Temperature can prime human peripheral blood neutrophils in a p38MAPKalpha-dependent manner

INTRODUCTION: Previous ex vivo experiments by others suggest that elevated body temperature can prime the respiratory burst of human neutrophils. The mechanism of the priming phenomenon induced by temperature has not been addressed so far. Furthermore, the priming temperature range was not defined. MATERIAL/METHODS: In the present study we explored ,under in vitro conditions, the influence of febrile-range temperatures on reactive oxygen species (ROS)generation by human peripheral blood neutrophils. ROS production was measured using whole.blood luminol-dependent chemiluminescence. Two elements of signal transduction pathways, calcium and p38 mitogen.activated protein kinase alpha (p38MAPKalpha) ,frequently underlying neutrophil priming were also examined.Calcium levels in the cytosol of resting and fMLP. stimulated isolated neutrophils were measured with the Fura-2AM spectrofluorimetric method. The activity of p38MAPKalpha was assessed indirectly with a specific inhibitor of the kinase, SB 203580. RESULTS: The study revealed a priming effect at 38 degrees C toward human peripheral blood neutrophil ROS production. Any concomitant effect on calcium response was not observed. Instead, experiments with SB 203580,a specific inhibitor of p38MAPKalpha, pointed to an increased activity of the kinase as a molecular background of temperature-induced priming. However, the priming effect of temperature was confined to 38 degrees C, while higher temperatures proved to exert no effect (39 and 40 degrees C)or even inhibited ROS generation by neutrophils (43 degrees C). CONCLUSIONS: Our study suggests a heterogeneous influence of temperature on human neutrophil functioning, including the priming of the cells by a low-febrile-range temperature. It also suggests a p38MAPKalpha-dependent molecular background of the priming phenomenon.     

The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency

Four patients with alpha-1 antitrypsin (alpha-1 AT) deficiency are presented: one woman with severe (phenotype PiZ) and 3 men with moderate (phenotype PiMZ) deficiency of alpha-1 AT. The variability of clinical presentation of hereditary emphysema is described. In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined.     

The sound of a mobile phone ringing affects the complex reaction time of its owner

Introduction

Mobile phone conversation decreases the ability to concentrate and impairs the attention necessary to perform complex activities, such as driving a car. Does the ringing sound of a mobile phone affect the driver''s ability to perform complex sensory-motor activities? We compared a subject''s reaction time while performing a test either with a mobile phone ringing or without.

Material and methods

The examination was performed on a PC-based reaction time self-constructed system Reactor. The study group consisted of 42 healthy students. The protocol included instruction, control without phone and a proper session with subject''s mobile phone ringing. The terms of the study were standardised.

Results

There were significant differences (p < 0.001) in reaction time in control (597 ms), mobile (633 ms) and instruction session (673 ms). The differences in female subpopulation were also significant (p < 0.01). Women revealed the longest reaction time in instruction session (707 ms), were significantly quicker in mobile (657 ms, p < 0.01) and in control session (612 ms, p < 0.001). In men, the significant difference was recorded only between instruction (622 ms) and control session (573 ms, p < 0.01). The other differences were not significant (p > 0.08). Men proofed to complete significantly quicker than women in instruction (p < 0.01) and in mobile session (p < 0.05). Differences amongst the genders in control session was not significant (p > 0.05).

Conclusions

The results obtained proofed the ringing of a phone exerts a significant influence on complex reaction time and quality of performed task.     

Electrophysiological features in patients with sinus node dysfunction and vasovagal syncope

Introduction

Syncope is a common presentation of sinus node dysfunction (SND). Some patients who receive a permanent pacemaker due to SND do not benefit from it and further diagnostic workup leads to the diagnosis of vasovagal syncope (VVS). The aim of the study was to identify electrophysiological criteria that can be used for identification of patients with SND and concurrent VVS.

Material and methods

Transoesophageal atrial pacing (TAP) was performed in 100 patients divided into four groups depending on symptoms and TAP results. Standard electrophysiological parameters of sinus node function and their variability were obtained in the basal state and after pharmacological autonomic blockade (AB).

Results

Patients with concurrent SND and VVS had a greater variability of sinoatrial conduction time assessed by Strauss’ method than patients without incidents of syncope (83.2 ±53.9 vs. 34.1 ±19.6, 47.8 ±33.6 and 32.1 ±22.99). Apart from abnormal sinus node recovery time and second pause, patients with SND had bigger basal state variability of these parameters. In patients with SND and concurrent vasovagal syncope the variability of sinus node recovery time (SNRT), corrected SNRT (cSNRT) and second pause (IIP) decreased after autonomic blockade.

Conclusions

Patients with concurrent SND and VVS have distinct electrophysiological features – greater sinoatrial conduction time (SACT) variability and the decrease of SNRT, cSNRT and IIP variability after AB. However, further studies in larger study groups are needed to validate our findings. Transoesophageal atrial pacing is a useful procedure in patients with syncope, especially when the coexistence of more than one cardiac cause is suspected.     

Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor

Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal to the splenic flexure. Nuclear TS was detected by immunohistochemistry with a TS 106 monoclonal antibody on tissue microarrays constructed from 269 CRCs. The median histological score of nuclear TS expression of all proximal tumors was two times higher (p = 0.0003) and in men three times higher (p = 0.00023) than that found in distal tumors. In multivariate analysis which included age, sex, Astler–Coller stage, histological grade, and site, only proximal location of the tumor was identified as an independent factor associated with higher TS expression (odds ratio 2.46, 95% confidence interval = 1.29–4.70, p = 0.0062). These results demonstrate significant differences in nuclear TS expression between proximal and distal cancers and suggest the potential importance of the site of the tumor for proper stratification of patients for chemotherapy.     

Inhibition of nitric oxide synthase delays the development of tolerance to LPS in rats

The role of nitric oxide (NO) was investigated in endotoxin (lipopolysaccharide, LPS) tolerance in freely moving biotelemetered rats. We monitored changes in febrile response and feeding behavior (food intake, water intake) during the development of tolerance to repeated intraperitoneal injections of LPS (50 microg/kg) along with injections of N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg), an inhibitor of NO synthase. Rats were treated with LPS and L-NAME for three consecutive days. On the fourth day, all rats were injected with LPS alone. Control rats were injected with saline along with saline or with L-NAME for four consecutive days. Rats repeatedly injected with LPS became tolerant to pyrogenic and hypophagic/cachexic effects of LPS as early as on the second day of experiment. The treatment with L-NAME prevented the attenuation of febrile response following the second LPS injection. Moreover, the depressive effects of LPS on body weight as well as on water and food intake were prolonged in rats treated with a combination of L-NAME and LPS. Injection of LPS caused a 3.5-fold increase in plasma nitrite within 3 h and nitrite levels remained significantly elevated 6 and 24 h after LPS. Rats injected secondly with LPS did have still 2.5- to 3-fold increase in plasma nitrite levels 3 and 6 h, but not 24 h, after injection. Third injection of LPS did not elevate nitrite level in plasma. Taken together, presented data provide clear evidence that NO formation is involved in mechanisms responsible for development of early-stage tolerance to endotoxin.     

VEGF (vascular endothelial growth factor) concentration in serum and pleural fluid of patients with pleural malignancy and pleural tuberculosis

The purpose of this study was comparison of VEGF (vascular endothelial growth factor) levels in serum and pleural fluid and estimation of this test usefulness in diagnosis of pleural effusions. VEGF levels were measured by ELISA method in 68 patients (45 males and 23 females) aged 19-81 years. By Light's criteria in 16 cases transudate and in 52 cases exudate was recognized. By means of fluid cytology, pleural biopsy, microbiology or thoracoscopy in 10 cases pleural metastases from distant organs, in 15 cases coexisting pulmonary neoplasm, in 11 cases mesothelioma and in 16 cases tuberculosis were determined as a cause of fluid accumulation in pleural space. The mean VEGF levels were significantly higher (p < 0.001) in patients with exudates than in patients with transudates (3833 pg/ml and 325 pg/ml respectively). Based on likelihood ratios analysis, as a cut off value in differentiation of exudates and transudates a value 700 pg/ml was accepted. The sensitivity of this test was 75% and the specificity 93% and likelihood ratio (LR) 12.5. The mean VEGF level in exudates was seven times higher than mean VEGF level in serum (3833 pg/ml and 573 pg/ml respectively). Mean VEGF levels in malignant exudates (4615 pg/ml) were significantly higher than in tuberculous exudates (2073 pg/ml). As a cut off value in differentiation between malignant and tuberculous exudates a value of 4500 pg/ml was accepted. We conclude that our results suggests the local VEGF production in pleural cavity and the significant role of this cytokine in pleural exudates accumulations and also suggests the usefulness of VEGF estimation in pleural fluid in differentiation transudates from exudates and malignant from tuberculous pleural fluids.     

Ultrastructural characteristics of the respective forms of hepatic stellate cells in chronic hepatitis B as an example of high fibroblastic cell plasticity. The first assessment in children

Purpose

Activation of hepatic stellate cells (HSCs), mainly responsible for extracellular matrix synthesis, is assumed to be central event in the process of liver fibrogenesis. The major objective of the research was to analyze the ultrastructural profile of activated HSCs in children with chronic hepatitis B (chB), with respect to fibrosis intensity.

Nogo‐B expression,in arterial intima,is impeded in the early stages of atherosclerosis in humans

Nogo‐B (Reticulon 4B) is considered to be a novel vascular marker, which may have a protective role in injury‐induced neointima formation and atherosclerosis. Nogo A/B is found to be crucial for monocyte/macrophage recruitment in acute inflammation and it is expressed in CD68 + macrophages. We hypothesize that macrophage infiltration in atherosclerosis is not dependent on Nogo‐B expression in arterial wall. We have assessed Nogo‐B expression and macrophage accumulation in the iliac arteries of healthy organ donors and organ donors with cardiovascular risk factors. Paraffin sections of 66 iliac arteries, from 44 deceased organ donors (17 women and 27 men), were studied. The healthy and cardiovascular risk (CVR) subgroups were created. With regard to staging of the atherosclerotic process, the thickness of arterial intima was measured in digitalized images of H+E stained tissue sections. Immunohistochemical reactions (Nogo‐B and CD68) were carried out in all arteries (66 samples). Western blotting (WB‐19 samples) and real‐time PCR (27 samples) were performed on selected arteries. Significantly higher Nogo‐B expression was demonstrated in the intima of the healthy subjects' subgroup, using immunohistochemistry. WB and real‐time PCR revealed a trend toward lower Nogo‐B expression in the adventitia of the CVR subgroup. Furthermore, the thickness of the intima was found to negatively correlate with the expression of Nogo‐B in the intima and media (r = ?0.32; p < 0.05; r = ?0.32; p < 0.05). Macrophage infiltrates were more prominent in intima of CVR subjects (0.65 vs 3.52 a.u.; p < 0.01). Macrophage density in intima increased with atherosclerosis progression (r = 0.37; p < 0.01). CD68 macrophages density in adventitia was lower in CVR arteries than in healthy arteries. The expression of Nogo‐B, in arterial intima, is impeded in the early stages of atherosclerosis. Accumulation of arterial intimal CD68 macrophages has been shown to progress; however, the overall macrophage density in the adventitia is reduced in arteries shown to have intimal thickening. Macrophage infiltration is not accompanied by Nogo‐B expression in atherosclerotic arteries.     

Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.