Peritoneal fluid cytokines and sICAM-1 in minimal endometriosis: search for discriminating factors between infertility and/or endometriosis

OBJECTIVE: To evaluate cytokine levels (IL-1beta, TNF-alpha, IL-6, IL-8), soluble intercellular adhesion molecule-1 (sICAM-1) and number of macrophages in peritoneal fluid (PF) of women with no minimal endometriosis and associated (or not) infertility in order to discriminate between infertility and/or endometriosis. STUDY DESIGN: Cytokines and sICAM-1 were measured by using quantitative enzyme-linked immunosorbent assay (ELISA) while the macrophages were identified by May-Grunwald-Giemsa and non-specific esterase staining and presented as medians. The measurements were performed in 78 women belonging to four selected subgroups according to their endometriosis and/or infertility status. Statistical analysis was performed using Kruskal-Wallis non-parametric ANOVA test. Additionally, discriminant function analyses were performed. RESULTS: We have found the most elevated macrophage numbers in the groups of women with endometriosis. IL-1beta did not present any statistically significant values differentiating the analysed subgroups. IL-6 (110.0 pg/ml) and TNF-alpha exhibited the highest concentrations (statistically significant) in a group of fertile women with endometriosis. IL-8 clearly differentiated between the subgroups with infertility and sICAM-1 was statistically significantly elevated in the subgroups of infertile women. In the forward discriminant analysis, when subdividing the studied population according to its infertility status (we considered macrophages, IL-8 and IL-6 in order of probability values), we have found striking probability value of 92% for the correct classification into an infertile population. CONCLUSION: Out of the range of the analysed factors we have found only the sICAM-1 to be singled out between the standard discriminant analysis and the forward one. However, this important flagging molecule might be of considerable value for discrimination between different types of pathology at the level of immune effector function. The increased levels of TNF-alpha and IL-6 signified a group of fertile women with endometriosis; however only IL-6 presented a discriminating value in multifunctional analysis of examined subgroups. The analysed range of factors had a greater tendency to discriminate between infertility status rather than endometriosis.     

Circadian behavior of blood pressure and heart rate following orthotopic heart transplantation. Studies before and during antihypertensive therapy

The de novo hypertension, which develops in most cardiac transplant recipients within the first postoperative months, is multicausal, though toxic side-effects of cyclosporin A seem to play a key role. In order to analyze the circadian behavior of arterial blood pressure and heart rate after cardiac transplantation (HTX) and to evaluate the effect of an antihypertensive regimen on these parameters, 24-h noninvasive ambulatory blood pressure and heart rate monitoring was performed in 10 hypertensive cardiac transplant recipients on cyclosporin A (mean age 42.3 +/- 11.2 years, 14.3 +/- 8.3 months after HTX) before antihypertensive therapy and after introduction of an antihypertensive regimen with the ACE-inhibitor enalapril plus furosemide alone or combined with verapamil. The study demonstrated a complete loss of the usual nocturnal decline in blood pressure in cardiac transplant recipients (mean systolic and diastolic blood pressure 149 +/- 8 and 102 +/- 7 mm Hg during daytime and 152 +/- 8 and 104 +/- 9 mmHg at night). Antihypertensive therapy lowered the blood pressure level effectively, but did not influence the circadian pattern (mean systolic and diastolic blood pressure 121 +/- 8 and 81 +/- 4 mmHg during daytime and 121 +/- 9 and 83 +/- 3 mmHg at night, all p less than or equal to 0.001). Heart rate, in contrast, showed a significant, though in comparison to normal, a blunted decrease at night (mean heart rate 94 +/- 6 beats per min during daytime and 84 +/- 8 beats per min at night, p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The evaluation of the properties of the silicone-rod and tissue reation after 5,5 years period of implantation

In this study we presented a case of prolonged detention of the temporary flexor tendon prosthesis after implantation in the hand. The silicone-rod removed after more than 5 years was subject to an examination: scanning microscopy, measurement of hardness, scanning differential calorimetry, spectroscopy in infra-red and resistance examinations. The obtained results were compared with a findings after examinations of the new, not used silicone-rod. The greatest changes were observed in maximum value of tensile strength (sigmaB) of the material after test of uniaxial tensile tests, which was about 30% smaller for a silicone-rod after implantation. The other result of investigations didn't reveal an important differences between a new and a used rod. The comparison of the tissue reaction was performed by collection a part of sheath in described case and a part of sheath produced around a rod after 10 weeks period of implantation. The generation of a capsules consisted of fibrous connective tissue with concomitant inflammation process was observed in both cases in histopathological view. Silicone rubber is a material which preserve its most important properties even after prolonged period of implantation.     

Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats

Angiotensin II type 1 (AT(1)) receptors are expressed within organs of the hypothalamo-pituitary-adrenal (HPA) axis and seem to be important for its stress responsiveness. Secretion of CRH, ACTH, and corticosterone (CORT) is increased by stimulation of AT(1) receptors. In the present study, we tested whether a blockade of the angiotensin II system attenuates the HPA axis reactivity in spontaneously hypertensive rats. Spontaneously hypertensive rats were treated with candesartan (2 mg/kg), ramipril (1 mg/kg), or mibefradil (12 mg/kg) for 5 wk. In addition to baseline levels, CORT and ACTH responses to injection of CRH (100 microg/kg) were monitored over 4 h. mRNA of CRH, proopiomelanocortin, AT(1A), AT(1B), and AT(2) receptors was quantified by real-time PCR. All treatments induced equivalent reductions of blood pressure and had no effect on baseline levels of CORT and ACTH. However, both candesartan and ramipril significantly reduced CRH-stimulated plasma levels of ACTH (-26 and -15%) and CORT (-36 and -18%) and lowered hypothalamic CRH mRNA (-25 and -29%). Mibefradil did not affect any of these parameters. Gene expression of AT(1A), AT(1B), and AT(2) receptors within the HPA axis was not altered by any drug. We show for the first time that antihypertensive treatment by inhibition of AT(1) receptors or angiotensin-converting enzyme attenuates HPA axis reactivity independently of blood pressure reduction. This action is solely evident after CRH stimulation but not under baseline conditions. Both a reduced pituitary sensitivity to CRH and a down-regulation of hypothalamic CRH expression have the potential to reduce HPA axis activity during chronic AT(1) blockade or angiotensin-converting enzyme inhibition.     

Posturography as objective evaluation of the balance system in Parkinson's disease patients after neurosurgical treatment. A preliminary report

BACKGROUND AND PURPOSE: In advanced stages of Parkinson's disease (PD) beside resting tremor, rigidity, and bradykinesia, most patients reveal severe balance instability. The goal of this study is to determine objectively postural control changes using static posturography after neurosurgical treatment (unilateral posteroventrolateral pallidotomy). MATERIAL AND METHODS: 15 patients with advanced idiopathic PD underwent unilateral posteroventrolateral pallidotomy. The study group was composed of 8 men and 7 women. The mean disease duration until operation was 12.5+/-3.5 years, and the mean age of the patients at the time of surgery was 65.8+/-4.1 years. Postural control changes were assessed objectively by static computerized posturography and subjectively according to items of posture, gait and postural stability derived from Part III (motor examination) UPDRS. All evaluations of the balance system were performed preoperatively in the off and on condition, and also two weeks postoperatively in the same conditions. RESULTS: It was found that the majority of posturographic parameters in the off condition were improved after neurosurgical treatment. The improvement in the on condition was less pronounced. For example, the mean path length in the off condition during eyes opened was 318+/-159 mm before pallidotomy, and after surgery it was 240.9+/-119.2 mm in off. The difference was statistically significant (p < 0.005, t=3.11). CONCLUSIONS: Pallidotomy improves postural control changes in the early postoperative period, which can be proved by static computerized posturography.     

The Effectiveness of Active Screen Method in Ion Nitriding Grade 5 Titanium Alloy

The study assessed the effect of ion nitriding on the properties of the surface layer of Grade 5 titanium alloy used, among others, in medicine. Titanium and its alloys have low hardness and insufficient wear resistance in conditions of friction which limits the use of these materials. The improvement of these properties is only possible by the appropriate modification of the surface layer of these alloys. The ion nitriding process was carried out in a wide temperature range, i.e., 530–590 °C, and in the time range 5–17 h. Two variants of nitriding were applied: cathodic (conventional) nitriding and nitriding using the active screen method. The research results presented in this article allow for stating that each of the applied nitriding variants improves the analysed properties (nitrogen diffusion depth, hardness, wear resistance, microstructure analysis and surface topography) of the surface layers in relation to the material before nitriding. The hardness increased in every nitriding variant (the use of the additional active screen increased the hardness to 1021 HK0.025). The greatest increase in titanium abrasion resistance was found for surfaces after cathodic nitriding with an active screen. Each of the applied nitriding variants resulted in surface development.     

Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia

Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal cortex in a neurodevelopmental model (MAM-E17) of schizophrenia. SI exposure occurred from postnatal day 30 to 40, followed by resocialization until late adolescence or early adulthood. PV mRNA and protein levels, as well as the number of PV cells, were analysed at these ages. Moreover, epigenetic regulation of PV expression by histone methylation was examined by measuring the total and PV gene-bound H3K4me3 levels. MAM only decreased levels of the PV mRNA and protein in adulthood. Decreases in total H3K4me3 levels and its level at the PV gene were also observed at this age. In contrast, in late adolescence, SI induced a decrease in the expression of the PV mRNA in the MAM group that was related to the reduction in total and PV gene-bound H3K4me3 levels. However, at this age, SI increased the levels of the PV protein in both the control and MAM groups. In adulthood, SI did not affect PV mRNA or H3K4me3 levels but decreased levels of the PV protein in both groups. Both MAM and SI failed to change the number of PV cells at any age. The results indicate that adolescent SI accelerated epigenetic impairments of PV expression in MAM-E17 rats; however, subsequent resocialization abolished this dysfunction, but failed to prevent alterations in PV protein.

     

Role of WNT/β-Catenin Pathway as Potential Prognostic and Predictive Factors in Renal Cell Cancer Patients Treated With Everolimus in the Second and Subsequent Lines

Background

The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway.

Characterization of a complex rearrangement with interstitial deletions and inversion on human chromosome 1

Deletion of the distal band of the short arm of chromosome 1 (monosomy 1p36) is the most common terminal deletion syndrome, occurring in about 1 in 5000 newborns. Of the 121 subjects ascertained for our study to date, 12 (9.9%) have interstitial deletions, three of which are complex rearrangements showing more than one deletion. Herein we report the characterization of a complex rearrangement with two interstitial deletions in the same chromosome 1p36.33-p36.23. We narrowed and analyzed the breakpoints and junctions between the sequence fragments involved in the rearrangement to determine the structure of this deleted chromosome 1. The analyses of the DNA sequence at the junctions showed additional complexity: an inversion and a third de-novo interstitial deletion. We reconstructed this complex rearrangement of 1p36 to understand the mechanism of formation. Analysis of the breakpoint junctions revealed that three of the four breakpoints each interrupted a gene. Alignments of the junctions showed the lack of any sequence similarity between the breakpoints, suggesting the involvement of non-homologous end joining (NHEJ) in the ligation of broken ends following deletion. The identification of translin recognition sites in the breakpoints suggests translin involvement in the repair of broken chromosomes. This report is one of the first to examine constitutional chromosomal rearrangements at the DNA sequence level. The discovery of cryptic events in seemingly simple chromosome rearrangements may provide the basis for proposing mechanisms of formation.     

NETs in cancer

Many aspects of neutrophil hyperactivity and its role in numerous immune responses still remain a mystery. A new neutrophil mechanism was discovered recently, i.e., the formation of neutrophil extracellular traps (NETs). These structures, composed of DNA strands and neutrophil granule proteins, are an element of the non-specific immune response and bind pathogens to prevent their spread and ensure increased local concentrations of toxic factors. Research on this phenomenon shows that tumor-associated neutrophils (TANs) also form and release NETs. Reports on the role of NETs in the course of cancer are scarce, and the opinions on the involvement of extracellular traps in the disease are divided, indicating a dual function. There is speculation about the anti-cancer properties of NETs connected with direct killing of cancer cells or stimulation of the immune system. On the other hand, the trap structures might promote migration and immune escape of cancer cells or constitute a physical barrier between cancer cells and immune-competent cells. This article summarizes our knowledge about the proven roles of NETs in the course of cancer with particular focus on the significance of NETs as prognosis biomarkers in the course of the neoplastic process and their potential use in therapy.