Whole Blood Levels Research Articles

Preventing platelet-derived microparticle formation--and possible side effects-with prestorage leukofiltration of whole blood.

Abstract Context.—Platelet-derived microparticles (PDMPs) probably function in hemostasis, thrombosis, inflammation, and transfusion-related immunomodulation. Objective.—To compare PDMP levels of leukocyte-filtered and unfiltered whole blood during storage. Design.—Ten whole blood donations were collected and processed. Half of each collection was filtered, half remained unfiltered, and both halves were measured for red cell, white cell, and platelet (PLT) content before storage. Samples were drawn on days 0, 1, 2, 3, 5, 7, 14, 21, 28, and 35 and analyzed by flow cytometry. Results.—Leukocyte filtration lowered prestorage PDMP and PLT counts by an average of 72% and 99%, respectively. Prestorage PDMP counts were 123 ± 51/µL in unfiltered whole blood supernatant versus 34 ± 18/µL after filtration. Prestorage PLT counts were 190 ± 49/µL in unfiltered whole blood supernatant versus 2 ± 4/µL after filtration. Moreover, PDMP and PLT counts in filtered whole blood remained low throughout storage, typically belo...

Abstract 143: Global DNA methylation level in whole blood and risk of non-Hodgkin lymphoma

Abstract Global DNA hypomethylation may result in chromosomal instability and cancer risk. This study was performed to determine the association between DNA hypomethylation in derived from whole blood and non-Hodgkin lymphoma. We analyzed DNA of 506 NHL and 1680 control subjects at Chonnam National University Hwasun Hospital, Korea. Global DNA methylation levels were assessed using bisulfited-PCR pyrosequencing of long interspersed nuclear element-1 (LINE-1). All participants were subsequently categorized into quartiles by mean % in control. When the highest quartile was considered as a reference category (Q4), the following adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were observed for decreasing methylation quartiles OR(Q3)=2.36 (95% CI:1.40-3.97); OR(Q2)=4.67 (95% CI: 2.89-7.55) and OR(Q1)=17.56 (11.19-27.56). This is, to the best of our knowledge, the first study to show that global DNA hypomethylation was significantly associated with increased for NHL risk in a large case-control study. These findings suggest that global methylation levels in genomic DNA may be play important role in the NHL risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 143.

Overcoming the effect of rifampin on the tacrolimus metabolism by itraconazole administration in an allogeneic hematopoietic stem cell transplant recipient

Rifampin, one of the first-line agents for tuberculosis, has a great potential to induce the activity of the cytochrome P450 (CYP) enzyme, CYP 3A4, and lowers the concentration of calcineurin inhibitors such as tacrolimus and cyclosporine A (CsA). When calcineurin inhibitors and rifampin are coadministered, increasing the dose of calcineurin inhibitors is essential in maintaining therapeutic blood levels, but this often fails and results in the induction of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) or graft rejection after solid organ transplantation [1–6]. Another option is the administration of agents which could compete with the activity of rifampin upon CYP 3A4. We here present a case in which rifampin was coadministered with tacrolimus after allogeneic HSCT, and administration of oral-solution itraconazole successfully offset the effect of rifampin on the tacrolimus metabolism, resulting in the achievement of a therapeutic blood level of tacrolimus. A 50-year-old woman with myelodysplastic syndrome underwent bone marrow transplantation from an unrelated donor. Tacrolimus and short-term methotrexate were given for the prophylaxis of GVHD. Tacrolimus was given at an initial dose of 0.03 mg/kg by continuous intravenous infusion from day -1, and its dose was adjusted to maintain its blood level at 15–20 ng/ml during the first 4 weeks, followed by oral administration to maintain the blood level at 5–10 ng/ml. She developed acute GVHD of the skin on day 33 post-transplant, which was successfully treated with prednisolone. Prednisolone was given at a dose of 1 mg/kg for 7 days, then tapered, and discontinued on day 96 posttransplant. During prednisolone therapy, voriconazole at dose of 400 mg/day was orally given for the prophylaxis of fungal infection. Antifungal agents were not given thereafter. Around day 150 post-transplant, when tacrolimus was still being orally administered (3 mg/day) and its whole-blood trough level was around 5.5 ng/mL, pulmonary tuberculosis was diagnosed. Anti-tuberculosis chemotherapy consisting of rifampin (300 mg/day), isoniazid (300 mg/day), ethambutol (750 mg/day), and pyrazinamide (1200 mg/day) was initiated. Shortly after initiating this combination therapy, the trough level of tacrolimus became undetectable by automated microparticle enzyme immunoassay (minimum detectable level: 3.0 ng/ mL). Doubling the dose of tacrolimus to 6 mg/day failed to achieve a detectable level of tacrolimus. Oral-solution itraconazole was then initiated at a dose of 200 mg/day for the prophylaxis of fungal infection. The trough level of tacrolimus began to rise, and reached 5.7 ng/ml with 3 mg/ day of oral tacrolimus in 8 days after initiating itraconazole. The patient did not develop GVHD during or after the period of undetectable blood levels of tacrolimus, and fungal infection throughout the clinical course. The combination antituberculosis therapy was effective, and the pulmonary tuberculosis was cured after the 12-month therapy. Coadministration of oral-solution intraconazole with tacrolimus, rifampin, and three other anti-tuberculosis agents caused no clinically significant adverse events. As seen in the present case, rifampin has a great impact on the pharmacokinetics of calcineurin inhibitors, and markedly increases the dose requirement of calcineurin inhibitors to maintain a therapeutic blood level during rifampin therapy [1]. Increasing the dose of calcineurin inhibitors is not always effective, and the reduced levels T. Mori (&) Y. Aisa J. Kato Y. Nakamura T. Shimizu S. Okamoto Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan e-mail: tmori@sc.itc.keio.ac.jp

Effects of zinc and cadmium on erythrocyte antioxidant systems of a freshwater fish Oreochromis niloticus

In this work to determine the effects of metals exposure of Oreochromis niloticus on erythrocyte antioxidant systems, fish were exposed to 5.0 mg/L Zn, 1.0 mg/L Cd, and 5.0 mg/L Zn + 1.0 mg/L Cd mixtures for 7 and 14 days and reduced glutathione (GSH) level, catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PD) activities were investigated. In addition, Zn or Cd levels in whole blood were studied. Erythrocyte GSH level and CAT and G6PD enzyme activities increased in response to single and combined Zn and Cd exposure. The elevation observed in the CAT activity was higher in the Cd alone, and in combination with Zn, than in Zn alone. Time-dependent alteration was not observed in all antioxidant parameters. Exposure to metals (alone and in mixture) resulted in elevatation of Zn and Cd levels in the blood. Concentration of metals in the blood of fish exposed to the Zn + Cd combination was lower than in fish exposed to the single metal. This study demonstrates that metals caused oxidative stress in fish erythrocytes, and an adaptation with an increase in CAT and G6PD activities and GSH level, which were important in the protection against metal damage, was observed.

Automated blood glucose monitor is insensitive to hematocrit variation and common saccharide interferents

Luminous Medical is developing an automated, patient-attached system (Argus Glucose Monitoring System) that uses a flow-through glucose oxidase sensor to measure plasma glucose levels in whole blood. The Argus GMS will aid caregivers in achieving glycemic control in critical care patients. The FDA has recently indicated that ICU glucose monitors need to satisfy tighter accuracy requirements than those specified by ISO 15197 (± 15 mg/dl or ± 20%). Luminous conducted a study to demonstrate Argus GMS accuracy under conditions of variable hematocrit, and in the presence of common saccharide interferents.

Oxidative stress and serum paraoxonase activity in patients on maintenance hemodialysis

Incidence of atherosclerosis is high in hemodialysis (HD) patients. Paraoxonase may have protective effects against atherosclerosis as it prevents oxidative modification of LDL. Hence, the aim of the present study was to assess the lipid peroxidation and the antioxidant status including paraoxonase activity in HD patients. Thirty HD patients and thirty controls were included in the study. Serum malondialdehyde (MDA) was assessed as a marker of oxidative stress, while antioxidant status was assessed in terms of whole blood reduced glutathione, erythrocyte catalase and serum paraoxonase activity. A statistically significant (p < 0.001) rise of 196 % in serum MDA levels and decline of 36% in erythrocyte catalase activity was noted in HD patients as compared to controls. However, reduced glutathione (GSH) level in whole blood was not altered. Both basal and salt stimulated serum paraoxonase activities were reduced significantly (p < 0.001) as compared to controls with percentage decline of 53% and 37% in basal and salt stimulated paraoxonase activities respectively. These findings indicate that in addition to increased oxidative stress, reduced serum paraoxonase activity could also contribute to development of atherosclerosis in HD through increased oxidative modification of LDL.

Whole blood viscosity issues VI: Association with blood salicylate level and gastrointestinal bleeding

Background:This series on whole blood viscosity issues has been trying to elucidate the sensitivity, specificity and usefulness of the laboratory parameter in clinical practice. The postulation has been that since antiplatelet is used in the management of stasis, of which blood viscosity is an index, the latter would be useful laboratory indication and/or contraindication.Aim:The aim of this study was to observe whether blood level of acetylsalicylic acid differs with the level of whole blood viscosity.Patients and Methods:Out of the ten years database, 538 cases that were concomitantly tested for haematocrit, total proteins and blood level of salicylate were selected for this study. A separate nine cases of positive faecal occult blood tests were audited for blood viscosity and reviewed.Results:A statistically significant difference is observed with lower blood viscosity being associated with higher salicylate level in comparison of the former between the highest vs. lowest quartiles (p < 0.002). This observation demonstrates the effect of aspirin in lowering blood stasis. Reviewing the positive faecal occult blood cases indicate that gastrointestinal bleeding is characterized by relative hypoviscosity and that hyperviscosity is not present during bleeding complications.Conclusion:The findings affirm that whole blood viscosity is a valid clinical laboratory parameter for evidence-based contraindication, indication and monitoring of antiplatelet medication. It calls for better appreciation and clinical utility of whole blood viscosity, which (in the absence of viscometer) can now be extrapolated from haematocrit and total proteins.

Absorption and Excretion of Colestilan in Healthy Subjects

Colestilan, an anion-exchange resin binding both phosphate and bile-acid anions, is under development for the treatment of hyperphosphataemia and dyslipidaemia, which occur in the majority of end-stage renal disease patients. This study using 14C-colestilan was conducted to investigate the absorption and excretion of colestilan in humans. Following a 28-day run-in period with administration of colestilan 3 g three times daily, 12 subjects received a single oral dose of 14C-colestilan 100 mg (approximately 4.0 MBq) and colestilan 3 g under fasted conditions on the morning of day 1. A total of 9 g of colestilan was administered three times daily on days 1-4. Total radioactivity levels in whole blood (at 4, 8, 12 and 24 hours and then at 24-hour intervals) and in the urine and faeces (from 0 to 24 hours and then at 24-hour intervals) were monitored up to 216 hours postdose (day 10). Total radioactivity measured in all whole-blood samples was below the lower limit of quantification (0.025 microg equivalent of 14C-labelled colestilan/mL of whole blood). Total radioactivity assessed in all urine samples was also below the lower limit of quantification (0.003 microg equivalent/mL for urine), except at 0-24 hours postdose, when 0.01% of the radioactive dose was excreted by all subjects. This level was below the predetermined water soluble impurity level of 0.04%. The mean cumulative excretion of total radioactivity in the faeces was 99.66% by 216 hours postdose, excluding one subject with incomplete collection of faecal samples. These results demonstrate that colestilan is not absorbed from the gastrointestinal tract and is completely excreted in the faeces.

Exposure to Supplemental Oxygen and Its Effects on Oxidative Stress and Antioxidant Enzyme Activity in Term Newborn Lambs

The optimal oxygen concentration for the resuscitation of term infants remains controversial. We studied the effects of 21 versus 100% oxygen immediately after birth, and also exposure for 24 h to 100% oxygen, on oxidant lung injury and lung antioxidant enzyme (AOE) activities in term newborn lambs. Lambs at 139 d gestation were delivered and ventilated with 21% (RAR) or 100% (OXR) for 30 min. A third group of newborn lambs were ventilated with 100% O2 for 24 h (OX24). Oxidized glutathione levels in whole blood were significantly different among the groups with lower values in the RAR group, and these values correlated highly with partial pressure of arterial oxygen (Pao2). The reduced to oxidized glutathione ratio was significantly different among the groups, the ratio decreasing with increasing oxygen exposure. Lipid hydroperoxide (LPO) activity was significantly higher in the OXR and OX24 groups. AOE activity was higher in the whole lung and in red cell lysate in the OX24 group. Increased myeloperoxidase (MPO) activity, percent neutrophils, and proteins in lung lavage suggested inflammation in the OX24 group after maximal oxygen exposure. We conclude that even relatively brief exposure of the lung to 100% oxygen increases systemic oxidative stress and lung oxidant injury in ventilated term newborn lambs.

Folate Deficiency Alters Hepatic and Colon MGMT and OGG-1 DNA Repair Protein Expression in Rats but Has No Effect on Genome-Wide DNA Methylation

Folate deficiency is implicated in human colon cancer. The effects of feeding rats a folate-deficient diet for 24 weeks on DNA damage (8-oxo-7,8-dihydroguanine), DNA repair [O(6)-methylguanine-DNA methyltransferase (MGMT) and 8-oxoguanine-DNA glycosylase (OGG-1) activity], and epigenetic parameters (genome-wide cytosine methylation and indices of cellular methylation status) were investigated. Relative to control diet, the folate-deficient diet resulted in significantly reduced levels of serum ( approximately 80%; P < 0.0001), whole blood ( approximately 40%; P < 0.0001), and tissue folate (between 25% and 60% depending on the tissue sampled; P < 0.05); increased plasma total homocysteine ( approximately 35%; P < 0.05); and decreased S-adenosylmethionine to S-adenosylhomocysteine concentrations ( approximately 11%; P < 0.05). There was no significant change in the levels of 5-methyldeoxycytidine in liver or colon DNA, nor in the activity of liver DNA cytosine methyltransferase. However, there were significant increases in 8-oxo-7,8-dihydroguanine (P < 0.001) in lymphocyte DNA and in levels of the DNA repair proteins OGG-1 ( approximately 27%; P < 0.03) and MGMT ( approximately 25%; P < 0.003) in the liver, but not in the colon. This may reflect the ability of the liver, but not the colon, to upregulate DNA repair enzymes in response to either elevated DNA damage or an imbalance in the nucleotide precursor pool. These results show that folate deficiency can significantly modulate DNA damage and DNA repair, providing mechanisms by which it plays a role in the etiology of human cancer. We speculate that the inability of colon tissue to respond to folate deficiency occurs in humans and may increase the potential for malignant transformation.

Accumulation of intravenously administered methamphetamine in stomach contents

The accumulation of intravenously administered methamphetamine (MAMP) in the stomach contents was investigated as part of a process used to discriminate between oral and intravenous administration of MAMP. Eight forensic autopsy cases, in which intravenous administration of MAMP was confirmed, were used. Total amounts and pH values of stomach contents were in the ranges of 20–500 g and 3–5 (determined in seven cases), respectively. Intervals between the last MAMP administration and each death could be roughly estimated in four cases: 1–3 h in two cases and 3–6 h in two cases. MAMP levels in stomach contents and whole blood were in the ranges of 0.816–43.4 µg/g (total amounts: 0.114–1.95 mg) and 0.236–14.6 µg/ml, respectively. The mean ratio of MAMP level in the stomach contents to that in whole blood was 8.23 ± 9.01, indicating accumulation of MAMP in the stomach contents against a concentration gradient. On the basis of the average plus three times the standard deviation, a tentative borderline ratio value for discriminating oral and intravenous administrations of MAMP was calculated to be 36. When the ratio is 36 or larger, a deceased can be diagnosed to have used MAMP orally; when it is smaller than 36, either possibility (oral or intravenous route) is considered possible.

Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children

The relationship between tacrolimus concentration and acute GVHD is not well known, with few published data available for lower target levels. We hypothesized that lower levels of tacrolimus would correlate with higher incidence of acute GVHD and poorer prognosis. Receiver operator characteristic curves (ROC) were used to quantify tacrolimus blood levels as predictors of grade II-IV acute GVHD. A total of 97 pediatric patients with hematological malignancies met the study criteria. On the ROC, a cutoff of 7 ng/ml provided the best balance between sensitivity and specificity (62.8 vs 68.2%, respectively). Cumulative incidence of acute GVHD was 65.9% (range 58.5-73.3%) in patients with mean tacrolimus concentration of < or =7 ng/ml and 34.8% (range 27.8-41.8%) in patients with mean tacrolimus concentration of >7 ng/ml (P=0.002). Incidence of non-relapse mortality (NRM) was higher in patients with tacrolimus of < or =7 ng/ml (42.9%; range 35.6-50.2%) than in patients with tacrolimus of >7 ng/ml (28.3%; range 17.4-39.2%; P=0.008). This translated into better EFS in patients with tacrolimus of >7 ng/ml (48.9%; range 39.8-58.0%) than in patients with tacrolimus of < or =7 ng/ml (31.8%; range 25.0-38.6%; P=0.031). Multivariate analysis showed that tacrolimus concentration was significantly associated with clinical outcomes. Mean whole-blood level of tacrolimus as continuous infusion should be maintained at > or =7 ng/ml for pediatric patients.

Manganese in Parenteral Nutrition: Who, When, and Why Should We Supplement?

Micronutrient requirements are not fully understood. Parenteral nutrition (PN) usually contains the trace element (TE) manganese (Mn) from fixed-concentration TE supplements. Multiple TE formulations may not be optimal in pediatric and home PN. Moreover, most PN products contain Mn as a ubiquitous contaminant. Excessive Mn can lead to Parkinson-like symptoms resulting from hypermanganesemia. A survey of 40 Australasian hospitals that contributed data on 108 patients to the annual home PN register and a systematic review of the literature were conducted to establish the scope of the potential problem of Mn toxicity in PN patients. Exposure to Mn doses 5-6 times current daily requirements, together with the TE contamination that is reported in PN products, can lead to neurotoxicity. Whole-blood levels are more accurate for monitoring and correlate well with signal intensity of magnetic resonance imaging. Current TE formulations restrict prescribing options. The regulatory mechanisms of Mn homeostasis are bypassed via the parenteral route so elimination via the hepatobiliary system is impaired, resulting in tissue or brain accumulation. Published dosage recommendations may be excessive and official guidelines require revision. Variability in clinical practices necessitates that individual TE additives are more widely available and multiple TE products reformulated. More frequent monitoring for any brain accumulation is recommended. The scarcity of PN-associated Mn deficiency, plus the growing evidence for Mn toxicity, leads to the conclusion that it is unnecessary for Mn to be prescribed routinely for pediatric or long-term PN patients.

DNA damage and glutathione level in children with asthma bronchiale: Effect of antiasthmatic therapy

When the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defences, a condition known as oxidative stress occurs and it has been implicated in many pathological conditions including asthma. Interaction of ROS with DNA may result in mutagenic oxidative base modifications such as 8-hydroxydeoxyguanosine (8-oxo-dGuo) and DNA strand breaks. Reduced glutathione (GSH) serves as a powerful antioxidant against harmful effects of ROS. The aim of this study was to describe DNA damage as level of DNA strand breaks and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites, which reflects oxidative DNA damage and GSH level in children with mild-to-moderate persistent asthma; and to examine the effect of antiasthmatic therapy on these DNA damage parameters and GSH level. Before and after 8 wk of antiasthmatic therapy blood samples were taken, DNA strand breaks and Fpg-sensitive sites in peripheral leukocytes were determined by comet assay, GSH level of whole blood was measured by spectrophotometric method. DNA strand breaks and Fpg-sensitive sites in the asthma group were found to be increased as compared with control group. GSH level in the asthma group was not significantly different from those in the control group. Levels of strand breaks, Fpg-sensitive sites and GSH were found to be decreased in the asthma group after the treatment. In conclusion, oxidative DNA damage (strand breaks and Fpg-sensitive sites) is at a high level in children with asthma. DNA damage parameters and GSH level were found to be decreased after therapy. Our findings imply that antiasthmatic therapy including glucocorticosteroids not only controls asthma but also decreases mutation risk in children with asthma bronchiale.

Inverse correlation of brain and blood BDNF levels in a genetic rat model of depression

There is accumulating evidence that brain-derived neurotrophic factor (BDNF) plays a critical role in the pathophysiology of depression. Decreased serum levels have been reported in major depression, and a correlation between BDNF reduction and the severity of the disease was found. Moreover, in post-mortem hippocampal tissue, increased levels of BDNF immunoreactivity have been reported in subjects treated with antidepressants compared to untreated subjects. These findings indicate parallel changes in brain and serum BDNF levels during depression. BDNF has been measured in selected brain areas in several animal models. In investigations between Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats, a genetic rat model of depression, no differences were found in BDNF levels in the frontal cortex and hippocampus, areas believed to be core brain regions in depression. However, to our knowledge brain and serum BDNF levels have never been reported in parallel for any psychiatric disease model. Therefore, we examined the levels of BDNF in whole blood, serum, cerebrospinal fluid (CSF), hippocampus, and frontal cortex in male FSL and FRL rats. BDNF levels in serum and whole blood of FSL rats were significantly increased compared to FRL rats. In contrast, in the hippocampus the BDNF level was significantly decreased in FSL compared to FRL rats while no differences were found in the frontal cortex and CSF. The differential regulation of the BDNF levels in hippocampus, serum, and whole blood in FSL/FRL rats adds to the hypothesis that neurotrophic factors are related to the pathophysiology of depression.

Polymorphisms at Cytokine Genes May Determine the Effect of Vitamin E on Cytokine Production in the Elderly , ,

Vitamin E has been shown to affect cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable and common single nucleotide polymorphisms (SNP) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals, including SNP at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled 1-y vitamin E (182 mg d,l-α-tocopherol) intervention study in elderly men and women (mean age 83 y) to test this hypothesis (vitamin E, n = 47; placebo, n = 63). We found that the effect of vitamin E on tumor necrosis factor (TNF)-α production in whole blood stimulated for 24 h with lipopolysaccharide (1.0 mg/L) is dependent on TNFα -308G > A. Participants with the A/A and A/G genotypes at TNFα -308G > A who were treated with vitamin E had lower TNFα production than those with the A allele treated with placebo. These observations suggest that individual immune responses to vitamin E supplementation are in part mediated by genetic factors. Because the A allele at TNFα has been previously associated with higher TNFα levels in whole blood and isolated immune cells, our observations suggest that the antiinflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies are needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNFα -308G > A and its implications for disease resistance.

Protective roles of vitamin E (α-tocopherol), selenium and vitamin E plus selenium in organophosphate toxicity in vivo: A comparative study

In the present study, we investigated the possible protective role of vitamin E, selenium (Se) and vitamin E plus Se in fenthion-induced organophosphates (OP) toxicity in rats. Serum concentrations of ascorbic acid, retinol, β-carotene, ceruloplasmin, nitrite and nitrate as well as levels of malondialdehyde (MDA) and reduced glutathion (GSH) in whole blood and in some tissues such as brain, heart, jejunum, kidney, liver, lung, muscle and pancreas were measured in sham, control, vitamin E, Se and vitamin E + Se groups. Compare to the sham group, the MDA ( p < 0.001) and GSH ( p < 0.01) levels in whole blood and some in tissues were significantly higher in the control animals. Ceruloplasmin levels of the control ( p < 0.05), vitamin E ( p < 0.05) and vitamin E + Se ( p < 0.01), groups were higher than the sham group. Ascorbic acid, retinol, β-carotene as well as nitrite and nitrate levels in the control group were significantly lower than sham, vitamin E, Se and vitamin E + Se groups. We concluded that fenthion toxicity-induced lipid peroxidation and generation of free radicals in whole blood and tissues. Additionally, the antioxidants we tested did show a significant protective effect against OP-induced tissue and blood injury at the biochemical level.

Inhaled Fluorescent Magnetic Nanoparticles Induced Extramedullary Hematopoiesis in the Spleen of Mice

Nanomaterials are used in a wide variety of industrial materials such as semiconductors, magnetic resonance imaging, gene delivery carriers for gene therapy and many others; thus, human seems to be frequently exposed to them. Such diverse applications of nanoparticles elicit the need to identify the positive aspects of nanomaterials while avoiding the potential toxic effects. In this study, inhalation toxicity of manufactured nanomaterials using fluorescent magnetic nanoparticles (FMNPs) was assessed to address the issue of potential nanoparticle toxicity. Biological samples from a previous mouse FMNP exposure experiment were analyzed for potential FMNP toxicity. Mice inhaled FMNPs for 4 wk through a nose-only exposure chamber developed by our group for 4 wk and the potential toxicity of FMNPs was analyzed. The nanoparticle distribution by scanning mobility particle sizer (SMPS) analysis showed that the mean values of number concentration (mass concentrations) in the nose-only exposure chamber were maintained at 4.89 x 10(5)/cm3 (approximately 159.4 microg/m3) for the low concentration and 9.34 x 10(5)/cm3 (approximately 319.5 microg/m3) for the high concentration, respectively. Inhalation of FMNPs caused a decrease of body weight and significant changes of white blood cells (WBCs) levels in whole blood. The FMNPs induced extramedullary hematopoiesis in the spleen without having a pulmonary effect. Our results support the proposition that extensive toxicity evaluation is needed for practical applications of anthropogenic nanomaterials and suggest that careful regulation of nanoparticle applications may be necessary to maintain a high quality of life as well as for facilitating the development of nanotechnology.

Effect of ingestion of copper bhasm on red cell indices, iron parameters and essential elements in chicks

In order to scientifically evaluate the effect of copper bhasm, it was orally administered in a dose of 2 mg/day for seven days to one month old male chicks. There was significant fall in total red cells, and rise in plasma iron, PCV and MCV indicating hemolysis, compensated by increased heme synthesis. A significant increase in plasma iron binding capacity points to beneficial effect of copper bhasm on liver as transferrin is synthesized in liver. Ferritin (storage iron) was unaltered in seven days treatment. The effect of copper bhasm on tissue distribution of essential elements was variable. Calcium, sodium and potassium were significantly increased in all the tissues. The last two may have been contributed by the bhasm itself. Magnesium behaviour was similar to calcium. Iron and zinc showed variable effects. Copper level in whole blood, plasma and erythrocytes increased significantly showing that copper bhasm was well absorbed and the effect observed can be ascribed to it. The bhasm was well tolerated and no growth retardation was seen.

In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative sepsis is associated with elevated levels of IL-1R-associated kinase M, an intracellular negative regulator of MyD88-dependent TLR signaling. In the present study, we investigated whether in vivo exposure of humans to LPS induces tolerance in circulating leukocytes to other TLR agonists that rely either on MyD88- dependent or on MyD88-independent signaling. Analysis of TNF, IL-1beta, IL-6, and IL-10 levels in whole blood demonstrated that leukocytes were hyporesponsive to ex vivo LPS restimulation 3-8 h after i.v. LPS injection (4 ng/kg). Reduced cytokine release during the same interval was also observed in whole blood further stimulated with MyD88-dependent ligands for TLR2, TLR5, and TLR7 or with whole bacteria. Strikingly, blood leukocytes were also tolerant to a ligand for TLR3, which signals solely through a MyD88-independent (Toll IL-1R domain-containing adaptor-inducing IFN-beta (TRIF)-dependent) pathway. The hyporesponsiveness of leukocytes to TLR3 ligation was associated with reduced rather than increased levels of the recently identified TRIF inhibitor SARM. Taken together, these data indicate that systemic LPS challenge of human volunteers induces cross-tolerance to multiple TLR ligands that signal in a MyD88-dependent or MyD88-independent manner and suggest that LPS exposure of human blood leukocytes may hamper the inflammatory response to various microbial components.