Case presentation of the smallest non-functional parathyroid carcinoma and review of the literature.

INTRODUCTION: Non functional parathyroid carcinoma (PC) is one of the rarest malignant neoplasms. Due to the lack of symptoms and laboratory findings, it is mostly diagnosed in late AQ2 stages, when local invasion and dissemination are already present. However, our case is an exception, because it was detected in early stage, with no local invasion present. We present a case of the smallest non-functional PC yet reported and review of the literature. CASE PRESENTATION: A 47-year-old woman was admitted to outpatient Clinic where fine-needle aspiration biopsy (FNAB) of bilateral thyroid nodules (slide 1) and central neck mass (slide 2), which was suspected to be an enlarged lymphatic nodule or parathyroid gland was performed. Results came back as Bethesda I-colloid (slide 1), and Bethesda IV (slide 2), stating that it is hard to distinguish thyroid gland oxyphil lesions from parathyroid cells. Total thyroidectomy was performed as well as excision of the left central neck mass, without any involvement of surrounding structures. Pathological examination revealed bilateral thyroid follicular nodular disease, papillary microcarcinoma, and parathyroid carcinoma with vascular and capsular invasion, measuring 10 × 8 × 7 mm. The immunohistochemical profile included positive PTH, Chromogranin A, and negative TTF1. CONCLUSION: Non-functional PC is usually diagnosed in advanced stages, already involving adjacent structures; however, this case presents a rare example. It is important not to exclude PC as a differential diagnosis in the absence of elevated Ca and PTH serum levels. Follow-up will be difficult, since there are no prognostic parameters to rely on.

Predictors of health-related quality of life in Serbian patients with head and neck cancer.

BACKGROUND: The aim of this study was to identify predictors of the Health-Related Quality of Life (HRQoL) in patients with head and neck cancers (HNCs). MATERIAL AND METHODS: In total, 345 patients with HNCs were interviewed. A self-report questionnaire was administered to collect data about demographic characteristics, health status, smoking, alcohol consumption habits, and HRQoL. It were used the EORTC Instruments - Quality of Life Questionnaire-Core 30-questions (QLQ-C30), Quality of Life Questionnaire - Head and Neck Module 35-questions (QLQ-H&N 35) and OHIP-14 instrument for HRQoL assessments. Clinical information and treatment data were collected from medical records. RESULTS: Five groups of HRQoL predictors were identified: demographic, socioeconomic, behavioral, psychophysical, and clinical/treatment. These HRQoL predictors had a strong (i.e., age, level of social support and social contact, level of education, depression, fatigue, presence of gastrostomy, comorbidities, and use of pain medications and supplements), a moderate (i.e., marital status, smoking, sexuality problems, time since diagnosis, presence of tracheostomy, and side effects outcomes of radio and chemotherapy) and a small impact (i.e., employment/financial difficulties, tumor site and stage, and surgical procedure). CONCLUSIONS: Study identified nineteen predictors that had significant, moderate and small impact on the HRQoL of patients with HNCs. Some of the predictors, like levels of social support and social contact, depression, and comorbidities could be targets for innervations to improve HRQoL.

ADIPONECTIN AS A POTENTIAL BIOMARKER OF LOW BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH METABOLIC SYNDROME.

CONTEXT: Adiponectin is an abundant adipokine, which has antiinflammatory, anti-atherosclerotic and vasoprotective actions, and potential antiresorptive effects on bone metabolism. It seems to be directly involved in the improvement and control of energy homeostasis, protecting bone health and predicting osteoporotic fracture risk. OBJECTIVE: To examine the relationship between adiponectin level and bone mineral density (BMD) in post-menopausal women with metabolic syndrome (MetS) and low BMD, and to estimate the prognostic significance of adiponectin in osteoporosis. DESIGN: Clinical-laboratory cross-sectional study including 120 middle-aged and elder women (average 69.18±7.56 years). SUBJECTS AND METHODS: The anthropometric parameters were measured for all examinees. Lumbar spine and hip BMD, as well as body fat percentage, were measured using a Hologic DEXA scanner. In all subjects serum adiponectin concentration was measured by ELISA method. RESULTS: The level of adiponectin was significantly positively correlated with BMD-total, BMD of the lumbar spine and BMD of the femoral neck (r=0.618, r=0.521, r=0.567; p<0.01). Levels of adiponectin and BMD are significantly lower in post-menopausal women with MetS and osteoporosis compared to patients with osteopenia (856.87±453.43 vs. 1287.32±405.21 pg/mL, p<0.01; BMD, p<0.05), and the highest values in healthy examinees. A cut-off value of adiponectin level for osteoporosis/osteopenia was 1076.22/1392.74 pg/mL. CONCLUSIONS: Post-menopausal women with MetS have significantly lower adiponectin level and low BMD compared to healthy examinees. Adiponectin may be an early, significant and independent predictor of developing osteoporosis in women with MetS, especially in post-menopausal period.

Enhanced International Prognostic Index (NCCN-IPI), Charlson Comorbidity Index and absolute lymphocyte count as predictors for survival of elderly patients with diffuse large B cell lymphoma treated by immunochemotherapy.

Diffuse large B cell lymphoma (DLBCL) affects more commonly patients over 60 years. These patients have vast number of comorbidities which can modify survival as well as other clinical parameters. The aim of this study was to evaluate prognostic significance of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), absolute lymphocyte count (ALC), absolute monocyte count (AMC), lymphocyte-to-monocyte ratio (LMR) and comorbidities expressed with Charlson Comorbidity Index (CCI). A total of 182 DLBCL patients 60 years old and older were included, focusing on whole group and patients older than 70. All patients were treated with immunochemotherapy.Overall treatment response was achieved in 84.6% of patients. The NCCN-IPI was of highly prognostic value in the analyzed group (p<0.0001). Survival analysis showed that ALC>1.1x109/L, AMC≤0.59x109/L, and LMR>2.8 were associated with more favorable outcome (p=0.029, p=0.019, p=0.028, respectively). The patients with CCI≥2 had poorer outcome (p=0.008) compared to the patients with CCI 0-1. Multivariate analysis showed that among ALC, AMC, LMR, NCCN-IPI and CCI, the NCCN-IPI was the critical parameter that significantly affected survival (p<0.0001). Furthermore, comorbidities were also valuable independent factors which influenced survival (p=0.031) as well as the ALC (p=0.024). In elderly DLBCL patients, NCCN-IPI and ALC proved their prognostic validity, while poorer outcome could be expected in older patients with high CCI (≥2). Furthermore, mentioned prognostic parameters retained their prognostic value in the group of patients older than 70.

Utility of MRI in detection of PET-CT proven local recurrence of pancreatic adenocarcinoma after surgery.

The aim of this prospective study was to investigate the accuracy and inter-observer reliability of MRI in detection of local recurrence (LR) of pancreatic adenocarcinoma (PAC) after surgery, which was proved by PET-CT and access correlation between functional MRI and PET parameters. Forty-five patients who underwent PET-CT and MRI for follow-up purposes after radical operation of PAC were included. Twenty-three were PET positive (study group) and 22 negative for LR (control group). MR examination was performed within one month after PET-CT and three readers who were blind for PET-CT findings searched LR in T2W, 3D-dynamic post-contrast T1W-FS and DWI sequences, respectively. Sensitivity and specificity were calculated while inter-reader agreement was estimated by Cronbach's Alpha reliability coefficient (CARC). Apparent diffusion coefficient (ADC) of LR was correlated with the size (maximal diameter) and functional PET-CT parameters: mean and maximum standardized uptake values (SUVmean, SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), using Spearman's correlation coefficient (rS). Sensitivity and specificity among three readers in detecting the LR were 70% and 77-84% in T2W (CARC 0.806), 91-100% and 100% in 3D post-contrast T1W-FS (CARC 0.980), and both 100% in DWI sequences (CARC 1.000). Moderate inverse correlation was found between the ADC and SUVmean (rS = - 0.484), MTV (rS = - 0.494), TLG (rS = - 0.519) and lesion size (rS = - 0.567). MRI with DWI shows high diagnostic accuracy in detecting the LR of PAC in comparison to PET-CT as reference standard. ADC significantly inversely correlates with standard and advanced PET parameters and size of LR.

Advantages of isolated application of fibrin glue over suture in preservation of second-grade spleen lesion.

OBJECTIVES: The aim of this procedure was to assess the safety and efficiency of glue application in the treatment of lienal second-degree lesions, compared with traditional suture method of treatment. BACKGROUND: The spleen is the most frequently injured intra-abdominal structure regardless of injury mechanisms. Fibrin glue is a useful bio-adhesive for safe and efficient treatment of diffuse parenchymatous spleen haemorrhages. METHODS: Seventy dogs under intravenous anaesthesia were subdued to spleen incision in length of 5 cm and depth of 2 cm. Forty animals from the experimental group were treated with fibrin glue preservation, and 30 animals from the control group were treated with suture. Removed spleens were histologically analyzed. No animal was sacrificed. RESULTS: The application of fibrin glue allowed reparation to be accomplished in all cases. The effectiveness of primary repair was registered in 95 %, with only 5 % of cases requiring an application of fibrin omentoplasty. Secondary bleeding was registered only in 1 (2.5 %) case. Preservation with suture is primarily effective only in 40 %, requires additional repair in 23 %, and even 37 % of cases are not feasible. This method is characterized by mortality of 21 %, secondary haemorrhage (32 %), appearance of focal necrosis (42 %) and abscess (11 %). CONCLUSIONS: Application of FG is a method of choice in cases of second-degree transcapsular spleen lesions and it has a considerable advantage over suture (Tab. 4, Fig. 6, Ref. 24).

Intermittent or continuous occlusion of hepatic inflow.

THE AIM OF THE STUDY: The aim was to compare the effects of intermittent and continuous inflow occlusion on liver I/R injury in an experimental model. METHOD: The experiment was done using the Wistar rats that underwent continuous and intermittent inflow liver vascular occlusion. Blood and liver tissue samples were taken and parameters of hepatic ischemia/reperfusion injury were analyzed and compared. RESULTS: Serum activities of ALT, AST and LDH were significantly higher and ALP activity and albumin concentration were markedly lower in rats with continuous liver ischemia. Also, histopathological examination revealed more severe changes in animals with continuous liver vascular occlusion. CONCLUSION: The results of biochemical assay and histopathological examination were concurrent, both indicating more serious parenchymatous damage caused by continuous hepatic pedicle clamping. Study results clearly demonstrated a better tolerance of the liver to intermittent Pringle maneuver (Tab. 1, Fig. 5, Ref. 9).

Age dependent influence of external temperature on the pathogenesis of idiopathic lower extremity deep vein thrombosis.

AIM: The aim of the present study was to investigate the relationship between the incidence of idiopathic lower extremity deep vein thrombosis (DVT), age, location of the thrombus, and changes of temperature. MATERIAL AND METHOD: During the two year period between May 2009 and April 2011, inclusive, 124 consecutive patients were diagnosed as having idiopathic lower extremity DVT at the Vascular Surgery Clinic, Clinical Center of Nis, Serbia. RESULTS: In patients younger than 45 years, the increase in average daily temperature with 1 degree C 7 days before the event took place was associated (p 0.05) with a decrease of the risk of occurrence of idiopathic DVT of the lower limbs of 3.6% (0.4 6.7%) as well as DVT above the knees (p 0.01) of 4.7 % (1.3 8.0%). In patients of the age of 45 years and over the age of 45 years the increase of average daily temperature with 1 degree C 7 days before the event took place was associated (p 0.01) with the increase of the risk of occurrence of DVT below the knees of 9.4% (3.3 15.9%). CONCLUSION: According to the results of this study, one can conclude that the influence of external temperature change on DVT incidence and location is based on age.

Challenges in Treating COVID-19 Patients With Severe Burn Injuries.

Here we present a case report of a young female patient with severe burn injury inflicting 27% of total body surface area (TBSA) associated with COVID-19 infection. Upon admission, Acinetobacter spp. (sensitive only to Colistin) was isolated from the wound swabs of the right arm, hand and thorax. On the fifth day after admission, a surgical excision was performed and 12% of TBSA was covered with homotransplants. The following day the patient had a sudden drop in oxygen saturation with hypotension (85/45 mmHg). Additionally, agitation, visual and auditory hallucinations were noticed. We found a massive pleural effusion on the left side and pneumonic foci on the right side. On the thirteenth day after admission the final surgical excision and homotransplantation of the skin were performed. In the following days, debridement of all necrotic tissue and covering of all the burned areas with homotransplants were done. Hemodynamic instability of the patient progressed along with the finding on the chest radiography, despite the local finding including adherent homotransplants with no signs of lysis or local infection at the wound beds. Due to low oxygen saturation, the patient was intubated on the fourteenth day after admission. Despite the measures taken, the lethal outcome occurred on the twenty-fifth day after admission to our Clinic. A decision on the right timing for surgical treatment in severely burned COVID-19 patients needs to be investigated in order to enable surgeons to make evidence-based decisions during the pandemic.

Nous présentons le cas d'une femme jeune souffrant d'une brûlure sur 27% SCT associée à une infection à COVID-19. À son entrée, elle était colonisée (zones brûlées du bras droit, de la main et du thorax) à Acinetobacter sensible uniquement à la Colistine. À J5 était réalisée une excision/homogreffe sur 12% SCT. Le lendemain survenaient brutalement un collapsus (PA 85/45 mm Hg) et une hypoxie profonde. Elle était agitée et souffrait d'hallucinations visuelles et auditives. Il existait un épanchement pleural gauche de grande abondance et une foyer de pneumopathie à droite. Elle a dû être intubée à J14. À J15, l'excision/homogreffe a été complétée. Elle était reprise le lendemain pour complément d'excision et reprise des homogreffes. L'instabilité hémodynamique et les signes radiographiques s'aggravaient quand les homogreffes ne lysaient pas. Elle est décédée à J25. Le positionnement temporel de l'excision chez les patients brûlés atteints de COVID-19 doit être mûrement réfléchi.

The Impact of the COVID-19 Pandemic on Self-Inflicted Burn Injuries in Patients With Previously Diagnosed Bipolar Disorder.

Here we present a case of a 52-year-old female patient who was admitted to the Clinic in December 2021 due to the presence of right side facial burns which were caused by a cigarette lighter under suspicious conditions. Her past medical history revealed she was diagnosed with bipolar disorder at the age of 20 and was hospitalized multiple times for the treatment of manic episodes. The last psychiatric hospitalization took place in October 2021. She had deep second-degree burns on the right side of the face, head and neck, with a total body surface area involvement of approximately 3%. On hospital day 18, she was found unresponsive, dyspnoic, with no palpable pulse and measurable tension. Electrocardiogram (ECG) monitoring revealed sinus bradycardia followed by cardiac asystole. After the first few minutes of cardiopulmonary resuscitation, heart and lung action was re-established. Due to the presence of ECG changes in the form of ST depression and negative T waves in V2-V6, D1 and aVL, also higher blood level of high sensitivity troponin T, she was urgently transported to the Coronary Unit where she was diagnosed with non-ST-elevation myocardial infarction. On hospital day 27, due to the presence of sub-febrile temperature and non-productive cough, she was tested for COVID-19 infection and transported to the COVID Hospital Batajnica. She was discharged with stable laboratory parameters and normal chest radiography 37 days following initial admission. Considering the great psychological impact related to the COVID-19 pandemic, extensive mental health support and regular monitoring of critical groups is indicated.

Nous présentons le cas d'une femme de 52 ans hospitalisée en décembre 2021 pour brûlures par briquet de la partie droite du visage, survenue dans des circonstances suspectes. Le diagnostic de trouble bipolaire avait été posé sur elle à l'âge de 20 ans et elle a été hospitalisée à de multiples reprises en raison d'épisodes maniaques, la dernière fois en octobre 2021. Les brûlures, profondes, siégeaient au niveau de la partie droite du cou, du visage et du cuir chevelu, représentant 3% de sa SCT. À j18, elle est retrouvée inconsciente, dyspnéique, sans pouls palpable ni pression artérielle mesurable. L'ECG montre une bradycardie sinusale puis une asystole. Le ressuscitation est un succès en quelques minutes. On observe un sous-décalage de ST en D1, aVL et de V2 à V6 ainsi qu'un mouvement de troponine motivant son transfert en cardiologie, où le diagnostic d'infarctus du myocarde est posé. A J27, le diagnostic d'infection à COVID-19 est avéré, à la suite d'un syndrome fébrile et d'une toux sèche, elle est transférée à l'hôpital Batajnica. Elle sort à J37, avec une biologie et une radiographie thoracique normales. En raison des conséquences psychologiques de la pandémie COVID-19, un support psychologique doit pouvoir être largement disponible et les populations les plus à risque doivent être régulièrement suivies.

The influence of the tooth preparation finish line position on the expression of matrix metalloproteinase-9 and the presence of periodontopathogens in the gingival crevicular fluid.

OBJECTIVE: The objective of the study was to determine the concentration of matrix metalloproteinase 9 (MMP-9) and changes in the presence of periodontopathogens in the gingival crevicular fluid before and after tooth preparation with the subgingival and equigingival finish line position. PATIENTS AND METHODS: The clinical prospective study included 20 subjects with an indication for upper canine preparation, with the subgingival (group 1) and equigingival finish line (group 2). Samples were taken in four observation intervals: 5 minutes before (control samples), as well as 15 minutes, 24 and 72 hours after tooth preparation (experimental samples). Measurement of MMP-9 was done using Enzyme-linked Immunosorbent Assay (ELISA). The presence of bacteria in the gingival fluid was proven by the Polymerase chain reaction (PCR) analysis. RESULTS: The MMP-9 values did not differ statistically significantly between the groups (p=0.524). The MMP-9 values showed a statistically significant difference in the given observation period (p<0.001) with a significant linear increase in values (p<0.001). A significant quadratic trend recorded a decrease in the MMP-9 values 15 minutes after preparation, and an increase 24 hours after preparation, without a significant difference in the interaction between groups (p=0.392). After preparation, a significant difference in the presence of periodontopathogens was confirmed, i.e., a decrease in the presence of Prevotella intermedia (p=0.025) and Tannerella forsythia (p=0.016) in group 1, and an increase in the presence of Aggregatibacter actinomycetemcomitans in both groups (p=0.029, p=0.026). CONCLUSIONS: The study is a good basis for determining the influence of tooth preparation on gingival inflammation, with therapeutic (choice of preparation technique) and preventive significance regarding the protection of the periodontal tissue from possible iatrogenic damage.

Prognostic value of survivin expression in Wilms tumor.

PURPOSE: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. METHODS: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. RESULTS: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). CONCLUSION: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT.

Relationship between the incidence of idiopathic lower extremity deep vein thrombosis and the location of the thrombus depending on the changes in atmospheric pressure.

AIM: The study analysed the relationship between the incidence of idiopathic lower extremity deep vein thrombosis (DVT) and the location of the thrombus with changes in atmospheric pressure. MATERIAL AND METHOD: During the two year period between May 2009 and April 2011, inclusively, 124 consecutive patients were diagnosed as having idiopathic lower extremity DVT at the Vascular Surgical clinic "Clinical Center of Nis", Serbia. RESULTS: The increased average daily values of atmospheric pressure for 1 millibar on the day when the event took place and 7 days before, were associated (p < 0,05) with the increase of the total risk of the occurrence of lower extremity idiopathic DVT for 5,1% (0,7-9,8%), as well as with the occurrence of idiopathic DVT above the knees (p < 0,05) for 5,9% (0,9-11,0%). The increase in the average atmospheric pressure by 1 millibar on the day when the event took place and 7 days before this in the subgroup of patients under the age of 45 years, and on the day when the event took place and 3 days before it in the subgroup of patients of the age of 45 and above, was related with the increased risk of the occurrence of lower extremity idiopathic DVT. CONCLUSION: The increase of daily values of atmospheric pressure shows a significant relationship with the incidences of idiopathic lower extremity DVT and the location of the thrombus above the knee.

Diagnostic value of the nuclear matrix protein 22 test and urine cytology in upper tract urothelial tumors.

OBJECTIVE: To investigate the diagnostic value of the nuclear matrix protein 22 (NMP22) test in comparison to urine cytology for the detection of upper tract urothelial carcinoma. PATIENTS AND METHODS: Patients with transitional cell carcinoma of the upper urinary tract (n = 34) and patients with renal calculosis (n = 25) were included in this study. Voided urine samples and separated catheter urine specimens were assayed for NMP22 and cytological examination. RESULTS: The sensitivity of the NMP22 test in separated and voided urine was 73.2 and 70.5%, respectively, compared to 64.7 and 58.8% of urine cytology. The specificity of the NMP22 test in separated and voided urine was 88 and 92%, respectively, compared to 96 and 96% of urine cytology. The combination of separated and voided urine is the best method because the sensitivity is 79.41% and specificity 88%. There is a high agreement of the NMP22 test in voided and separated urine (kappa = 0.795, p < 0.01), indicating that the voided urine is adequate for diagnosis. CONCLUSIONS: The NMP22 test has higher sensitivity but lower specificity than cytology. The combination of these two tests could be a very useful diagnostic method for detection of upper urothelial tumors.

Can the official soccer game be considered the most important contribution to player's physical fitness level?

AIM: During competitive soccer match play, elite players are subdued to vigorous physical and psychological strains. Thus, some changes in overall physical fitness can be expected. The objective of this paper was to determine whether official games influence physical fitness in soccer players. METHODS: The participants were divided according to the number of minutes spent in the game as well as according to some additional criteria into starters (STA; N.=33, >1000 minutes spent in the official game) and non-starters (NON; N.=31, <1000 minutes spent in the official game). Both groups participated in the initial (end of pre-season) and in the final testing procedures (one week after the end of the competition period). The total of 24 variables covered players' power performance, kicking the ball, aerobic capacity, agility and flexibility. RESULTS: The STA group showed positive significant differences (P<0.05) from the NON group in 21 out of 24 variables. The most significant findings of this study point to the fact that official games help in maintaining and improving agility parameters (6 out of 7 tests) as well as in maintaining and improving overall power performance of soccer players which includes sprinting, jumping and kicking the ball. CONCLUSION: Due to specific physiological and psychological factors, official matches make it possible for the starters to develop the mentioned aspects to a higher level when compared to the non-starting team colleagues.

Prevalence and risk factors for thyroid cancer in patients with multinodular goitre.

BACKGROUND: Rates of thyroid cancer in patients with multinodular goitre (MNG) vary widely, from 3 per cent in older studies to 35 per cent in more recent studies. The purpose of the present study was to evaluate the prevalence of thyroid cancer in patients operated on for MNG, and to determine risk factors for incidental thyroid malignancy. METHODS: A prospectively developed database of all patients who underwent thyroidectomy for a benign MNG at the high-volume endocrine surgery unit of a tertiary referral university hospital was interrogated. RESULTS: A total of 3233 patients were analysed, separated into three groups according to their functional thyroid status (hypothyroid, hyperthyroid or euthyroid). There were 2788 women (86.2 per cent); the mean patient age was 56.4 years and mean preoperative disease duration was 106.2 months. Incidental thyroid cancer was identified in 1026 patients (31.7 per cent), of which 917 (89.4 per cent) were papillary cancers. Multivariable regression analysis identified functional thyroid status, younger age, male sex, smaller adenoma size, smaller thyroid glands, Hashimoto's thyroiditis and chronic non-specific thyroiditis as independent risk factors for thyroid cancer. CONCLUSION: MNG was associated with a considerable rate of incidental thyroid cancer, which has been underestimated. A variety of factors should be taken into account when considering the malignant potential of a presumed benign MNG.

Interleukin-6 stimulates cell migration, invasion and integrin expression in HTR-8/SVneo cell line.

Interleukin-6 (IL-6) is present in human endometrium throughout menstrual cycle and in pregnancy. Trophoblast also expresses IL-6. IL-6R and its associated signal transducer gp130 were found in trophoblast as well. IL-6 is generally assumed to be relevant for trophoblast invasion. This study was undertaken to determine influence of endogenous and externally added IL-6 on invasion and migration of first trimester of pregnancy trophoblast in vitro. Integrins alpha(5)beta(1) and alpha(1)beta(1) have been shown to play an important role in trophoblast invasion and the effect of IL-6 on the expression of these integrin subunits was studied. We are showing that in both isolated first trimester of pregnancy cytotrophoblast (CTB) and HTR-8/SVneo cell line IL-6 and IL-6R are present. The effect on migration was studied using cell wounding and migration test on HTR-8/SVneo cells. Effect of IL-6 and function blocking anti-IL-6 antibody in Matrigel invasion tests was studied on both cell types. The effect of IL-6 on integrin subunit expression was determined by cell-based ELISA and Western blot on HTR-8/SVneo cells. The results obtained show that exogenous IL-6 has stimulatory effect on cell migration in HTR-8/SVneo and invasion by both cell types. Function blocking anti-IL-6 inhibited unstimulated invasion by isolated first trimester cytotrophoblast and both cell migration and invasion in unstimulated HTR-8/SVneo. Integrin alpha(5) expression was stimulated by IL-6 to 134% (p<0.05), alpha(1) to 135% (p<0.005), and beta(1) to 134% (p<0.001) of control in cell-based ELISA, but also in Western blot. The data obtained show for the first time sensitivity of extravillous trophoblast cell line HTR-8/SVneo to IL-6, in addition to isolated first trimester cytotrophoblast. We conclude that both exogenous and endogenous IL-6 stimulate trophoblast cell migration and invasion, which may be partly attributable to stimulation of expression of the studied integrin subunits.

Analysis of cutaneous melanoma in the province of Vojvodina.

PURPOSE: To analyse the incidence and mortality of melanoma in the province of Vojvodina - the north part of Serbia- from the epidemiologic and clinical point of view. PATIENTS AND METHODS: In this retrospective study, we used databases of the Cancer Registry of Vojvodina, Oncology Institute of Vojvodina in Sremska Kamenica; Clinical Centre of Vojvodina in Novi Sad; Institute of Public Health of Vojvodina in Novi Sad; and Institute of Public Health of Serbia in Belgrade. RESULTS: The incidence and mortality of melanoma in Vojvodina is permanently increasing over the last three decades. The number of newly diagnosed and deceased patients was higher in men and in women in Vojvodina than in central Serbia. Considering the incidence rate, the region of Vojvodina would be placed in the middle of the European countries. The results are more unfavorable with mortality, especially in male population, similar to the range of higher mortality rates among European countries. CONCLUSION: These upsetting facts call for improvement of primary and secondary prevention. Education of the population, continuous efforts to recognize groups of population at high risk for developing melanoma and detection of early phases of the disease increases the chances for cure and significantly reduces treatment costs.

Functional and pharmacological analysis of agmatine administration in different cerebral ischemia animal models.

Agmatine (AgM, 100 mg/kg i.p.) effect was tested in parallel at two animal models of cerebral ischemia - rat MCAO model (60'/24 h, 60'/48 h, 90'/24 h, 90'/48 h) and gerbil global ischemia (10') model, administrated 5 min after reperfusion. Aim was to evaluate AgM effect on functional outcome 24 and 48 h after MCAO on neurological and sensor-motor function, and coordination in rats. AgM administration significantly reduced infarct volume, improved neurological score and improved post-ischemic oxidative status. Results of behavioral tests (cylinder test, beam walking test, and adhesive removal test) have shown very effective functional recovery after AgM administration. Efficiency of AgM administration in gerbils was observed in forebrain cortex, striatum, hippocampus, and cerebellum at the level of each examined oxidative stress parameter (nitric oxide level, superoxide production, superoxide dismutase activity, and index of lipid peroxidation) measured in four different time points starting at 3 h up to 48 h after reperfusion. The highest levels were obtained 6 h after the insult. The most sensitive oxidative stress parameter to AgM was nitric oxide. Additionally, we performed pharmacological analysis of AgM on rat isolated common carotid arteries. The findings imply that mixed population of potassium channels located on the smooth muscle cells was involved in common carotid artery response to AgM, with predominance of inward rectifying K+ channels. In our comparative experimental approach, judged by behavioral, biochemical, as well as pharmacological data, the AgM administration showed an effective reduction of ischemic neurological damage and oxidative stress, hence indicating a direction towards improving post-stroke recovery.

Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore be pivotal to elucidate the molecular mechanisms of TRAIL resistance. Here, we identify X-linked inhibitor of apoptosis (XIAP) as a regulator of TRAIL sensitivity in pancreatic carcinoma cells. Full activation of effector caspases, loss of mitochondrial membrane potential and cytochrome c release following TRAIL treatment were markedly impaired in pancreatic carcinoma cell lines, which poorly responded to TRAIL (PaTuII, PancTu1, ASPC1, DanG), compared to TRAIL-sensitive Colo357 pancreatic carcinoma cells. Stable downregulation of XIAP by RNA interference significantly reduced survival and enhanced TRAIL-induced apoptosis in pancreatic carcinoma cells. Also, downregulation of XIAP significantly increased CD95-induced cell death. Importantly, knockdown of XIAP strongly inhibited clonogenicity of pancreatic cancer cells treated with TRAIL indicating that XIAP promotes clonogenic survival of pancreatic carcinoma cells. Thus, our findings for the first time indicate that targeting XIAP represents a promising strategy to enhance the antitumor activity of TRAIL in pancreatic cancer, which has important clinical implications.