for differentiating these lesions. We present this rare case for both surgeons and pathologists due to its importance as it can be confused with malignancy.

Is there a correlation between the aggressiveness of chronic asymptomatic prostatitis National Institutes of Health category IV and the Gleason score in patients with prostate cancer?

INTRODUCTION: We evaluated the correlation between the International Society of Urological Pathology (ISUP) grades and the aggressiveness grades of prostate inflammation in newly diagnosed prostate cancer patients with chronic asymptomatic prostatitis National Institiutes of Health (NIH) category IV (CAPNIHIV). METHODS: The study comprised 357 consecutive patients with prostate cancer in whom a cancer diagnosis had been made via a prostate needle biopsy. Histological sections of the prostate biopsy specimens of the patients were reviewed and scored. Prostatic inflammation was scored using the aggressiveness grade of inflammation. The associations between the ISUP grades and the aggressiveness grades of inflammation were analyzed using logistic regression. The limitations of the study were its retrospective design and the limited number of cases. RESULTS: In 110 (31%) patients, CAPNIHIV was detected: 56 (51%) patients had a grade 0 aggressiveness score, 34 (31%) patients had a grade 1 aggressiveness score, and 20 (18%) patients had a grade 2 aggressiveness score. The patients who had prostatic inflammation had 1.65 times (95% confidence interval [CI] 1.05-2.61) greater likelihood of a high ISUP grade (grade ≥3) compared with the patients who did not have prostatic inflammation. The association between the ISUP grade and the aggressiveness grade of inflammation was more pronounced for a grade 2 aggressiveness score (n= 20; odds ratio 2.97; 95% CI 1.14-7.71). CONCLUSIONS: In prostate cancer patients with CAPNIHIV, there was a positive correlation between the inflammation aggressiveness grade and the ISUP grade. The aggressiveness of intraprostatic inflammation may be an important morphological factor affecting the Gleason score.

The Suppression of Wound Healing Response with Sirolimus and Sunitinib Following Experimental Trabeculectomy in a Rabbit Model.

PURPOSE: To investigate the effects of sirolimus and sunitinib on wound healing in experimental glaucoma filtering surgery (GFS). MATERIAL AND METHODS: Thirty-five male New Zealand pigmented rabbits were randomly assigned to five groups, each including seven rabbits: The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the mitomycin-C (MMC) group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the sirolimus group underwent trabeculectomy and 30 ng/mL sirolimus-soaked sponge was applied intraoperatively to the scleral surgical site for three minutes. Sunitinib 0.5 mg/mL four drops in a day were applied in the sunitinib group for 14 days after surgery. On day 14 of the experiment, eyes were enucleated and histologically and immunohistochemically analyzed. Statistical analyses of the study were performed with Kruskal-Wallis variance analysis and Mann-Whitney U test. RESULTS: The mean fibroblast and MNC numbers and the mean immunostaining intensities of transforming growth factor-ß (TGF-ß), fibroblast growth factor-ß (FGF-ß) and platelet derived growth factor (PDGF) in the MMC, sirolimus and sunitinib groups were statistically significantly lower than those of the sham group (p < 0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-ß, FGF-ß and PDGF in the MMC, sirolimus and sunitinib groups were similar (p > 0.05). CONCLUSIONS: Our study suggests that the applications of sirolimus and sunitinib effectively suppress the subconjunctival scarring after experimental GFS.

Efficacy of Cortexin and Methylprednisolone on Traumatic Facial Nerve Paralysis.

OBJECTIVE: The aim was to investigate the efficacy of cortexin and methylprednisolone on recovery in cases of traumatic facial nerve paralysis occurring after facial nerve trauma. MATERIALS AND METHODS: The study was performed on 21 healthy rabbits. The buccal branches of the left facial nerves of all the rabbits were pressed, and facial nerve paralysis occurred. The rabbits were randomly divided into three equal groups: 3 mg/day cortexin intramuscularly, 1 mg/kg/day methylprednisolone intramuscularly, and 3 mg/day saline intramuscularly were administered for 10 days in Group I (cortexin group), Group II (methylprednisolone group), and Group III (control group), respectively. Electromyography was performed on the 7th, 14th, and 21st days to evaluate their improvement. Following this, the traumatic buccal branches of the facial nerves of rabbits were extracted and subjected to histopathological examination. RESULTS: There was a significant difference between the cortexin and methylprednisolone groups and the control group in terms of neural fibrotic degeneration, myelin degeneration, axonal degeneration, normal myelin production, and edema. When the cortexin and methylprednisolone groups were compared with each other, there was no significant difference between them, except for an increase in collagen fibers. Cortexin significantly reduced the collagen fiber increase to a greater extent than methylprednisolone. The electromyography findings did not show any significant difference between the groups or within the groups. CONCLUSION: Our study suggests that cortexin and methylprednisolone are effective for healing traumatic facial nerve paralysis with intact nerve integrity; however, cortexin is unable to cause significant improvement, which is superior to that caused by methylprednisolone.

Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery.

BACKGROUND: The purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC). METHODS: Twenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed. RESULTS: The mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-ß (TGF-ß), fibroblast growth factor-ß (FGF-ß), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P<0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-ß, FGF-ß, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-ß, FGF-ß, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P>0.05). CONCLUSION: Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities of TGF-ß, FGF-ß, and PDGF.

Spontaneous Rupture of Intracranial Dermoid Cyst Mimicking a Primary Psychiatric Disorder.

We discussed the case of a 14-year-old patient with acute onset of psychiatric symptoms for two months who had been examined and different antipsychotic drugs had been prescribed by several psychiatrists without any neuroradiological imaging. Because of unresponsiveness to the antipsychotic drugs, computed tomography and magnetic resonance imaging were performed which revealed a ruptured intracranial dermoid cyst. The patient underwent surgery and antipsychotic medications were withdrawn in short time. The emphasis of this case is that intracranial lesions can present with neuropsychiatric symptoms and findings only without any neurological deficit or signs.

Renal leiomyoma: ultrasonography and computed tomography features with histopathologic correlation.

Renal leiomyomas are not uncommon mesenchymal neoplasms of the kidney, found in 5% of autopsy specimens and comprising 0.3% of all treated tumors. These tumors arise from the smooth muscle cells of the kidney and are mostly located in the renal capsule. Typical imaging features of renal leiomyomas include a peripheral location, well-defined margins, and hyperattenuation on nonenhanced computed tomography (CT) images. The differential diagnosis of renal leiomyomas includes benign and malignant solid neoplasms of the kidney. Familiarity with typical renal leiomyoma imaging findings may help in the management of these patients and prevent unnecessary surgery.

A case of asymptomatic riedel thyroiditis with follicular adenoma in a patient with a multinodular goiter: an unusual association.

BACKGROUND: Riedel's thyroiditis (RT) is a rare inflammatory disease that results in fibrosis of the thyroid gland and invasion to the surrounding structures of the neck. Follicular adenoma (FA) of the thyroid is the most common benign neoplasm of the gland. PATIENT FINDINGS: A 42-year-old woman was referred to the outpatient clinic due to a multinodular goiter and thyroiditis. The patient was euthyroid and thyroid function tests were within normal limits. Thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody) were high. Thyroid ultrasonography showed multiple iso-hypoechoic nodules and thyroiditis. Fine-needle aspiration cytology was performed, and it was consistent with 'suspicious for a follicular neoplasm' according to the Bethesda system. Due to the clinical findings, which included weight loss and sweating, and the cytological results indicative of a follicular neoplasm, the patient underwent a total thyroidectomy. The histopathological diagnosis was RT associated with FA. The patient was started on thyroid hormone (thyroxine) replacement therapy after surgery and was evaluated for additional fibrosis related to RT. CONCLUSIONS: To our knowledge, this is the first case of RT associated with FA in an asymptomatic patient with a multinodular goiter and high thyroid antibodies reported in the literature.

[Ruptured pulmonary hydatid cyst: a case report]. / Çocukta Rüptüre Akciger Kist Hidatigi Olgusu.

Hydatid cyst (HD), a very common disease in the world, is often transmitted to humans through dog feces. HD is especially common in countries where agriculture and animal husbandry is prevalent. HD is caused by Echinococcus granulosus. The clinic course of HD usually features settling in the liver and lungs. Lung involvement with chest pain, cough, shortness of breath can cause non specific symptoms such as fever and hemoptysis. Diagnostic interventions for HD include chest X-ray tomography, and physical examination. Although the treatment options of HD vary according to the clinical findings of the patients, the primary treatment may be considered as surgery. The most frequently applied methods of surgical treatment are cystectomy and capitonnage. Medical treatment is usually warranted for complicated cases, including the patients with multiple and unresectable lesions, patients who refuse surgery and the patients who cannot tolerate surgery. Treatment with albendazole and its derivatives are used. In this case report, we present a child with primary complaints of cough, chest pain, dyspnea, fatigue and fever who was latterly diagnosed with lung HD.

Factors predicting non-sentinel lymph node involvement in sentinel node positive breast carcinoma.

OBJECTIVE: In routine practice, axillary lymph node dissection is performed in early invasive breast cancer patients with positive sentinel node biopsy. However, sentinel node is the only involved axillary node in 40-70% of patients, and determining factors that predict axillary non-sentinel node involvement will therefore prevent unnecessary axillary lymph node dissection and decrease morbidity. MATERIAL AND METHOD: In this study, 119 invasive breast cancer patients with sentinel node metastasis who underwent axillary lymph node dissection between 1998-2009 at our institution were studied. Primary tumor characteristics and features of the metastatic tumors in sentinel nodes, such as microanatomic location, size of metastasis, and the ratio of metastatic tumor area to the total sentinel node area were evaluated. Student's t-test and multivariate logistic regression were used for statistical analysis. RESULTS: The mean age of the patients was 50.7 years (28-80). Forty-three patients (36%) had invasive ductal and 25 patients (21%) had invasive lobular carcinoma. Most of the patients had either pT1 (44%) or pT2 (54%) tumors. Fifty-four patients (45%) had no further positive nodes in the axilla. The metastatic deposits in the sentinel node were subcapsular in 16 patients (13%). The percent area of sentinel node occupied by tumor (p < 0.001), number of sentinel nodes (p=0.041), and microanatomic location of metastatic tumor (p=0.002) were significantly associated with non-sentinel node metastasis in univariate analysis. The percent area of sentinel node occupied by tumor (p < 0.001) and number of sentinel nodes (p=0.033) remained significantly associated with non-sentinel node involvement in multivariate analysis. CONCLUSION: In patients with invasive breast cancer and positive sentinel node, area percent of sentinel node occupied by tumor, and the number of sentinel nodes removed are independently predictive of non-sentinel node involvement.