The role of purinergic P2Y12 receptor blockers on the angiogenic properties of endothelial cells: an in vitro study.

Pharmacotherapy with agents that inhibit platelet function has proven to be effective in the treatment of acute coronary syndrome. Proper re-endothelization after angioplasty prevents adverse cardiovascular events. Therefore, in this in vitro study we examined how antiplatelet P2Y12 receptor blockers can affect endothelial cells' angiogenic properties. Endothelial cells were exposed to ticagrelor, prasugrel and clopidogrel in their highest concentrations obtained in serum after the treatment with loading and clinical doses. Further, the viability, apoptosis, and necrosis were tested and the following angiogenic properties such as proliferation, migration, invasiveness, tube formation, wound healing and the production of angiogenic mediators (bFGF, PDGF, MMP-2, Ang-2, TIMP-1). The results of this study showed that P2Y12 receptor blockers in the tested concentrations are safe for endothelial cells. They neither induced necrosis or apoptosis nor changed the endothelial cell viability, migration, invasiveness, tube formation, wound healing, the production of VEGF or its receptors. However, they reduced cell proliferation. It was shown that out of these three drugs, ticagrelor in its loading concentration had the most potent angiogenic property. It reduced cell proliferation and changed the production of angiogenic (bFGF, MMP-2) and angiostatic mediators (Ang-2). In conclusion, P2Y12 receptor blockers in the concentrations obtained in the serum during standard therapy reduced endothelial cell proliferation. Despite this slight antimitogenic effect, they did not change endothelial cell tube formation or wound healing. Out of the three tested drugs, ticagrelor had the most potent angiogenic effect in vitro, but not strong enough to disturb tube formation and wound healing.

Cerebrospinal fluid and serum IL-8, CCL2, and ICAM-1 concentrations in astrocytic brain tumor patients.

BACKGROUND: The aim of the study was the evaluation of serum and CSF concentrations of CCL2, IL-8, and sICAM-1 in patients with astrocytic tumors as compared to a group of non-tumoral patients. METHODS: Chemokine concentrations were measured using the ELISA method. RESULTS: Regardless of the parameter tested and the patient group (brain tumor or non-tumoral patients), statistical differences (P < 0.05) were found between concentrations obtained in CSF compared to values obtained in serum for all proteins tested. CSF IL-8 concentrations were significantly elevated in CNS tumor patients as compared to non-tumoral individuals (P = 0.000); serum CCL2 and sICAM-1 concentrations were significantly decreased in CNS tumors in comparison with the comparative group (P = 0.002 and P = 0.026, respectively). Among proteins tested in the serum, a higher area under the ROC curve (AUC) revealed CCL2 compared to sICAM-1 in differentiating subjects with CNS brain tumors from non-tumoral subjects. AUC for CSF IL-8 was higher than for its index (CSF IL-8/serum IL-8). CONCLUSIONS: For individual biomarkers (IL-8 and CCL2, sICAM-1), measured in CNS brain tumor patients, the appropriate material, respectively CSF or serum, should be chosen and quantitatively tested. Increased cerebrospinal fluid IL-8 with decreased serum CCL2 create a pattern of biomarkers, which may be helpful in the management of CNS astrocytic brain tumors.

Prognostic role of tumor volume for radiotherapy outcome in patient with T2 laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor volume (TV) is recognized as a prognostic factor of treatment outcome for head and neck tumors but is not routinely included in the treatment decision-making process. The purpose of the study was to define its prognostic role for patients with T2 laryngeal cancer. MATERIAL AND METHODS: TV of 160 patients who underwent RT between 2002 and 2006 for T2 laryngeal squamous cell carcinoma were reviewed. The tumor was located in the glottis and epiglottis in 82 (51%) and 78 (49%) patients, respectively. TV was manually contoured on pretreatment, planning, contrast-enhanced CT scans and the volumetric measurement (cm3) was calculated by the volume algorithm. RESULTS: The median TV value was 2.01 cm3 (range 0.15-21.68 cm3). The median TV was significantly lower in patients with glottic tumors (p<0.0001), N0 (p<0.001), or well histopatologically differentiated tumors (p=0.01). A significant correlation between TV, hemoglobin concentration (p<0.01), and total dose (TD; p<0.001) was observed. On univariate analyses, TV influenced local control (LC; p=0.02) and overall survival (OS, p<0.001). On multivariate analysis, both age (HR 1.038, p=0.03) and TV (HR=1.075, p=0.01) remained significantly related to LC and OS (age: HR 1.038, p=0.005; TV: HR 1.097, p=0.0001). CONCLUSION: Large TV worsen prognosis of patients with T2 laryngeal cancer. A large TV is more common for supraglottic, poorly differentiated tumors and may suggest higher risk of nodal spread. The routine estimation of TV prior to therapy may be essential in order to select the best treatment option for patients with T2 laryngeal cancer.

Predictors of radiotherapy outcome in patients with T2 supraglottic carcinoma.

The decision regarding treatment of early supraglottic carcinoma remains controversial. Single institution clinical data of patients with T2 supraglottic carcinoma treated exclusively with radiotherapy in terms of prognostic factors and treatment results were analyzed. Patient-related factors that would potentially by useful for optimal therapeutic decision to be undertaken were especially investigated. Between 1994 and 2004, 78 patients with T2 supraglottic carcinoma underwent radiotherapy (RT) in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland. There were 54 (69%) males and 24 (31%) females in the median age of 61 years. There were 17 (22%) patients with N+. Median body mass of patients before (BM0) and after RT (BM1) was 74 kg (range 45.2-130 kg) and 72.9 kg (range 49.9-122.5 kg), respectively. Median hemoglobin concentrations before (Hb0) and after (Hb1) RT were 14.3 and 13.4 g/dl, respectively. Median change of Hb concentration during RT (dHb) was -0.8 g/dl. All were treated up to total doses (TD) ranged from 62.5 to 72 Gy. The overall treatment time (OTT) ranged from 30 to 70 days. Estimates of local control (LC), ultimate local control (uLC), and overall survival (OS) were calculated using the Kaplan-Meier method. Log rank statistics, Cox proportional hazard model and step-wise Cox regression hazard model were employed to identify prognostic factors for LC, uLC, and OS in univariate and multivariate analyses. The 5-year LC, RC, uLC and OS rates were 85, 92, 88, and 56%, respectively. In multivariate analysis N+ (p = 0.01) and prolonged OTT (p = 0.03) significantly decreased LC. Females (p = 0.02), higher BM0 (p = 0.03), and HB0 (p = 0.006) significantly prolonged OS. Patient-related factors like gender, hemoglobin concentration, and body mass may predict treatment outcome. Radiotherapy is effective for T2 supraglottic carcinoma of the larynx unless higher dose intensity is provided. Involved regional lymph nodes significantly deteriorate locoregional cure.

Effect of aerobic exercise on insulin, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in overweight and obese postmenopausal women.

AIM: The purpose of presented study was to verify the influence of aerobic physical activity program on the serum insulin, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations in overweight and obese postmenopausal women. METHODS: Somatic parameters and serum concentrations of insulin, IGF-1 and IGFBP-3 were measured in 21 overweight and obese women, before and after 8-week cycloergometer physical workout and 16 age-matched, controls. Age of all studied women ranged from 54 to 78 years. RESULTS: The comparative analysis of biochemical indices measured before and after the training program showed that the systematic exercise cause the significant decrease in insulin (P<0.05) and IGF-1 concentrations (P<0.05). There were no differences in these parameters in controls over the studied period. The level of IGFBP-3 was not significantly changed in both investigated groups. In women participating in the training program the positive correlation (P<0.05) between changes in IGF-1 levels (Δ) and changes in insulin concentrations (Δ) within two terms of the study were found. The magnitude of changes (Δ) in insulin and IGF-1 levels over the study period correlated with their concentrations measured before the training program (P<0.01). CONCLUSION: Results of the present study indicate that regular aerobic physical activity decreases serum insulin and IGF-1 levels in postmenopausal women. The magnitude of insulin and IGF-1 concentration changes depend on their initial levels. Changes of IGF-1 levels are associated with insulin concentration modifications.

Endoscopic repair of CSF leaks in the postero-superior wall of the frontal sinus - report of 2 cases.

BACKGROUND: Bony defects extending laterally or superiorly within the posterior wall of the frontal sinus are generally deemed too difficult for endoscopic repair in spite of significant progress in surgical endoscopic techniques. PATIENTS AND METHODS: We describe a technique of endoscopic repair of posttraumatic cerebrospinal fluid (CSF) leak from the postero-superior aspect of the frontal sinus in a 40- and a 29-year-old male. In both cases after careful assessment of the surgical anatomy the sinus was widely opened transnasally (Draf IIB and Draf III approach, respectively). Angled (45 and 70°) optics and malleable, individually profiled instruments were used to fit specific anatomic variations encountered during the procedure. RESULTS: Endoscopic manipulation near the dome of the sinus proved to be very limited in spite of a wide surgical opening. In our cases the site of the leak could be identified and successfully sealed with gentle pressure on the dura mater. The bony defects were repaired with a 2-layer reconstruction technique. There were no signs of recurrence during 6 months follow-up. CONCLUSION: With contemporary endoscopic instrumentation, endoscopic closure of CSF leaks in the supero-posterior wall of the frontal sinus is feasible, especially in patients with favourable anatomy of the frontal sinus.

Assessment of the ability of mononuclear blood cells to produce IFN-gamma in patients with laryngeal cancer.

The ability of mononuclear blood cells (PBMC), derived from patients with cancer of the larynx, to produce IFN-gamma in vitro was assessed in this paper. Thirty patients (27 male, 3 female) were qualified to the study. Their mean age was 65 (range: 41 to 78 years), tumour sizes found in the group were from T2 to T4, levels of pathologic malignancy G2 or G3. The percentage rates different blood cells phenotypes (CD3+, CD3+ HLADR+, CD4+, CD8+, CD14+ HLADR+, CD19+, CD56+) were evaluated by means of flow cytometry (Coulter EPICS XL). The control group consisted of 20 healthy blood donors. PBMC were derived by centrifugation of heparinized venous blood on Lymphoprep gradient according to Boyum method. Double cell cultures were performed for 24 hours with antibody anti-CD3 or recombinant interleukins 12 (rhIL-12) or 18 (rhIL-18). The statistic analysis was based on Student t and Mann-Whitney's test with significancy at p<0.05. A significant decrease in the production of IFN-gamma by PBMC in patients with laryngeal cancer after stimulation with antiCD3 (p=0.018), rhIL-12 (p=0.027), rhIL-18 (p=0.016) was found in comparison with the controls. The results suggest a decreased production of IFN-gamma in patients with cancer of the larynx.

Voice analysis after the partial laryngectomy in patients with the larynx carcinoma.

The paper presents 170 cases of patients with the larynx carcinoma after the partial laryngectomy. According to the procedure which we used, vertical, horizontal and subtotal supraglottis laryngectomies were distinguished. Voice pattern was analysed with the use of subjective and objective spectrography. The lowest degree of dysphonia was found in patients after the horizontal laryngectomy, while the highest degree dysphonia in those after subtotal supraglottis laryngectomy.

Evaluation of the voice function after the supraglottis subtotal laryngectomy.

Voice quality was analysed in 39 patients with the larynx carcinoma after the supraglottis subtotal laryngectomy. Voice pattern was analysed with the use of subjective and objective spectrography before and after the surgery. A deteriorated voice quality was found after the surgery. The spectrographic examination revealed decreased frequency levels of the formants F3 and F4 and the presence of a noise component generated in the glottis area.

[Cytokines in allergic inflammatory process]. / Cytokiny wplywajace na alergiczny proces zapalny.

In our review article we intend to show the importance of IL-4, IL-5, IL-13, IL-10, IFN gamma and IL-12 in pathomechanism of allergic inflammatory process, especially in bronchial asthma. We also want to illustrate the relationships between lymphocytes T, monocytes, macrophages, eosinophils and other inflammatory cells which take part in allergic inflammation.

Identification and localisation of auditory areas in guinea pig cortex.

The organisation of guinea pig auditory cortex was studied by combining histological methods with microelectrode mapping. This allowed the location of seven auditory areas to be determined in relation to the visual and primary somatosensory areas. The auditory areas were identified by single-unit recordings and their borders defined by evoked potential mapping. The visual areas were identified by their relatively high densities of myelinated fibres, while the primary somatosensory cortex was identified by its characteristic barrels of high cytochrome oxidase (CYO) activity in layer IV. The auditory region had moderate levels of CYO and myelin staining. When staining was optimal, there was a clear edge to the moderate CYO activity, which apparently corresponds to the dorsal border of the primary auditory area (AI) and the other core field that lies dorsocaudal to it (DC). Thus the primary somatosensory area and the visual and auditory regions were separated from each other by a region with lower levels of CYO and myelin staining. The ventral borders of AI and DC could not be determined histologically as there were no sharp transitions in the levels of CYO or myelin staining. The two core areas were partially surrounded by belt areas. The dorsorostral belt and most of the belt around DC responded more strongly to broad-band stimuli than pure tones, while the ventrorostral belt, small field and a belt zone ventral to the rostral part of DC responded better to pure tones. Units in the small field (S) typically had higher thresholds and broader tuning to pure tones than AI, while units in the ventrorostral belt typically had longer onset latencies and gave more sustained responses than units in AI.

Organisation of binaural interactions in the primary and dorsocaudal fields of the guinea pig auditory cortex.

This study investigated the nature and topography of binaural interactions in the primary auditory field (AI) and dorsocaudal field (DC) of the urethane anaesthetised guinea pig auditory cortex. Single and multi-units were classified by their responses to monaural and binaural stimulation. In both AI and DC, units displayed binaural facilitation, binaural inhibition, or a level dependent mixture of facilitation and inhibition. There was a significant difference in the distribution of binaural response types between the two fields. Facilitated units predominated in DC (facilitated: 58%; inhibited: 24%; mixed: 6%; non-interacting: 12%), while inhibited units were the most common class in AI (facilitated: 15%; inhibited: 44%; mixed: 18%; non-interacting: 22%). It has previously been suggested that inhibited and facilitated units are concerned with processing different areas of space suggesting a possible separation of function between the two core fields. Topographically, the binaural response properties in AI and DC varied along isofrequency bands, with neurones displaying similar interactions aggregating in clusters. These clusters were similar in size for the two fields and often overlapped neighbouring isofrequency bands. However, their shape and position varied between different animals. This clustered organisation of binaural interactions is similar to that reported in recent studies of AI in other mammals.

Phase-locked responses to pure tones in guinea pig auditory cortex.

Phase-locked responses to pure tones are a characteristic of most auditory cells at the level of the brain stem and allow sophisticated analyses based on coincidence detection. Phase-locking to tones has not previously been shown at the level of the auditory cortex in single unit studies. We have now identified phase-locked responses in 10% of low-frequency (< 1 kHz) units in the ventrorostral belt, a strip of cortex immediately ventral to the primary auditory area. All of these units showed phase-locking in their response to binaural tone pips of 60-200 Hz and showed narrow band pass characteristics within this range.

A ventrorostral belt is adjacent to the guinea pig primary auditory cortex.

The previously defined anterior area (A) of guinea pig auditory cortex has been divided into a large dorsal portion identified as the primary area (AI) and a smaller ventrorostral belt (VRB). This division is based on: (1) the much longer response latency of units in VRB (21.7 ms) than AI (14.1 ms); (2) the absence of pure onset units in VRB (i.e. units that lacked a sustained response), which are common in AI; (3) the weakness of noise-induced evoked potentials in VRB compared to AI; (4) units in VRB had lower thresholds and stronger phase locking to amplitude modulated stimuli than in AI.

Cohesion and organization patterns among family members coping with rheumatoid arthritis.

The effects of rheumatoid arthritis (RA) on family functioning are described from two perspectives, cohesiveness and organization. These concepts are believed to be essential for assessing levels of family stability following the onset of a life crisis. In this study we characterized the ways in which families organize their daily activities and achieve family cohesiveness. Fifteen families participated in the study. The data showed family members have positive perceptions about their family cohesiveness and organizational behaviors, which were characterized in personal interviews. Families also discussed active and passive coping styles in response to RA. Implications for social work practice and issues for future research are presented.

[Markers of proliferation and morpho-immunologic parameters in evaluation of prognostic factors in endometrial tumors]. / Markery proliferacji oraz parametry morfoimmunologiczne w ocenie czynników rokowniczych w rakach blony sluzowej macicy.

There were analysed prognostic factors in endometrial carcinomas. To essential prognostic factors were counted; proportion of cells in S-phase, DNA ploidy, proportion of Ki-67 positive cells and vascular invasion by cancer cells. All above-mentioned factors were not correlated to either the stage or the histopathologic subtype of the cancers. Application of proliferating markers may be useful for selecting a subgroup of patients for adjuvant therapy.

DNA ploidy in malignant melanoma, skin cancer and pigmented nevi.

The determination of DNA content in human cancers is the subject of increasing interest, particularly in view of its potential clinical applications. There are relatively few studies which describe DNA content of skin neoplasms and pigmented nevi. These studies have shown conflicting results. In the present investigation the authors measured DNA ploidy using flow and video-imaging cytometry in 51 malignant melanomas, 20 skin cancers and 48 pigmented nevi. For DNA measurement paraffin embedded tissues and fresh cell smears were used. Clinical and histological data of malignant melanomas were recorded and correlated with DNA ploidy. DNA histograms were examined for DNA aneuploidy by DNA Index. DNA ploidy in primary lesions of melanomas and their metastases were compared. The aneuploidy rate, found in our observation, was significantly higher in whole malignant melanoma group, in clinical Stage II and III, in tumors with thickness greater then 1.5 mm, tumors with Clark level III, IV and V. Another clinical and histological factors did not show significant correlation with ploidy. Aneuploidy was found in 8 of 20 (45.0%) skin cancers. In the whole population of pigmented nevi aneuploid DNA content was identified in 10 nevi (20.1%). The results of this study suggest that aneuploidy seems to be connected with advanced stage of malignant melanoma but it does not replace other prognostic factors. Both cytometric methods can be used for routine DNA ploidy analysis. Ploidy studies are not useful for predicting metastatic potential of primary melanoma. Results obtained from fresh cell smears and paraffin embedded tissues were identical.