bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into dendritic cell-like cells
Authors: Huang Xiangyang , Shen Nan , Bao Chunde , Gu Yueying , Wu Li , Chen Shunle
Published: August 2008

Introduction

Using oligonucleotide microarray, many IFN-inducible genes have been found to be highly expressed in peripheral blood mononuclear cells (PBMCs) from most patients with systemic lupus erythematosus (SLE). Among these IFN-inducible genes, IFN-induced protein with tetratricopeptide repeats 4 (IFIT4) is a novel gene whose function is unknown.

Methods

In this study we examined the role played by IFIT4 in monocyte differentiation and the correlation between IFIT4 expression and the clinical manifestation of SLE. To this end, we used plasmid transfection, flow cytometry, mixed leucocyte responses, ELISA, quantitative RT-PCR and Western blotting.

Results

We found that both IFIT4 mRNA and protein expression levels were significantly higher in PBMCs and monocytes from SLE patients than in those from healthy control individuals. IFIT4 expression was positively correlated with antinuclear antibodies, anti-double-stranded DNA, and anti-Sm auto-immune antibodies in SLE. Patients with SLE exhibiting higher expression of IFIT4 had a higher prevalence of leucopenia, thrombocytopenia and C3/C4 decrease. IFIT4 protein was localized exclusively to the cytoplasm, and it was significantly upregulated by IFN-α in normal PBMCs. To determine the role played by IFIT4 in monocyte differentiation, the monocytic cell line THP-1 was transfected with pEGFP-IFIT4 expression plasmid and stimulated with granulocyte-macrophage colony-stimulating factor/IL-4 to generate IFIT4-primed dendritic cell-like cells (DCLCs). IFIT4-primed DCLCs acquired morphological characteristics of dendritic cells more quickly, with greater resemblance to dendritic cells, as compared with DCLCs primed with pEGFP-C1 control plasmid trasfection. Furthermore, they exhibited higher expressions of CD40, CD86, CD80, HLA-DR and CD83, along with lower expression of CD14; increased IL-12 secretion; and an increased ability to stimulate T-cell proliferation. In addition, IFIT4-primed DCLCs enhanced IFN-γ secretion (about 2.4-fold) by T cells compared with controls.

Conclusion

Our findings suggest that IFIT4 might play roles in promoting monocyte differentiation into DCLCs and in directing DCLCs to modulate T-helper-1 cell differentiation; these actions might contribute to the autoimmunity and pathogenesis of SLE.
Recombinant human activated protein C attenuates endotoxin-induced lung injury in awake sheep
Authors: Waerhaug Kristine , Kuklin Vladimir N , Kirov Mikhail Y , Sovershaev Mikhail A , Langbakk Bodil , Ingebretsen Ole C , Ytrehus Kirsti , Bjertnaes Lars J
Published: August 2008

Introduction

Acute lung injury often complicates severe sepsis. In Gram-negative sepsis, bacterial endotoxin activates both coagulation and inflammation. Enhanced lung vascular pressures and permeability, increased extravascular lung water content and deteriorated gas exchange characterize ovine endotoxin-induced lung injury, a frequently used model of acute lung injury. Recombinant human activated protein C (rhAPC), with its anticoagulant, anti-inflammatory, fibrinolytic and antiapoptotic effects, reportedly reduces the respirator-dependent days and the mortality of patients with severe sepsis. We speculate whether rhAPC antagonizes endotoxin-induced lung injury in sheep.

Methods

Two groups of sheep were exposed to Escherichia coli endotoxin (lipopolysaccharide) 15 ng/kg/minute intravenously from 0 to 24 hours; one group received only lipopolysaccharide throughout (n = 8), and the other group received lipopolysaccharide in combination with rhAPC 24 μg/kg/hour from 4 to 24 hours (n = 9). In addition, one group received rhAPC as above as the only intervention (n = 4), and four sham-operated sheep were used for determination of the α and ε isoforms of protein kinase C in pulmonary tissue. Data were assessed by one-way analysis of variance for repeated measurements. Biochemical data were analyzed using Student's t test, or using the Mann–Whitney U test when appropriate.

Results

Infusion of endotoxin caused lung injury, manifested by increments in pulmonary artery pressure, in pulmonary micro-occlusion pressure, in pulmonary vascular downstream resistance, in pulmonary vascular permeability index, in extravascular lung water index and in deterioration of oxygenation that were all attenuated by infusion of rhAPC. Endotoxemia led to changes in inflammation and coagulation, including pulmonary neutrophil accumulation paralleled by increased TNFα and decreased protein C and fibrinogen in animal plasma, which all improved following infusion of rhAPC. Moreover, rhAPC prevented the translocation of protein kinase C α and ε isoforms from the cytosolic fraction of lung tissue extracts.

Conclusion

In awake sheep, rhAPC alleviates endotoxin-induced lung injury – as characterized by improvements of oxygenation, coagulation and inflammation, as well as by reversal of pulmonary hemodynamic and volumetric changes.
Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients
Authors: Wang HaiHong , Cheng BaoLi , Chen QiXing , Wu ShuiJing , Lv Chen , Xie GuoHao , Jin Yue , Fang XiangMing
Published: August 2008

Introduction

Gelsolin is an actin-binding plasma protein that is part of an 'actin-scavenging' system. Studies suggest that plasma gelsolin may play a crucial role in the pathophysiology of sepsis. Little is known about the course of plasma gelsolin levels over time in patients with severe sepsis. The aim of the study was to investigate plasma gelsolin levels in severe septic patients and to determine whether these levels predict the severity or clinical outcome of severe sepsis.

Methods

Ninety-one patients who were diagnosed with severe sepsis at admission to a surgical intensive care unit were enrolled, and admission plasma gelsolin levels were recorded. Plasma gelsolin levels were recorded daily in 23 of these patients. Daily plasma gelsolin levels were recorded in an additional 15 nonseptic critically ill patients. Fifteen volunteers served as healthy control individuals. Plasma gelsolin levels were measured using an enzyme-linked immunosorbent assay. Concentrations of IL-6, IL-10 and tumour necrosis factor (TNF)-α were also measured on intensive care unit admission.

Results

The admission gelsolin levels were significantly decreased in severe sepsis (20.6 ± 11.7 mg/l) compared with nonseptic critically ill patients (52.3 ± 20.3 mg/l; P < 0.001) and healthy control individuals (126.8 ± 32.0 mg/l; P < 0.001). Severe septic patients had increased IL-6 levels compared with nonseptic critically ill patients (20.0 ± 10.7 pg/ml versus 11.4 ± 13.9 pg/ml; P = 0.048), whereas no significant difference in IL-10 or TNF-α levels was observed (IL-10: 97.9 ± 181.5 pg/ml versus 47.4 ± 91.5 pg/ml, respectively [P = 0.425]; TNF-α: 14.2 ± 13.9 pg/ml versus 6.9 ± 5.3 pg/ml, respectively; P = 0.132). Survivors of severe sepsis exhibited substantial recovery of their depressed plasma gelsolin levels, whereas gelsolin levels in nonsurvivors remained at or below their depleted admission levels.

Conclusion

Plasma gelsolin may be a valuable marker for severe sepsis. Recovery of depleted plasma gelsolin levels correlated with clinical improvement. The prognostic role of plasma gelsolin in critical illness requires further investigation in a large cohort.
MotifCluster: an interactive online tool for clustering and visualizing sequences using shared motifs
Authors: Hamady Micah , Widmann Jeremy , Copley Shelley D , Knight Rob
Published: August 2008

MotifCluster finds related motifs in a set of sequences, and clusters the sequences into families using the motifs they contain. MotifCluster, at http://bmf.colorado.edu/motifcluster, lets users test whether proteins are related, cluster sequences by shared conserved motifs, and visualize motifs mapped onto trees, sequences and three-dimensional structures. We demonstrate MotifCluster's accuracy using gold-standard protein superfamilies; using recommended settings, families were assigned to the correct superfamilies with 0.17% false positive and no false negative assignments.
Vitamin D3 induces pro-LL-37 expression in myeloid precursors from patients with severe congenital neutropenia
Authors: Karlsson Jenny , Carlsson Göran , Larne Olivia , Andersson Mats , Pütsep Katrin
Published: August 2008

The innate immune system produces a number of effector molecules that are important for protection against bacterial infections. Neutrophils and antimicrobial peptides are major components of innate defense with the capacity of rapid bacterial killing. Patients with severe congenital neutropenia (SCN) experience recurrent and chronic infections despite recombinant G-CSF-mobilized neutrophils. We have shown previously that these neutrophils are deficient in that they lack the antimicrobial peptide LL-37. Here, we show that pro-LL-37 mRNA is not expressed in neutrophil precursors from patients with SCN, although the gene and promoter region for pro-LL-37, CAMP, does not display any mutations. The hormonal form of vitamin D3 [1,25(OH)2D3] induced the expression of pro-LL-37 in isolated neutrophil progenitors and in EBV-transformed B cells from patients with SCN, whereas all-trans retinoic acid only induced expression in transformed B cells. These results demonstrate that myeloid cells of patients with SCN can produce pro-LL-37, suggesting that other pathways are impaired.
Impact of Estradiol on γ-Aminobutyric Acid- and Glutamate-Mediated Calcium Responses of Fetal Baboon (Papio anubis) Hippocampal and Cortical Neurons
Authors: Nuñez Joseph L. , Aberdeen Graham W. , Albrecht Eugene D. , McCarthy Margaret M.
Published: August 2008

High levels of maternal estrogens are likely to gain access to the fetal brain, yet little is known regarding the role of the steroid hormone 17β-estradiol in neuronal differentiation and maturation of primate neurons. Previous research documented the presence of estrogen receptors during development in the hippocampus and cortex of the primate brain, but the functional significance of steroid exposure has not been widely investigated. Using both an in vitro preparation of primary hippocampal and frontal cortex neurons and Western blot analysis of fetal hippocampal and frontal cortex tissue, we documented the effects of in utero and acute in vitro exposure to 17β-estradiol on the development of neuronal responsiveness to the amino acid transmitters γ-aminobutyric acid (GABA) and glutamate in fetal baboon, Papio anubis, hippocampal, and cortical neurons. We found that in utero 17β-estradiol exposure enhanced the excitatory action of the GABAergic system on immature cortical and hippocampal neurons, as manifest by increases in intracellular calcium after transient muscimol application and changes in the relevant ion cotransporters. Acute exposure to 17β-estradiol in vitro had limited effect on GABAergic responses in cultured hippocampal and frontal cortex neurons. Moreover, there was limited effect of both prolonged in utero and acute estradiol on the response to glutamatergic system activation, consistent with previous findings in the rat. Along with documenting a prominent role for 17β-estradiol in maturation of the GABAergic system, these findings increase our understanding of neuronal differentiation and maturation in the fetal primate brain.
Dicer1 Is Essential for Female Fertility and Normal Development of the Female Reproductive System
Authors: Hong Xiaoman , Luense Lacey J. , McGinnis Lynda K. , Nothnick Warren B. , Christenson Lane K.
Published: August 2008

The ribonuclease III endonuclease, Dicer1 (also known as Dicer), is essential for the synthesis of the 19–25 nucleotide noncoding RNAs known as micro-RNAs (miRNAs). These miRNAs associate with the RNA-induced silencing complex to regulate gene expression posttranscriptionally by base pairing with 3′untranslated regions of complementary mRNA targets. Although it is established that miRNAs are expressed in the reproductive tract, their functional role and effect on reproductive disease remain unknown. The studies herein establish for the first time the reproductive phenotype of mice with loxP insertions in the Dicer1 gene (Dicer1fl/fl) when crossed with mice expressing Cre-recombinase driven by the anti-müllerian hormone receptor 2 promoter (Amhr2Cre/+). Adult female Dicer1fl/fl;Amhr2Cre/+ mice displayed normal mating behavior but failed to produce offspring when exposed to fertile males during a 5-month breeding trial. Morphological and histological assessments of the reproductive tracts of immature and adult mice indicated that the uterus and oviduct were hypotrophic, and the oviduct was highly disorganized. Natural mating of Dicer1fl/fl;Amhr2Cre/+ females resulted in successful fertilization as evidenced by the recovery of fertilized oocytes on d 1 pregnancy, which developed normally to blastocysts in culture. Developmentally delayed embryos were collected from Dicer1fl/fl; Amhr2Cre/+ mice on d 3 pregnancy when compared with controls. Oviductal transport was disrupted in the Dicer1fl/fl;Amhr2Cre/+ mouse as evidenced by the failure of embryos to enter the uterus on d 4 pregnancy. These studies implicate Dicer1/miRNA mediated posttranscriptional gene regulation in reproductive somatic tissues as critical for the normal development and function of these tissues and for female fertility.
Functional Potentiation of Leptin-Signal Transducer and Activator of Transcription 3 Signaling by the Androgen Receptor
Authors: Fan WuQiang , Yanase Toshihiko , Nishi Yoshihiro , Chiba Seiichi , Okabe Taijiro , Nomura Masatoshi , Yoshimatsu Hironobu , Kato Shigeaki , Takayanagi Ryoichi , Nawata Hajime
Published: August 2008

Hypogonadism is associated with increased fat mass and dysregulation of metabolic homeostasis in men. Our previous study revealed that androgen receptor (AR)-null male mice (ARL-/Y) develop late-onset obesity and are leptin-resistant. The present study evaluated how hypothalamic AR contributes to central leptin-signal transducer and activator of transcription 3 (STAT3) signaling. We evaluated leptin action in wild-type and ARL-/Y mice, the anatomic co-relationship between AR and leptin signaling in the hypothalamus, and the effects of AR on leptin-mediated STAT3 transactivation and nuclear translocation. AR deletion in male mice results in a weaker leptin-induced suppression of food intake and body weight drop even before the onset of overt obesity. In wild-type male but not female mice, AR was highly expressed in various hypothalamic nuclei that also expressed the long-form leptin receptor (OBRB) and co-resided with OBRB directly in the arcuate neurons. In vitro, AR significantly enhanced STAT3-mediated transcription of leptin target genes including POMC and SOCS3. This effect relied on the AR N-terminal activation function-1 (AF-1) domain and was specific to AR in that none of the other sex steroid hormone receptors tested showed similar effects. AR enhanced the low concentrations of leptin-induced STAT3 nuclear translocation in vitro, and ARL-/Y mice receiving leptin had impaired STAT3 nuclear localization in the arcuate neurons. These findings indicate that AR in the hypothalamus functions as a regulator of central leptin-OBRB-STAT3 signaling and has a physiological role in energy homeostasis and metabolic regulation in male mice.
Functional Characterization of Naturally Occurring Pathogenic Mutations in the Human Leptin Receptor
Authors: Kimber Wendy , Peelman Frank , Prieur Xavier , Wangensteen Teresia , O'Rahilly Stephen , Tavernier Jan , Farooqi I. Sadaf
Published: August 2008

We have recently reported the first naturally occurring missense mutations in the leptin receptor (LR) in patients with severe obesity. We have examined the molecular mechanisms by which these extracellular domain mutations disrupt LR signaling. The Ala409Glu mutant receptor is expressed at the cell surface, binds leptin normally but fails to signal to downstream pathways. A409 is present on the surface-exposed region of the Ig-like domain that forms the binding site III for interaction with leptin. This binding site does not appear to contribute to the binding affinity of leptin to its receptor but is critical for receptor activation in response to ligand binding. The Trp664Arg and His684Pro mutations are predicted to impair receptor folding. Both mutants result in a complete inability to signal to downstream pathways despite evidence for some residual cell surface expression and ligand binding. The Arg612His mutant falls in the second subdomain of the high-affinity binding site for leptin, and results in a receptor that shows evidence for intracellular retention but retains some residual signaling. These studies, which represent the first detailed characterization of the functional properties of naturally occurring missense mutations in the human LR, indicate that most such mutations affect receptor folding and expression at the cell surface rather than primarily impairing ligand binding. The exception is Ala409Glu, which interferes with the coupling of ligand binding to receptor activation. Naturally occurring mutations associated with human obesity are valuable tools with which to explore structure/function relationships within the LR.
Insulin-Like Growth Factor-I Activates KiSS-1 Gene Expression in the Brain of the Prepubertal Female Rat
Authors: Hiney Jill K. , Srivastava Vinod K. , Pine Michelle D. , Dees W. Les
Published: August 2008

KiSS-1 gene expression has been shown to increase as puberty approaches, and its peptide products, kisspeptins, are involved in LHRH secretion at puberty. Factors contributing to increased KiSS-1 expression, however, have not been identified; thus, the purpose of this study was to assess whether IGF-I could induce transcription of this gene in prepubertal female rats. IGF-I or saline was centrally administered to immature rats that were killed 2, 4, and 6 h later. Real-time PCR revealed that IGF-I induced (P < 0.01) KiSS-1 gene expression at 6 h in a tissue fragment that contained both the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. Subsequently, the AVPV and ARC nuclei were separated to assess whether region-specific effects could be identified. IGF-I stimulated (P < 0.01) KiSS-1 gene expression in the AVPV nucleus at 6 h after injection, with no change observed in the ARC nucleus. Serum estradiol (E2) levels were not altered at any time point after IGF-I, demonstrating that the increased KiSS-1 expression observed was not caused by an elevation in E2. Additionally, the IGF-I action to induce KiSS-1 gene expression in the AVPV nucleus was further demonstrated when the IGF-I was administered systemically. E2 appears to play an important permissive role because 1-d ovariectomized rats responded to IGF-I with increased (P < 0.01) KiSS-1 expression, whereas, 20 d after ovariectomy, when the E2 levels had fallen below assay sensitivity, the IGF-I was unable to induce KiSS-1 expression. The IGF-I effect was further demonstrated by showing that the IGF-I receptor antagonist, JB-1, blocked the IGF-I-induced increase in KiSS-1 expression. Collectively, these data indicate that IGF-I is an activator of the KiSS-1 gene in the prepubertal female rat.

IGF-1 is an early activator of the KiSS-1 gene at the time of female puberty.
Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique
Authors: Shinde Vikram R , Shelake Makarand R , Shetty Sandeep S , Chavan-Patil Amit B , Pore Yogesh V , Late Sameer G
Published: August 2008

The solid-state properties and dissolution behaviour of lamotrigine in its inclusion complex with β-cyclodextrin (βCD) and solid dispersions with polyvinylpyrrolidone K30 (PVP K30) and polyethyl-eneglycol 6000 were investigated. The phase solubility profile of lamotrigine with βCD was classified as AL-type, indicating formation of a 1:1 stoichiometry inclusion complex, with a stability constant of 369.96 ± 2.26 M−1. Solvent evaporation and kneading methods were used to prepare solid dispersions and inclusion complexes, respectively. The interaction of lamotrigine with these hydrophilic carriers was evaluated by powder X-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies revealed that the drug was no longer present in crystalline state but was converted to an amorphous form. Among the binary systems tested, PVP K30 (1:5) showed greatest enhancement of the solubility and dissolution of lamotrigine.
Compatibility of chewing gum excipients with the amino acid l-cysteine and stability of the active substance in directly compressed chewing gum formulation
Authors: Kartal Alma , Björkqvist Mikko , Lehto Vesa-Pekka , Juppo Anne Mari , Marvola Martti , Sivén Mia
Published: August 2008

Using l-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth during smoking has recently been introduced. Besides its efficacy, optimal properties of the gum include stability of the formulation. However, only a limited number of studies exist on the compatibility of chewing gum excipients and stability of gum formulations. In this study we used the solid-state stability method, Fourier transform infrared spectroscopy and isothermal microcalorimetry to investigate the interactions between l-cysteine (as a free base or as a salt) and excipients commonly used in gum. These excipients include xylitol, sorbitol, magnesium stearate, Pharmagum S, Every T Toco and Smily 2 Toco. The influence of temperature and relative humidity during a three-month storage period on gum formulation was also studied. Cysteine alone was stable at 25°C/60% RH and 45°C/75% RH whether stored in open or closed glass ambers. As a component of binary mixtures, cysteine base remained stable at lower temperature and humidity but the salt form was incompatible with all the studied excipients. The results obtained with the different methods corresponded with each other. At high temperature and humidity, excipient incompatibility with both forms of cysteine was obvious. Such sensitivity to heat and humidity during storage was also seen in studies on gum formulations. It was also found that cysteine is sensitive to high pressure and increase in temperature induced by compression. The results suggest that the final product should be well protected from temperature and humidity and, for example, cooling process before compression should be considered.
Pharmacokinetics of tramadol in rat plasma and cerebrospinal fluid after intranasal administration
Authors: Zhao Yan , Tao Tao , Wu Jinjin , Pi Jiaxin , He Ning , Chai Xuyu , Chen Qinghua
Published: August 2008

We have evaluated the potential of intranasal administration of tramadol. The pharmacokinetic behaviour of tramadol in rat plasma and cerebrospinal fluid (CSF) after intranasal administration was determined and compared with those after intravenous and oral administration. Serial plasma and CSF samples were collected for 6 h, and the drug concentrations were assayed by an HPLC-fluorescence method. The plasma absolute bioavailability values of tramadol after intranasal and oral administration were 73.8% and 32.4%, respectively, in conscious rats. The Cmax (maximum concentration) value after the intranasal dose was lower (P < 0.05), and the MRT (mean retention time) was longer (P < 0.05) than the values obtained after intravenous administration. A pharmacokinetic study of tramadol in plasma and CSF was undertaken in anaesthetized rats. The absolute bioavailability values in plasma and CSF after intranasal administration were 66.7% and 87.3%, respectively. The Cmax values in plasma and CSF after a nasal dose were lower (P < 0.05) than after the intravenous dose. The values of Cmax and AUC0→6h in plasma and CSF after intranasal administration were higher than after the oral dose. The mean drug-targeting efficiency after intranasal administration was significantly greater than after the oral dose. In conclusion, intranasal administration of tramadol appeared to be a promising alternative to the traditional administration modes for this drug.
Protective effect of caffeine on streptozotocin-induced beta-cell damage in rats
Authors: Kagami Keisuke , Morita Hajime , Onda Kenji , Hirano Toshihiko , Oka Kitaro
Published: August 2008

Many epidemiological studies have shown that coffee consumption reduces the risk of type 2 diabetes mellitus (T2D), although the reasons as to why remain unclear. In this study we investigated the effect of caffeine on pancreatic beta-cell damage in rats using the diabetogenic agent, streptozotocin (STZ). Wistar rats were given intraperitoneal injections of saline or caffeine (10, 50 or 100 mgkg−1). After 15 min, the rats were injected with a citrate buffer or 65 mgkg−1 STZ. Three days after injection, an oral glucose tolerance test (OGTT) was performed on the rats. Furthermore, three days after the OGTT, the pancreas was isolated and homogenized, followed by determination of insulin content. STZ treatment significantly increased the plasma glucose level compared with the control at all times during the OGTT, which was significantly diminished by caffeine pretreatment at all doses. STZ treatment significantly decreased the plasma insulin level, however, which was not recovered by caffeine pretreatment. Pancreatic insulin content was significantly reduced by STZ treatment compared with the control, which was significantly recovered by caffeine pretreatment at a dose of 100 mgkg−1 (P < 0.01). We showed that caffeine protects pancreatic beta-cells against STZ toxicity. Further investigation will be required to understand the protective effect of caffeine against beta-cell destruction in T2D.
Penehyclidine prevents nuclear factor-kB activation in acute lung injury induced by lipopolysaccharide
Authors: Li Juan , Li Jun , Zhang Lei , Huang Yan , Pan Jian-hui , Chen Kun-zhou
Published: August 2008

Penehyclidine (PHCD) has been proposed to reduce lung and lethal toxicity. The present study was undertaken to investigate the mechanisms responsible for the protective effect of PHCD against acute lung injury (ALI) in rats. Tail-vein injection of lipopolysaccharide (LPS; 5 mgkg−1) was used to induce ALI in rats. Secondary increases in total protein, lactate dehydrogenase activity in bronchoalveolar lavage fluid and myeloperoxidase in lung tissue were used to evaluate the effects of PHCD on ALI in rats. Activated DNA binding activity and expression of nuclear factor kB (NF-kB) in lung tissue were measured using electrophoretic mobility shift assays assay and immunohistological staining. Levels and mRNA expression of tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Pretreatment with PHCD (0.03 mgkg−1, 0.1 mgkg−1 and 0.3 mgkg−1 i.p.) significantly attenuated the LPS-induced changes in lung injury parameters and inhibited the activation and expression of NF-kB in lung tissue. Furthermore, PHCD also substantially reduced the LPS-induced TNF-α and IL-1β mRNA expression and production in lung tissue and suppressed neutrophil recruitment. The results suggest that PHCD attenuates LPS-induced acute lung responses through inhibition of NF-kB activation and LPS-induced TNF-α and IL-1β production and resulting neutrophil recruitment associated with acute lung inflammation and injury. PHCD may be a useful adjuvant to treatment strategies targeting clinical situations of acute inflammation.
Anti-inflammatory action of Cudrania tricuspidata on spleen cell and T lymphocyte proliferation
Authors: Chang Sung Ho , Jung Eun Jung , Lim Dong Gyun , Oyungerel Baatartsogt , Lim Kwan Il , Her Erk , Choi Wahn Soo , Jun Myung Ha , Choi Kang Duk , Han Duck Jong , Kim Song Cheol
Published: August 2008

This study examined whether an extract of Cudrania tricuspidata shows anti-proliferative effects in anti-CD3/CD28-mediated spleen and CD4+CD25− T cells and decreases the production of the pro-inflammatory cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ) in anti-CD3/CD28-mediated CD4+CD25− T cells. The proliferation of anti-CD3/CD28-mediated spleen cells and CD4+CD25− T cells was effectively suppressed by C. tricuspidata. This extract, however, did not show cytotoxicity in spleen cells under conditions where the antigen was not stimulated using CCK-8 analysis. C. tricuspidata also decreased the production of the pro-inflammatory cytokines IL-2 and IFN-γ by selective inhibition of this extract on proliferating cells in anti-CD3/CD28-mediated CD4+CD25− T cells. These results suggest that C. tricuspidata may be useful in the treatment of autoimmune diseases and organ transplantation through the inhibitory action of T cells in inflammation.
Frequent inadequate supply of micronutrients in fast food induces oxidative stress and inflammation in testicular tissues of weanling rats
Authors: El-Seweidy Mohamed M , Hashem Reem M , Abo-El-matty Dina M , Mohamed Rasha H
Published: August 2008

Fast food is high in energy density and low in essential micronutrient density, especially zinc (Zn), of which antioxidant processes are dependent. We have tested the hypothesis that frequent fast food consumption could induce oxidative damage associated with inflammation in weanling male rats in relevance to Zn deprivation, which could adversely affect testis function. Zn and iron (in plasma and testicular tissue), plasma antioxidant vitamins (A, E, and C), as well as testicular superoxide dismutase (SOD) and reduced glutathione (GSH), lipid peroxidation indexes (thiobarbituric acid reactive substances (TBARS) and lipoprotein oxidation susceptibility (LOS)), and inflammatory markers (plasma C-reactive protein (CRP) and testicular tumour necrosis factor-alpha (TNF-α)) were determined. Serum testosterone and histological examination of the testis were performed also. We found a severe decrease in antioxidant vitamins and Zn, with concomitant iron accumulation. Zinc deficiency correlated positively with SOD, GSH, anti-oxidant vitamins and testosterone, and negatively with TBARS, LOS, CRP and TNF-α, demonstrating a state of oxidative stress and inflammation. We concluded that micronutrient deficiency, especially Zn, enhanced oxidative stress and inflammation in testicular tissue leading to under-development of testis and decreased testosterone levels.
Slovenia's Defense Policy in a Euro-Atlantic Reality
Authors: Grizold Anton
Published: August 2008

Anton Grizold is professor of sociology and dean of social sciences at the University of Ljubljana, Republic of Slovenia. He served as minister of defense from 2000 to 2004.
Genotyping β-Globin Gene Mutations on Copolymer-Coated Glass Slides with the Ligation Detection Reaction
Authors: Battistella Stefania , Damin Francesco , Chiari Marcella , Delgrosso Kathleen , Surrey Saul , Fortina Paolo , Ferrari Maurizio , Cremonesi Laura
Published: August 2008

Background: Methods are needed to analyze small amounts of samples for variation in disease-causing genes. One means is to couple the sensitivity and multiplexing capability of the ligation detection reaction (LDR) with the use of simple glass slides specifically functionalized with a novel polymer coating to enhance sensitivity.

Methods: We developed an array-based genotyping assay based on glass slides coated with copolymer (N,N-dimethylacrylamide, N,N-acryloyloxysuccinimide, and 3-(trimethoxysilyl)propyl methacrylate). The assay consists of an LDR with genomic DNA followed by a universal PCR (U-PCR) of genomic DNA–templated LDR product. The LDR occurs in the presence of 3 primers for each sequence variant under investigation: 2 distinguishing primers (allele specific and perfectly complementary to wild-type and mutant alleles) and 1 common locus-specific primer. The 2 allele-specific primers have different capture sequences for binding different complementary probes on a tag array. The LDR product templated from genomic DNA is made fluorescent during the U-PCR via incorporation of a Cy5-labeled universal primer into all LDR products; detection occurs on the coated glass slides.

Results: The assay was designed to detect 7 prevalent mutations in the β-globin gene (HBB, hemoglobin, beta) in a multiplex format, and signals for the different alleles are detected by their fluorescence. The assay was applied to 40 genomic DNA samples from both control individuals and patients with known β-thalassemia mutations. Results show good correspondence between the patients’ genotypes as assessed by DNA sequence analysis and those generated from the LDR assays.

Conclusions: The developed technology allows accurate identification of sequence variants in a simple, cost-effective way and offers good flexibility for scaling to other applications with different numbers of single-nucleotide polymorphisms or mutations to be detected.
Cabergoline and cardiac valve disease in prolactinoma patients: additional studies during long-term treatment are required
Authors: Kars M , Pereira A M , Bax J J , Romijn J A
Published: August 2008

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Six cross-sectional studies have been published recently, of which five studies do not show an association between the treatment of prolactinoma with cabergoline during 45–79 months and clinically relevant valvular regurgitation in a total of 413 patients. Nonetheless, concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications and increased mitral tenting area. At present, the clinical relevance of these findings is still uncertain, but concern is raised with respect to the safety of the use of cabergoline in the long-term treatment of prolactinomas. Echocardiographic evaluation should be considered in patients, who require long-term treatment with cabergoline, especially in high doses. There is a need for larger, preferably prospective, studies with careful echocardiographic assessment and with longer durations of follow-up than the currently available studies.
Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH
Authors: Sirotkin A V , Benčo A , Tandlmajerova A , Vašíček D , Kotwica J , Darlak K , Valenzuela F
Published: August 2008

The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosis-related (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P4), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P4, and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P4, but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P4 secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P4 secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary.
Sinais e sintomas associados às doenças sexualmente transmissíveis no Brasil, 2005
Authors: Bastos Francisco I , Cunha Cynthia B , Hacker Mariana A
Published: August 2008

OBJETIVO: As doenças sexualmente transmissíveis (DST) constituem um dos principais determinantes da carga de doença das populações em todo o mundo. O objetivo do estudo foi avaliar a morbidade auto-referida associada à ocorrência de DST, segundo gênero. MÉTODOS: Os dados analisados referem-se à pesquisa realizada em 2005 e foram obtidos a partir de amostra probabilística em múltiplos estágios de 5.040 entrevistados, com 16-65 anos de idade, moradores nas regiões urbanas do Brasil. Esses dados foram cotejados com aqueles de pesquisa anterior, de 1998. Realizaram-se análises bivariadas, utilizando teste qui-quadrado de Pearson e regressão linear simples, seguidas por regressão logística. RESULTADOS: Tanto para homens quanto para mulheres as variáveis: testagem anterior para o HIV, crença pessoal de que pode haver amor sem fidelidade e número de pessoas com quem teve relações sexuais na vida mostraram-se significativamente associadas ao desfecho. Porém, somente entre as mulheres as covariáveis a seguir se mostraram independentemente associadas ao desfecho: renda familiar baixa, residência na Região Centro-Oeste, Sudeste e Sul, e relato de violência física. Para os homens, as variáveis independentemente associadas foram: faixa etária (35 anos ou mais), residência na Região Sul e Estado de São Paulo, e auto-avaliação de risco de se infectar com o HIV. CONCLUSÕES: Sinais e sintomas associados às DST apresentam forte diferencial de gênero na população geral, devendo ser objeto de intervenções educativas claramente distintas.
Prescrição, dispensação e regulação do consumo de psicotrópicos anorexígenos em Belo Horizonte, Minas Gerais, Brasil
Authors: Carneiro Mônica de Fátima Gontijo , Guerra Júnior Augusto Afonso , Acurcio Francisco de Assis
Published: August 2008

Estudo retrospectivo, realizado na cidade de Belo Horizonte, Minas Gerais, Brasil, para avaliar indicadores de dispensação e consumo de substâncias anorexígenas. Ocorreu em duas etapas: na primeira, foram analisadas 2.906 das 168.237 notificações de receitas aviadas por estabelecimentos farmacêuticos da cidade, em 2003. Observou-se uma baixa qualidade nas notificações. O consumo projetado foi de 19,75 DDD/mil habitantes/dia. A substância mais consumida foi o fenproporex (59,8%). Uma farmácia foi responsável por 39,8% das dispensações. Na segunda etapa, foram analisados 14.554 registros do livro de receituário geral da farmácia que mais dispensou tais produtos, no período de abril a agosto de 2005. Os anorexígenos responderam por 9,2% das manipulações e 91,8% deles foram prescritos para uso concomitante com outra substância: 43% com clordiazepóxido, 50,6% com fluoxetina, 7,5% com outro anorexígeno e 28,2% com bromazepam. Os resultados observados sugerem um uso indiscriminado e irracional de anorexígenos neste município, sendo fundamental aprimorar a regulação do mercado de produtos manipulados. Para tanto, é necessário uma melhor compreensão do papel da farmácia nessa regulação e o papel dos prescritores no uso racional dessas substâncias.
When Muddy Flowers Bloom: The Shakespeare Project at Racine Correctional Institution
Authors: Shailor Jonathan
Published: August 2008

About one hundred inmates are seated in the prison gym, waiting for the performance of king lear to begin. Then Jamal, as Edmund, steps out from behind the makeshift set and paces across the stage, his sharply trimmed goatee pointing outward like an accusing finger, his burning gaze fixed on the audience. He raps: “Secret fears are brought to life on stage. / My life is in a rage, and to write my life / One page is not enough. / But if I had one mike I might be able to / Escape this cage … bring Shakespeare to life through my high beams.” Appropriating Cordelia's words, he declares that “I am not the first who have incurred the worst / But I have concurred with those who oppose my life's worth. …” He continues:

They label me violent because I stay bottled up and silentAnd although my life is like a raging seaMy heart sings … no life is quiet.Stop complaining, you say, but I can't becauseI'm trapped on the stage of life's lies.And I ask youWhy brand they us with base? With baseness?Bastardy? Base? Base?
Can the Penitentiary Teach the Academy How to Read?
Authors: Franklin H. Bruce
Published: August 2008

As the shadow of the colossal american prison lengthens amid the encroaching nightfall of our twenty-first-century security state, it is pierced by a brilliant though flickering illumination: the literature created by those who have endured the terrors of America's walls and cells, with their unremitting surveillance, relentless brutality, and overpowering hopelessness. When I began teaching American prison literature back in 1975, there were 360,000 people incarcerated in the nation's jails and prisons. Today there are more than 2.4 million—almost twenty-five percent of all the prisoners in the world. During these thirty-three years, this country has constructed on average one new prison every week. Many states annually spend more on prisons than they do on higher education. More than five million Americans have been permanently disenfranchised because of felony convictions. More than seven million are under the direct control of the criminal-justice system. And the experience of these millions of prisoners and ex-prisoners becomes ever more integral to American culture, not just to the culture of the devastated neighborhoods where most prisoners grew up and to which they return but also to the culture of an entire society grown accustomed to omnipresent surveillance cameras, routine body and car searches, and police patrolling the corridors of high schools.
Methodologies of Imprisonment
Authors: Gordon Avery F.
Published: August 2008

For a little while now, i've been trying to understand the nature of captivity and confinement in four overlapping but distinct models prominent today. These four are the United States' model of mass imprisonment of surplus racial and ethnic populations as a form of socioeconomic abandonment; military imprisonment, especially in the course of permanent security wars; the European model of the detention of migrants, asylum seekers, and refugees (“Fortress Europe”); and the Israeli model of occupation by encirclement and immobilization. In all these forms, or zones, of captivity, the status of the worker, the enemy, the criminal, the migrant, the resident—and thus the prisoner himself or herself—is being modified and mutated in profound ways. In each, older recognizable dynamics of race and class power persist and extend in new directions. In each, the very physicality of the prison takes at the same time more extreme and more abstract concretization as isolation unit, as camp, as safe haven, as city. I've wanted to develop a conceptual and evocative vocabulary for linking the socioeconomic dynamics of accumulation, dispossession, and political power to the dialectic of social death and social life as these meet in the ontological and epistemological status of the prisoner.
Religious Literacy in the Faith-Based Prison
Authors: Erzen Tanya
Published: August 2008

At lawtey correctional institution in florida, a group of around two hundred men gather in the prison chapel. They watch raptly as the Christian-based drama group, His Majesty's Productions, performs One Thing. The stage is set to look like the prison yard, where three groups of men banter with one another. As one group begins talking, the other two freeze into tableaus. In the first exchange, the character Buster says to Jim that when he gets out, he's never coming back. “Yeah, how do you know that?” Jim asks skeptically.
Changing Lives through Literature
Authors: Waxler Robert P.
Published: August 2008

There is something ugly about incarceration. Over 2.2 million people are locked in jails and prisons in the united states; $60 billion a year is spent to support this effort. But there is also the old comparison of the prison with the monk's cell, a place of contemplation and self-reflection, and Jean Genet's sense of “a close relationship between flowers and convicts” (9). As a probation officer I know likes to remind me, “If you want to find Jesus, just go into the prisons. He is always there.” In any discussion of prisons, there are always opposing terms to consider: incarceration and freedom, body and consciousness, the hard core and the vulnerable, mind-forged manacles and visionary imagination.
“The Indies”: Baudelaire's Colonial World
Authors: Lionnet Françoise
Published: August 2008

[Les critiques] ont en commun avec les tyrans de plier le monde à leurs désirs.

[Critics] and tyrants have this in common: they bend the world to their desires.

—Yasmina Reza, L'aube le soir ou la nuit (9)

If there is anything that radically distinguishes the imagination of anti-imperialism, it is the primacy of the geographical element. Imperialism after all is an act of geographical violence through which virtually every space in the world is explored, charted, and finally brought under control.

—Edward Said, Culture and Imperialism (225)

Denis Diderot's Encyclopédie is explicit about “Les Indes” ‘The Indies.‘ in explaining why distant landmasses were charted under the incorrect rubrics “East Indies” and “West Indies,” the Encyclopédie states in 1765 that these designations refer to countries situated on either side of the Cape of Good Hope, the southern extremity of Africa:

[L]es modernes moins excusable que les anciens ont nommé Indes, des pays si différens par leur position & par leur étendue sur notre globe, que pour ôter une partie de l'équivoque, ils ont divisé les Indes en orientales & occidentales. … De-là vint l'usage d'appeller Indes orientales, ce qui est à l'orient du cap de Bonne-Espérance, & Indes occidentales, ce qui est à l'occident de ce cap. … [P]ar un nouvel abus, qu'il n'est plus possible de corriger, on se sert dans les relations du nom d'Indiens, pour dire les Amériquains. (“Indes”)

[T]he moderns, who are less forgivable than the ancients, have called Indies countries so different by virtue of their location and their size on our globe that these had to be divided into East and West Indies in order to correct the ambiguity. … Hence the custom of calling East Indies what lies to the east of the Cape of Good Hope and West Indies what lies to the west of that cape. … [T]hrough a new misuse, which can no longer be corrected, the name Indians is used in travel relations to refer to Americans.
The New Modernist Studies
Authors: Mao Douglas , Walkowitz Rebecca L.
Published: August 2008

In our introduction tobad modernisms, we traced the emergence of the new modernist studies, which was born on or about 1999 with the invention of the Modernist Studies Association (MSA) and its annual conferences; with the provision of exciting new forums for exchange in the journalsModernism/Modernityand (later)Modernist Cultures; and with the publication of books, anthologies, and articles that took modernist scholarship in new methodological directions. When we offered that survey, one of our principal interests was to situate these events in a longer critical history of modernism in the arts. In the present report, we want to attend more closely to one or two recent developments that may be suggestive about the present and the immediate future of the study of modernist literature. Part of the empirical, though certainly far from scientific, basis of our considerations lies in our recent service on the MSA Book Prize committee (Walkowitz in 2005, Mao in 2006), through which we became acquainted with dozens of recent contributions to the field.