Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats.

BACKGROUND: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. METHODS AND RESULTS: Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-ß), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-ß, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group. CONCLUSION: It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.

Protective effect of alpha-lipoic acid against apical periodontitis-induced cardiac injury in rats.

This study was designed to assess the possible protective effect of alpha-lipoic acid (ALA) on apical periodontitis (AP)-induced cardiac injury. Wistar albino rats were randomized into four groups: control; ALA; AP; and ALA + AP. Rats of the control and ALA groups were not endodontically treated, but saline and ALA (100 mg kg-1 ) were administered. In rats of the AP and ALA + AP groups, the pulp chambers of mandibular first molar teeth were exposed and left open for 30 d to induce AP. Saline and ALA (100 mg kg-1 ) were administered intraperitoneally every 24 h during the experiment. At the end of the experiment, the rats were killed. Establishment of AP was verified by radiographic and histopathological evaluation. Serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and superoxide dismutase (SOD) activities were determined using an automated biochemical analyzer, and the structural cardiac injury was assessed pathologically. Serum ALP, LDH, and CK activities were elevated, and SOD activities were decreased, in the AP group. The changed enzyme activities were significantly normalized by treatment with ALA. We conclude that ALA administration alleviated the AP-induced heart injury and improved cardiac structure and function, and therefore this agent may be of potential therapeutic value in protecting cardiac tissue from systemic injury caused by AP.

Expression of voltage gated potassium channel ether à go-go in pituitary adenomas of patients with acromegaly: A preliminary study.

OBJECTIVE: To determine immunohistochemical expression of Eag1 in pituitary adenomas of patients with acromegaly and to assess the correlation between Eag1 expression with cavernous sinus invasion, tumoral Ki-67 labeling index (LI), age and gender of the patients. METHODS: The paraffin embedded pituitary adenoma tissue sections of 28 patients with acromegaly who were diagnosed as monohormonal growth hormone (GH) secreting adenomas were immunostained for Eag1 using the avidin-biotin-peroxidase complex method. Eag1 immunoreactivity was scored according to the extensity of the cytoplasm and cell membrane immunoreactivity for Eag1 (score 1 = <10%, score 2 = 10-25%, score 3 = 25-50% and score 4 = >50% of the adenoma cells showed immunoreactivity for Eag1, respectively). RESULTS: Overall, GH secreting pituitary adenomas displayed diverse levels of Eag1 immunoreactivity, however, 64% of the adenomas displayed a strong Eag1 immunoreactivity (score 3 and 4). Five of the tumors displayed Eag1 immunoreactivity score 1, 5 displayed score 2, 10 displayed score 3 and 8 displayed score 4, respectively. No correlation was found between Eag1 immunoreactivity with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. CONCLUSIONS: Our results suggest Eag1 is strongly expressed in the majority of GH secreting pituitary adenomas. However, we could not find any correlation between immunoreactivity of Eag1 with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. Further studies with larger sample sizes are required to demonstrate the role of Eag1 on tumorigenesis, angiogenesis, invasion and response to the treatment in GH secreting pituitary adenomas.

MGMT immunoexpression in adamantinomatous craniopharyngiomas.

At present, no effective medical treatment exists for recurrent and aggressive craniopharyngiomas that are resistant to conventional therapies, including surgery and adjuvant radiotherapy. Temozolomide is an alkylating chemotherapeutic agent used routinely in the management of high grade gliomas. The response to temozolomide is suggested to be dependent on the tumoral expression of O-6 methylguanine DNA methyltransferase (MGMT). Evidence supports that low MGMT immunoexpression correlates with positive response to temozolomide. Therefore, we aimed to assess MGMT immunoexpression in adamantinomatous craniopharyngiomas, in an effort to predict the likelihood of response to temozolomide. The MGMT immunostaining was performed on 23 adamantinomatous craniofaryngiomas operated at the Sisli Etfal Training and Research Hospital and identified by histological analysis. Paraffin embedded tissue sections were immunostained for MGMT and were evaluated semi-quantitatively. Of the 23 cases evaluated, 22 (96%) demonstrated negative (<10%) and 1 (4%) demonstrated low (10%) MGMT immunoexpression. Data from this study suggest a high proportion of adamantinomatous craniopharyngiomas exhibit negative/low MGMT immunoreactivity and could be treated with temozolomide, if conventional therapy fails.

Anti-Inflammatory Effects of Melatonin and 5-Methoxytryptophol on Lipopolysaccharide-Induced Acute Pulpitis in Rats.

AIM: The aim of this study was to investigate the possible therapeutic impacts of two pineal hormones, melatonin and 5-methoxytryptophol (5-MTX), in a rat model of acute pulpitis by analyzing biochemical and histopathological parameters. METHODS: This research was done using 32 male and female Wistar albino rats with weight between 200 and 250 g. The rats were randomly divided into four groups: a control group (rats without any treatment), acute pulpitis (AP) group, AP+melatonin group, and AP+5-MTX group. In the AP-induced groups, the crowns of the upper left incisors were removed horizontally. Lipopolysaccharide solution was applied to the exposed pulp tissue before the canal orifices were sealed with a temporary filling material. Melatonin (10 mg/kg) and 5-MTX (5 mg/kg) were administered intraperitoneally. The rats were sacrificed 24 hours after pulp injury, and trunk blood and pulp samples were collected. The concentrations of TNF-α, IL-1ß, MMP-1, and MMP-2 in sera and pulp samples were determined using ELISA assay kits. RESULTS: TNF-α, IL-1ß, MMP-1, and MMP-2 levels in the serum and pulp tissues were considerably higher in the AP group than the control group (p < 0.01-0.001). In the AP+melatonin and AP+5-MTX groups, TNF-α, IL-1ß, MMP-1, and MMP-2 levels in the serum and pulp tissues were significantly lower than in the AP group (p < 0.05-0.001). CONCLUSIONS: Both melatonin and 5-MTX provided protective effects on acute pulpitis, which indicates they may be promising as a therapeutic strategy for oral disease.

Altered tonsillar toll-like receptor (TLR)-1 and TLR-2 expression levels between periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), and group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis patients.

INTRODUCTION: Tonsillar microenvironment is thought to contribute to innate immune dysregulation responsible for the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) because of beneficial effects of tonsillectomy on treatment of the syndrome. Accordingly previous studies reported altered lymphocyte frequency, cytokine level and microbial composition in PFAPA tonsils. The aim of our study is to monitor expression levels of pro-inflammatory cell surface Toll-like receptors (TLRs) which have important role in induction of inflammation and maintaining tissue haemostasis. MATERIALS AND METHODS: Seven patients with PFAPA syndrome, and eight patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis were included in our study. Tonsillar expression levels of TLR-1, -2, -4, -5, and -6 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: IHC analysis demonstrated expression of all TLRs in tonsillar surface epithelium (SE) and lymphoid interior (LI) except for TLR-6 which was not present in the former. There has not been any statistically significant difference in TLR expression levels between PFAPA and GAßHS tonsils, except for TLR-1 and TLR-2 which were higher on LI and lower on SE of PFAPA tonsils, respectively, than that of the GAßHS samples. CONCLUSIONS: Altered TLR expression levels may be involved in PFAPA pathogenesis. Future studies with higher patient number, uninflamed tonsils and cellular markers are required to further enlighten the role of TLRs in the development of syndrome.

Platelet-rich fibrin can accelerate the healing of common bile duct anastomosis in a rat.

OBJECTIVES: This study aimed to evaluate the effect of platelet-rich fibrin (PRF) concentrate on the bile duct anastomosis healing process in rats. MATERIAL AND METHODS: Thirty male Sprague Dawley (SD) rats were used for the study. The animals were allocated into three groups: Group I Control Group (n=10): Anastomosis to the common bile duct (CBD) with a stent. Group II PRF Group (n=10): Anastomosis to the CBD with a stent and covered with PRF. Group III Sham Group (n=10): Preparation of the common bile duct, no anastomosis. The animals were followed up for 1 month, then sacrificed. Study parameters were adhesions around the anastomosis, thickness of the bridging bile duct tissue over the stent, and histopathologic examination of the bridging bile duct tissue. RESULTS: CBD anastomosis using a stent caused severe adhesion around the anastomosis, bridging bile duct tissues were weak and histopathologically, healing was incomplete in most of the control animals. However, PRF application significantly reduced the adhesions, increased the quality of the bridging bile duct tissues, and caused complete healing histologically. CONCLUSION: PRF is an autologous, easily prepared membrane. The present study findings show that PRF prevents local complications and increases the healing capacity of the bile duct after CBD anastomosis. Therefore, it might be a new treatment option for preventing complications following common bile duct anastomosis in liver transplantation patients.

The effects of cryopreserved human amniotic membrane on fracture healing: Animal study.

OBJECTIVE: The aim of this study was to investigate the effects of human amniotic membrane (HAM) on fracture healing in an animal model. METHODS: Standard tibial diaphysial fractures were created in twenty-eight Wistar-Albino rats and treated with intramedullary Kirschner wire (K-wire) and HAM (HAM (+) group) or K-wire only (HAM (-) group). Fracture healing was evaluated by histological analysis, radiologic X-ray views and callus diameter measurements at 3rd and 6th weeks postoperatively. RESULTS: Fracture healing was histologically better in the HAM (+) group and the difference was statistically significant at both 3rd and 6th weeks postoperatively (p < 0.05). The highest histologic scores and entire woven bone formation (Huo Stage 8-9) were obtained at 6th weeks postoperatively in the HAM (+) group. Histological examination also revealed predominant fibrous tissue and partial cartilage formation (Huo Stage 2) at the postoperative 3rd week in the HAM (-) group. Equal amounts of woven bone and cartilage formation (Huo Stage 6-7) were observed at 3rd weeks postoperatively in the HAM (+) group and at 6th weeks postoperatively in the HAM (-) group. The callus diameters were greater in the HAM (+) group and the difference was statistically significant (p < 0.05) at 3rd and 6th weeks postoperatively. Although there was only a statistically significant difference (p < 0.05) at the postoperative 3rd week, radiological scores tended to be higher in the HAM (+) group at both the 3rd and 6th weeks postoperatively. CONCLUSION: HAM is a cheap and easily accessible alternative biological material. HAM may be used to support surgical treatment of fractures, particularly where bone healing is expected to last longer.

A case of lipomembranous panniculitis with a dramatic response to the treatment of venous insufficiency.

Lipomembranous panniculitis (LP) is a peculiar type of fat necrosis and is reported with various clinical conditions, mostly with peripheral vascular diseases. Here, a case of a 57-year-old woman with a painful erythematous swelling of the right leg in association with venous insufficiency has been reported. Although LP is frequently associated with venous insufficiency, to the best of our knowledge, this is the first report on the beneficial effect of venous insufficiency treatment in LP.

Tonsillar antimicrobial peptide (AMP) expression profiles of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) patients.

INTRODUCTION: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) is the most frequent non-infectious cause of high fever observed among the European child population. While its cause is still not yet fully identified, PFAPA patients were previously shown to have altered tonsillar microbiome composition. Our study hypothesized that this is associated with a change in antimicrobial peptide (AMP) expression levels, as in the case of Crohn's disease which is another autoinflammatory disorder. METHODS AND MATERIALS: The tonsil specimens were isolated from seven patients with PFAPA syndrome, and six patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis. Tonsillar expression levels of human beta-defensin 1-2, cathelicidin, ribonuclease-7, and liver expressed antimicrobial peptide-1 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: Our results showed no significant difference in AMP expression levels between PFAPA and GAßHS patients. Immunolocalization of human beta-defensin 1 was different between the two groups; expressed at higher levels on tonsil surface epithelium (SE) than lymphoid interior (LI) in PFAPA patient group, while this was not evident in GAßHS patients group. CONCLUSIONS: Our results suggest that, PFAPA patients may be associated with altered AMP expression as in other autoinflammatory diseases. Future studies with subjects without any inflammatory condition are required for more precise conclusions.

Successful resection and reconstruction of primary cardiac lymphoma.

Primary cardiac lymphoma (PCL) is one of the rarest tumors of the heart. The most common type is diffuse, large B-cell lymphoma. Most often, the right atrium and the right ventricle are involved, and if not diagnosed and treated in time, it can be fatal. In this case, a female patient underwent an urgent operation for a large, infiltrative, right atrial mass. Extensive resection of the lateral walls of both atria and the interatrial septum as well as reconstruction were performed successfully. The pathological evaluation suggested PCL. The aim of this case is to raise awareness of this disease and to highlight clinical and surgical approaches.

Mucosal Malignant Melanoma of Nasal Cavity Recurring a Year After Radiotherapy.

OBJECTIVE: Sinonasal mucosal malignant melanoma is a rare entity. In this report we present a nasal mucosal malignant melanoma case with its histopathological and clinical features. CASE REPORT: An 88-year-old female patient presented with epistaxis a month ago. Examination revealed a polypoid mass lesion of right nasal cavity originating from the middle concha. Her medical history revealed that she had been found to have a mass lesion in the right nasal cavity 15 months ago. She then underwent a punch biopsy from that lesion. A definitive histopathological diagnosis was not made but it was declared that the lesion had been a malignant epithelial tumor. The patient then had radiotherapy and the lesion showed complete regression. One year after completion of radiotherapy, the lesion recurred. Her last PET-CT showed multiple metastatic foci. Endoscopic excisional biopsy was performed for her recurrent lesion. Fragmented tumoral tissues were measured as 3,6x3x0,5 cm. Macroscopically the tumor was brownish in color. Histopathologically the tumor consisted of spindled and epitheloid cells. Immunohistochemically the tumor cells displayed positivity for S-100, HMB-45 and Melan-A. Findings were consistent with malignant melanoma. DISCUSSION: Mucosal malignant melanomas have a poor prognosis despite chemotherapy and radiotherapy. Five-year survival for sinonasal melanoma is reported to be lower than 35%. Sinonasal melanomas show a high recurrence rate. The immunohistochemical markers showing high specificity for malignant melanoma such as S-100, HMB-45 and Melan-A are used in order to reach a correct diagnosis. In our case the tumor showed recurrence and multiple metastases 1 year after completion of radiotherapy. For this recurrent tumor, chemotherapy and radiotherapy have been planned.

Symplastic Glomus Tumor.

Glomus tumors showing nuclear pleomorphism without any other malignant features have been defined as symplastic glomus tumors. This type of glomus tumor is rarely encountered. Another case of symplastic glomus tumor is described in this study. A 37-year-old woman referred to the hospital with the complaint of a palpable tender nodule on the fourth finger tip of her left hand. The lesion had been present for about a year and aggravation of tenderness upon cold exposure was conspicuous. It was a 0.5 cm well circumscribed lesion with round to cuboidal epithelioid cells showing high grade nuclear pleomorphism. Nests of cells more uniform in shape and showing punched out nucleus representative of typical glomus tumor could also be observed. Immunohistochemical study showed expression of smooth muscle actin, caldesmon and vimentin. Ki-67 labeling index was undetectable. Investment of tumor cells was shown by type IV collagen. In contrast to its atypical cellular morphology, symplastic glomus tumor clinically behaves benign, and it is important to differentiate it from malignant glomus tumor as well as other primary or metastatic malignant tumors.

Evaluation of Breast Cancer Cases Diagnosed In the Breast Cancer Screening Program In the Near East University Hospital of North Cyprus.

OBJECTIVE: This study is about determination and eveluation of the breast cancer cases which were diagnosed during the early diagnosis and screening programs covering a three years of digital mammography images at the Near East University Hospital. MATERIALS AND METHODS: This study covers 2136 women patients who applied to the early diagnosis and screening program of the Near East University Hospital between July 2010 and July 2013. The mamographic images were re evaluated retrospectively according to ACR's (The American College of Radiology) BIRADS (Breast Imaging Reporting and Data System). The mamographic results as required were correlated with breast ultrasound (US) and compared with the pathologic results of materials obtained by surgery or biopsy. The results were analyzed statistically in comparison with the literature data. RESULTS: The women who were screened aged between 34-73 years with a median of 53.5 (SD = 27.5). Suspected malignancy were evaluated in 54 patients, which 42 of them were diagnosed BIRADS 4 and 12 patients BIRADS 5 and 21 patients were correleted breast cancer based on histopathologic examination. 17 patients had the breast-conserving surgery and 4 patients were treated with mastectomy. CONCLUSION: Breast cancers that are detected at early stages by breast cancer screening tests are more likely to be smaller and still confined to the breast resulting in more simple operations and more succesfull treatment. Promoting the breast cancer screening and registration programs in our country will help to control the desease at our region.

MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with Ki-67 labeling index and cytokeratin distribution pattern.

Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.