Polymorphous low grade adenocarcinoma of the buccal mucosa.

PLGA is a rare tumor of the salivary gland that is limited, to a great extent, to the minor salivary glands. However, the most common subsite being the hard or soft palate. This study presents clinical report of PLGA located very rarely on the buccal mucosa, with brief overview on the importance of adequate surgical therapy, PH analysis and cooperation with a pathologist. KEY WORDS: Buccal Mucosa, Multidisciplinary Management PLGA.

Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway.

Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 µM) for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS) production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 µM) with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin.

Potentially inappropriate prescribing of drugs in elderly patients on chronic hemodialysis treatment
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PURPOSE: The aim of this study was to determine the prevalence of potentially inappropriate drug prescription (PIP) in older patients who were on chronic hemodialysis treatment and to explore the factors that lead to PIP. MATERIALS AND METHODS: The study was performed at the Department of Nephrology, Clinical Center Nis, Serbia. It included patients who were 65 years old and older who suffered from the end-stage of kidney failure and were treated by hemodialysis. Univariate and subsequent multivariate logistic regression was used to analyze risk factors for PIP or omission (PPO) according to the STOPP and START criteria. RESULTS: The study included 83 patients. According to the START criteria, PPO was found in 18 (22%) patients, and 32 (39%) patients experienced PIPs according to the STOPP criteria. The following factors were associated with PIP according to the START criteria: a number of comorbidities, reading the patient leaflet, and having the habit of drinking coffee. According to the STOPP criteria, polypharmacy was associated with PIP (OR = 1.287, p = 0.021): each additional drug increased the risk of potentially inadequate medications (PIM) by 28.7%. CONCLUSION: Adequate consideration of potential risk factors, as well as the implementation of valid criteria for assessment of PIP, are just some of the measures that would contribute to solving complex therapeutic problems and designing strategies for rational prescribing according to the individual characteristics of patients.
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Simultaneous self-created transobturator tape and laparoscopic extraperitoneal vaginal support in patients with stress urinary incontinence and prolapse of the anterior and apical vaginal compartments.

OBJECTIVE: Stress urinary incontinence (SUI) is frequently associated with prolapse of the apical and anterior vaginal compartments. The standard treatment of SUI is transobturator tape (TOT). The usual treatment of prolapse (anterior colporrhaphy) has a high recurrence rate. The aim of this study is to evaluate the results of the treatment of SUI and concomitant anterior and apical prolapse with self-created transobturator tape and simultaneous laparoscopic anterior and apical support. STUDY DESIGN: A total of 36 patients with SUI and prolapse of the anterior and apical compartments were underwent operations. The mean follow-up was 18 months. Self-created transobturator tape and laparoscopical support of the anterior and apical compartment prolapse were performed in all patients. The most important symptoms of prolapse and incontinence, the anatomical outcome, and complications were evaluated before and after the surgery. RESULTS: Treatment of incontinence and anterior and apical prolapse was successful in 33/36 (91.7%), 30/36 (83.3%) and 31/36 (86.1%) patients, respectively (p<0.0001). There is a significant reduction of vaginal bulging and pelvic pressure (p<0.0001). Frequency and urgency were significantly reduced (p<0.0007 and p<0.03 respectively). There was no significant deterioration of the posterior compartment. The most important complications were bladder perforation in 2/36 (5.5%) patients and temporary urinary retention in 3/36 (8.3%) patients (Clavien-Dindo grade 3). CONCLUSION: Simultaneous laparoscopic anterior and lateral extraperitoneal support and transobturator tape are effective in the treatment of patients with both conditions.

TGF-ß-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition.

ID genes are required for breast cancer colonization of the lungs, but the mechanism remains poorly understood. Here, we show that Id1 expression induces a stem-like phenotype in breast cancer cells while retaining epithelial properties, contrary to the notion that cancer stem-like properties are inextricably linked to the mesenchymal state. During metastatic colonization, Id1 induces a mesenchymal-to-epithelial transition (MET), specifically in cells whose mesenchymal state is dependent on the Id1 target protein Twist1, but not at the primary site, where this state is controlled by the zinc finger protein Snail1. Knockdown of Id expression in metastasizing cells prevents MET and dramatically reduces lung colonization. Furthermore, Id1 is induced by transforming growth factor (TGF)-ß only in cells that have first undergone epithelial-to-mesenchymal transition (EMT), demonstrating that EMT is a prerequisite for subsequent Id1-induced MET during lung colonization. Collectively, these studies underscore the importance of Id-mediated phenotypic switching during distinct stages of breast cancer metastasis.

[Multiple gigantic renal cysts].

INTRODUCTION: Cystic renal lesions are very heterogeneous lesions which differ in ethiopathogenesis, morphological and clinical manifestations, and also in evolution and therapy. Classification of cystic lesions is complex, symptomatology is poor, and diagnosis is based on complete radiological diagnostic procedures. CASE REPORT: We presented a 20-year old patient with mild subjective symptoms. Objectively, he was without positive clinical signs and changes in biochemistry of blood. Using ultrasonography (US) multiple serous simple cysts were found in both kidneys. Using computed tomography (CT) multiple serous cysts were found, without changes in cystic walls, with preserved renal parenchyma and without cystic changes on other parenchymatous organs. CONCLUSION: Although renal cystic lesions are frequent in adult population, this is a rare example of a young adult man with simple, gigantic, serous cysts which do not produce clinical manifestations nor functional renal difficulty so far.

[Histopathological characteristics and coexpression of p53 and p16(INK4a) proteins in renal cancer].

BACKGROUND/AIM: Renal carcinoma represents histologically heterogeneous group of malignant tumors, with various clinical aggressiveness. The frequency of p53 mutation in primal renal carcinoma is rare, although there are information about its heterogeneous accumulation. The loss of protein p16 expression in primal renal carcinoma is detected in 20-30% of the cases. The aim of this paper was to determine frequency of mutated protein p53 and expression of protein p16(INK4a) in renal carcinoma, to analyze their correlative relation and relation with the examined clinicopathological parameters. METHODS: The examination included 12 patients (66.7% men, 33.3% women), with patohistologically verified renal carcinoma. Expression of mutated form of protein p53 and protein p16 was determined in tissue samples, by immunohistochemical analysis using of mice monoclonical antibodies produced by DAKO, Denmark RESULTS: In 9 (75%) of the cases was detected mutated protein p53, of whom 66.6% had higher histological gradus of tumor (G3-4) and higher pathological stadium of the disease (pT3a-b) at the same time. In 7 (58.3%) and 5 (41.7%) of the cases expression of protein p16, the loss of expression of protein p16 were detected respectively. A statistically significant positive correlation was determined between pathological stadium of disease (TNM) and the degree of tumor differentiation (G) (p = 0.834; p < 0.001), as well as between TNM and mitotic index (p = 0.622; p = 0.031). CONCLUSION: A mutated form of protein p53 exists in 75% of the cases with the renal carcinoma and 66.6% of then have higher histological gradus of tumor and higher stadium of tumor disease at the same time. Coexpression of mutated protein p53 and protein p16(INK4a) in renal carcinoma is not statistically significant and it is not in correlation with clinicopathological parameters. Immunohistochemical analysis of mutated protein p53 in renal carcinoma can have predictive significance.

Aging, aluminium and basal forebrain lesions modify substrate kinetics of erythrocyte membrane Na,K-ATPase in the rat.

Several studies suggested that the activity of erythrocyte Na,K-ATPase declines with aging. Here, it is postulated that alterations in the substrate kinetics of the erythrocyte membrane Na,K-ATPase could be more aggravated in conditions of brain cholinergic dysfunction seen in Alzheimer's disease than in normal aging. To test this hypothesis, we compared the Na,K-ATPase activity (Vmax/Km parameters) in aged rats with those in young rats with brain cholinergic dysfunction induced by electrolytic-, kainic acid-lesioned nucleus basalis magnocellularis (NBM) or by intracerebroventricular AlCl_{3} administration. In the above mentioned groups, Vmax values were significantly lower in comparison to the control animals. Furthermore, Km values were significantly higher in animals with electrolytic-induced NBM lesions, AlCl_{3} treated rats and aged animals. However, Km was significantly lower in kainic acid-induced NBM lesions compared to the control group. The Na,K-ATPase catalytic efficiency, estimated by the ratio Vm/Km, decreased as followed: young animals > aged animals > kainic acid lesion > electrolityc lesion > AlCl_{3}. Our data suggest that neurodegenerative processes similar to those seen in Alzheimer's disease affect the sodium/potassium pump functionality which might be detected in peripheral blood erythrocyte membranes.

[Superficial urinary bladder tumors treatment results--a 10-year experience].

BACKGROUND/AIM: The most common urinary bladder tumors are superficial tumors. Due to their tension to relapse and progress towards deeper layers after surgical therapy, an adequate therapy significantly contributed to the improvement of the results of urinary bladder tumors treatment. Staging and gradus of the tumor, presence of the cardnoma in situ (CIS) or relapses significantly influenced the choice of the therapy. The aim of this study was to ascertain the effectiveness of the intravesicelly applied BCG (Bacille Colmette-Guerin) vaccine or chemiotherapy in the prevention of the relapses and further progression of superficial urinary bladder tumors. METHODS: All of the diagnosed superficial tumors of bladder were removed by transurethral resection (TUR). After receiving the patohistological finding they were subjected to adjuvant therapy, immune BCG vaccine or chemiotherapy (epirubicin, doxorubicin, mitomycin-C). The third group did not accept adjuvant therapy, but had regularly scheduled cystoscopic controls. The appearance of relapses, progression of stage and gradus of the tumor, as well as possible unwanted effects of adjuvant therapy were registered. RESULTS: The applied immunotherapy (BCG) influenced decreased tumor relapses (7%) and statistically important difference between patients who had taken adjuvant chemotherapy (relapses 18.4%) and those without this therapy was acknowledged. Gradus of tumor did not show statistically significant difference on tumor relapse. A significantly longer period of time in the appearance of tumor relapse after BCG (29.33 months), had significant importance comparing to chemio (9.44 months) or non-taken adjuvant therapy (9.84 months). Very small number of unwanted effects suggested an obligatory undertaking adjuvant therapy after TUR of superficial tumors. CONCLUSION: A significant decrease of relapses as well as avoidance of further progression of urinary bladder tumors, has introduced adjuvant therapy in all of the protocols, while the dosing scheme is not unique yet due to trying to find the optimal dose, the length of application and possible dose maintenance.

Targeting prostaglandin E2 receptors as an alternative strategy to block cyclooxygenase-2-dependent extracellular matrix-induced matrix metalloproteinase-9 expression by macrophages.

COX-2-dependent prostaglandin (PG) E2 synthesis regulates macrophage MMP expression, which is thought to destabilize atherosclerotic plaques. However, the administration of selective COX-2 inhibitors paradoxically increases the frequency of adverse cardiovascular events potentially through the loss of anti-inflammatory prostanoids and/or disturbance in the balance of pro- and anti-thrombotic prostanoids. To avoid these collateral effects of COX-2 inhibition, a strategy to identify and block specific prostanoid-receptor interactions may be required. We previously reported that macrophage engagement of vascular extracellular matrix (ECM) triggers proteinase expression through a MAPKerk1/2-dependent increase in COX-2 expression and PGE2 synthesis. Here we demonstrate that elicited macrophages express the PGE2 receptors EP1-4. When plated on ECM, their expression of EP2 and EP4, receptors linked to PGE2-induced activation of adenylyl cyclase, is strongly stimulated. Forskolin and dibutryl cyclic-AMP stimulate macrophage matrix metalloproteinase (MMP)-9 expression in a dose-dependent manner. However, an EP2 agonist (butaprost) has no effect on MMP-9 expression, and macrophages from EP2 null mice exhibited enhanced COX-2 and MMP-9 expression when plated on ECM. In contrast, the EP4 agonist (PGE1-OH) stimulated macrophage MMP-9 expression, which was inhibited by the EP4 antagonist ONO-AE3-208. When compared with COX-2 silencing by small interfering RNA or inhibition by celecoxib, the EP4 antagonist was as effective in inhibiting ECM-induced proteinase expression. In addition, ECM-induced MMP-9 expression was blocked in macrophages in which EP4 was silenced by small interfering RNA. Thus, COX-2-dependent ECM-induced proteinase expression is effectively blocked by selective inhibition of EP4, a member of the PGE2 family of receptors.