First assessment of butyltins (BuTs) contamination of the Montenegrin coast (Southeast Adriatic): Tributyltin (TBT) poses a threat to the marine ecosystem.

This study presents the first assessment of butyltins (BuTs) pollution of the Montenegrin coast. The distribution of tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) was investigated in mussels, sediments and water overlying sediment after the sediment resuspension. The results showed that the investigated sites (marinas, ports, shipyards) are contaminated with BuTs (19-402 ng (Sn)/g in mussels; 43-20,641 ng (Sn)/g in sediments; 9-566 ng (Sn)/L in overlying waters). The measured TBT concentrations indicate that toxic effects on marine organisms are expected at most locations. The simultaneous analysis of BuTs and total Sn in sediment cores allowed the assessment of TBT historical input, while it was demonstrated that resuspension of contaminated sediments leads to the release of all BuTs into the water column. This study shows that, despite the ban of TBT-based antifouling paints more than a decade ago, pollution of the marine environment with TBT is still a problem and regular monitoring remains essential.

Immunotherapy in the treatment of lymphoma.

Relapsed or refractory non-Hodgkin's lymphomas, especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases. Patients who do not respond to initial therapy or experience relapse are treated with salvage regimens, and if eligible for aggressive therapy, treatment is continued with high-dose chemotherapy and autologous stem cell transplantation. Current therapy options can cure substantial numbers of patients, however for some it is still an uncurable disease. Numerous new drugs and cell therapies are being investigated for the treatment of relapsed or refractory lymphomas. Different types of immunotherapy options have shown promising results, and some have already become the standard of care. Here, we review immunotherapy options for the treatment of lymphoma and discuss the results, positions, practical aspects, and future directions of different drugs and cellular therapies for the treatment of this disease.

Effect of heavy metals on stem anatomical characteristics of Trapa natans L from Skadar Lake (Montenegro)

This study aimed to analyze stem anatomical characteristics of Trapa natans from five Skadar Lake locations (L1 - Milovica bay, L2 ­ inflow of the Moraca river, L3 - Kamenik, L4 - Grmozur, L5 - Lipovik) with different concentrations of Cu, Mn, Zn, Co and Pb, during the summer period of the year 2012. Cross sections of stem were made using cryotechnic procedure. For all analyzed quantitative anatomical parameters, the minimum values at the location L2 were recorded, with the presence of maximum content for all investigated metals in stem of Trapa natans. On the other hand, except for cobalt, at the location L4 the minimum concentration for all investigated metals were recorded. Plants collected from this location have the largest average values of the most measured anatomical parameters. The results of Discriminant Analysis showed that plants from different location could be clearly classified into three groups according to their stem quantitative anatomical characteristics which corresponds with heavy metals content. Our research also showed that there is no statistically significant correlation between the content of most investigated metals (Co, Cu, Pb and Zn) and the values of anatomical parameters. Statistically significant negative correlation was found between Mn content in stem and values of two anatomical characters (stem cross-sectional area and Mn content, r = - 0.88; p < 0.05; number of hypodermal cell layers and Mn content, r = - 0.90; p < 0.05).

The Effect of Cu, Zn, Cd, and Pb Accumulation on Biochemical Parameters (Proline, Chlorophyll) in the Water Caltrop (Trapa natans L.), Lake Skadar, Montenegro.

The aim of the present study is to investigate the bioaccumulation and translocation of various heavy metals, notably copper, zinc, cadmium and lead, in the different plant organs of Trapa natans L. (the root, stem, and leaf) at nine sampling locations, as well as examining the variability in proline accumulation and chlorophyll content due to these heavy metals. Our analysis shows the existence of a statistically significant positive correlation (r = 0.75; p < 0.05) between the Zn content and the accumulation of proline in the root of the examined species. On the other hand, a statistically significant negative correlation was registered between the content of chlorophyll a and the concentration of Zn in the leaf (r = -0.68; p < 0.05). This indicates that Trapa natans L. can be used in biomonitoring Zn-polluted aquatic ecosystems using proline and chlorophyll as sensitive biomarkers.

Effects of Sideritis scardica Extract on Glucose Tolerance, Triglyceride Levels and Markers of Oxidative Stress in Ovariectomized Rats.

Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells.

Splenomegaly in Sarcoidosis: Frequency, Treatment, Prognosis and Long-term Follow-up.

INTRODUCTION: The splenic involvement is common in sarcoidosis, but its real frequency is still obscure depending doubtless on the method of splenomegaly detection. Splenomegaly may be accompanied with pain or anemia, leucopenia and thrombocytopenia. OBJECTIVE: The aim of this study was to investigate the frequency of splenomegaly related to clinical characteristics of sarcoidosis and to solve the dilemma--whether to introduce medicaments, and when to perform splenectomy. METHODS: The method of the study is a retrospective and prospective analysis of the patients'material. RESULTS: The study included 540 patients with sarcoidosis in a 20-year period. Of them, 26% had splenomegaly detected by computerized tomography screening. Splenomegaly was more frequently registered in the patients with a longer history of sarcoidosis (38%), as compared to those with a shorter history of the disease (23%) (p < 0.05). Splenomegaly was more frequently registered in the patients with other extrapulmonary lesions detected (33%) than in those who had no extrapulmonary manifestations of sarcoidosis (17%) (p < 0.01). Indications, possible benefits and complications of splenectomy were analysed in 11 sarcoidosis patients undergoing this intervention for various reasons, of which the follow-up period ranged from one to 20 years. CONCLUSION: Splenomegaly was more frequent in chronic cases or in the patients with established sarcoid lesions of other extrapulmonary organs.The primary treatment of uncomplicated symptomatic splenic sarcoidosis includes medicamentous therapy. Occasionally, splenectomy is required. Prognostically, splenomegaly indicates an unfavorable course of the disease.

High dose chemotherapy with stem cell support in the treatment of testicular cancer.

Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.

Concurrent chronic lymphocytic leukemia and merkel cell carcinoma in primary skin tumor and metastatic lymph node.

Association between chronic lymphocytic leukemia and other malignancies has been known for a long time. This epidemiological phenomenon is explained by immunosuppression caused by disease itself or by the applied therapy. Merkel cell carcinoma is a rare malignant tumor of the skin of neuroendocrine origin diagnosed almost exclusively in immunocompromised host. We presented an unique case of coexisting infiltration of chronic lymphocytic leukemia cells within primary cutaneous Merkel cell carcinoma and metastatic lymph node in young HIV-negative female patient.

Comparison of prognostic impact of absolute lymphocyte count, absolute monocyte count, absolute lymphocyte count/absolute monocyte count prognostic score and ratio in patients with diffuse large B cell lymphoma.

BACKGROUND: The combination of absolute lymphocyte count (ALC) and absolute monocyte count (AMC) at diagnosis has prognostic relevance in patients with diffuse large B cell lymphoma (DLBCL). AIMS: The present study was designed to investigate the prognostic significance of ALC and AMC and to determine whether ALC/AMC ratio or ALC/AMC prognostic score is better predictor of outcome in DLBCL. METHODS: We retrospectively analyzed the prognostic significance of ALC and AMC, ALC/AMC ratio and ALC/AMC prognostic score at diagnosis in 222 DLBCL patients treated with R-CHOP. RESULTS: ROC analysis showed that optimal cut-off values of AMC and ALC/AMC ratio with the best sensitivity and specificity were 0.59×10(9)/L and 2.8, respectively. Cut-off of ALC was determined according to the literature data (1×10(9)/L). Low ALC, high AMC, low ALC/AMC ratio and high ALC/AMC prognostic score were in significant association with lower rate of therapy response and survival. In contrast, these parameters were not in significant correlation with relapse rate. The patients with low ALC, "high" AMC, low ALC/AMC ratio and high ALC/AMC prognostic score at diagnosis had significantly shorter EFS and OS. In multivariate analysis all tested parameters (ALC, AMC, ALC/AMC prognostic score and ALC/AMC ratio) are independent risk factors along with "bulky" disease and IPI. CONCLUSION: All tested parameters (ALC, AMC, ALC/AMC score and ALC/AMC ratio) may be useful prognostic factors in DLBCL patients. ALC/AMC score has a slight advantage as it allows the classification of patients into three prognostic groups. Further studies are needed to determine which of these parameters has the highest predictive value.

Intellectual functioning and behavioral disorders.

The paper discusses areas of behavioral functioning of children with intellectual disability, such as behavior with or without hyperactivity. The study covered 124 children with intellectual disability attending elementary schools in Belgrade. The Conners Rating Scale was used, and the areas of behavior in the classroom, participation in the group and attitude towards authority were covered. The results of our study suggest the presence of disorders in behavior and social-emotional functioning ranging from 11.2 to 40.4%. We have highlighted the importance of the use of multimodal approach and method of reeducation of psychomotor activity in rehabilitation of the studied children.

[Metastases of unknown origin--principles of diagnosis and treatment].

DEFINITION: Cancer of unknown primary (CUP) origin refers to patients who present with histologicaly confirmed metastatic cancer in whom a detailed medical history, complete physical examination, including pelvic and rectal examination, full blood count and biochemistry, urinalysis and stool occult blood testing, hisinpathological review oJ biopsy speimens with the use of immunohistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mammography, fail to identify the primary site. EPIDEMIOLOGY OF CUP: The cancer of unknown primary accounts for 3%-5% of all human cancers. DIAGNOSIS OF CUP: The standard diagnostic procedure for the majority of patients includes histopathologic review of biopsy specimens with the use of immunoltistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mamography, fail to identify the abdomen and pelvis. The four common histologic diagnoses are: adenocarcinoma (70%), poorly differentiated carcinoma (20%), squamous carcinoma (10%), and poorly differentiated neoplasms (5%). PROGNOSIS OF CUP: The prognosis for most patients with unknown primary tumors is poor, with survival often less than 6 months from diagnosis. THERAPY OF CUP: Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. CONCLUSION: Metastatic tumors of unknown origin have a unique clinical presentation due to a specific biology. Insight into the molecular biology of unknown primary tumors will be essential for the development of more effective treatments.

Examination of the health status of populations from depleted-uranium-contaminated regions.

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low. Because of the presence of depleted uranium (uranium-238) in the soil and in plants, the prevention of consequences necessitates the identification of the initial biological effects on sensitive tissues. Early identification of serious blood cell changes is important for appropriate medical treatment.