Radical-promoting "free" iron level in the serum of rats treated with ferric nitrilotriacetate: comparison with other iron chelate complexes.

&lt;p&gt;Iron plays a critical role in the production of activated oxygen species and the activity of chelated iron in the biological system depends on the chemical forms of the chelators. In the present study, we used ferric nitrolotriacetate (Fe-NTA, molar ratio of iron to chelators = 1:3), ferric ethylenediaminetetraacetate (Fe-EDTA, 1:3 complex) and ferric Desferal (Fe-Des, 1:1.1 complex) to see their &quot;free&quot; iron content in aqueous solutions in vitro and in the serum obtained after a single intraperitoneal injection of the chelates to rats (7.5 mg of iron/kg). &quot;Free&quot; iron was measured by the bleomycin-assay system. When Fe-NTA was dissolved in water, &quot;free&quot; iron increased linearly with total iron concentration up to 10 microM, whereas Fe-EDTA and Fe-Des showed no &quot;free&quot; iron with corresponding iron concentrations. When these three ferric chelates were dissolved in normal rat serum, &quot;free&quot; iron in Fe-NTA increased abruptly between 40 microM and 60 microM iron concentrations, then increased slowly up to 100 microM. Fe-Des did not show any &quot;free&quot; iron at comparable iron concentrations. Fe-EDTA had an intermediate &quot;free&quot; iron level in the serum. Among the ferric chelate complexes, Fe-NTA showed a much faster increase of and a higher content of &quot;free&quot; iron in the serum than the other two complexes after a single injection of the chelates into rats.(ABSTRACT TRUNCATED AT 250 WORDS)&lt;/p&gt;</p

GR@PPA 2.8: initial-state jet matching for weak boson production processes at hadron collisions

The initial-state jet matching method introduced in our previous studies has been applied to the event generation of single $W$ and $Z$ production processes and diboson ($W^{+}W^{-}$, $WZ$ and $ZZ$) production processes at hadron collisions in the framework of the GR@PPA event generator. The generated events reproduce the transverse momentum spectra of weak bosons continuously in the entire kinematical region. The matrix elements (ME) for hard interactions are still at the tree level. As in previous versions, the decays of weak bosons are included in the matrix elements. Therefore, spin correlations and phase-space effects in the decay of weak bosons are exact at the tree level. The program package includes custom-made parton shower programs as well as ME-based hard interaction generators in order to achieve self-consistent jet matching. The generated events can be passed to general-purpose event generators to make the simulation proceed down to the hadron level.Comment: 29 pages, 14 figures; minor changes to clarify the discussions, and corrections of typo

In vitro transformation of rat renal cells by treatment with ferric nitrilotriacetate.

Administration of ferric nitrilotriacetate (Fe-NTA) in vivo causes acute renal tubular injury and finally induces renal cell carcinoma. There is accumulating evidence that these processes involve free radicals generated by Fe-NTA. To study the mechanism of renal carcinogenesis by Fe-NTA, we attempted to induce malignant transformation of primary cultured renal cells by treatment with Fe-NTA. When primary cultured renal cells (PRC) were treated continuously with Fe-NTA, all of the PRC died without transformation. On the other hand, when PRC were treated intermittently with Fe-NTA, transformed epithelial colonies were observed at 3 weeks after the first treatment. The established transformed cell line (RK523) showed drastic morphological transformation, grew in soft agar, and formed tumors when transplanted into athymic nude mice. These results indicate that the balance between cytotoxicity and mutagenecity is important for Fe-NTA induced transformation. The RK523 cell line may be a useful model for studying renal carcinogenesis in vitro.</p

Prediction of bending rigidity for laminated fabric with adhesive interlining by a laminate model considering tensile and in-plane compressive moduli

The purpose of this study is to predict bending rigidity of laminated fabric with adhesive interlining considered tensile and in-plane compressive moduli. The predicting method considering those moduli was proposed by theoretical derivation based on laminate model. Tensile and in-plane compressive moduli of neutral surface for face fabric and adhesive interlining respectively before laminating and modulus for bending rigidity were considered independently. The calculating equation for in-plane compressive modulus was proposed from the relationship between bending rigidities and tensile properties. The proposed predicting method was verified experimentally. Bending rigidities, tensile properties and thicknesses of adhesive interlinings, face fabrics and laminated fabrics with adhesive interlinings were measured by KES-FB system. The in-plane compressive moduli of adhesive interlinings were calculated by the proposed equation with the results of tensile properties for face fabrics. With the results of tensile and in-plane compressive moduli, the bending rigidities of laminated fabric with adhesive interlinings were calculated. The predicted bending rigidities considered with measured tensile properties and calculated in-plane compressive moduli were precisely closer to experimental results than the ones of the laminated model from our previous study. Therefore, this model gives a new way to predict bending rigidity of laminated fabric with adhesive interlining.ArticleTEXTILE RESEARCH JOURNAL. 82(4):385-399 (2012)journal articl

Evaluation of Bronchoalveolar Lavage as a Diagnostic Procedure for Primary Pulmonary B-cell Lymphoma

We evaluated retrospectively the role of bronchoalveolar lavage (BAL) in the diagnosis of primary pulmonary B-cell lymphoma in four patients. Histological examination of transbronchial lung biopsy specimens showed nonspecific infiltration of small lymphocytes. Examination of BAL fluid (BALF) samples showed lymphocytosis in all samples with dominant B-cell in two patients and T-cell in the remaining patients. In two patients only, there was a increase in B-cell bearing IgM light-chain or M-protein in BALF samples. our results suggest that the diagnostic value of BAL in primary pulmonary B-cell lymphoma is limited and that new molecular biological techniques should be adapted for analysis of BALF samples

A Central Role for Foxp3+ Regulatory T Cells in K-Ras-Driven Lung Tumorigenesis

BACKGROUND: K-Ras mutations are characteristic of human lung adenocarcinomas and occur almost exclusively in smokers. In preclinical models, K-Ras mutations are necessary for tobacco carcinogen-driven lung tumorigenesis and are sufficient to cause lung adenocarcinomas in transgenic mice. Because these mutations confer resistance to commonly used cytotoxic chemotherapies and targeted agents, effective therapies that target K-Ras are needed. Inhibitors of mTOR such as rapamycin can prevent K-Ras-driven lung tumorigenesis and alter the proportion of cytotoxic and Foxp3+ regulatory T cells, suggesting that lung-associated T cells might be important for tumorigenesis. METHODS: Lung tumorigenesis was studied in three murine models that depend on mutant K-Ras; a tobacco carcinogen-driven model, a syngeneic inoculation model, and a transgenic model. Splenic and lung-associated T cells were studied using flow cytometry and immunohistochemistry. Foxp3+ cells were depleted using rapamycin, an antibody, or genetic ablation. RESULTS: Exposure of A/J mice to a tobacco carcinogen tripled lung-associated Foxp3+ cells prior to tumor development. At clinically relevant concentrations, rapamycin prevented this induction and reduced lung tumors by 90%. In A/J mice inoculated with lung adenocarcinoma cells resistant to rapamycin, antibody-mediated depletion of Foxp3+ cells reduced lung tumorigenesis by 80%. Likewise, mutant K-Ras transgenic mice lacking Foxp3+ cells developed 75% fewer lung tumors than littermates with Foxp3+ cells. CONCLUSIONS: Foxp3+ regulatory T cells are required for K-Ras-mediated lung tumorigenesis in mice. These studies support clinical testing of rapamycin or other agents that target Treg in K-Ras driven human lung cancer

Correlation between frontal lobe oxy-hemoglobin and severity of depression assessed using near-infrared spectroscopy

AbstractIntroductionThe search for objective biomarkers of psychiatric disorders has a long history. Despite this, no universally accepted instruments or methods to detect biomarkers have been developed. One potential exception is near-infrared spectroscopy, although interpreting the measures of blood flow recorded with this technique remains controversial. In this study, we aimed to investigate the relationship between recorded blood flow and depression severity assessed using the Hamilton depression scale in patients with various psychiatric disorders.MethodsEnrolled patients (n=43) had DSM-IV diagnoses of major depressive disorder (n=25), bipolar disorder I (n=5), schizophrenia (n=3), dysthymic disorder (n=3), psychotic disorder (n=3), panic disorder (n=2), and Obsessive Compulsive Disorder (n=2). The verbal fluency task was administered during blood flow recording from the frontal and temporal lobes.ResultsWe found that severity of depression was negatively correlated with the integral value of blood flow in the frontal lobe, irrespective of psychiatric diagnosis (F=5.94, p=0.02).DiscussionOur results support blood flow in the frontal lobe as a potential biomarker of depression severity across various psychiatric disorders.LimitationLimited sample size, no replication in the second set

In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia.

KRP-109 is a novel specific inhibitor of neutrophil elastase (NE). Various studies suggest that NE inhibitors reduce lung injury associated with systemic inflammatory response syndrome (SIRS). In this study, the efficacy of KRP-109 was examined using a murine model of severe pneumonia induced by Streptococcus pneumoniae (S. pneumoniae). Female mice (CBA/J, aged 5 weeks) were inoculated intranasally with penicillin-susceptible S. pneumoniae (ATCC49619 strain, 2.5 × 10(8) CFU/mouse). KRP-109 (30 or 50 mg/kg) or physiological saline as a control was administered intraperitoneally every 8 h beginning at 8 h after inoculation, and survival rate was evaluated over 7 days. Histopathological and bacteriological analyses of the lung, and bronchoalveolar lavage were performed at 48 h post-infection. The mice treated with KRP-109 (KRP-109 mice) tended to have higher survival rate than those given saline. The lung tissues of the KRP-109 mice had few neutrophils in the alveolar walls and less inflammation. Furthermore, KRP-109 decreased significantly total cell and neutrophil counts, and cytokine levels (interleukin 1β and macrophage inflammatory protein 2) in bronchoalveolar lavage fluid. Viable bacterial numbers in lung were not influenced by treatment of KRP-109. The present results indicate that KRP-109 reduces lung inflammation in a murine model, and that KRP-109 may be useful for the treatment of patients with severe pneumonia