THE EXPRESSION OF STEM CELL MARKERS (CD133, NESTIN, OCT4, SOX2) IN INVASIVE PITUITARY ADENOMAS.

INTRODUCTION: The pituitary gland serves as the center of the endocrine system. Stem cells are typically found in a specialized microenvironment of the tissue, called the niche, which regulates their maintenance, self-renewal, fate determination, and reaction to external influences. The aim of this study is to elucidate the role of stem cells in the initiation, invasion, and progression of pituitary adenomas. MATERIALS AND METHODS: All specimens were collected between January 2007 and April 2015. Radiological classification (invasiveness) for all cases was performed according to the Wilson-Hardy classification system. Immunohistochemical staining was performed to all specimens for CD133, Oct4, Sox2 and nestin. RESULTS: The study included 48 patients. Of 48 patients, 17 (35.4%) were male and 31 (64.6%) were female. Mean age is 47.10±14.14 (17-86 yrs.). According to the Wilson-Hardy classification system, 27 (56.3%) were non-invasive adenomas. There was no statistical significance between the expression of pituitary stem cell markers (CD133, OCT4, SOX2, nestin) and invasiveness. CONCLUSION: All stem cell markers are stained extensively in pituitary adenomas, except for SOX2 which was stained weakly. However, there is no effect of stem cells on invasiveness of pituitary adenomas because we cannot find a difference of the staining level between invasive and non-invasive adenomas. Nestin was stained extensively in functional adenomas, especially for GH, PRL, and gonadotropin secreting adenomas. SOX2 was stained extensively for ACTH-secreting adenomas.

LOW O6-METHYLGUANINE-DNA METHYTRANSFERASE (MGMT) AND PAN-CYTOKERATIN (PAN-CK) EXPRESSION VIA IMMUNOHISTOCHEMISTRY IN PITUITARY ADENOMAS.

INTRODUCTION: Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. MATERIAL AND METHOD: All patients who underwent surgical decompression consecutively between 2007-2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. RESULTS: The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH- and LH-secreting adenomas. CONCLUSION: Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

Human brains found in a fire-affected 4000-years old Bronze Age tumulus layer rich in soil alkalines and boron in Kutahya, Western Anatolia.

Undecomposed human bodies and organs always attracted interest in terms of understanding biological tissue stability and immortality. Amongst these, cases of natural mummification found in glaciers, bog sediments and deserts caused even more attention. In 2010, an archeological excavation of a Bronze Age layer in a tumulus near the Western Anatolia city Kütahya revealed fire affected regions with burnt human skeletons and charred wooden objects. Inside of the cracked skulls, undecomposed brains were discernible. To analyze the burial taphonomy of the rare phenomenon of brain preservation, we analyzed brains, bone, teeth and surrounding soils elements using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Adipocere formation or saponification of postmortem tissue fat requires high levels of alkalinity and especially potassium. Indeed, ICP-MS analysis of the brain, teeth and bone and also of the surrounding soil revealed high levels of potassium, magnesium, aluminum and boron, which are compatible with the famous role of Kütahya in tile production with its soil containing high level of alkalines and tile-glazing boron. Fatty acid chromatography revealed simultaneous saturation of fats and protection of fragile unsaturated fatty acids consistent with soil-presence of both pro-oxidant and anti-oxidant trace metals. Computerized tomography revealed protection of diencephalic, metencephalic and occipital tissue in one of the best-preserved specimens. Boron was previously found as an intentional preservative of Tutankhamen and Deir el Bahari mummies. Here, in natural soil with its insect-repellant, anti-bacterial and fire-resistance qualities it may be a factor to preserve heat-affected brains as almost bioporcellain specimens.

Giant chordoid meningioma symptomatic immediately after pregnancy: report of a rare case.

BACKGROUND: Chordoid meningioma is a very rare subtype of meningioma with less than 90 cases reported in the literature. Meningiomas related with a pregnancy are also very rare. Herein, we present a pregnancy-associated case of a chordoid meningioma and briefly discuss possible mechanisms. CASE HISTORY: Approximately 10 hours after a Caesarean section, a 37-year-old woman became stuporous with a Glasgow coma scale score of 9 - 10 and the right pupil became dilated without reaction to light. An emergency computed tomography scan showed a right frontotemporal lesion measuring 8 x 7 x 6 cm which enhanced moderately and homogenously after intravenous contrast injection. The patient's hemoglobin level was slightly lower than normal level but there was no dysgammaglobulinemia or lymphoid hyperplasia. The patient was immediately taken to the operating theater and the tumor was gross totally removed. The postoperative period was uneventful; and histopathological diagnosis was chordoid meningioma. CONCLUSION: The exact mechanism causing a pregnancy-associated increase in the size of meningiomas and the amount of peritumoral edema has not been clearly elucidated. As for this case of chordoid meningioma associated with pregnancy, we think mucin accumulation in tumor could be involved in an increase in the tumor size while delivery procedures with the common anaesthetic and sedative drugs may also have enhanced the peritumoral edema by causing a relative decrease in the cerebral blood flow.

Intraosseous soft tissue perineurioma: report of a vertebral example.

OBJECTIVE: To describe a unique intraosseous perineurioma affecting the L2 vertebral body and pedicle of a 28-year-old female. MATERIAL: A lytic, expansive lesion virtually limited to bone was gross totally excised; only minimal epidural extension was noted. METHODS: Histologic, immunohistochemical and ultrastructural studies were performed. RESULTS: The tumor was partially encapsulated, moderately cellular, and showed classic features of benign soft tissue perineurioma, being composed of interlacing fascicles of spindle cells with undulating nuclei and long, very narrow, cytoplasmic processes. Immunohistochemistry showed reactivity for EMA, Glut-1, claudin, collagen-4 and CD34; no S-100 or neurofilament protein staining was seen to suggest an origin in nerve. CONCLUSION: Perineurioma, a tumor affecting soft tissue, and presumably nerve-unassociated, may affect bone. No prior entirely osseous examples have been reported. This tumor expands the differential diagnosis of spindle cell tumors of bone.

Oncocytic choroid plexus carcinoma: case report.

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of spinal cord and cortical motoneurons. Despite improved understanding of the mechanisms underlying ALS, in clinical practice the management of ALS remains essentially supportive and focused on symptom relief. However, over the past few years stem cell research has expanded greatly as a tool for developing potential new therapies for treating incurable neurodegenerative diseases. METHODS: Thirteen patients with sporadic amyotrophic lateral sclerosis (SALS) were included in this study, and bone marrow (BM)-derived hematopoietic progenitor stem cells were used. We selected patients with bulbar involvement and severe loss of movement. Our aim was to put the stem cells into the end of the brain stem and at the beginning of the spinal cord because the blood-brain barrier is intact in ALS and this region was the most affected part in our patients. Under general anesthesia, a total laminectomy was performed at the C1-C2 level. Stem cells were injected to the anterior part of the spinal cord. RESULTS: During the follow-up of 1 year after stem cell implantation, nine patients became much better compared with their pre-operative status, confirmed by electro neuro myography (ENMG). One patient was stable without any decline or improvement in his status. Three patients died 1.5, 2 and 9 months, respectively, after stem cell therapy as a result of lung infection and myocardial infarction (MI). DISCUSSION: These results show that stem cell therapy is a safe, effective and promising treatment for ALS patients.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis.

BACKGROUND: Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production. OBJECTIVES: To investigate the possible role of leptin in psoriasis pathogenesis. METHODS: Forty-three patients with psoriasis, 10 diseased and 10 healthy controls with normal body mass index were included. Serum fasting leptin levels of the study group were examined by enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression of both patients and controls were investigated by immunohistochemistry. RESULTS: Serum leptin levels, tissue leptin and leptin receptor expression were significantly higher in patients with severe psoriasis than patients with mild-moderate psoriasis and controls (P < 0.05). Serum leptin levels showed a positive correlation with Psoriasis Area and Severity Index and involved body surface area in patients with psoriasis. In addition, serum leptin levels, tissue leptin and leptin receptor expression showed a positive correlation with disease duration in patients with psoriasis (P < 0.01, r = 0.979; P < 0.01, r = 0.691; P < 0.01, r = 0.428, respectively). CONCLUSIONS: We assume that leptin might serve as a marker of severity in psoriasis and also may be a pathogenetic cofactor contributing to chronicity of the disease. Consequently, its role in obesity and cardiovascular disease in patients with psoriasis deserves to be studied. In addition, drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.

The effects of quantum energy surgical device and of bipolar coagulation: a comparative experimental study.

OBJECTIVE: The quantum energy surgical device (QESD) employs an innovative, "no-touch" thermal coagulation, incision and evaporation technique in which thermal energy is delivered to tissue in the format of high-energy neutral argon gas atoms. The aim of this study is to compare QESD and bipolar coagulation (BC) through assessment of both haemostasis and histological damage to isolated femoral arteries of rats. METHODS: Sixty rats were randomly divided into acute and short-term experimental groups. In the acute group (n=20) histopathological evaluation was performed immediately following coagulation, whereas in the short-term experimental group (n=20) the evaluation was performed 10 days later. Each sham group consisted of ten rats. Viewed under the surgical microscope, only normal-appearing, freshly sectioned, and bleeding femoral arteries were studied. Right femoral arteries subject to QESD coagulation, and left femoral arteries to BC. Haemorrhaging was controlled using the minimal coagulation time necessary to stop it. All vascular layers, including endothelium, internal elastic lamina, media and adventitia were examined histologically and ultrastructurally in a "blind" fashion to critically compare morphological damage due to QESD and BC. RESULTS: Surgical haemostasis induced by QESD was found to be as safe as BC. Light microscopy revealed more marked histopathological changes in the BC than in the QESD group. These involved mainly the endothelial and medial compartments and, at the ultrastructural level, consisted of endothelial degeneration and exfoliation, irregularity of internal elastic lamina, degeneration, and loss of medial smooth muscle. CONCLUSION: The results indicate that QESD coagulation induces significantly less histological damage than does BC. Thus QESD coagulation is a safe, less tissue destructive, and equally effective method of haemostasis.

MR imaging, CT, and angiography features of endolymphatic sac tumors: report of two cases.

Low-grade adenocarcinoma of endolymphatic sac origin is a rare tumor of the temporal bone. There are some difficulties in its differential diagnosis from other vascular and non-vascular tumors of the temporal bone. However its radiological differentiation from other tumors of the temporal bone is important for surgical planning. We present a report on two endolymphatic sac tumors with some specific radiological findings which can support a correct diagnosis.

Vascularization pattern of C6 glioma is modified with medroxyprogesterone acetate and ibuprofen in Wistar rat brain.

Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.

Medroxyprogesterone acetate alone or synergistic with chemotherapy suppresses colony formation and DNA synthesis in C6 glioma in vitro.

We have studied the effects of medroxyprogesterone acetate (MPA) on C6 glioma growth in vitro in order to prove the hypothesis that it could arrest growth and induce drug sensitisation in a glial tumour as it does in breast cancer cells. Plating, thymidine-labelling index, ultra-structure, and soft agar colony growth were determined after incubation with MPA, and/or cisplatin, procarbazine and methotrexate (MTX). MPA (microg/ml) reduced the thymidine-labelling index by 41 and 73% at 48 and 96 h, respectively, and decreased colony growth by 61%. Soft agar colony inhibition by MPA was almost as potent as MTX (0.3 microg/ml), but the latter drug showed very high cytotoxicity. Electron microscopy revealed that in medroxyprogesterone treated cells myeloid bodies developed, but MTX treatment caused mainly necrosis. Medroxyprogesterone increased procarbazine and cisplatin-induced colony growth and S-phase inhibition, but reduced MTX-induced thymidine-labelling inhibition. In conclusion, progesterone may inhibit growth and sensitize to drugs.

Spinal solitary fibrous tumor: seventh reported case and review of the literature.

We present the clinical, radiological, and pathological features of a solitary fibrous tumor in the spinal cord. This case is the seventh spinal solitary fibrous tumor in the literature. The tumor caused clinical symptoms in a 70-year-old female, which indicated compression of the spinal cord. Magnetic resonance imaging showed an intradural extramedullary mass at T3 vertebral level. Surgically, the tumor was firm, in an intradural extramedullary location and attached to the dura. Histologically, the tumor was composed of spindle cells in a collagen-rich matrix but exhibited regional variations. CD34 and vimentin were diffusely positive during immunohistochemical stain testing. The tumor displayed no positive staining for epithelial membrane antigen, cytokeratin, S-100 protein, smooth muscle actin or desmin. The Ki-67 labeling index was low. Solitary fibrous tumors have been found in a variety of locations suggesting that a solitary fibrous tumor has a mesenchymal origin. This rare tumor should be considered in the differential diagnosis of spinal tumors.

Tumor in tumor: metastasis of breast carcinoma to intracranial meningioma.

This report presents magnetic resonance imaging (MRI) findings of a breast carcinoma metastasis in an intracranial meningioma with correlated pathological findings. MRI showed multiple foci of intense enhancement with hypointense surrounding areas. The described foci appeared to be metastatic disease from the patient's known breast carcinoma. In addition, this is the first study reported in the literature to have investigated the expression of a possibly common carcinogenic molecule in breast carcinoma metastatic to a coexisting meningioma: overexpressed c-myc oncogene was found both in the breast carcinoma compartment and in the meningioma component of the tumor.

The effect of tizanidine on chronic vasospasm in rats.

BACKGROUND: Cerebral vasospasm after subarachnoid hemorrhage (SAH) has remained a major cause of morbidity and mortality in patients with SAH. Excitatory neurotransmitters are gathered in the extracellular space during ischemia due to cerebral vasospasm and initiate or stimulate a series of pathophysiological biochemical processes which consequently lead to neuronal death. Tizanidine (Sandoz compound DS 103-282, 5-chloro-4,2 (2-imidazolin-2-yl-amino)-2,1,3-benzothiazol hydrochloride) is a centrally-acting muscle relaxant and a selective alpha 2 adrenoreceptor agonist which shows its effect by stimulating presynaptic alpha 2 adrenoreceptors in central ASPergic and GLUergic system by inhibiting aspartic acid and glutamic acid release. In this study, the effect of Tizanidine on vasospasm was evaluated. METHODS: We used a femoral artery vasospasm model in rats which has been described by Okada et al. 60 rats were examined in three groups. The first group was used as control group (Control) (n = 20), in the second group subarachnoid hemorrhage was performed (SAH) (n = 20), in the third group Tizanidine was administered in addition to SAH (SAH + Tizanidine administration) (n = 20). Animals in SAH + Tizanidine administration group received 0.3 mg/kg/day intraperitoneally for 7 days. Seven days after the experiment, after perfusion-fixation, 10 mm segments of both femoral arteries were removed and the femoral artery was prepared for light microscope examination, scanning and transmission electron microscopy and for morphometric analysis. RESULTS: There was a statistically significant difference between the electron, scanning and light microscopic observations and morphometric analysis of SAH + Tizanidine administration group and SAH group, and no statistically significant difference between SAH + Tizanidine administration group and control group. CONCLUSION: This study has disclosed that Tizanidine administration before the vasospasm reduces ultrastructural and morphometric vasospastic insult significantly. However, the clinical application of Tizanidine as a protective and therapeutic agent in cerebral vasospasm needs further studies including the employment of clinically more relevant SAH models.

Fat prefabrication using a fascial flap in the rat model.

Prefabrication of fat tissue using a fascial flap based on the superficial inferior epigastric artery was studied in rats. First, the superficial inferior epigastric fascia was transposed over the inguinal fat pad. Two weeks later fascia and fat were elevated together as a prefabricated composite flap. At this stage, a pilot study was done in ten rats and perfusion of the flaps was tested with fluorescein. After confirming fluorescein staining of the prefabricated flaps, the study continued with experimental and control groups of rats. In the experimental group, prefabricated flaps were transposed to the subcostal area. In the control group, the pedicles of the flaps were severed, creating composite grafts. These grafts were transferred to the subcostal area in the same manner as in the experimental group. One week later the flaps were re-elevated and grafts were exposed. Fluorescein tests and Indian ink microangiography were carried out. In the experimental group, the flaps were stained, while grafts in the control group were not stained. Fat and fascia were found to be viable in the experimental group, while they were necrotic in the control group on histopathological examination. Based on these findings, we can conclude that the prefabrication of fat by vascular fascia is successful and may have application in plastic surgery.

Serial MRI and MRS studies with unusual findings in Rasmussen's encephalitis.

Rasmussen's syndrome is characterized by intractable seizures and progressive neuropsychiatric deterioration secondary to unilateral cortical inflammation and tissue destruction. Diagnosis of Rasmussen's syndrome in the early phase depends mainly on the clinical features. Neuroimaging and histopathologic examinations may not be specific during this period. We report a case of Rasmussen's syndrome followed by serial MRI and magnetic resonance spectroscopy (MRS) studies over a 3- to 16-month period. A healthy 6-year-old boy presented with focal motor seizures. An MRI study demonstrated prominent enlargement and T2 hyperintensity of the left mesial temporal lobe and perisylvian region. This early finding evolved to volume loss and later progressive atrophy of the ipsilateral hemisphere when epilepsia partialis continua occurred. Being aware of those early MRI features in a patent with increasing frequency of focal motor seizures should suggest Rasmussen's syndrome. In addition, we found prominently increased myoinositol concentration in atrophic cortex which might reflect increased gliosis in the late period of the disease.

Hemimegalencephaly and Hirschsprung's disease: a unique association.

A 2-year-old boy with hemimegalencephaly and Hirschsprung's disease is reported. The unique association of these two entities is considered to be the presence of a common insult or insults that affect the innervation of the bowel and the formation of the cerebral cortex. Short-segment subtype of Hirschsprung's disease may suggest that this effect occurred between the eighth and twelfth weeks of gestation. Although there is a well-known coexistence of Hirschsprung's disease with the malformations that share a common neurocristopathic origin (abnormalities of neural crest cell growth, migration, or differentiation), a few extremely rare cases, as in this case, might reflect the coexistence of Hirschsprung's disease with a cerebral malformation (i.e., hemimegalencephaly) that is a nonneurocristopathic entity by itself.

Enzymatic treatment of ileal segments used for urinary tract reconstruction.

Urinary tract reconstruction by using various gastrointestinal segments is not devoid of complications which may hamper to a great extent the beneficial effects of the procedure. Intestinal mucosa is the primary site responsible for these complications and any procedure aiming at the prevention of untoward effects of intestinal interposition should abolish the absorptive and secretory functions of the mucosa. Augmentation cystoplasties by ileal segments were performed on 24 male albino Wistar rats. In 12 animals de-epithelialization of the mucosa with an enzymatic cock-tail, consisting of type I and type V collagenases and trypsin, preceded the cystoplasty. The functional capacity of the epithelium was determined by a simplified glucose absorption test in the third postoperative week. Morphological examination before the absorption test did not reveal any fibrosis or shrinkage of the ileal segments. Complete elimination of the absorptive capability in enzyme treated mucosa was found during the glucose absorption test, while a rapid and highly effective absorption was observed in the control group (p < 0.05). As a result, it seems possible to obtain intestinal segments covered with a mucosa which acquired similar characteristics to uro-epithelium, therefore closely resembling the original urinary tissues.