Levels Of Th Research Articles

Comparing the effects of progressive and mild intensity treadmill running protocols on neuroprotection of parkinsonian rats

AimsParkinson's disease (PD) is characterized by progressive loss of dopamine cells. It is suggested that exercise could be employed as a non-pharmacological approach for reducing the risk of PD incidence. The purpose of this study was to compare the effects of 4-week Mild-intensity (MIEx) and progressive exercise (PEx) protocols on rotational behavior, GFAP, DA, TH, MANF, CDNF and NGF levels in striatum of parkinsonian rats induced by 6-hydroxydopamine. Methods42 Wistar male rats were divided into 6 groups including, healthy and PD controls, MIEx, PEx, healthy MIEx, and healthy PEx. MIEx protocol was performed as follows: 5 days a week, 2 sessions a day of 15 min at a speed of 15 m/min. PEx protocol encompassed a training regimen of 5 days a week initiating by 20 min in the first day reaching 50 min on the fifth day and 60 min in the next 3 weeks. PD was induced after training protocol by injection of 6-OHDA into the striatum of rats. For confirming PD, apomorphine rotational test was employed. Key findingsThe MIEx protocol did not have any positive impacts on the variables except for CDNF (P < 0.0001). Levels of DA (P < 0.0001) and TH (P = 0.0004) increased significantly after performing PEx protocol. Moreover, PEx protocol considerably reduced rotational behavior of rats (P = 0.0244). SignificanceThe findings of this research confirm positive effects of PEx in protecting against PD. This progressive training protocol has explicitly shown a neuroprotective effect against PD-inducing nervous toxin through increasing neurotrophins.

Protein Phosphatase 2A Affects the Symptoms of Depressive Rats by Regulating Extracellular Signal-regulated Kinases/Glycogen Synthase Kinase 3β Signaling Pathway

As one of the world's more common mental disorders, the incidence of depression has increased yearly, seriously affecting the lives and health of many people. Protein phosphatase 2A (PP2A) is a protein that is enriched in the brain tissue, is the major serine/threonine phosphatase in the central nervous system, and plays a very important role in many aspects of cellular function. To explore the role of PP2A in the pathogenesis of depression in our study, we constructed the depressive disorder model, which involves the exposure of Sprague Dawley rats to chronic unpredictable stress (CUS). The rats with depression were then treated with different concentrations (low, moderate, high) of okadaic acid (OA), and the optimal OA concentration (OOA) for the follow-up study was selected based on PP2A activity. The results showed that the use of higher OA concentrations corresponded with stronger inhibition of PP2A activity. Moreover, the behavioral test performed on the depression model rats showed that OOA group exhibited significant improvements in weight, as well as in their results in the sucrose preference test, open-field test, and Morris water maze test compared to the model group (P &lt; 0.05). Moreover, when compared with the model group, the amounts of NE and 5-HT increased significantly (P &lt; 0.05), and the expression levels of TH, ERK1, AKT1, as well as the phosphorylation of TH, ERK1, AKT1, and GSK-3β, were observed to be increased in the OOA group (P &lt; 0.05). Furthermore, the content of CORT decreased significantly (P &lt; 0.05), and the expression levels of GSK-3β were decreased in the OOA group (P &lt; 0.05). Thus, the potential mechanism of how OA ameliorates depression in model rats may be through the inhibition of PP2A activity, the increase in phosphorylation levels of AKT and GSK-3β, and through the PP2A/AKT/GSK-3β signal pathway; these components may serve as important intracellular targets for antidepressant drugs.

The deglycase activity of DJ-1 mitigates α-synuclein glycation and aggregation in dopaminergic cells: Role of oxidative stress mediated downregulation of DJ-1 in Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the degeneration of dopamine neurons of the substantia nigra pars compacta (SNpc) and the presence of intra-neuronal aggregates of α-synuclein and its post-translational products. Based on emerging reports on the association between glycated α-synuclein and PD; and the newly identified deglycase activity of DJ-1, we sought to find the relevance of deglycase activity of DJ-1 on glycation of α-synuclein and its plausible role in PD. Our results demonstrate that DJ-1 has a higher affinity towards the substrate methylglyoxal (MGO) (Km = 900 mM) as compared to its familial mutant, L166P (Km = 1900 mM). Also, CML α-synuclein (CML-syn) served as a substrate for the deglycase activity of DJ-1. Treatment of cells with Parkinsonian mimetic, 1-methyl-4-phenylpyridinium ion (MPP+); oxidants, such as H2O2 and methylglyoxal (MGO) lead to a dose-dependent decrease in the levels of DJ-1 with a concomitant increase in CML-syn. Also, MGO induced cytosolic α-synuclein aggregates in cells which stained positive with the anti-CML antibody. Further, unilateral stereotaxic administration of MGO into the SNpc of mice induced α-synuclein aggregates and CML-syn with a concomitant reduction in the number of TH positive neurons, protein levels of TH and DJ-1 at the site of injection. Interestingly, overexpression of DJ-1 enhanced the clearance of preformed CML-syn in cells, mitigated MGO induced CML-syn and intracellular α-synuclein aggregates. Overall, the findings of our present study demonstrate that DJ-1 plays a pivotal role in the glycation and aggregation of α-synuclein. Reduced DJ-1 activity due to mutations or oxidative stress may lead to the accumulation of glycated α-synuclein and its aggregates.

Potential effects and molecular mechanisms of melatonin on the dopaminergic neuronal differentiation of human amniotic fluid mesenchymal stem cells

Melatonin, a highly lipophilic molecule secreted by the pineal gland in the brain, plays a role in various biological functions. Previous studies reported that melatonin exerts its effect on mesenchymal stem cell (MSC) survival and differentiation into osteogenic- and adipogenic-lineage. However, the effect of melatonin in neurogenic differentiation in amniotic fluid (AF)-MSCs remains to be explored, thus we investigated the potential role of melatonin on dopaminergic neuron differentiation in AF-MSCs. The results showed that various concentrations of melatonin did not affect cell viability and proliferative effects of AF-MSCs. Increases in the levels of neuronal protein marker (βIII-tubulin) and dopaminergic neuronal markers (tyrosine hydroxylase, TH and NURR1), but decrease in the level of glial fibrillary acidic protein (GFAP), were observed in melatonin-treated AF-MSCs. Melatonin induced alteration in differential expression patterns of mesenchymal stem cell antigens by reducing CD29, CD45, CD73, CD90 and CD105, but no changing CD34 expressing cells. AF-MSCs were sequentially induced in neurobasal medium containing standard inducing cocktails (ST: bFGF, SHH, FGF8, BDNF), 1 μM melatonin, or a combination of ST and melatonin. The levels of TUJ1, TH, MAP2, NURR1 and dopamine transporter (DAT) were significantly increased in all treated groups when compared with control-untreated cells. Pretreated AF-MSCs with non-selective MT1/MT2 receptors antagonist, luzindole and selective MT2 receptor antagonist, 4-P-PDOT diminished melatonin-induced increase in dopaminergic neuronal markers and phosphorylated ERK but did not diminish increase in phosphorylated CaMKII by melatonin. Pretreatment with mitogen-activated protein kinase (MEK) inhibitor, PD98059 and CaMKII inhibitor, KN-93 were able to abolish increase in the levels of dopaminergic markers in melatonin-treated AF-MSCs. These findings suggest that melatonin promotes dopaminergic neuronal differentiation of AF-MSCs possibly via the induction in ERK and CaMKII pathways through melatonin receptor-dependent and -independent mechanisms, respectively.

Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease

It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against α-syn, and of which only a small part can penetrate the blood-brain barrier, resulting in an extremely low level of effective antibodies in the brain, and limiting the beneficial effect of IVIG on PD mice. Here, we first isolated naturally occurring autoantibodies against α-syn (NAbs-α-syn) from IVIG. Our further investigation results showed that NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-α-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble α-syn, total human α-syn and α-syn oligomers, decreasing the intracellular p-α-synser129 deposits and axonal pathology, inhibiting the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines, increasing the levels of PSD95, synaptophysin and TH in the brain of A53T transgenic mice. These findings suggest that NAbs-α-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD.

The human biomonitoring study in Serbia: Background levels for arsenic, cadmium, lead, thorium and uranium in the whole blood of adult Serbian population

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ± 2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies.

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis.

AIMTo investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis.METHODSAcute colitis was induced in C57Bl/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon.RESULTSProgressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in pro-inflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80+, T helper CD4+ (Th), T cytotoxic CD8+ (Tcyt) and T regulatory CD25+ (Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut.CONCLUSIONThese results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS.

Palmitic Acid-Enriched Diet Increases α-Synuclein and Tyrosine Hydroxylase Expression Levels in the Mouse Brain.

Background: Accumulation of the α-synuclein (α-syn) protein and depletion of dopaminergic neurons in the substantia nigra are hallmarks of Parkinson’s disease (PD). Currently, α-syn is under scrutiny as a potential pathogenic factor that may contribute to dopaminergic neuronal death in PD. However, there is a significant gap in our knowledge on what causes α-syn to accumulate and dopaminergic neurons to die. It is now strongly suggested that the nature of our dietary intake influences both epigenetic changes and disease-related genes and may thus potentially increase or reduce our risk of developing PD.Objective: In this study, we determined the extent to which a 3 month diet enriched in the saturated free fatty acid palmitate (PA) influences levels of α-syn and tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis in mice brains.Methods: We fed the m-Thy1-αSyn (m-Thy1) mouse model for PD and its matched control, the B6D2F1/J (B6D2) mouse a PA-enriched diet or a normal diet for 3 months. Levels of α-syn, tyrosine hydroxylase, and the biogenic amines dopamine and dopamine metabolites, serotonin and noradrenaline were determined.Results: We found that the PA-enriched diet induces an increase in α-syn and TH protein and mRNA expression levels in m-Thy1 transgenic mice. We also show that, while it didn’t affect levels of biogenic amine content in the B6D2 mice, the PA-enriched diet significantly reduces dopamine metabolites and increases the level of serotonin in m-Thy1 mice.Conclusion: Altogether, our results demonstrate that a diet rich in the saturated fatty acid palmitate can modulate levels of α-syn, TH, dopamine, and serotonin which all are proteins and neurochemicals that play key roles in increasing or reducing the risk for many neurodegenerative diseases including PD.

Methylmercury causes epigenetic suppression of the tyrosine hydroxylase gene in an in vitro neuronal differentiation model

Methylmercury (MeHg) is the causative substance of Minamata disease, which is associated with various neurological disorders such as sensory disturbance and ataxia. It has been suggested low-level dietary intake of MeHg from MeHg-containing fish during gestation adversely affects the fetus. In our study, we investigated the toxicological effects of MeHg exposure on neuronal differentiation focusing on epigenetics. We used human fetal brain-derived immortalized cells (LUHMES cells) as a human neuronal differentiation model. Cell viability, neuronal, and catecholamine markers in LUHMES cells were assessed after exposure to MeHg (0–1000 nM) for 6 days (from day 2 to day 8 of neuronal differentiation). Cell viability on day 8 was not affected by exposure to 1 nM MeHg for 6 days. mRNA levels of AADC, DBH, TUJ1, and SYN1 also were unaffected by MeHg exposure. In contrast, levels of TH, the rate-limiting enzyme for dopamine synthesis, were significantly decreased after MeHg exposure. Acetylated histone H3, acetylated histone H3 lysine 9, and tri-methyl histone H3 lysine 9 levels at the TH gene promoter were not altered by MeHg exposure. However, tri-methylation of histone H3 lysine 27 levels, related to transcriptional repression, were significantly increased at the TH gene promotor after MeHg exposure. In summary, MeHg exposure during neuronal differentiation led to epigenetic changes that repressed TH gene expression. This study provides useful insights into the toxicological mechanisms underlying the effects of developmental MeHg exposure during neuronal differentiation.

Foliar Application of Thiamin Stimulates the Growth, Yield and Biochemical Compounds Production of Coriander and Fenugreek

Abstract This study was aimed to investigate the effect of thiamine (Th) foliar application on some morpho-physiological aspects in coriander and fenugreek. Three levels of Th (250, 500 and 750 ppm) plus control treatment (distilled water) were studied under controlled greenhouse conditions. All the levels of Th, in particular the concentration of 500 ppm, increased the vegetative growth of coriander. 1000-grain weight, contents of nitrogen and phosphorus, carotenoid and chlorophyll b contents were the highest at a concentration of 750 ppm. Fenugreek vegetative growth also responded positively to the application of Th especially at a concentration of 750 but also 500 ppm increased the content of leaf nitrogen, chlorophyll b, carotenoids, phenolics and antioxidant activity. Overall, the performance of coriander and fenugreek was improved by the application of Th foliar at all levels.

Triethylamine-assisted Mg(OH)2 coprecipitation/preconcentration for determination of trace metals and rare earth elements in seawater by inductively coupled plasma mass spectrometry (ICP-MS)

In this paper, we report an improved magnesium hydroxide, Mg(OH)2, coprecipitation method for the determination of 16 trace elements (Al, V, Cr, Mn, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Sb, Sn and Pb) and 18 rare earth elements (REEs), including Sc, Y, U and Th in seawater and estuarine water samples. The procedure involves coprecipitation of the trace elements and REEs on Mg(OH)2 upon addition of a small volume of triethylamine (TEA) followed by analysis of the dissolved pellet solutions by inductively coupled plasma mass spectrometry (ICP-MS). Three-step sequential coprecipitation was carried out on 10 mL aliquots of seawater to eliminate the matrix ions and to preconcentrate the analytes of interest into a 1 mL final volume. Spike recoveries varied from 85% (Th) to 105% (Y). Calcium (Ca), sodium (Na) and potassium (K) matrices were virtually eliminated from the analysis solutions. Collision reaction interface (CRI) technology utilizing H2 and He gases was employed to determine its effectiveness in removing the spectral interferences originating from the residual Mg matrix, TEA and plasma gases. H2 was more effective than He in reducing spectral interferences from TEA and plasma gases. Limits of detection (LODs) ranged from 0.01 ng L−1 (Ho) to 72 ng L−1 (Al). The method was validated by using certified seawater (CASS-4) and estuarine water (SLEW-3) reference materials. Precision for five (n = 5) replicate measurements were between 1.2% (Pr) and 18% (Lu). Fe, Pb, Sn, and Zn impurities in TEA were significant in comparison to the levels in CASS-4 and SLEW-3, while relatively high background signals impacted determinations of low levels of Sc and Th. The effects of these hurdles on precision and accuracy were alleviated by measuring these elements in spiked CASS-4 and SLEW-3.

Depleted uranium residues, NORMs and 137Cs in the coastal zone soil of Musandam Peninsula, Hurmuz strait region, Sultanate of Oman

Musandam peninsula located at one of the most important marine strait overlooking the Arabian/Parisian Gulf. Environmentally, this area is characterized by its primitivistic status and vulnerable to any natural or manmade disturbances. This work presents the second phase of a comprehensive radiation measurement in Musandam Peninsula environment amid to investigating the presences of depleted uranium (DU) residues and assessing the current levels of 226Ra, 228Ra, 40K and 137Cs in surface soil of coastal area. For this purpose, thirty representative soil samples were collected and analyzed for 235U using gamma rays spectrometry and for total U using ICP-OES techniques. Results revealed that the range of isotopic abundance of 235U was (0.70%–0.77%) with an average of 0.72%, confirming the detected uranium is naturally originated from the geological formations of investigated soil. Additionally, the values of Th/U ratios were calculated to be ranged from 0.37 to 1.95 with an average of 1.5 indicating the dominant geological formations are metamorphic sedimentary rocks that contain low levels of Th. The averages of radioactivity levels of NORMs indicated 16.02 Bqkg−1, 7.83 Bqkg−1 and 174.03 Bqkg−1 for 226Ra, 228Ra, and 40K respectively. The average of areal concentrations for 137Cs was 2481.5 Bqm−2 ranges from 1040 Bq/m2 to 9225 Bqm−2. The total external annual effective dose from all measured radionuclides was 23 μSv 237Cs contribution is 1% while 238U, 232Th series and 40K radionuclides contributions are 32%, 28% and 39% respectively. Radium equivalent, external, and internal radiation hazard indices indicate no radiological anomaly.

Cytokine Profiles in Acute Brucellosis, Compared with Those in Other Febrile Illnesses

Background: It seems that activation of the T helper 1 (Th 1) cell response, including production of Interleukin-12 (IL-12) and Interferon-gamma (IFN-γ), leads to the resolution of disease and the dominance of Th 2 cells, and related cytokines like IL-4 may reduce the process of Brucella eradication. Objectives: The aim of this study was to evaluate the levels of serum cytokines, IL-12, INF-γ, Tumor Necrosis Factor alpha (TNF-α), and IL-4 in acute brucellosis and compare them with those in other febrile diseases. Methods: This prospective cross-sectional study was done on 80 consecutive patients in Azerbaijan, Iran. The research defined 2 groups in the survey; (group 1) one group with brucellosis and the other group (group 2) without brucellosis; each consisting of 40 patients. All the patients had constitutional symptoms of fever, malaise, and anorexia. Serum agglutination and 2 ME (2 mercaptoethanol) tests were performed on the sera. Data were analyzed using the SPSS version 16 software. Results: Serum TNF-α (group-1: 210.38 ± 168.35 and group-2: 19.53 ± 16.36), INF-γ (group-1: 64.72 ± 19.73 and group-2: 12.18 ± 5.37) and IL-12 (group-1: 283.10 ± 253.51 and group-2: 20.87 ± 12.58) levels were elevated significantly in brucellosis patients compared to the levels in other febrile patients (P value ≤ 0.001). The IL-4 level showed no significant difference between brucellosis and other febrile patient’s sera (P value = 0.870). Conclusions: The current study showed that serum levels of Th 1 cytokines, including INF-γ and IL-12 levels are elevated significantly in systemic brucellosis patients. However, IL-4 levels, a Th 2 cytokine, had no significant difference between the 2 groups.

Parametric CI+MBPT calculations of Th I energies and g-factors for even states

In this paper, we study energies and g-factors for a large number of levels of Th I. We found that the accuracy of configuration-interaction many-body perturbation theory can be substantially improved by using multiple adjustment parameters, which are introduced to regulate the second-order MBPT corrections for single-valence energies and Coulomb interaction. The results for energies and g-factors are in excellent agreement with experiment, with accuracy sufficient to positively assign theoretical states of given angular momentum and parity to experimental levels. This theory will be further developed in the future to treat other, even more complicated, actinides such as U I.

High Hydrostatic Pressure Extract of Ginger Exerts Antistress Effects in Immobilization-Stressed Rats.

Stress contributes to physiological changes such as weight loss and hormonal imbalances. The aim of the present study was to investigate antistress effects of high hydrostatic pressure extract of ginger (HPG) in immobilization-stressed rats. Male Sprague-Dawley rats (n = 24) were divided into three groups as follows: control (C), immobilization stress (2 h daily, for 2 weeks) (S), and immobilization stress (2 h daily, for 2 weeks) plus oral administration of HPG (150 mg/kg body weight/day) (S+G). Immobilization stress reduced the body weight gain and thymus weight by 50.2% and 31.3%, respectively, compared to the control group. The levels of serum aspartate transaminase, alanine transaminase, and corticosterone were significantly higher in the stress group, compared to the control group. Moreover, immobilization stress elevated the mRNA levels of tyrosine hydroxylase (Th), dopamine beta-hydroxylase (Dbh), and cytochrome P450 side-chain cleavage (P450scc), which are related to catecholamine and corticosterone synthesis in the adrenal gland. HPG administration also increased the body weight gain and thymus weight by 12.7% and 16.6%, respectively, compared to the stress group. Furthermore, the mRNA levels of Th, Dbh, phenylethanolamine-N-methyltransferase, and P450scc were elevated by the HPG treatment when compared to the stress group. These results suggest that HPG would have antistress effects partially via the reversal of stress-induced physiological changes and suppression of mRNA expression of genes related to corticosterone and catecholamine synthetic enzymes.

Hydrothermal titanite from the Chengchao iron skarn deposit: temporal constraints on iron mineralization, and its potential as a reference material for titanite U–Pb dating

Uranium–lead isotopes and trace elements of titanite from the Chengchao iron skarn deposit (Daye district, Eastern China), located along the contact zones between Triassic marine carbonates and an early Cretaceous intrusive complex consisting of granite and quartz diorite, were analyzed using laser ablation inductively coupled plasma mass spectrometry to provide temporal constraints on iron mineralization and to evaluate its potential as a reference material for titanite U–Pb geochronology. Titanite grains from mineralized endoskarn have simple growth zoning patterns, exhibit intergrowth with magnetite, diopside, K-feldspar, albite and actinolite, and typically contain abundant primary two-phase fluid inclusions. These paragenetic and textural features suggest that these titanite grains are of hydrothermal origin. Hydrothermal titanite is distinct from the magmatic variety from the ore-related granitic intrusion in that it contains unusually high concentrations of U (up to 2995 ppm), low levels of Th (12.5–453 ppm), and virtually no common Pb. The REE concentrations are much lower, as are the Th/U and Lu/Hf ratios. The hydrothermal titanite grains yield reproducible uncorrected U–Pb ages ranging from 129.7 ± 0.7 to 132.1 ± 2.7 Ma (2σ), with a weighted mean of 131.2 ± 0.2 Ma [mean standard weighted deviation (MSWD) = 1.7] that is interpreted as the timing of iron skarn mineralization. This age closely corresponds to the zircon U–Pb age of 130.9 ± 0.7 Ma (MSWD = 0.7) determined for the quartz diorite, and the U–Pb ages for zircon and titanite (130.1 ± 1.0 Ma and 131.3 ± 0.3 Ma) in the granite, confirming a close temporal and likely genetic relationship between granitic magmatism and iron mineralization. Different hydrothermal titanite grains have virtually identical uncorrected U–Pb ratios suggestive of negligible common Pb in the mineral. The homogeneous textures and U–Pb characteristics of Chengchao hydrothermal titanite suggest that the mineral might be a suitable internal reference material for U–Pb dating.

Immune status parameters in lung cancer patients with various levels of circulating tumor cells.

e20018 Background: The purpose of the study was to evaluate parameters of cellular immunity in lung cancer patients with various levels of circulating tumor cells (CTCs) and different tumor histogenesis. Methods: Blood samples of 28 patients (24 men, 4 women, mean age 62±1.3 years) were studied. 18 (64.3%) patients had neuroendocrine tumors (small cell lung cancer, SCLC), and 10 (35.7%) patients had adenocarcinoma (AC). 11 (39.3%) patients were diagnosed with stage III disease and 17 (60.7%) – stage IV. CTCs were detected in the blood before treatment using the CellSearch System (Janssen Diagnostics, LLC) with iron microparticles coated with antibodies to EpCAM, CD45 and cytokeratins 8, 18 and 19; subsets of lymphocytes, including minor ones, were studied on FACSCantoII flow cytometer (BD). Results: CTCs were found in 25 patients (89.3%); their number ranged 1-6888. 15 (83.3%) patients with SCLC had 0-6888 CTCs, with an average of 655.7, median 38.5. All 10 patients with AC had 1-486 CTCs, with an average of 57.2, median 5.0. The number of CTCs in CTC-positive patients with SCLC was, despite high individual variability, significantly higher than in patients with AC (786.9±474 vs. 57.2±47.9, respectively; p &lt; 0.05). Such differences were accompanied by higher levels of Th-lymphocytes with activation/apoptosis markers (CD3+CD4+CD95+): 84.2±2.7 vs. 72.2±3.7%, and cytotoxic CD16bright/56dim NKcells: 91.4±1.8 vs. 83.4±3.7%. Patients with CTC+ AC had higher levels of IFNγ-producing NK-cells, compared to SCLC patients (15.3±3.8 vs. 7.2±1.6%), as well as levels of Th with the early activation marker (CD4+CD38+) (27.8±3.5 vs. 17.4±2.3%). Presence of CTCs in SCLC patients was associated with lower levels of activated lymphocytes of various subsets: T-cells (CD4+CD38+, CD8+CD38+, CD3+CD8+HLA-DR+) and NК-cells (Granzyme B+ and CD335+). Conclusions: Levels of CTCs were significantly higher in patients with SCLC than in those with AC; immune status parameters had a number of differences in CTC+ tumors with various histogenesis. The presence of CTCs in SCLC was accompanied by reduced blood levels of activated T- and NK-cells. The reported study was partially supported by RFBR, research project No. 16-34-00244mol_a

The interaction between lipid exchange and thyroid status in the conditions of prolonged influence of small doses of radiation

We studied the interaction between the indicators of lipid exchange and thyroid status among the inhabitants of radiation contaminated territories under additional psycho-emotional load. We observed 170 students aged between 18–24 and divided them into a control group of students who were from areas unaffected by radiation (70 people) and the main experimental group of students from territories of increased radio-ecological load (IV radiation zone, 100 people). We determined the content of thyrotropic hormone (TTH), triiodothyronine (T3), thyroxin (T4), total cholesterin (TC), triglycerides (TG), cholesterin of lipoproteins of high density (Ch-LPHD) and cholesterin of lipoproteins of low density (Ch-LPLD). We found that people who had lived since birth in territories which were contaminated with radionuclides and were affected by prolonged influence of small doses of ionizing radiation had significant fluctuations of indicators of concentrations of TTH, T3 and T4, forming manifestations of hypothyroidism and hyperthyrosis among some of those tested. Independently from hyperthyrosis, the effect was accompanied by growth in the level of TH, TG, Ch-LPHD and Ch-LPLD. Persons with manifestations of hypothyroidism had the content of TH above the upper limit of the homeostatic norm and the level of Ch-LPLD was higher than the norm in sub-groups with features of hypo- and hyperthyrosis. All those tested from the main group showed a significant positive correlation connection between the level of TTH and levels of TH and Ch-LPLD. The subgroup with manifestations of hyperthyrosis had a positive correlation between the levels of TTH and TG, the subgroups with manifestations of euthyroidism and hyperthyrosis had a negative correlation between the levels of TTH and Ch-LPHD. The hyperthyrosis subgroup had a significant positive correlation connection between T3 and TH and Ch-LPLD. The euthyroidism and hypothyroidism subgroups had a significant negative correlation between T3 concentration and Ch-LPLD. The cortisol indicator positively correlated with levels of TH and Ch-LPLD in all subgroups divided according to thyroid status. In the conditions of additional psycho-emotional load (examinations), those tested had an increased level of TP (higher than the norm in the subgroups of hyperthyrosis and hypothyroidism) caused by the increase in cortisol level and a tendency of decrease in TTH. At the same time, the level of Ch-LPLD increased (higher than the upper norm) as a result of decrease in the content of Ch-LPHL. The coefficient of correlation between the level of TTH and levels of TH and Ch-LPLD lost statistical significance in all subgroups divided according to thyroid status. In the hyperthyrosis subgroup, the effect of loss of correlation with TH and Ch-LPLD was also observed for T3. Thus, the individuals tested from territories polluted by radionuclides, had proaterogenic changes dependant on thyroid status,which can become a precondition for the development of metabolic syndrome. The risk of dyslipidemia increases in the conditions of additional psycho-emotional load, when the regulatory effect of the thyroid gland`s hormones is reduced.

Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice

Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson’s disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus-maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD.

Socio – economic and environmental impact of artisanal mining in parts of Naraguta sheet 168, north central Nigeria

The aim of this study was to assess the socio – economic and environmental impact of artisanal mining in parts of Naraguta Sheet 168. Geochemical data, environmental analysis from previous studies and on the spot interviews and interactions were employed to obtain the data for this study. Results revealed over 5000 abandoned pits with varying depths ranging from12 to 15 meters. Analysis of soils and water samples collected from the mining pits, some hand dug wells and boreholes in the area, indicate low levels of most trace and rare earth elements in the waters. However, individual elements concentration showed that farm soils generally have high levels of Pb and Th and in some places Cd. The calculated Index of geo-accumulation classified the soils as uncontaminated to moderately contaminated. With over 5000 pits already dug in the area, the arable lands have been devastated, with diversion in flow directions of most streams. Trees and shrubs have been uprooted rendering the land susceptible to erosion. Opened mined pits serve as death traps to animals and breeding grounds for mosquitoes, making the area prone to malaria disease. About N450, 000 (3000 Dollars) at the end of every week is obtained from sales of the ore, shared amongst 8 – 10 team members. However, the social vices associated with it, such as child labour, school drop-out, the use of drugs, deaths due to flooding and collapse of lotto pits, theft, inflation, and prostitution, sexually transmitted diseases is prevalent. The study suggest interventions such as; reclaiming open pits, dredging of streams, rivers and remediation of contaminated soils and health awareness campaign to ameliorate the negative impacts of artisanal mining on the communities. Key Words: Artisanal Mining, Trace Elements, Land Degradation, Tin Mining