The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis.

Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Patients with first-in-life stroke were analysed according to: plasma concentration of the following markers on the first day of stroke: interleukin 2 (IL-2) and interleuki 6 (IL-6), S100B, tumor necrosis factor-α (TNF-α), progranulin (GRN), neuron specific enolase (NSE), urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). The study included 138 patients with mean age: 73.11 ± 11.48. Patients with a higher score on the NIHSS showed significantly higher concentrations of TNF-α, white blood cells (WBC), CRP, NSE, IL-6 and S100B. Patients with a higher score on the modified Rankin Score (mRS) showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, total blood platelet (PLT) count, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, IL-6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis, as compared to others, were older (P = 0.003) and had higher levels of CRP, IL-6, and S100B. In each case, the differences were statistically significant. We conclude that the concentration of Il-6 and S100B on the first day of stroke are important for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke seem to be more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis. The expression of inflammatory parameters may indicate the importance of the inflammatory process starting during the early days of ischemic stroke, for the post-stroke neurological deficit.

The presence of Tau protein in blood as a potential prognostic factor in stroke patients.

Tau protein is found in the blood of 40 - 50% of patients in the acute phase of a stroke, as a result of the degradation of neurons and damage to the blood-brain barrier. The aim of the study was to assess the incidence of tau protein in the blood of stroke patients, as well as to evaluate the potential impact of tau protein presence in the blood of patients on their neurological state during the first 24 hours, and their functional condition three months after the stroke. Eighty-seven patients aged 39 - 99 (42 females and 45 males) diagnosed with stroke were enrolled in the prospective study (August 2014 - April 2015). The following parameters were analyzed in enrolled participants: the age at which first ischemic stroke occurred, neurological state during the first 24 hours (National Institutes of Health Stroke Scale - NIHSS), blood tau protein and brain derived neurotrophic factor (BDNF) concentrations on day 2 of stroke, the functional condition on day 90 after stroke onset (mRankin). A multifactorial analysis was carried out to establish independent factors for the presence of serum tau protein and to identify independent factors for poor prognosis. Eighty-seven patients of the mean age of 71.7 ± 11.8 years (median 74; min. 39 max. 99 years) took part in the study. The tau protein was found in the serum of 42 (48.27%) patients in the concentrations between 29.56 and 19 023.50 ng/ml. The female sex was the only independent factor for the presence of tau protein in blood (RR 4.49 (1.68 - 11.97), P = 0.003). The mean BDNF concentration in the evaluated group was: 9.96 ± 5.21; median 10.39. Three independent factors for poor functional condition of patients on day 90 after the stroke were identified: the presence of tau protein in blood (RR 3.90 (1.45 - 10.49), P = 0.007), BDNF concentration below the mean value for the study (RR 14.49 (4.60 - 45.45); P = 0.000) and NIHSS score > 4 during the first 24 hours of stroke (RR 1.14; 95% CI: 1.00 - 1.31; P = 0.027). The presence of the tau protein, low BDNF concentrations, and moderate/serious neurological state during the first 24 hours of stroke can be considered as negative prognosis for the patient's functional condition. The coincidence of high BDNF concentrations and absence of tau in blood during the acute phase of an ischemic stroke is a predictor of patient's good state in 3 months after stroke.

Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

UNLABELLED: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. RESULTS: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. CONCLUSIONS: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

Apoptotic proteins and markers of differentiation in childhood pineal parenchymal tumors: relationships and prognostic value.

Pineal parenchymal tumors (PPTs) in children and adolescents are uncommon and more data on their biological activity and behavior are still needed. The aim of our study was to estimate the expression and prognostic value of some proteins regulating apoptosis and cell cycle as well as being markers of cellular differentiation in PPTs. Tumor specimens obtained from 27 patients who underwent surgical treatment for PPTs were evaluated in immuno-histochemical analysis. The expression of Bcl-2, Bax, p53, NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein), beta-III tubulin and nestin were studied. Co-localization of two chosen antibodies (e.g. Bcl-2/Bax, BCl-2/NSE, p53/NSE, etc.) was also made with a scanning confocal microscope. Histopathological examination revealed: 15 pineocytomas, 1 intermediately differentiated PPT and 11 pineoblastomas. For further analysis two groups were created: Group I: patients with pineocytoma or intermediately differentiated PPTs (16 cases) Group II: patients with pineoblastoma (11 cases). A statistically significant positive correlation between patients' survival time and tubulin and NSE expression was found. Bcl-2, p53 and nestin correlated negatively with survival time.

Polymer hollow fiber-encapsulated peripheral nerve extracts change their activity towards injured hippocampal neurites in rats.

The regeneration of the adult mammalian central nervous system (CNS) requires changes of the nonpromising environment. Applying peripheral nerve grafts and their extracts are both the useful method to induce regeneration of injured CNS neurites. Our previous reports showed that degeneration of peripheral nerves enhanced their neurotrophic activity in a time-dependent manner. Electrophoretical analysis of proteins obtained from degenerating sciatic nerves revealed significant changes in fractions of low molecular mass. The aim of the present work was to examine the influence of fractionated extracts from 7-day-predegenerated and non-predegenerated peripheral nerves upon injured hippocampal neurites in adult rats. The extracts were closed in fibrin-filled connective tissue chambers (CTC) or within CTC-wrapped polymer hollow fibers (PHF) of 30 kDa cut-off. The cell bodies of regrowing fibers were labeled with FITC-HRP. The CTCs appeared to be useful tool for implantation of artificial grafts into mammalian CNS. Full-spectrum nerve extracts induced strong regeneration of injured hippocampal neurites. The number of labeled cells within hippocampus was significantly lower in PHF groups than in CTC ones, indicating that low-mass proteins present in peripheral nerve extracts are not sufficient to induce successful regeneration.

The role of melatonin in the neurodegenerative diseases.

Melatonin is a product of the pineal gland. Synthesis and release of this hormone is inhibited by light. The biological activity of melatonin is associated with its receptors--ML1 and ML2. Melatonin plays a role in the biologic regulation of circadian rhythms, sleep, mood, reproduction, tumor growth and aging. It may also modulate the activity of various receptors in cancer cells. The hormone is a free radical scavenger, an antioxidant and immunomodulatory agent. Antioxidant properties of melatonin are connected with its neuroprotective activity in several degenerative disorders. The etiology of the neurodegenerative diseases which are characterized by the progressive and irreversible destruction of specific neuronal populations is complex and multifactorial. One of causes of neurodegenerative damage in the nervous system is oxidative injury, which results from an inbalance between free radical formation and antioxidative mechanisms. The efficacy of melatonin in the inhibition of the oxidative stress was estimated in various neurodegenerative disorders whose pathogenesis is associated with cytotoxic activity of free oxygen radicals, such as Alzheimer's or Parkinson's disease. Melatonin may have a clinical potential for the treatment of neurodegenerative disorders in the central as well as peripheral nervous system. (Ref. 38.)

Dead-ended autologous connective tissue chambers in peripheral nerve repair--early observations.

The effects of the repair of nerve gap injuries are still unsatisfactory, despite the great progress in microsurgery. Until now, there is no effective method to induce the regeneration of the transected peripheral nerve when its distal stump is missing. The aim of this work was to examine whether the implantation of dead-ended connective tissue chambers can promote the outgrowth of injured peripheral neurites. This method differs from all previous nerve guides because it totally eliminates the distal part of the nerve and restricts the influence of surrounding tissues. We have also tried to establish whether some neurotrophic factors can be applied by means of these chambers. The results of this work show that dead-ended autologous connective tissue chambers can be a useful tool in peripheral nerve injuries treatment, even when the distal part of the nerve is missing.

Predegenerated peripheral nerve grafts rescue retinal ganglion cells from axotomy-induced death.

The inability of axons to grow across damaged central nervous system tissue is a well-known consequence of injury to the brain and spinal cord of adult mammals. Our previous studies showed that predegenerated peripheral nerve grafts facilitate neurite outgrowth from the injured hippocampus and that this effect was particularly distinct when 7-, 28-, and 35-day-predegenerated nerve grafts were used. The purpose of the present study was to use the above method to induce and support the regrowth of injured nerve fibers as well as the survival of retinal ganglion cells (RGCs). Adult Sprague-Dawley rats were assigned to three groups. In the experimental groups transected optic nerve was grafted with peripheral nerve (predegenerated for 7 days (PD) or nonpredegenerated). In the control group, the optic nerve was totally transected. RGCs and growing fibers labeled with fluorescent tracers were examined. They were counted and the results were subjected to statistical analysis. Retinal ganglion cells survived in the groups treated with predegenerated as well as nonpredegenerated grafts; however, the number of surviving retinal ganglion cells was significantly higher in the first one. In both groups the regrowth of the transected optic nerve was observed but the distance covered by regenerating fibers was longer in the PD group. No fibers inside grafts and no labeled cells in retinas were present in the control animals. On the basis of the obtained results we can state that the predegeneration of grafts enhance their neurotrophic influence upon the injured retinal ganglion cells.

Lipid profiles in Polish adolescents from high- and low-risk families: tracking unfavourable lipid levels over a one-year period.

In a country with a high cardiovascular mortality rate, lipid profiles were studied in 929 adolescents (440 from affected and 489 from non-affected families for cardiovascular disease and hypercholesterolaemia). In 334 children with elevated or borderline total cholesterol level, lipid profiles were re-measured after a 1-y period. In boys from affected families, in contrast to boys from non-affected families, significantly higher total cholesterol levels (4.36 +/- 0.81 vs 4.19 +/- 0.78 mmol/L, p < 0.05) and LDL-C level (2.1 +/- 0.72 vs 1.89 +/- 0.79 mmol/L, p < 0.05) and significantly lower HDL-cholesterol levels (1.81 +/- 0.34 vs 1.93 +/- 0.38 mmol/L, p < 0.05) were found. The odds ratio for being in the most unfavourable decile for LDL-cholesterol was significantly higher for girls from affected families (2.17, p = 0.02). A relatively high HDL-C level as well as a favourable TC/HDL-C ratio was demonstrated in all groups, being lowest in boys from affected families. A significant correlation was found between baseline lipids and their values re-measured after 1 y. It is concluded that (1) adolescents with a positive family history are at increased risk for unfavourable lipid profile, (2) adolescents with elevated total cholesterol and LDL-cholesterol levels remain hypercholesterolaemic after a 1-y period and are therefore candidates for further biochemical and clinical monitoring, and (3) children with elevated total cholesterol may not be at high risk for cardiovascular disease owing to the favourable TC/HDL-C ratio. The study results do not indicate that general cholesterol screening in Polish adolescents is necessary, as the proportion of children with elevated LDL-cholesterol is relatively low.

[Thelarche praecox in young girls: recent approaches to the pathogenesis and clinical evaluation]. / Przedwczesny rozwój gruczolów piersiowych u dziewczat--wspólczesne poglady na patogeneze i postepowanie diagnostyczne.

Premature breast development (premature thelarche) is a common reason of referring prepubertal girls for endocrinological evaluation. It is considered as a benign condition but its pathogenesis is still unknown. It is postulated that it may be due to premature partial activation of hypothalamo-pituitary axis or to the increased sensitivity of breast tissue to normal, prepubertal estradiol levels. Although it rarely progresses to central precocious puberty the differential diagnostics is essential, as the latter pathology should be treated as early as possible. So called "exaggerated thelarche" or "telarche variant" may constitute a diagnostic challenge.

[The role of the bcl-2 gene in programmed death of neurons]. / Rola genu bcl-2 w programowanej smierci neuronów.

Alterations in counterbalance between proliferation and cell death contribute to the pathogenesis of many neurological disorders. The main form of cell death that occurs in the developing nervous system and in many pathological states is apoptosis. Many factors participate in the regulation of programmed cell death. Bcl-2 gene family members modulate the sensitivity of cells to death. Some of them promote cell death and the others, such as bcl-2, prevent apoptosis. Bcl-2 shows a wide expression in the nervous system and protects neurons from various toxic insults. This review focuses on the role of bcl-2 in the apoptosis occurring in some neurological diseases. Understanding of apoptotic threshold may lead to new strategies for the treatment in neurology.

Postmicrosomal protein fractions from short-time-predegenerated rat sciatic nerve.

The postmicrosomal protein fraction obtained from distal stumps of rat sciatic nerves at 0-6 days following transection were investigated by means of one- and two-dimensional electrophoresis. In all experimental groups, total amount of protein was significantly higher than in the control group. Proteins were resolved into 27 bands after SDS-PAGE. Their molecular weights ranged between 16.2 and 335.4 kDa. Eleven fractions displayed significant quantitative differences. After 2-D-electrophoresis, the pI of the proteins ranged from 4.2 to 7.4. They were resolved to 28 molecular masses from 13.5 kDa to 335.4 kDa. The greatest numbers of fractions (90-109) were observed on the 3rd, 4th, 5th and 6th day after nerve transection. Thus, during first 6 days after transection intensive changes in protein fraction content and composition take place in the distal stump of peripheral nerve. These processes seem to be most prominent on the 4th day after lesion. Results confirm our earlier in vivo findings.

[Influence of birth weight on pubertal development of fourteen years old children]. / Wplyw urodzeniowej masy ciala na dojrzewanie plciowe 14-letnich dzieci.

Intrauterine growth restriction may have a life-long impact on growth and general health status. The aim of the study was to evaluate the influence of birth weight on height, BMI and pubertal stage in fourteen years old children. The study was carried out in 437 children (230 girls and 207 boys) in the mean age of 14.2+/-1.1 years. Data of parental height, mothers' age of menarche and family socioeconomic status were obtained through the inquiry. A significant correlation between the birth weight and height of 14 years old girls and boys was found, but there was no correlation of birth weight with their BMI. Age of the first menses in girls correlated with mothers' menarche only - neither birth weight nor socioeconomic factors influenced it significantly. Birth weight did not correlate with pubertal stage attained by the children examined, however in girls with low birth weight, as opposed to the girls with birth weight >2500 g, there was no acceleration of menarche. The results of the study indicate that birth weight may influence height but it has no influence on weight and pubertal staging in 14 years old children.

[Growth dynamics in the first six years of life in respect to the birth weight]. / Dynamika wzrastania w pierwszych 6 latach zycia w zaleznosci od urodzeniowej masy ciala.

The aim of the study was to examine growth dynamics in girls and boys during the first six years of life and to establish how and to what extend it can be modified by their birth weight. The study was carried out in 437 children (230 girls and 207 boys). Growth dynamics during first two years, between 2 and 4 and 4 and 6 years of life was established and compared between the groups of children with birth weight below 2500 g, 2501-3500 g and above 3500 g. In girls with lowest birth weight highest dynamics of the body mass accretion was found between birth and 2 years of life. Their linear growth velocity was highest between 2 and 4 years of life. In boys no relation of the birth weight and dynamics of body mass increase was found. However, in boys with lowest birth weight linear growth velocity was highest between 2 and 4 years of life. It is concluded that high growth velocity between the second and fourth year of life can be beneficial for the "catch-up" growth in children with low birth weight who remain short at the end of the 2nd year of life.

[Disturbance of the normal cell cycle by T antigens of SV40 viruses and JC cause some tumors]. / Zaburzenia prawidlowego przebiegu cyklu komórkowego przez antygeny T wirusów SV40 i JC przyczyna niektórych nowotworów.

The mechanism that may lead to tumor formation in SV40 or JCV infected tissues based on previously reported interactions between T antigens and two factors (p53 and pRb) controlling cell cycle has been discussed. p53 is a known tumor suppressor protein that delays S phase entry causing cell arrest in G1 phase or apoptosis when the DNA damage occurs. Phosphorylation of pRB releases E2F family proteins that activate genes encoding S phase promoting factors. Binding of T antigens to pRB induces tumor formation, whereas tumor proliferation requires knockout of p53 activity.

Autologous connective tissue bars as vehicles for the administration of growth-influencing substances to the brain.

One of the main problems in the introduction of growth factors or other substances into the CNS is that most of these do not pass the blood-brain barrier, and so they have to be delivered directly to the target cells. Recently, different methods of intracerebral administration have been introduced such as release of drugs from polymer matrix or hollow polymer fibres, implantation of solution-soaked gel foam pieces or genetically modified cells secreting growth factors. In our studies on regeneration in CNS, the problem of introducing active substances into the brain arose. For this reason we elaborated a new method for the administration of soluble factor by means of autologous connective tissue chambers filled with fibrin. This method is particularly suitable in studies in which the visualization of the regrowth of nerve fibres is one of the main purposes. Presence of an active substance inside the chamber fibres to grow in the direction of the chamber and such fibres can be visualized here. Such visualization is impossible while using other methods of trophic substance delivery into the CNS, e.g. intraventricular steel cannula connected to an osmotic minipump, because there is neither space nor appropriate milieu to allow the fibres' ingrowth. Retrograde tracing methods allow to establish the cells of origin of these fibres. This method is inexpensive, simple and adaptable to histological procedures.

Purified extracts from short-time-predegenerated rats' sciatic nerves promote the regrowth of injured hippocampal neurites.

Our previous studies revealed that purified extracts (submicrosomal fractions) obtained from peripheral nerves predegenerated for 7-, 28-, and 35-days facilitated neurite outgrowth from the injured hippocampus. It is recently known that totally transected peripheral nerve exhibits biphasic neurite-promoting activity. The early phase lasts 7 days. The aim of the present study was to find whether extracts obtained from short-time predegenerated (1-6 days) peripheral nerves exert any neurotrophic effect and when this influence is maximal. Experiments were carried out on adult male Wistar rats. Sciatic nerves were totally transected and following 1, 2, 3, 4, 5 and 6 days their distal stumps were homogenized and centrifuged. Extracts were implanted into the hippocampus by means of autologous connective tissue chambers. Reference groups were treated with extracts from non-predegenerated nerves, NGF solution or fibrin (groups C, NGF and B + F, respectively). In all groups FITC-HRP was injected into the extracranial end of chamber six weeks following surgery. Histochemic technique showed AChE-positive fibres inside the chambers of all examined groups. Fluorescence microscopic examination revealed the labeled cells in all examined groups, however their number was different in each group. They were most numerous at the fourth day of predegeneration.

Short-time predegenerated peripheral nerve grafts promote regrowth of injured hippocampal neurites.

Our previous studies revealed that predegenerated peripheral nerve grafts facilitated neurite outgrowth from the injured hippocampus and that this effect was particularly distinct when 7-, 28-, and 35-days predegenerated nerve grafts were used. It is recently known that a totally transected peripheral nerve exhibits biphasic neurite-promoting activity. The early phase lasts 7 days. The aim of the present study was to find whether short-time predegenerated (1-6 days) peripheral nerve grafts exert any neurotrophic effect and when this influence is maximal. Experiments were carried out on adult male Wistar rats. Sciatic nerves were totally transected and following 1, 2, 3, 4, 5 and 6 days their distal stumps were implanted into the hippocampus. Control animals were treated with non-predegenerated sciatic nerve grafts. In all groups FITC-HRP was injected into the free end of graft six weeks following surgery. Special histochemic technique showed AChE-positive fibres inside the grafts of all examined groups. Fluorescence microscopic examination revealed the labeled cells in all examined groups, however their number was different in each group, depending on the predegeneration stage. They were most numerous at the fourth day of predegeneration.

Autologous connective tissue chamber as a tool for introducing active substances into the CNS.

A new method of introducing active substances into the CNS is described. The autologous connective tissue chambers were obtained by implantation of a silicone tube under the back skin of rats. Subsequently they were filled with fibrine and additionally with NGF or submicrosomal fractions from nonpredegenerated and predegenerated peripheral nerves. Filled chambers were implanted stereotaxically into the injured hippocampus. The neurite outgrowth was examined by means of FITC-HRP and acetylcholinesterase-method. Implanted connective tissue chambers are very useful in getting active substances into the CNS. This method allows to avoid inflammatory processes and does not hinder the histological procedures.

[Occupational exposure of workers in chemical factors and selected parameters of the respiratory system]. / Narazenie zawodowe pracowników zakladów chemicznych a wybrane parametry ukladu oddechowego.

Workers employed in chemical factories are chronically exposed to harmful substances present in the air of the occupational environment. The aim of this paper was to find out whether this situation produces adverse effects on the respiratory system despite the observance of admissible concentrations of toxic substances in the air. Spirometric values such as FVC1 and FEV1%FVC were measured in 647 workers. It was found that workers in some departments (power station and polystyrene) showed restrictive and obturative disturbances of ventilation. In other departments workers exhibited less expressed respiratory disorders. Adverse effect of smoking and long period of employment on the respiratory system of workers was also revealed. These results indicate that apart from substances present in the occupational environment there are other factors which affect as well the respiratory system of persons employed in the chemical industry.