Long noncoding RNA CCAT1 rs67085638 SNP contribution to the progression of gastric cancer in a Polish population.

The role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported. Therefore, we assessed the prevalence of rs67085638 in patients with gastric cancer (GC). We also evaluated the effect of rs67085638 on B-cell-specific Moloney leukaemia virus insertion site 1 (BMI1) transcripts in primary GC and counterpart histopathologically confirmed disease-free margin tissue. Using high-resolution melting analysis, we evaluated rs67085638 frequency in patients with the GC genotype (n = 214) and controls (n = 502) in a Polish Caucasian population. qRT-PCR was used to determine BMI1 transcripts. We observed the trend of rs67085638 association in all patients with GC (ptrend = 0.028), a strong risk of the GC genotype in male (ptrend = 0.035) but not female (ptrend = 0.747) patients, and the association with non-cardia GC (ptrend = 0.041), tumour stages T3 (ptrend = 0.014) and T4 (ptrend = 0.032), differentiation grading G3 (ptrend = 0.009), lymph node metastasis stage N3 (ptrend = 0.0005) and metastasis stage M0 (ptrend = 0.027). We found that significantly increased BMI1 transcripts were associated with the primary GC genotype classified as grade G3 (p = 0.011) and as lymph node metastasis N3 (p = 0.010) and counterpart marginal tissues (p = 0.026, p = 0.040, respectively) from carriers of the T/T versus C/C genotypes. rs67085638 may contribute to increased BMI1 transcripts and the progression and rapid growth of GC.

Fluoride concentration in teeth of the roe deer (Capreolus capreolus) and red deer (Cervus elaphus) from areas of Poland industrially uncontaminated with fluoride compounds.

The last biomonitoring study in Poland on intoxication with fluoride compounds of deer was conducted almost two decades ago. Given the fact that fluoride level in air and water is not widely monitored in Poland, it is justified to undertake monitoring of F- levels in people and other long-lived mammals. This paper provides the assessment of the present level of fluoride accumulation in mineralized tissue of large herbivorous mammals. The aim of the present study was to determine fluoride concentration in teeth of deer inhabiting the areas of Poland which are industrially uncontaminated with fluoride compounds, to establish possible correlations between the analysed parameters, and to provide a comparison of the present results with those obtained in other studies. Mean concentration of fluoride in all analysed samples amounted to 231.0 F mg/kg, with the minimum value of 22.0 F mg/kg and the maximum of 935.0 F mg/kg. This results from the development of industry and a widespread use of fluoride-supplemented caries prevention products which contributes to an intense accumulation of these substances in vertebrates, predominantly in mineralized tissue.

Environmental and Human Health Impacts of Spreading Oil and Gas Wastewater on Roads.

Thirteen states in the United States allow the spreading of O&G wastewaters on roads for deicing or dust suppression. In this study, the potential environmental and human health impacts of this practice are evaluated. Analyses of O&G wastewaters spread on roads in the northeastern, U.S. show that these wastewaters have salt, radioactivity, and organic contaminant concentrations often many times above drinking water standards. Bioassays also indicated that these wastewaters contain organic micropollutants that affected signaling pathways consistent with xenobiotic metabolism and caused toxicity to aquatic organisms like Daphnia magna. The potential toxicity of these wastewaters is a concern as lab experiments demonstrated that nearly all of the metals from these wastewaters leach from roads after rain events, likely reaching ground and surface water. Release of a known carcinogen (e.g., radium) from roads treated with O&G wastewaters has been largely ignored. In Pennsylvania from 2008 to 2014, spreading O&G wastewater on roads released over 4 times more radium to the environment (320 millicuries) than O&G wastewater treatment facilities and 200 times more radium than spill events. Currently, state-by-state regulations do not require radium analyses prior to treating roads with O&G wastewaters. Methods for reducing the potential impacts of spreading O&G wastewaters on roads are discussed.

Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys.

BACKGROUND: Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. METHOD: Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). RESULTS: Disaster-related PTSD prevalence was 0.0-3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. CONCLUSION: Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions.

Genetic Variants in IL-12B and IL-27 in the Polish Patients with Systemic Lupus Erythematosus.

To investigate the potential association between IL-12B and IL-27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case-control study based on the Polish population. Patients with SLE and healthy individuals were examined for -6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL-12B and -924A/G (rs153109) and 4730T/C (rs181206) in IL-27 gene polymorphisms using the high-resolution melting method, PCR-RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL-12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL-12B rs3212227 and IL-27 rs153109 and rs181206 variants between patients with SLE and controls. IL-27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL-12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL-12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL-12B rs17860508 and IL-27 haplotype CG are genetic risk factors for SLE and that both IL-12B rs17860508 and rs3212227 predict disease phenotype.

JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications. OBJECTIVE: We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls. RESULTS: Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047). CONCLUSION: Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.

Determination of cocaine and benzoylecgonine in nails by liquid chromatography-electrospray ionization-tandem mass spectrometry.

Nails and hair are a biological matrix which can be analyzed to confirm the use of a xenobiotic even several months after intake. Results of nail analysis can be used, for example, as evidence in civil and criminal law cases in which a history of drug use can influence the court's decision. The paper presents results of analysis of a nail sample taken from a man who was suspected of trafficking cocaine. The suspect pleaded guilty to the possession of the drug for his own use because, as he claimed, he was addicted to cocaine. A nail sample was taken. Detection and quantification were carried out using liquid chromatography-mass spectrometry (LC-ESI-MS). The concentration of cocaine in nails was found to be 47 ng/mg, and benzoylecgonine - 14 ng/mg.

Single nucleotide polymorphism of CD40 region and the risk of systemic lupus erythematosus.

There is one study on the association of the CD40 G > T (rs4810485) single nucleotide polymorphism (SNP) as a risk factor of systemic lupus erythematosus (SLE). Therefore, we studied the prevalence of the CD40 G > T SNP in patients with SLE (n = 261) and controls (n = 545) in a Polish population. We did not find significant differences between the CD40 G > T genotype and allele frequency in patients with SLE and healthy individuals. However, the frequency of the CD40 TT and GT genotypes was statistically different between patients with arthritis and neurologic manifestations and patients without these symptoms (OR = 0.2009 (95% CI = 0.07547-0.5348, p = 0.0004, p (corr) = 0.0068) and OR = 0.2876 (95% CI = 0.1371-0.6031, p = 0.0005, p (corr) = 0.0085) respectively). Our observations indicate that the CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE.

CD24 Ala57Val gene polymorphism and the risk of systemic lupus erythematosus.

It was recently shown that the CD24 Ala57Val (rs 52812045) polymorphism plays a significant role in susceptibility to systemic lupus erythematosus (SLE) in a Spanish population, which has not been confirmed in other ethnic groups. We investigated the distribution of the CD24 Ala57Val polymorphism in patients with SLE (n = 250) and controls (n = 350) in Poland. The odds ratio (OR) for patients with SLE with the Ala/Val genotype compared with Ala/Ala genotype was 1.490 [95% confidence interval (CI) = 1.052-2.111, P = 0.0275], and OR for the Val/Val genotype compared with Ala/Ala genotypes was 2.001 (95% CI = 1.154-3.467, P = 0.0154). Moreover, we observed a significant association between the CD24 Val allele and the presence of anti-Scl-70 antibody (Ab) OR = 2.155 (1.438-3.229, P = 0.0002). There was also an association of Val allele with the presence of anti-snRNP Ab OR = 1.984 (1.266-3.110, P = 0.0034) in patients with SLE. We also found that the CD24 Val/Val and Ala/Val genotypes contribute to immunologic manifestations OR = 2.244 (1.323-3.806, P = 0.0037). Our observations indicate that the CD24 Ala57Val polymorphism may predispose to SLE incidence and can be linked to immunologic manifestations and production of autoantibodies in this disease.

The CD3Z 844 T>A polymorphism within the 3'-UTR of CD3Z confers increased risk of incidence of systemic lupus erythematosus.

Recently, a family-based association analysis showed that the haplotype carrying a low expression of the variant CD3Z 844 T>A (rs1052231) polymorphism located in the 3'-untranslated region of CD3Z predisposes to systemic lupus erythematosus (SLE) incidence. We analyzed the prevalence of the CD3Z 844 T>A polymorphism in SLE patients (n = 152) and controls (n = 304) in Poland. We observed that women with the CD3Z AA and CD3Z AT genotypes exhibited a 1.845-fold increased risk of SLE [95% confidence intervals (95% CI) = 1.222-2.787, P = 0.0038]. However, we did not find an increased risk for the homozygous CD3Z AA genotype (odds ratio = 1.204, 95% CI = 0.2838-5.108, P = 1.0000). This observation confers that genetic factors causing a decreased level of CD3-zeta in T cells may predispose to SLE incidence.

Contribution of polymorphism in codon 72 of p53 gene to systemic lupus erythematosus in Poland.

The contribution of the p53 Arg72Pro polymorphism in the development of systemic lupus erythematosus (SLE) remains controversial. We investigated the frequency of the p53 Arg72Pro genotype in patients with SLE (n = 155) and in controls (n = 150) in Poland. We found a weak contribution of the Arg/Arg genotype to the morbidity of SLE. Odds ratio (OR) for patients with SLE and p53 Arg/Arg genotype was 1.875 [95% CI = 1.180-2.979], P = 0.0075 and OR of the Arg/Arg and Arg/Pro genotypes was 1.549 [95% CI = 0.752-3.195], P = 0.2328. Since the p53Arg variant supports apoptosis better than the p53Pro variant, our findings can be linked to an increase in the number of apoptotic leucocytes in SLE patients. The distinction between various populations may be because of differences in racial composition and/or exposure to distinct environmental factors that have a different impact on SLE incidence along with the changed Argp53Pro genotype.

Contribution of the R620W polymorphism of protein tyrosine phosphatase non-receptor 22 to systemic lupus erythematosus in Poland.

The protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with systemic lupus erythematosus (SLE) and other autoimmune diseases. However, its contribution to SLE has been found to be disputable. We therefore examined the association of PTPN22 1858 C>T polymorphism with susceptibility to SLE in the Polish population, among patients with SLE (n=150) and controls (n=300). We found a contribution of the PTPN22 1858 C>T polymorphism to the incidence of SLE. Women with the PTPN22 TT and PTPN22 CT genotypes displayed a 2.016-fold increased risk of SLE (95% CI=1.324 - 3.070, P=0.0014). However, we did not observe an increased risk for the homozygous PTPN22 TT genotype OR= 2.552 (95% CI=0.6748-9.64, p=0.1675). Our results confirm an association of the 1858 C>T polymorphism of the PTPN22 gene with SLE, which was previously observed in other populations.

A toxicity evaluation and predictive system based on neural networks and wavelets.

A computational approach has been developed for performing efficient and reasonably accurate toxicity evaluation and prediction. The approach is based on computational neural networks linked to modern computational chemistry and wavelet methods. In this paper, we present details of this approach and results demonstrating its accuracy and flexibility for predicting diverse biological endpoints including metabolic processes, mode of action, and hepato- and neurotoxicity. The approach also can be used for automatic processing of microarray data to predict modes of action.

Mechanisms of vascular dysfunction after subarachnoid hemorrhage.

The main consequence of subarachnoid hemorrhage, for those who survive bleeding, is delayed, persistent vasospasm of intracranial conduit arteries which occurs between the third and seventh day after the insult and results in symptomatic brain ischemia in about 40% of cases. This vasospasm is considered to be a major cause of disability of post-SAH patients. Despite extensive experimental and clinical research, mechanisms of vasospasm are not fully understood. Dysfunction of the endothelium resulting in enhanced production of vasoconstrictors, phenotypic changes of the receptors in endothelium and smooth muscle cells, increased sensitivity of vascular smooth muscle cells to vasoconstrictors, release of spasmogens from lysed blood clot and inflammatory response of the vascular wall have been demonstrated and discussed as pathological mechanisms participating in the development of spasm. In recent years more attention is paid to the functional and structural changes in microcirculation and a concept of microvascular spasm is evolving. Our experimental studies in rat model of SAH strongly suggest that microcirculatory dysfunction and delayed vasospasm are related to the severity of acute, transient ischemia caused by critical decrease of perfusion pressure and active vasoconstriction immediately after the bleeding.

Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants.

Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants--coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme--caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment.

Comparative studies on the adhesion of a silicone elastomer to a chromium-cobalt dental alloy.

Rocatec, Kevloc and Siloc bonding systems were used to bond Molloplast-B silicone elastomer to a metal alloy denture base material. The mechanical strength of the bonds was examined using tensile tests. Two groups of tests were performed, 30 samples after one day storage in water and 30 samples after 6 months in water at 37 degrees C. At both testing times, the Rocatec system exhibited high reproducibility and the highest mean results. For the Kevloc system the values were lower while the Siloc system yielded the lowest values. The strength of samples, bonded with the Rocatec system, was improved by storage in distilled water at 37 degrees C.

The experimental squalene encephaloneuropathy in the rat.

Accumulation of squalene in the CNS is observed after administration of tellurium and squalene has been proposed to be a mediator of tellurium encephaloneuropathy. The aim of this study was to investigate the effects of squalene on the central and peripheral nervous systems in rat at the ultrastructural level. Squalene was administered at a dose of 20 g/kg body weight, once daily for 4 days, and the animals were sacrificed 7 days and 30 days after the initiation of the experiment. After 7 days a mild swelling of mitochondria and dilation of the Golgi complex cisterns in few neurons in the cerebral cortex and hippocampus were observed. The swelling of astrocytes and their processes was also seen. Some myelin sheaths in the cerebral white matter were disintegrated. In the peripheral nervous system (the sciatic nerve), a damage of the Schwann cells, a destruction of the myelin sheaths, and lipid-like deposits between myelin lamellae causing a secondary compression of axons were present. Squalene administration caused a stimulation of fibroblast to synthesize collagen and an activation of macrophages in the perineurium. After 30 days, the lipid-like material was present in some neurons as well as in the myelin sheaths in the central nervous system. Endothelial cells were hypertrophic and a few demonstrated features of apoptosis. Endothelial cell hypertrophy caused a narrowing of vessel lumen associated with an aggregation of blood morphological elements. Disturbances in myelination and swelling of astrocytic processes persisted in the central nervous system. In the peripheral nervous system, lipid-like deposits were localized in some fibroblasts and extracellularly between the collagen fibers in the perineurium. In conclusion, our electron microscopic studies indicate that squalene produces characteristic pathological changes both in the central and peripheral nervous systems. However, these alterations differ in some aspects (changes in endothelia, accumulation of lipid-like material) from the known features of tellurium encephaloneuropathy.

Morphology of experimental diabetes and cerebral ischemia in the rat brain.

Male Wistar rats were subjected to streptozotocin administration (85 mg/kg i.p.) and to cerebral air embolia with common carotids ligation. Light microscopy studies showed foci of neuronal loss and dark neurons especially in hippocampus, dentate gyrus, amygdaloid, thalamus and hypothalamus in the diabetic rats. Cerebral ischemia aggravated above changes and additionally, small hemorrhagic foci in putamen close to globus pallidus were observed. Our results indicate on chronic, generalized pathologic process in diabetic-rat's brain, which may be related to an oxidative stress and leads to a death of neurons in necrotic or apoptotic way.

Electron microscopy studies on experimental diabetes and cerebral ischemia in the rat brain.

Male Wistar rats were subjected to streptozotocin administration (85 mg/kg i.p.) and to cerebral air embolia with common carotids ligation. Electron microscope studies showed dark neurons, degeneration of endothelial cells and changes in basement membrane of brain capillaries, and changed astroglia in diabetic rats. Our results seem to support our previous findings in light microscopy and correspond with some others authors' suggestions that diabetes leads to chronic, generalized pathologic process in diabetic-rat brain, not-only dependent on vascular pathology, but which may be related to an oxidative/metabolic stress leading to a death of neurons in necrotic or apoptotic way.