Drosophila PAF1 Modulates PIWI/piRNA Silencing Capacity.

PubMed

Clark, Josef P; Rahman, Reazur; Yang, Nachen; Yang, Linda H; Lau, Nelson C

2017-09-11

To test the directness of factors in initiating PIWI-directed gene silencing, we employed a Piwi-interacting RNA (piRNA)-targeted reporter assay in Drosophila ovary somatic sheet (OSS) cells [1]. This assay confirmed direct silencing roles for piRNA biogenesis factors and PIWI-associated factors [2-12] but suggested that chromatin-modifying proteins may act downstream of the initial silencing event. Our data also revealed that RNA-polymerase-II-associated proteins like PAF1 and RTF1 antagonize PIWI-directed silencing. PAF1 knockdown enhances PIWI silencing of reporters when piRNAs target the transcript region proximal to the promoter. Loss of PAF1 suppresses endogenous transposable element (TE) transcript maturation, whereas a subset of gene transcripts and long-non-coding RNAs adjacent to TE insertions are affected by PAF1 knockdown in a similar fashion to piRNA-targeted reporters. Additionally, transcription activation at specific TEs and TE-adjacent loci during PIWI knockdown is suppressed when PIWI and PAF1 levels are both reduced. Our study suggests a mechanistic conservation between fission yeast PAF1 repressing AGO1/small interfering RNA (siRNA)-directed silencing [13, 14] and Drosophila PAF1 opposing PIWI/piRNA-directed silencing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1998-06-01

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

[Association between platelet-activating factor acetylhydrolase gene polymorphisms and gastrointestinal bleeding in children with Henoch-Schönlein purpura].

PubMed

Wang, Bao-Xiang; Mei, Hong; Peng, Han-Ming; Gao, Yuan; Ding, Yan

2017-04-01

To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP). A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe. The plasma PAF-AH activity was measured, as well as the levels of platelet-activating factor (PAF), granular membrane protein-140 (GMP-140), β-thromboglobulin (β-TG), and platelet factor 4 (PF4). The Val279Phe genotype and allele frequencies were in Hardy-Weinberg equilibrium, and the homozygous genotype TT and heterozygotes accounted for 0.97% and 6.05% respectively. The gastrointestinal bleeding group had a significantly higher allele frequency than the control group (5.22% vs 3.33%; P<0.01). The HSP patients with GG genotype in the gastrointestinal bleeding group had significantly higher levels of plasma PAF and GMP-140 than those in the non-gastrointestinal bleeding group (P<0.05), while the non-gastrointestinal bleeding group had a significantly higher PAF-AH activity than the gastrointestinal bleeding group (P<0.05). There were no significant differences in β-TG and PF4 between the two groups (P>0.05). Val279Phe gene polymorphisms in PAF-AH are associated with PAF-AH activity and PAF and GMP-140 levels and may be a risk factor for HSP with gastrointestinal bleeding.

IL-1β-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes.

PubMed

Kim, Nari; Sun, Hwa-Young; Youn, Min-Young; Yoo, Joo-Yeon

2013-04-01

To determine the functional specificity of inflammation, it is critical to orchestrate the timely activation and repression of inflammatory responses. Here, we explored the PAF1 (RNA polymerase II associated factor)-mediated signal- and locus-specific repression of genes induced through the pro-inflammatory cytokine interleukin (IL)-1β. Using microarray analysis, we identified the PAF1 target genes whose expression was further enhanced by PAF1 knockdown in IL-1β-stimulated HepG2 hepatocarcinomas. PAF1 bound near the transcription start sites of target genes and dissociated on stimulation. In PAF1-deficient cells, more elongating RNA polymerase II and acetylated histones were observed, although IL-1β-mediated activation and recruitment of nuclear factor κB (NF-κB) were not altered. Under basal conditions, PAF1 blocked histone acetyltransferase general control non-depressible 5 (GCN5)-mediated acetylation on H3K9 and H4K5 residues. On IL-1β stimulation, activated GCN5 discharged PAF1 from chromatin, allowing productive transcription to occur. PAF1 bound to histones but not to acetylated histones, and the chromatin-binding domain of PAF1 was essential for target gene repression. Moreover, IL-1β-induced cell migration was similarly controlled through counteraction between PAF1 and GCN5. These results suggest that the IL-1β signal-specific exchange of PAF1 and GCN5 on the target locus limits inappropriate gene induction and facilitates the timely activation of inflammatory responses.

Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

PubMed

Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

2013-12-01

Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection

PubMed Central

Jeewandara, Chandima; Gomes, Laksiri; Wickramasinghe, N.; Gutowska-Owsiak, Danuta; Waithe, Dominic; Paranavitane, S. A.; Shyamali, N. L. A.; Ogg, Graham S.; Malavige, Gathsaurie Neelika

2015-01-01

Background Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. Materials and Methods PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. Results PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. Conclusion Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. PMID:25646838

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

PubMed

Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

2012-03-16

To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

Candidate's thesis: Platelet-activating factor-induced hearing loss: mediated by nitric oxide?

PubMed

Rhee, Chung-Ku

2003-12-01

Platelet-activating factor (PAF)in middle ear effusion is thought to induce hearing loss. The purpose of this study is to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by studying the effects of PAF application on the round window membrane (RWM) with and without PAF-antagonist NO-blocker. Longitudinal study on randomized guinea pigs using PAF to induce hearing loss. METHODS Guinea pigs were divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 microg of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB 2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected intraperitoneally prior to PAF 20 microg application on the RWM. The following three tests were performed on each animal group: Hearing was tested with an auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide synthase (iNOS). The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in the SEM group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and the L-NAME groups did not show significant elevation of ABR threshold and cochlear hair cell damage compared with the group administered PAF 20 microg, but in the PAF-antagonist group, the elevation of ABR threshold was significant compared with that of the PBS control group, whereas it was not significant compared with the PBS group in the L-NAME group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB 2170, and L-NAME groups. This study demonstrated that PAF placed on the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L-NAME may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media. The results of this study have significant potential clinical application.

A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced obesity but PAF/PAF receptor signaling does not contribute to the development of obesity-induced chronic inflammation.

PubMed

Yamaguchi, Masahiko; Matsui, Masakazu; Higa, Ryoko; Yamazaki, Yasuhiro; Ikari, Akira; Miyake, Masaki; Miwa, Masao; Ishii, Satoshi; Sugatani, Junko; Shimizu, Takao

2015-02-15

Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute inflammatory responses. In the present study, we investigated whether PAF/PAF receptor signaling contributed to chronic inflammation in the white adipose tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-α mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. Although PAF receptor signaling up-regulated the expression of TNF-α and lipopolysaccharide induced the expression of acyl-CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow-derived macrophages, no significant differences were observed in the expression of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal diet-fed mice. In addition to our previous finding in which energy expenditure in PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue function, the present study demonstrated that PAF/PAF receptor signaling up-regulated the expression of Ucp1 mRNA, which is essential for cellular thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT, which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT mice, and PAF/PAF receptor signaling may regulate energy expenditure and adiposity. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibody production of wild-type and enzyme V279F variants of PAF-AH as a risk factor for Cardiovascular disease

NASA Astrophysics Data System (ADS)

Ramadhani, Anggia N.; Puspitarini, Sapti; Sari, Anissa N.; Widodo

2017-11-01

Coronary artery disease (CAD) has emerged as a leading cause of death in Indonesia nowadays. WHO data in 2012 revealed that 37% of the Indonesian population died from this disease. CAD occurs because of endothelial dysfunction in the arteries. Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase (PAF-AH), is a phospholipase A2 enzyme, encoded by the PLA2G7 gene. This protein is predicted to be involved in inflammatory phospholipid metabolism so it can be used as a biomarker of CAD in the early phase. Thus, the purpose of this research is to discover the difference in antibody production between wild-type and mutant V279F. The PAF-AH enzyme was isolated from mice lymphocyte cells in order to develop this enzyme as a biomarker of cardiovascular disease. PAF-AH migrates at 55kDa according to SDS-PAGE analysis. Flow cytometry analysis showed that mutant PAF-AH (V279F) is more antigenic than wild-type PAF-AH. The missense mutation of V279F PAF-AH means this enzyme cannot catabolize the acetyl group at the sn-2 position of PAF.

Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, W.J.

1988-01-01

The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF ormore » thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).« less

PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

PubMed

Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

2018-03-12

The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus.

PubMed

Serban, M; Tanaseanu, Cristina; Kosaka, T; Vidulescu, Cristina; Stoian, Irina; Marta, Daciana S; Tanaseanu, S; Moldoveanu, Elena

2002-01-01

Non-insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Plasma platelet - activating factor - acetylhydrolases (PAF-AHs) are a subgroup of Ca(2+)-independent phospholipase A(2) family (also known as lipoprotein-associated phospholipases A(2)) that hydrolyze and inactivate the lipid mediator platelet-activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF-AH activity and LDL-cholesterol / HDL-cholesterol (LDL-ch / HDL-ch) ratio in NIDDM patients as compared to controls. serum PAF-AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL-ch, HDL-ch, triglyceride and blood glucose were determined in all subjects. All NIDDM patients display hiperlipidemia, with increased LDL-ch and triglyceride levels. There is a significant correlation between LDL-ch levels (especially LDL-ch / HDL-ch ratio) and PAF-AH activity in dyslipidemic and NIDDM patients. Diabetic and dyslipidemic patients have an increased plasma PAF-AH activity correlated with their LDL-ch levels and mainly with LDL-ch / HDL-ch ratio. Plasma PAF-AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats

PubMed Central

Tanaka, Yoshio; Hayakawa, Sachiko; Imai, Toshiyasu; Akutsu, Aya; Hirano, Haruko; Tanaka, Hikaru; Nakahara, Tsutomu; Ishii, Kunio; Shigenobu, Koki

2000-01-01

In anaesthetized rats, platelet activating factor (PAF; 1 μg kg−1) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg−1), indicating the role of PAF-specific receptor in the response.NG-nitro-L-arginine methyl ester (L-NAME; 50 mg kg−1), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 μg kg−1) normalized against that to sodium nitroprusside (SNP) (10 μg kg−1) was not substantially different between rats treated without and with L-NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03–1.0 μg kg−1) normalized against that of SNP (10 μg kg−1) was significantly attenuated by L-NAME (n=5).Charybdotoxin (0.4 mg kg−1) plus apamin (0.2 mg kg−1) significantly attenuated the depressor response to PAF (1 μg kg−1) (n=5) without affecting the blood pressure change due to SNP (1 mg kg−1) (n=3). Charybdotoxin (0.4 mg kg−1) (n=4) or apamin (0.2 mg kg−1) (n=4) alone did not affect the PAF-induced depressor response.These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine. PMID:11082118

Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the Zebrafish larvae assay.

PubMed

Fitzgerald, Ciarán; Gallagher, Eimear; O'Connor, Paula; Prieto, José; Mora-Soler, Leticia; Grealy, Maura; Hayes, Maria

2013-12-01

The vascular inflammatory role of platelet activating factor acetylhydrolase (PAF-AH) is thought to be due to the formation of lysophosphatidyl choline and oxidized non-esterified fatty acids. This enzyme is considered a promising therapeutic target for the prevention of atherosclerosis and there is a need to expand the available chemical templates of PAF-AH inhibitors. This study demonstrated how natural PAF-AH inhibitory peptides were isolated and characterized from the red macroalga Palmaria palmata. The dried powdered alga was hydrolyzed using the food grade enzyme papain, and the resultant peptide containing fraction generated using RP-HPLC. Several oligopeptides were identified as potential PAF-AH inhibitors following bio-guided fractionation, and the amino acid sequences of these oligopeptides were confirmed by Q-TOF-MS and microwave-assisted solid phase de novo synthesis. The most promising PAF-AH inhibitory peptide had the amino acid sequence NIGK and a PAF-AH IC50 value of 2.32 mM. This peptide may constitute a valid drug template for PAF-AH inhibitors. Furthermore the P. palmata hydrolysate was nontoxic when assayed using the Zebrafish toxicity model at a concentration of 1mg/ml. Copyright © 2013 Elsevier Inc. All rights reserved.

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

PubMed Central

Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

2006-01-01

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells. PMID:16651609

Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response

PubMed Central

1976-01-01

The secretion of vasoactive amines from rabbit platelets induced by the platelet-activating factor (PAF) derived from IgE-sensitized rabbit basophils, was examined. The secretion required calcium has previously been shown to be noncytotoxic and was optimal in both rate and extent at 37 degrees C and pH 7.2. Different temperature-sensitive steps were rate limiting for secretion above or below 20 degrees C. The rate of secretion was dependent upon the concentration of PAF and also of platelets. Maximal rates were observed with relatively low concentrations of platelets (2.5 X 10(8)/ml), sharply contrasting with other platelet stimuli such as C3 or thrombin. The extent of secretion was dependent upon PAF concentration until a maximum of 50 or 60% of the serotonin was released and then declined with increasing amounts of PAF. This was interpreted to result from the platelets becoming desensitized to the PAF, a process that shuts off the secretion. Such a desensitization was demonstrated and was shown to be stimulus specific, i.e., other stimuli could still induce secretion from PAF-desensitized platelets. PAF extracted with ethanol from the albumin to which it is usually bound during preparation, exhibited similar characteristics, except that secretion of up to 90% of the serotonin was induced. The extracted PAF thus seemed less able to induce the desensitization. Its use did provide important evidence that populations of rabbit platelets are relatively homogenous in their ability to respond to PAF. PMID:3618

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

PubMed

Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain. © 2013 International Society for Neurochemistry.

Platelet Activating Factor-Induced Ceramide Micro-Domains Drive Endothelial NOS Activation and Contribute to Barrier Dysfunction

PubMed Central

Predescu, Sanda; Knezevic, Ivana; Bardita, Cristina; Neamu, Radu Florin; Brovcovych, Viktor; Predescu, Dan

2013-01-01

The spatial and functional relationship between platelet activating factor-receptor (PAF-R) and nitric oxide synthase (eNOS) in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs) as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO) production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM) on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min) increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles. PMID:24086643

Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of Inflammation in Chickens

PubMed Central

Garrido, Damien; Chanteloup, Nathalie K.; Trotereau, Angélina; Lion, Adrien; Bailleul, Geoffrey; Esnault, Evelyne; Trapp, Sascha; Quéré, Pascale; Schouler, Catherine; Guabiraba, Rodrigo

2017-01-01

Lipid mediators are known to play important roles in the onset and resolution phases of the inflammatory response in mammals. The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their functions are still poorly characterized, and the role of PAF as an inflammatory mediator has not yet been investigated. In the present study we demonstrate that primary chicken macrophages express PAFR and lysophosphatidylcholine acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during inflammation. Also, exogenous PAF treatment induces intracellular calcium increase, reactive oxygen species release, and increased phagocytosis by primary chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes to the Escherichia coli lipopolysaccharide (LPS)-induced pro-inflammatory response and boosts the macrophage response to E. coli LPS via phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated intracellular signaling pathways. Exogenous PAF treatment also increases avian pathogenic E. coli intracellular killing by chicken macrophages, and PAFR and LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary colibacillosis. Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). In addition to these vascular phenomena, PAF boosts the chAEC inflammatory response to bacteria-associated molecular patterns in a PAFR-dependent manner. In conclusion, we identified PAF as an inflammation amplifier in chicken macrophages and ECs, which suggests that PAF could play important roles in the endothelium-innate immunity interface in birds during major bacterial infectious diseases such as colibacillosis. PMID:29326957

Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.

PubMed Central

Stafforini, D M; Carter, M E; Zimmerman, G A; McIntyre, T M; Prescott, S M

1989-01-01

Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances. Images PMID:2928339

The burden of cancer attributable to modifiable risk factors: the Australian cancer-PAF cohort consortium.

PubMed

Arriaga, Maria E; Vajdic, Claire M; Canfell, Karen; MacInnis, Robert; Hull, Peter; Magliano, Dianna J; Banks, Emily; Giles, Graham G; Cumming, Robert G; Byles, Julie E; Taylor, Anne W; Shaw, Jonathan E; Price, Kay; Hirani, Vasant; Mitchell, Paul; Adelstein, Barbara-Ann; Laaksonen, Maarit A

2017-06-14

To estimate the Australian cancer burden attributable to lifestyle-related risk factors and their combinations using a novel population attributable fraction (PAF) method that accounts for competing risk of death, risk factor interdependence and statistical uncertainty. 365 173 adults from seven Australian cohort studies. We linked pooled harmonised individual participant cohort data with population-based cancer and death registries to estimate exposure-cancer and exposure-death associations. Current Australian exposure prevalence was estimated from representative external sources. To illustrate the utility of the new PAF method, we calculated fractions of cancers causally related to body fatness or both tobacco and alcohol consumption avoidable in the next 10 years by risk factor modifications, comparing them with fractions produced by traditional PAF methods. Over 10 years of follow-up, we observed 27 483 incident cancers and 22 078 deaths. Of cancers related to body fatness (n=9258), 13% (95% CI 11% to 16%) could be avoided if those currently overweight or obese had body mass index of 18.5-24.9 kg/m 2 . Of cancers causally related to both tobacco and alcohol (n=4283), current or former smoking explains 13% (11% to 16%) and consuming more than two alcoholic drinks per day explains 6% (5% to 8%). The two factors combined explain 16% (13% to 19%): 26% (21% to 30%) in men and 8% (4% to 11%) in women. Corresponding estimates using the traditional PAF method were 20%, 31% and 10%. Our PAF estimates translate to 74 000 avoidable body fatness-related cancers and 40 000 avoidable tobacco- and alcohol-related cancers in Australia over the next 10 years (2017-2026). Traditional PAF methods not accounting for competing risk of death and interdependence of risk factors may overestimate PAFs and avoidable cancers. We will rank the most important causal factors and their combinations for a spectrum of cancers and inform cancer control activities. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome.

PubMed

Zhang, Renjiao; Song, Qi; Liu, Hongwei; Bai, Huai; Zhang, Yujin; Liu, Qingqing; Guan, Linbo; Fan, Ping

2017-03-20

The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women. A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed. No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women. There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 → H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.

PAF53 is essential in mammalian cells: CRISPR/Cas9 fails to eliminate PAF53 expression.

PubMed

Rothblum, Lawrence I; Rothblum, Katrina; Chang, Eugenie

2017-05-15

When mammalian cells are nutrient and/or growth factor deprived, exposed to inhibitors of protein synthesis, stressed by heat shock or grown to confluence, rDNA transcription is essentially shut off. Various mechanisms are available to accomplish this downshift in ribosome biogenesis. Muramatsu's laboratory (Hanada et al., 1996) first demonstrated that mammalian PAF53 was essential for specific rDNA transcription and that PAF53 levels were regulated in response to growth factors. While S. cerevisae A49, the homologue of vertebrate PAF53, is not essential for viability (Liljelund et al., 1992), deletion of yA49 results in colonies that grow at 6% of the wild type rate at 25°C. Experiments described by Wang et al. (2015) identified PAF53 as a gene "essential for optimal proliferation". However, they did not discriminate genes essential for viability. Hence, in order to resolve this question, we designed a series of experiments to determine if PAF53 was essential for cell survival. We set out to delete the gene product from mammalian cells using CRISPR/CAS9 technology. Human 293 cells were transfected with lentiCRISPR v2 carrying genes for various sgRNA that targeted PAF53. In some experiments, the cells were cotransfected in parallel with plasmids encoding FLAG-tagged mouse PAF53. After treating the transfected cells with puromycin (to select for the lentiCRISPR backbone), cells were cloned and analyzed by western blots for PAF53 expression. Genomic DNA was amplified across the "CRISPRd" exon, cloned and sequenced to identify mutated PAF53 genes. We obtained cell lines in which the endogenous PAF53 gene was "knocked out" only when we rescued with FLAG-PAF53. DNA sequencing demonstrated that in the absence of ectopic PAF53 expression, cells demonstrated unique means of surviving; including recombination or the utilization of alternative reading frames. We never observed a clone in which one PAF53 gene is expressed, unless there was also ectopic expression In the absence of ectopic gene expression, the gene products of both endogenous genes were expressed, irrespective of whether they were partially mutant proteins or not. Copyright © 2016 Elsevier B.V. All rights reserved.

Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH) administration.

PubMed

Teixeira-da-Cunha, Mariana G A; Gomes, Rachel N; Roehrs, Nathassia; Bozza, Fernando A; Prescott, Stephen M; Stafforini, Diana; Zimmerman, Guy A; Bozza, Patricia T; Castro-Faria-Neto, Hugo C

2013-01-01

Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model.

Physalin B inhibits Rhodnius prolixus hemocyte phagocytosis and microaggregation by the activation of endogenous PAF-acetyl hydrolase activities.

PubMed

Castro, D P; Figueiredo, M B; Genta, F A; Ribeiro, I M; Tomassini, T C B; Azambuja, P; Garcia, E S

2009-06-01

The effects of physalin B (a natural secosteroidal chemical from Physalis angulata, Solanaceae) on phagocytosis and microaggregation by hemocytes of 5th-instar larvae of Rhodnius prolixus were investigated. In this insect, hemocyte phagocytosis and microaggregation are known to be induced by the platelet-activating factor (PAF) or arachidonic acid (AA) and regulated by phospholipase A(2) (PLA(2)) and PAF-acetyl hydrolase (PAF-AH) activities. Phagocytic activity and formation of hemocyte microaggregates by Rhodnius hemocytes were strongly blocked by oral treatment of this insect with physalin B (1mug/mL of blood meal). The inhibition induced by physalin B was reversed for both phagocytosis and microaggregation by exogenous arachidonic acid (10microg/insect) or PAF (1microg/insect) applied by hemocelic injection. Following treatment with physalin B there were no significant alterations in PLA(2) activities, but a significant enhancement of PAF-AH was observed. These results show that physalin B inhibits hemocytic activity by depressing insect PAF analogous (iPAF) levels in hemolymph and confirm the role of PAF-AH in the cellular immune reactions in R. prolixus.

Effects of platelet activating factor on contractile force and 45Ca fluxes in guinea-pig isolated atria.

PubMed Central

Diez, J.; Delpón, E.; Tamargo, J.

1990-01-01

1. The effects of platelet activating factor (PAF) were studied on the electromechanical properties and 45Ca2+ fluxes of guinea-pig isolated atria. 2 Both in spontaneously beating and electrically driven atria, PAF (10(-12)-10(-7) M) increased atrial rate but produced a biphasic effect on contractile force. At low concentrations (up to 10(-10) M) it produced a positive inotropic effect, while at higher concentrations PAF exerted a negative inotropic effect. A similar biphasic effect was observed in the slow contractions elicited by isoprenaline in K(+)-depolarized atrial fibres. 3. The positive inotropic effect of PAF was prevented by verapamil, whereas pretreatment of atria with propranolol, phentolamine, indomethacin or atropine did not modify its positive and negative inotropic actions. BN 52021, a specific PAF antagonist, abolished both the positive and negative inotropic effects. 4. PAF had no effect on the characteristics of the action potentials recorded in either normally polarized or K(+)-depolarized (slow action potential) atrial fibres. 5. At concentrations at which it increased contractile force, PAF potentiated the contractile responses to Ca2+ (0.9-9 mM), whereas at negative inotropic concentrations it inhibited them. The negative inotropic effect of PAF was partially reversed in 70% Na+ medium. 6. At 10(-11) M, PAF increased 45Ca2+ uptake and reduced the rate coefficient (kcm) for the 45Ca2+ efflux. This increase in 45Ca2+ uptake was abolished in atria pretreated with verapamil or BN 52021. However, 10(-7) M PAF modified neither 45Ca2+ uptake nor efflux in atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2379035

Effect of platelet activating factor with and without receptor antagonist (WEB2170) on morphology of isolated cochlear outer hair cells.

PubMed

Jung, Timothy T K; John, Earnest O; Park, Seong Kook; Park, Yong Soo; Rhee, Chong-Ku

2004-02-01

Platelet activating factor (PAF), generated from biologically active phospholipids, has been implicated as a potent inflammatory mediator and has been shown to be involved in many pathological processes, especially in inflammation and allergy. It has been suspected that PAF may be one of the inflammatory mediators in middle ear effusion that can induce sensorineural hearing loss, as observed in chronic otitis media. The PAF receptor antagonist WEB2170 has been studied extensively, and its inhibitory effects against various PAF actions are well proven in otologic systems. The purpose of our study was to determine the effect of superfusion of PAF and WEB2170 on morphological changes in isolated cochlear outer hair cells (OHCs). Isolated OHCs from adult chinchilla cochleas were exposed to albumin-phosphate-buffered saline solution (1 mg/mL), WEB2170 (5 mg/30 mL), PAF (1 micromol/L), or both PAF (I micromol/L) and WEB2170 (5 mg/30 mL). All experiments were performed at an osmolality of 305 +/- 5 mOsm at room temperature for 30 minutes. The cells were observed with an inverted microscope; the images were stored and analyzed on the Image Pro-Plus program. The OHCs exposed to control albumin-phosphate-buffered saline solution or to WEB2170 did not show any significant change in cell shape or length. The cells exposed to 1 micromol/L of PAF showed ballooning and significant shortening of the mean cell length in 15 to 20 minutes. These morphological changes in OHCs can be prevented by pretreating OHCs with WEB2170. This study demonstrated that exposure to PAF causes morphological changes in isolated OHCs that can be prevented by the PAF receptor antagonist WEB2170.

Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants.

PubMed

Jantan, I; Rafi, I A A; Jalil, J

2005-01-01

Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

PubMed Central

Domingues, Patricia; Golebiowski, Filip; Tatham, Michael H.; Lopes, Antonio M.; Taggart, Aislynn; Hay, Ronald T.; Hale, Benjamin G.

2015-01-01

Summary Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID:26549460

The effects of platelet activating factor and retinoic acid on the expression of ELAM-1 and ICAM-1 and the functions of neutrophils

PubMed Central

1995-01-01

Preincubation of pulmonary microvascular endothelial cells (PMVECs) with platelet-activating factor (PAF) for 3.5 h increased the adhesion rate of polymorphonuclear leukocytes (PMNs) to PMVECs from 57.3% to 72.8% (p < 0.01). Preincubation of PMNs with PAF also increased PMN-PMVEC adhesion rate. All-trans retinoic acid (RA) blocked the adherence of untreated PMNs to PAF-pretreated PMVECs but not the adherence of PAF-pretreated PMNs to untreated PMVECs. PAF increased the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selection (ELAM-1) on PMVECs, PMN chemotaxis to zymosan-activated serum and histamine, and PMN aggregation and the release of acid phosphatase from PMNs. Co-incubation of RA inhibited PAF-induced PMN aggregation, the release of acid phosphatase from PMNs, and PMN chemotaxis to zymosan-activated serum and histamine while the expression of ICAM-1 and ELAM-1 did not change. Our results suggest that RA can be used to ameliorate PMN-mediated inflammation. PMID:18475624

[Efficacy of Transdermal Patch of Bisoprolol for Paroxysmal Atrial Fibrillation after Open Heart Surgery].

PubMed

Yamamoto, Kenji; Yamada, Tomoyuki; Hamuro, Mamoru; Kawatou, Masahide; Enomoto, Sakae

2017-11-01

2014 American Association for Thoracic Surgery (AATS) guidelines recommend beta blocker for prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. In recent years, transdermal patch of bisoprolol (TDPB) has become available in Japan. We examined the efficacy of TDPB for paroxysmal atrial fibrillation (PAF) after open heart surgery. Among 289 patients who had undergone open heart surgery in our hospital from December 2013 to April 2016, 48(16.6%)patients, for whom TDPB was used for PAF, were analyzed retrospectively. The summary of our PAF protocol:HR >80;a sheet of TDPB (4 mg) is pasted, HR≤60;TDPB is removed, HR >140 persisted;another sheet of TDPB is added. Eighteen of the 48 (37.5%) patients recovered sinus rhythm within 24 hours. Six patients( 12.5%), because of persistent tachycardia, shifted to continuous infusion of landiolol. Ten underwent electrical defibrillation during hospitalization. In 3 patients, TDPB was removed due to advanced bradycardia. TDPB could be used safely and feasibly for PAF after open heart surgery.

Canadian military personnel's population attributable fractions of mental disorders and mental health service use associated with combat and peacekeeping operations.

PubMed

Sareen, Jitender; Belik, Shay-Lee; Afifi, Tracie O; Asmundson, Gordon J G; Cox, Brian J; Stein, Murray B

2008-12-01

We investigated mental disorders, suicidal ideation, self-perceived need for treatment, and mental health service utilization attributable to exposure to peacekeeping and combat operations among Canadian military personnel. With data from the Canadian Community Health Survey Cycle 1.2 Canadian Forces Supplement, a cross-sectional population-based survey of active Canadian military personnel (N = 8441), we estimated population attributable fractions (PAFs) of adverse mental health outcomes. Exposure to either combat or peacekeeping operations was associated with posttraumatic stress disorder (men: PAF = 46.6%; 95% confidence interval [CI] = 27.3, 62.7; women: PAF = 23.6%; 95% CI = 9.2, 40.1), 1 or more mental disorder assessed in the survey (men: PAF = 9.3%; 95% CI = 0.4, 18.1; women: PAF = 6.1%; 95% CI = 0.0, 13.4), and a perceived need for information (men: PAF = 12.3%; 95% CI = 4.1, 20.6; women: PAF = 7.9%; 95% CI = 1.3, 15.5). A substantial proportion, but not the majority, of mental health-related outcomes were attributable to combat or peacekeeping deployment. Future studies should assess traumatic events and their association with physical injury during deployment, premilitary factors, and postdeployment psychosocial factors that may influence soldiers' mental health.

Effect of BN 52021, a specific antagonist of platelet activating factor (PAF-acether), on calcium movements and phosphatidic acid production induced by PAF-acether in human platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, M.F.; Chap, H.; Braquet, P.

1987-02-15

/sup 32/P-labelled human platelets loaded with quin 2 and pretreated with aspirin were stimulated with 1-100 nM platelet activating factor (PAF-acether or 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in a medium containing the ADP-scavenging system creatine phosphate/creatine phosphokinase. Under these conditions, PAF-acether evoked a characteristic fluorescence change allowing to quantify elevations in cytoplasmic free Ca/sup 2 +/ from internal stores (Ca/sup 2 +/ mobilization) or from external medium (Ca/sup 2 +/ influx), as well as an increased production of phosphatidic acid, reflecting phospholipase C activation. These effects, which can be attributed to PAF-acether only and not to released products such as ADP or thromboxane A2,more » were strongly inhibited in a dose-dependent manner by BN 52021, a specific antagonist of PAF-acether isolated from Ginkgo biloba. As the drug remained inactive against the same effects elicited by thrombin, it is concluded that BN 52021 does not interfere directly with the mechanism of transmembrane signalling involving inositol-phospholipids or (and) some putative receptor-operated channels, but rather acts on the binding of PAF-acether to its presumed membrane receptor.« less

Intravenous infusion of PAF affects ovulation, fertilization and preimplantation embryonic development in NZB x NZW F1 hybrid mice.

PubMed

Sakellariou, Maria; Drakakis, Peter; Antonopoulou, Smaragdi; Anagnostou, Elli; Loutradis, Dimitris; Patargias, Theoxaris

2008-03-01

Platelet Activating Factor (PAF) is a bioactive phospholipid, which exhibits a variety of biological activities and plays a significant role in all aspects of reproduction. In this work, a single intravenous injection of various concentrations of PAF shortly after Human Chorionic Gonadotropin (HCG) administration as well as 24 and 48 h before HCG administration was studied in NZB x NZW F1 hybrid mice. Optimum results were observed when PAF was injected just after the administration of HCG. In this protocol, the concentrations of PAF exhibited bell-shaped response to every stage of development. Any concentration of PAF between 5.5 x 10(-11) and 5.5 x 10(-15)g/g b.w., caused an improved ovulation rate, an increased fertilization rate, an increased rate of cell cycle and an enhanced hatching blastocyst rate (P<0.05 for all stages). Injection of lyso-PAF had no effect in any stage. Our data show that the effect of PAF on early stages of embryo development in vitro is dependent on its way of administration, on the concentrations used as well as on the time PAF is injected.

A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?

PubMed Central

Lagopati, Nefeli; Tsilibary, Effie C.

2017-01-01

In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors. PMID:28458618

PAF levels and PAF-AH activities in placentas from normal and preeclamptic pregnancies.

PubMed

Gu, Y; Burlison, S A; Wang, Y

2006-01-01

The aim of this study was to determine: (1) platelet-activating factor (PAF) levels and PAF-acetylhydrolase (PAF-AH) activities in normal and preeclamptic placentas; (2) lipid peroxide production by placental tissues stimulated with PAF. Placentas were obtained immediately after delivery from normal and preeclamptic pregnancies. Tissue pieces were snap frozen in liquid nitrogen and stored at -70 degrees C. One gram of tissue from each placenta was used for PAF extraction and for total RNA isolation. PAF was measured by PAF [3H] scintillation proximity assay (SPA) system. Trophoblast PAF-AH activity was determined by enzyme-linked immunosorbent assay (ELISA). mRNA expression for PAF receptor was assessed by RNase protection assay (RPA). Normal placental explants were incubated with PAF at concentrations of 1 and 10 microg/ml for 48 h. Lipid peroxide productions of 8-isoprostane and malondialdehyde (MDA) were measured by ELISA and thiobarbituric acid reaction, respectively. Data were presented as mean+/-SE and analyzed by nonparametric Mann-Whitney U test and ANOVA. A p level less than 0.05 was considered statistically significant. (1) The mean tissue level for PAF was elevated, but not statistically different, in preeclamptic (n=7) than in normal (n=8) placentas, 6.45+/-1.05 versus 4.47+/-0.60 ng/g, p=0.42. (2) PAF-AH activity was higher in trophoblasts from preeclamptic (n=7) placentas than that in trophoblasts from normal (n=8) placentas, 0.69+/-0.16 versus 0.38+/-0.03 micromol/min/microg protein, p<0.05. (3) The relative mRNA expression for PAF receptor was not different between normal (0.70+/-0.08) and preeclamptic (0.76+/-0.13) placental tissues, p=0.60. (4) Productions of 8-isoprostane and MDA were not increased in tissues with PAF in culture, 8-isoprostane: 0.37+/-0.09 ng/mg (control) versus 0.32+/-0.09 ng/mg (1 microg/ml) and 0.37+/-0.07 ng/mg (10 microg/ml), p>0.5; MDA: 0.62+/-0.05 nmol/mg (control) versus 0.68+/-0.04 nmol/mg (1 microg/ml) and 0.69+/-0.03 nmol/mg (10 microg/ml), p>0.5. Increased PAF-AH activity in trophoblasts may be a compensatory effect to control PAF level in the preeclamptic placenta. The co-existence of PAF-AH and PAF receptor in trophoblasts suggests an autocrine regulation of PAF in these cells to limit PAF and its metabolites within the placenta.

The platelet-activating factor acetylhydrolase gene derived from Trichoderma harzianum induces maize resistance to Curvularia lunata through the jasmonic acid signaling pathway.

PubMed

Yu, Chuanjin; Fan, Lili; Gao, Jinxin; Wang, Meng; Wu, Qiong; Tang, Jun; Li, Yaqian; Chen, Jie

2015-01-01

Platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum was upregulated by the interaction of T. harzianum with maize roots or the foliar pathogen Curvularia lunata. PAF-AH was associated with chitinase and cellulase expressions, but especially with chitinase, because its activity in the KO40 transformant (PAF-AH disruption transformant) was lower, compared with the wild-type strain T28. The result demonstrated that the colonization of maize roots by T. harzianum induced systemic protection of leaves inoculated with C. lunata. Such protection was associated with the expression of inducible jasmonic acid pathway-related genes. Moreover, the data from liquid chromatography-mass spectrometry confirmed that the concentration of jasmonic acid in maize leaves was associated with the expression level of defense-related genes, suggesting that PAF-AH induced resistance to the foliar pathogen. Our findings showed that PAF-AH had an important function in inducing systemic resistance to maize leaf spot pathogen.

Platelet-activating factor dilates efferent arterioles through glomerulus-derived nitric oxide.

PubMed

Arima, S; Ren, Y; Juncos, L A; Ito, S

1996-01-01

Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation is poorly understood. It was recently reported that at picomolar concentrations, PAF dilates isolated microperfused afferent arterioles (Af-Art) via nitric oxide (NO). The present study tested the hypothesis that PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were perfused from the distal end (retrograde perfusion [RP]) to eliminate the influence of the glomerulus, or through the glomerulus from the end of the Af-Art (orthograde perfusion [OP]) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with norepinephrine and increasing doses of PAF were added to both the arteriolar perfusate and bath. Only with OP did PAF at picomolar concentrations cause significant dilation: at 400 pmol, the diameter increased by 64 +/- 11% from the preconstricted level (N = 6, P < 0.01). This dilation was completely abolished by pretreatment with an NO-synthesis inhibitor. To study its possible constrictor action, PAF was added to nonpreconstricted Ef-Art. At nanomolar concentrations, PAF constricted Ef-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P < 0.01) and 20 +/- 2% (N = 6, P < 0.01), respectively. This constriction was attenuated by pretreatment with indomethacin (Indo) in both RP (14 +/- 2%, N = 7; P < 0.02 versus without Indo) and OP (10 +/- 2%, N = 6; P < 0.02 versus without Indo). (1) at picomolar concentrations, PAF stimulates the glomerulus to release NO, which in turn dilates the Ef-Art; and (2) at nanomolar concentrations, PAF constricts the Ef-Art partly through release of cyclooxygenase metabolites. Thus, PAF may play a role in glomerular hemodynamics under various physiological and pathological conditions.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

PubMed

Oba, Kageyuki; Maeda, Minetaka; Maimaituxun, Gulinu; Yamaguchi, Satoshi; Arasaki, Osamu; Fukuda, Daiju; Yagi, Shusuke; Hirata, Yukina; Nishio, Susumu; Iwase, Takashi; Takao, Shoichiro; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Harada, Masafumi; Masuzaki, Hiroaki; Sata, Masataka; Shimabukuro, Michio

2018-05-25

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Platelet-activating factor drives eotaxin production in an allergic pleurisy in mice

PubMed Central

Klein, André; Pinho, Vanessa; Alessandrini, Ana Letícia; Shimizu, Takao; Ishii, Satoshi; Teixeira, Mauro M

2002-01-01

The activation of eosinophils via G-protein-coupled seven transmembran receptors play a necessary role in the recruitment of these cells into tissue. The present study investigates a role for PAF in driving eotaxin production and eosinophil recruitment in an allergic pleurisy model in mice. The intrapleural injection of increasing doses of PAF (10−11 to 10−9 moles per cavity) induced a dose- and PAF receptor-dependent recruitment of eosinophils 48 h after stimulation. Intrapleural injection of PAF induced the rapid (within 1 h) release of eotaxin into the pleural cavity of mice and an anti-eotaxin antibody effectively inhibited PAF-induced recruitment of eosinophils. Eosinophil recruitment in the allergic pleurisy was markedly inhibited by the PAF receptor antagonist UK-74,505 (modipafant, 1 mg kg−1). Moreover, recruitment of eosinophils in sensitized and challenged PAF receptor-deficient animals was lower than that observed in wild-type animals. Blockade of PAF receptors with UK-74,505 suppressed by 85% the release of eotaxin in the allergic pleurisy. Finally, the injection of a sub-threshold dose of PAF and eotaxin cooperated to induce eosinophil recruitment in vivo. In conclusion, the production of PAF in an allergic reaction could function in multiple ways to facilitate the recruitment of eosinophils  –  by facilitating eotaxin release and by cooperating with eotaxin to induce greater recruitment of eosinophils. PMID:11877329

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

PubMed

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1.

PubMed

Nimmakayala, Rama Krishna; Seshacharyulu, Parthasarathy; Lakshmanan, Imayavaramban; Rachagani, Satyanarayana; Chugh, Seema; Karmakar, Saswati; Rauth, Sanchita; Vengoji, Raghupathy; Atri, Pranita; Talmon, Geoffrey A; Lele, Subodh M; Smith, Lynette M; Thapa, Ishwor; Bastola, Dhundy; Ouellette, Michel M; Batra, Surinder K; Ponnusamy, Moorthy P

2018-06-01

Cigarette smoking is a major risk factor for pancreatic cancer. Aggressive pancreatic tumors contain cancer cells with stem cell features. We investigated whether cigarette smoke induces stem cell features in pancreatic cancer cells. Kras G12D ; Pdx1-Cre (KC) mice were exposed to cigarette smoke or clean air (controls) for up to 20 weeks; pancreata were collected and analyzed by histology, quantitative reverse transcription PCR, and confocal immunofluorescence microscopy. HPNE and Capan1 cells were exposed to cigarette smoke extract (CSE), nicotine and nicotine-derived carcinogens (NNN or NNK), or clean air (controls) for 80 days and evaluated for stem cell markers and features using flow cytometry-based autofluorescence, sphere formation, and immunoblot assays. Proteins were knocked down in cells with small interfering RNAs. We performed RNA sequencing analyses of CSE-exposed cells. We used chromatin immunoprecipitation assays to confirm the binding of FOS like 1, AP-1 transcription factor subunit (FOSL1) to RNA polymerase II-associated factor (PAF1) promoter. We obtained pancreatic ductal adenocarcinoma (PDAC) and matched non-tumor tissues (n=15) and performed immunohistochemical analyses. Chronic exposure of HPNE and Capan1 cells to CSE caused them to increase markers of stem cells, including autofluorescence and sphere formation, compared to control cells. These cells increased expression of ABCG2, SOX9 and PAF1, via cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) signaling to mitogen-activated protein kinase 1 and FOSL1. Pancreatic cell lines with knockdown of PAF1 did not develop features of stem cells upon exposure to CSE. Exposure of cells to NNN and NNK led to increased expression of CHRNA7, FOSL1, and PAF1 along with stem cell features. Pancreata from KC mice exposed to cigarette smoke had increased levels of PAF1 mRNA and protein, compared with control mice, as well as increased expression of SOX9. Levels of PAF1 and FOSL1 were increased in PDAC tissues, especially those from smokers, compared with non-tumor pancreatic tissue. CSE exposure increased expression of PHD finger protein 5A, a pluripotent transcription factor and its interaction with PAF1. Exposure to cigarette smoke activates stem cell features of pancreatic cells, via CHRNA7 signaling and FOSL1 activation of PAF1 expression. Levels of PAF1 are increased in pancreatic tumors of humans and mice with chronic cigarette smoke exposure. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Pettorossi, V E; Grassi, S

2001-01-01

In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

Low acylation stimulating protein levels are associated with cardiometabolic disorders–secondary to autoimmune activation?

PubMed Central

Onat, Altan; Altay, Servet; Yüksel, Murat; Karadeniz, Yusuf; Can, Günay; Yüksel, Hüsniye; Ademoğlu, Evin

2017-01-01

Objective: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. Methods: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as “healthy.” Results: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in “healthy” men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years’ follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles. Conclusion: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for “reduced” values and increased likelihood of cardiometabolic disorders. PMID:27599666

Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression.

PubMed

Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X; Walterscheid, Jeffrey P; Ullrich, Stephen E

2004-03-15

Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependent manner. The release of biological response modifiers, particularly prostaglandin E2 (PGE2), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE2 secretion. Jet fuel-induced PGE2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin.

Risk and protective factors for falls on stairs in young children: multicentre case–control study

PubMed Central

Kendrick, D; Zou, K; Ablewhite, J; Watson, M; Coupland, C; Kay, B; Hawkins, A; Reading, R

2016-01-01

Aim To investigate risk and protective factors for stair falls in children aged <5 years. Methods Multicentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. Results Cases’ most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). Conclusion Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries. PMID:26662926

Dietary supplementation with soybean lecithin increases pulmonary PAF bioactivity in asthmatic rats.

PubMed

Muehlmann, Luis A; Zanatta, Ana L; Farias, Carolina L A; Bieberbach, Eloyse W; Mazzonetto, Ana C; Michellotto, Pedro V; Fernandes, Luiz C; Nishiyama, Anita

2010-06-01

The prevalence of asthma has risen over the last few decades, and some studies correlate this with the greater consumption of polyunsaturated fatty acids (PUFAs). Dietary PUFAs are known to increase the susceptibility of biological structures to lipid peroxidation, a process by which platelet-activating factor (PAF)-like lipids can be generated. These lipids functionally mimic the bioactivity of PAF, a potent proinflammatory mediator that exerts several deleterious effects on asthma. Thus, this work aimed to investigate if dietary supplementation with soybean lecithin (SL), a source of PUFAs, increases lipid peroxidation and PAF bioactivity in lungs of asthmatic Wistar rats. Animals were separated into groups: control, supplemented, asthmatic, asthmatic supplemented with SL (2 g/kg body weight), asthmatic supplemented with SL (2 g/kg body weight) and DL-alpha-tocopheryl acetate (100 mg/kg body weight). Asthmatic inflammation increased pulmonary lipid peroxidation, PAF bioactivity, alveolar-capillary barrier permeability and production of nitric oxide. In asthmatics, dietary supplementation with SL promoted an increase in pulmonary lipid peroxidation and PAF bioactivity, and an increase in the permeability of the alveolar-capillary barrier. Moreover, the treatment of asthmatic rats with DL-alpha-tocopheryl acetate inhibited the lipid peroxidation and decreased the PAF bioactivity. Therefore, the increase in pulmonary PAF bioactivity in asthmatic individuals elicited by the dietary supplementation with SL probably involves the generation of PAF-like lipids. This finding suggests that PAF-like lipids may account for the deleterious effects of dietary PUFAs on asthma. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Lin; Hu, Kuan; Wang, Tong

Here, the human pathogen Mycobacterium tuberculosis ( Mtb) requires a proteasome system to cause lethal infections in mice. We recently found that proteasome accessory factor E (PafE, Rv3780) activates proteolysis by the Mtb proteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence of Mtb. Here, we show that PafE subunits formed four-helix bundles similar to those of the eukaryotic ATP-independent proteasome activator subunits of PA26 and PA28. However, unlike any other known proteasome activator, PafE formed dodecamers with 12-fold symmetry, which required a glycine-XXX-glycine-XXX-glycine motif that is not found in previously described activators. Intriguingly,more » the truncation of the PafE carboxyl-terminus resulted in the robust binding of PafE rings to native proteasome core particles and substantially increased proteasomal activity, suggesting that the extended carboxyl-terminus of this cofactor confers suboptimal binding to the proteasome core particle. Collectively, our data show that proteasomal activation is not limited to hexameric ATPases in bacteria.« less

Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis

DOE PAGES

Bai, Lin; Hu, Kuan; Wang, Tong; ...

2016-03-21

Here, the human pathogen Mycobacterium tuberculosis ( Mtb) requires a proteasome system to cause lethal infections in mice. We recently found that proteasome accessory factor E (PafE, Rv3780) activates proteolysis by the Mtb proteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence of Mtb. Here, we show that PafE subunits formed four-helix bundles similar to those of the eukaryotic ATP-independent proteasome activator subunits of PA26 and PA28. However, unlike any other known proteasome activator, PafE formed dodecamers with 12-fold symmetry, which required a glycine-XXX-glycine-XXX-glycine motif that is not found in previously described activators. Intriguingly,more » the truncation of the PafE carboxyl-terminus resulted in the robust binding of PafE rings to native proteasome core particles and substantially increased proteasomal activity, suggesting that the extended carboxyl-terminus of this cofactor confers suboptimal binding to the proteasome core particle. Collectively, our data show that proteasomal activation is not limited to hexameric ATPases in bacteria.« less

Exogenous platelet-activating factor improves the motility of human spermatozoa evaluated with C.A.S.A.: optimal concentration and incubation time.

PubMed

Grassi, G; Cappello, N; Gheorghe, M F; Salton, L; Di Bisceglie, C; Manieri, C; Benedetto, C

2010-11-01

The objective of this study is to determine the optimal conditions for human semen incubation treated with exogenous platelet activating factor (ePAF) for intra-uterine insemination (IUI). This prospective study was carried out on 32 infertile men and each semen sample was processed with the ISolate Sperm Separation Medium, washed with sperm washing medium (SWM) and resuspended either in SWM alone (control samples), or with ePAF 0.1, 0.5, and 1.0 μM. Each concentration was subsequently incubated and evaluated at 5, 15, 30, and 60 min. The motility parameters were evaluated by the computer-aided sperm analysis (C.A.S.A.) system. Curvilinear velocity, straight line velocity, average path velocity, rapid and progressive motility significantly increased compared to control samples at an ePAF concentration of 0.1 μM (with at least 15 min of incubation). The best results were obtained with ePAF concentrations of: 0.1 μM (60 min of incubation) and 0.5 μM (30-60 min of incubation). In conclusion, results are enhanced when ePAF is added to standard semen preparation for IUI. An ePAF concentration of 0.1 μM, with an incubation time of 15 min, can be used for semen samples with normal motility. Whilst, for semen samples with poor motility, the ePAF concentration is best increased to 0.5 μM and/or the incubation time prolonged to 60 min.

The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils

PubMed Central

Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-01-01

Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia–reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated. PMID:12871223

The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

PubMed

Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-08-01

Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated.

Clustering of risk factors and the risk of incident cardiovascular disease in Asian and Caucasian populations: results from the Asia Pacific Cohort Studies Collaboration

PubMed Central

Peters, Sanne A E; Wang, Xin; Lam, Tai-Hing; Kim, Hyeon Chang; Ho, Suzanne; Ninomiya, Toshiharu; Knuiman, Matthew; Vaartjes, Ilonca; Bots, Michael L; Woodward, Mark

2018-01-01

Objective To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster. Setting Asia Pacific Cohort Studies Collaboration. Participants Individual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline. Outcome measures Clusters were 11 possible combinations of four individual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol). Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with individual risk factors and risk factor clusters. Population-attributable fractions (PAFs) were calculated. Results During a mean follow-up of 7 years, 6203 CVD events were recorded. The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia; clusters including BP consistently showed the highest HRs and PAFs. The BP–smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ. Corresponding PAFs were 24% and 11%, respectively. For individuals with three risk factors, the BP–smoking–cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ). Corresponding PAFs were 13% and 10%. Conclusions Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations. Clusters including elevated BP were associated with the highest excess risk of CVD. PMID:29511013

Effect of platelet activating factor on endothelial permeability to plasma macromolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Handley, D.A.; Arbeeny, C.M.; Lee, M.L.

The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of /sup 125/I-albumin (6.7 nm), /sup 125/I-low density lipoproteins (22.0 nm) or /sup 125/I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest thatmore » PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins.« less

Inhibition of rabbit platelet activation in vitro by antagonists of platelet-activating factor (PAF)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, C.P.; Wood, K.L.

1986-03-05

The authors used washed, (/sup 3/H)serotonin-labeled rabbit platelets to study the in vitro aggregation and secretion responses induced by graded doses of PAF in the presence or absence of specific antagonists of PAF. These antagonists included CV-3988, L-652,731, triazolam and alprazolam. Platelets were pretreated with either an antagonist or the appropriate diluent for 60 sec prior to the addition of PAF (2 x 10/sup -10/ to 2 x 10/sup -7/ M). Aggregation was monitored continuously and recorded as the height of the aggregation tracing at 60 sec post-PAF. Secretion of (/sup 3/H)-serotonin was measured in a sample of the plateletsmore » removed at 60 sec post-PAF. When 2 x 10/sup -10/ M PAF was used as the stimulus, the concentration of antagonist needed for 50% inhibition (IC/sub 50/) of secretion was obtained at 0.05 ..mu..M, 0.15 ..mu..M, 0.6 ..mu..M and 2.5 ..mu..M, respectively, for L-652,731, CV-3988, triazolam and alprazolam. The corresponding IC/sub 50/ for aggregation was obtained at 0.2 ..mu..M, 0.1 ..mu..M, 1.5 ..mu..M and 6.5 ..mu..M, respectively. The inhibitory effects of these antagonists could be overcome by increasing the dose of PAF used. Although all of the antagonists were capable of completely inhibiting platelet aggregation and secretion, L-652,731 was the most potent PAF antagonist on a molar basis.« less

Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.

PubMed

Jocks, T; Freudenberg, J; Zahner, G; Stahl, R A

1998-01-01

These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.

Paf receptor expression in the marsupial embryo and endometrium during embryonic diapause.

PubMed

Fenelon, Jane C; Shaw, Geoff; O'Neill, Chris; Frankenberg, Stephen; Renfree, Marilyn B

2014-01-01

The control of reactivation from embryonic diapause in the tammar wallaby (Macropus eugenii) involves sequential activation of the corpus luteum, secretion of progesterone that stimulates endometrial secretion and subsequent changes in the uterine environment that activate the embryo. However, the precise signals between the endometrium and the blastocyst are currently unknown. In eutherians, both the phospholipid Paf and its receptor, platelet-activating factor receptor (PTAFR), are present in the embryo and the endometrium. In the tammar, endometrial Paf release in vitro increases around the time of the early progesterone pulse that occurs around the time of reactivation, but whether Paf can reactivate the blastocyst is unknown. We cloned and characterised the expression of PTAFR in the tammar embryo and endometrium at entry into embryonic diapause, during its maintenance and after reactivation. Tammar PTAFR sequence and protein were highly conserved with mammalian orthologues. In the endometrium, PTAFR was expressed at a constant level in the glandular epithelium across all stages and in the luminal epithelium during both diapause and reactivation. Thus, the presence of the receptor appears not to be a limiting factor for Paf actions in the endometrium. However, the low levels of PTAFR in the embryo during diapause, together with its up-regulation and subsequent internalisation at reactivation, supports earlier results suggesting that endometrial Paf could be involved in reactivation of the tammar blastocyst from embryonic diapause.

Platelet Activating Factor: A Growth Factor for Breast Cancer

DTIC Science & Technology

2006-09-01

synthase (ADS) increases ether lipid content, growth and PAF synthesis in MCF-7 cells. 4. Eicosapentaenoic acid (EPA) inhibits the synthesis of PAF...Schmitt, J. D., Bullock, B. C. Wykle, R. L. Reacylation of platelet activating factor with eicosapentaenoic acid in fish-oil-enriched monkey...breast cancer. Recent studies have shown that the ratio of two families of essential fatty acids is important in regulating many cellular processes

Antibronchospastic activity of MEN10,627, a novel tachykinin NK2 receptor antagonist, in guinea-pig airways.

PubMed

Perretti, F; Ballati, L; Manzini, S; Maggi, C A; Evangelista, S

1995-01-24

The antibronchospastic activity against acetylcholine, antigen, histamine plus platelet-activating factor (PAF) or the selective tachykinin neurokinin (NK)1 and NK2 receptor agonists of the novel tachykinin NK2 receptor antagonist, MEN10,627 (cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)), was studied in anesthetized guinea-pigs. MEN10,627 (30-100 nmol/kg i.v.) reduced in a dose-dependent manner the bronchospasm induced by the tachykinin NK2 receptor agonist [beta Ala8]neurokinin A-(4-10) and the effect of the highest dose lasted up to 5 h from its administration. Conversely, airway constriction induced by the NK1 receptor agonist [Sar9]substance P sulfone or acetylcholine was unaffected by MEN10,627 up to a dose of 3 mumol/kg i.v. In animals sensitized with ovalbumin and pretreated with the endopeptidase inhibitor phosphoramidon, the aerosolized antigen produced a bronchospasm which was inhibited by MEN10,627 (30-100 nmol/kg i.v.) but not by the tachykinin NK1 receptor antagonist, (+/-)-CP96,345 ([2R,3R-cis- and [2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine]) (3 mumol/kg i.v.). Both MEN10,627 (30-100 nmol/kg i.v.) and (+/-)-CP96,345 (30-300 nmol/kg i.v.) reduced the PAF-induced hyperresponsiveness to histamine, without affecting the hypotension induced by PAF or the bronchospasm induced by histamine in guinea-pigs not exposed to PAF, showing the involvement of both tachykinin NK1 and NK2 receptors in this model. In summary, MEN10,627 behaves as a potent, selective and long-lasting tachykinin NK2 receptor antagonist in vivo. Further, tachykinin NK2 receptors could be activated during allergic responses and in the development of airway hyperresponsiveness.

Crystallographic analysis of the conserved C-terminal domain of transcription factor Cdc73 from Saccharomyces cerevisiae reveals a GTPase-like fold.

PubMed

Chen, Hongkai; Shi, Nuo; Gao, Yongxiang; Li, Xu; Teng, Maikun; Niu, Liwen

2012-08-01

The yeast Paf1 complex (Paf1C), which is composed of the proteins Paf1, Cdc73, Ctr9, Leo1 and Rtf1, accompanies RNA polymerase II from the promoter to the 3'-end formation site of mRNA- and snoRNA-encoding genes. As one of the first identified subunits of Paf1C, yeast Cdc73 (yCdc73) takes part in many transcription-related processes, including binding to RNA polymerase II, recruitment and activation of histone-modification factors and communication with other transcriptional activators. The human homologue of yCdc73, parafibromin, has been identified as a tumour suppressor linked to breast, renal and gastric cancers. However, the functional mechanism of yCdc73 has until recently been unclear. Here, a 2.2 Å resolution crystal structure of the highly conserved C-terminal region of yCdc73 is reported. It revealed that yCdc73 appears to have a GTPase-like fold. However, no GTPase activity was observed. The crystal structure of yCdc73 will shed new light on the modes of function of Cdc73 and Paf1C.

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PubMed

Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

1981-12-01

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

A cross-ethnic comparison on incidence of suicide.

PubMed

Liu, I C; Liao, S F; Lee, W C; Kao, C Y; Jenkins, R; Cheng, A T A

2011-06-01

Suicide rates vary widely across nations and ethnic groups. This study aims to explore potential factors contributing to inter-ethnic differences in suicide rates. Study subjects came from a case-control psychological autopsy study conducted in Taiwan, including 116 consecutive suicides from two aboriginal groups and Taiwanese Han; 113 of them each matched with two living controls. Gender-, age- and method-specific suicide rates, population attributable fraction (PAF) of suicide for five major risk factors, help-seeking before suicide and emergency medical aid after suicide were compared between the three ethnic groups. One aboriginal group (the Atayal) had significantly higher adjusted rate ratios (RR) of suicide than the other aboriginal group (the Ami) [RR 0.20, 95% confidence intervals (CI) 0.12-0.34] and the Han (RR 0.26, 95% CI 0.16-0.40). Such differences can be explained by higher PAFs of suicide for three major risk factors (substance dependence, PAF 47.6%, 95% CI 25.5-64.2; emotionally unstable personality disorder, PAF 52.7%, 95% CI 32.8-69.0; family history of suicidal behaviour, PAF 43.5%, 95% CI 23.2-60.2) in this group than in the other two groups. This higher suicide rate was substantially reduced from 68.2/100 000 per year to 9.1/100 000 per year, comparable with the other two groups, after stepwise removal of the effects of these three risk factors. Suicide rates by self-poisoning were also significantly higher in this group than in the other two groups. Higher rates of specific risk factors and use of highly lethal pesticides for suicide contributed to the higher suicide rate in one ethnic group in Taiwan. These findings have implications for developing ethnicity-relevant suicide prevention strategies.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

PubMed Central

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

PubMed

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.

PubMed

Goyal, J; Wang, K; Liu, M; Subbaiah, P V

1997-06-27

Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia.

PubMed

Krishnamurthy, Sateesh; Behlke, Mark A; Apicella, Michael A; McCray, Paul B; Davidson, Beverly L

2014-07-15

Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells.

A role for the RNA pol II–associated PAF complex in AID-induced immune diversification

PubMed Central

Willmann, Katharina L.; Milosevic, Sara; Pauklin, Siim; Schmitz, Kerstin-Maike; Rangam, Gopinath; Simon, Maria T.; Maslen, Sarah; Skehel, Mark; Robert, Isabelle; Heyer, Vincent; Schiavo, Ebe; Reina-San-Martin, Bernardo

2012-01-01

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions. PMID:23008333

CryoPAF4: a cryogenic phased array feed design

NASA Astrophysics Data System (ADS)

Locke, Lisa; Garcia, Dominic; Halman, Mark; Henke, Doug; Hovey, Gary; Jiang, Nianhua; Knee, Lewis; Lacy, Gordon; Loop, David; Rupen, Michael; Veidt, Bruce; Wierzbicki, Ramunas

2016-07-01

Phased array feed (PAF) receivers used on radio astronomy telescopes offer the promise of increased fields of view while maintaining the superlative performance attained with traditional single pixel feeds (SPFs). However, the much higher noise temperatures of room temperature PAFs compared to cryogenically-cooled SPFs have prevented their general adoption. Here we describe a conceptual design for a cryogenically cooled 2.8 - 5.18 GHz dual linear polarization PAF with estimated receiver temperature of 11 K. The cryogenic PAF receiver will comprise a 140 element Vivaldi antenna array and low-noise amplifiers housed in a 480 mm diameter cylindrical dewar covered with a RF transparent radome. A broadband two-section coaxial feed is integrated within each metal antenna element to withstand the cryogenic environment and to provide a 50 ohm impedance for connection to the rest of the receiver. The planned digital beamformer performs digitization, frequency band selection, beam forming and array covariance matrix calibration. Coupling to a 15 m offset Gregorian dual-reflector telescope, cryoPAF4 can expect to form 18 overlapping beams increasing the field of view by a factor of 8x compared to a single pixel receiver of equal system temperature.

Estimating the attributable fraction for melanoma: a meta-analysis of pigmentary characteristics and freckling.

PubMed

Olsen, Catherine M; Carroll, Heidi J; Whiteman, David C

2010-11-15

Epidemiologic research has demonstrated convincingly that certain pigmentary characteristics are associated with increased relative risks of melanoma; however there has been no comprehensive review to rank these characteristics in order of their importance on a population level. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of pigmentary characteristics to melanoma, estimated by the population-attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and hair colour, eye colour, skin phototype and presence of freckling; we identified 66 such studies using citation databases, followed by manual review of retrieved references. We calculated summary relative risks using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. The pooled RRs for pigmentary characteristics were: 2.64 for red/red-blond, 2.0 for blond and 1.46 for light brown hair colour (vs. dark); 1.57 for blue/blue-grey and 1.51 for green/grey/hazel eye colour (vs. dark); 2.27, 1.99 and 1.35 for skin phototypes I, II and III respectively (vs. IV); and 1.99 for presence of freckling. The highest PAFs were observed for skin phototypes 1/II (0.27), presence of freckling (0.23), and blond hair colour (0.23). For eye colour, the PAF for blue/blue-grey eye colour was higher than for green/grey/hazel eye colour (0.18 vs. 0.13). The PAF of melanoma associated with red hair colour was 0.10. These estimates of melanoma burden attributable to pigmentary characteristics provide a basis for designing prevention strategies for melanoma.

Population attributable fraction of type 2 diabetes due to physical inactivity in adults: a systematic review.

PubMed

Al Tunaiji, Hashel; Davis, Jennifer C; Mackey, Dawn C; Khan, Karim M

2014-05-18

Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic review was to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sport participation or exercise for men and women. We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screened studies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs for studies missing these data using a substitution method. Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) and six were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM and adjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women. The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factor for T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity is defined as the absence of 'sport' or absence of 'exercise'.

Occupational Burden of Cancer in Korea

PubMed Central

Lee, Hye-Eun; Kang, Seong-Kyu

2010-01-01

Objectives The extent of the occupational cancer burden has rarely been estimated in Korea. The aim of this study is to provide an estimation of the population attributable fraction (PAF) of occupational cancer in Korea. Methods Nine kinds of Group 1 carcinogens addressed by the International Agency for Research on Cancer (IARC) and 7 kinds of cancer were selected for the target carcinogens and diseases, respectively. The prevalence of carcinogen-exposed workers was estimated and correction factors were applied so that the value would be representative of the total population. Data on relative risk (RR) were taken from IARC reports and were compared with the RRs from the studies on Korean workers. The PAF was estimated according to Levin's formula. Results The proportion of the general Korean population exposed to carcinogens was 9.7%. The PAF of total cancer was 1.1% for incident cancer cases and 1.7% for cancer deaths. The PAFs of lung cancer and leukemia were 7.0% and 4.%, respectively. With the RRs reported from Korean studies, the PAF for lung cancer and leukemia were 3.7% and 3.4%, respectively. Conclusion The PAF in this study (1.1%) was lower than that reported in previous studies (2-4%) from developed countries. Considering that only 9 of the 29 kinds of Group 1 carcinogens were included in this study, the PAF might be underestimated. However, because the process of industrialization in Korea differs from that which occurred in other developed countries, 1.1% of the PAF might be appropriate for Korea. PMID:22953164

25 CFR 170.221 - What funding is available for distribution using the PAF?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false What funding is available for distribution using the PAF? 170.221 Section 170.221 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor...

25 CFR 170.221 - What funding is available for distribution using the PAF?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false What funding is available for distribution using the PAF? 170.221 Section 170.221 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor...

25 CFR 170.221 - What funding is available for distribution using the PAF?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What funding is available for distribution using the PAF? 170.221 Section 170.221 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor...

25 CFR 170.221 - What funding is available for distribution using the PAF?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false What funding is available for distribution using the PAF? 170.221 Section 170.221 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor...

25 CFR 170.221 - What funding is available for distribution using the PAF?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true What funding is available for distribution using the PAF? 170.221 Section 170.221 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor...

Premenstrual syndrome and fibromyalgia: the frequency of the coexistence and their effects on quality of life.

PubMed

Soyupek, Feray; Aydogan, Cigdem; Guney, Mehmet; Kose, Seyit Ali

2017-07-01

We aimed to investigate the association between Premenstrual syndrome (PMS) and fibromyalgia syndrome (FMS), to assess common symptoms and quality of life (QOL) of them. Patients with PMS formed the PMS group and age-matched healthy normal controls were included in the control group. The diagnosis of the FMS and PMS were based on new American College of Rheumatology FMS criteria and DSM-IV PMS criteria. FMS-related symptoms assessed by visual analog scale and number of tender points (TePs) were analyzed. QOL, PMS severity and FMS severity were assessed with SF-36, fibromyalgia impact questionnaire (FIQ) and premenstrual assessment form (PAF), respectively. Patients with PMS were divided into two subgroups according to coexistence of FMS or not. The frequency of FMS in PMS and control group were 20 and 0%, respectively (p = 0.002). FMS-related symptoms, number of TePs in the PMS group were higher than those in the control group. The mean mental component summary (MCS) score of SF-36 was low in the PMS group. The mean PAF score in PMS with FMS subgroup was higher than those in without FMS subgroup. The mean physical component summary of SF-36 was low in the PMS patient with FMS. There was correlation between PAF score and FIQ score (r = 0.476, p < 0.001). FMS was common among the patients with PMS and frequently seen in the PMS patients having severe premenstrual complaints. Mental QOL was distressed in the patients with PMS but while FMS accompanied to PMS, the physical QOL was decreased.

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

PubMed Central

Krishnamurthy, Sateesh; Behlke, Mark A; Apicella, Michael A; McCray, Paul B; Davidson, Beverly L

2014-01-01

Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells. PMID:25025465

Differential inhibitory effects of 2-azafluorenones on PI-PLC activation but not on PC-PLC- or PC-PLD-activation induced by histamine, PAF, PMA or A23187 in C6 glioma cells.

PubMed

Wang, Hai-Long; Wang, Li-Chuan; Wei, Jiann-Wu

2013-02-28

In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [³H]-labeled inositol phosphate (IP1) formation by histamine (100 μM) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 μM of 2-azafluorenones. Histamine induced the increase of IP1 formation, but failed to cause an increase in extracellularly releasing of [3H]choline metabolites, or intracellular accumulation of [³H]phosphscholine. However, platelet activation factor (PAF) from 0.2 to 1 μM, and phorbol 12-myristate-13-acetate (PMA) at 1 μM caused an increase in extracellularly releasing of [³H]choline metabolites, and intracellular accumulation of [³H]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at high concentration (10⁻⁴ M). A23187 induced an increase of intracellular [³H]choline release via the activation of PCphospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at a high concentration of 10⁻⁴ M. In summary, the inhibitory effect of 2-azafluorenone and its related compound 4-methyl-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.

The potential impact of a social redistribution of specific risk factors on socioeconomic inequalities in mortality: illustration of a method based on population attributable fractions.

PubMed

Hoffmann, Rasmus; Eikemo, Terje Andreas; Kulhánová, Ivana; Dahl, Espen; Deboosere, Patrick; Dzúrová, Dagmar; van Oyen, Herman; Rychtaríková, Jitka; Strand, Bjørn Heine; Mackenbach, Johan P

2013-01-01

Socioeconomic differences in health are a major challenge for public health. However, realistic estimates to what extent they are modifiable are scarce. This problem can be met through the systematic application of the population attributable fraction (PAF) to socioeconomic health inequalities. The authors used cause-specific mortality data by educational level from Belgium, Norway and Czech Republic and data on the prevalence of smoking, alcohol, lack of physical activity and high body mass index from national health surveys. Information on the impact of these risk factors on mortality comes from the epidemiological literature. The authors calculated PAFs to quantify the impact on socioeconomic health inequalities of a social redistribution of risk factors. The authors developed an Excel tool covering a wide range of possible scenarios and the authors compare the results of the PAF approach with a conventional regression. In a scenario where the whole population gets the risk factor prevalence currently seen among the highly educated inequalities in mortality can be reduced substantially. According to the illustrative results, the reduction of inequality for all risk factors combined varies between 26% among Czech men and 94% among Norwegian men. Smoking has the highest impact for both genders, and physical activity has more impact among women. After discussing the underlying assumptions of the PAF, the authors concluded that the approach is promising for estimating the extent to which health inequalities can be potentially reduced by interventions on specific risk factors. This reduction is likely to differ substantially between countries, risk factors and genders.

Hydrolysis of platelet-activating factor by human serum paraoxonase.

PubMed Central

Rodrigo, L; Mackness, B; Durrington, P N; Hernandez, A; Mackness, M I

2001-01-01

Human serum paraoxonase (human PON1) has been shown to be important in the metabolism of phospholipid and cholesteryl ester hydroperoxides, thereby preventing the oxidation of low-density lipoprotein (LDL) and retarding atherogenesis. However, the exact substrate specificity of PON1 has not been established. In the present study we show that purified PON1 hydrolyses platelet-activating factor (PAF). We could find no evidence for contamination of our preparation with authentic platelet-activating-factor acetylhydrolase (PAFAH) by immunoblotting with a PAFAH monoclonal antibody or by sequencing the purified protein. In addition the specific PAFAH inhibitor SB-222657 did not affect the ability of PON1 to hydrolyse PAF (30.1+/-2.8 micromol/min per mg of protein with no inhibitor; 31.4+/-2.2 micromol/min per mg of protein with 100 nM inhibitor) or phenyl acetate (242.6+/-30.8 versus 240.8+/-31.5 micromol/min per mg of protein with and without inhibitor respectively). SB-222657 was also unable to inhibit PAF hydrolysis by isolated human high-density lipoprotein (HDL), but completely abolished the activity of human LDL. Ostrich (Struthio camelus) HDL, which does not contain PON1, was unable to hydrolyse PAF. These data provide evidence that PON1 may limit the action of this bioactive pro-inflammatory phospholipid. PMID:11171072

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

PubMed Central

2010-01-01

Background Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Methods Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Results Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. Conclusions We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours. PMID:20465821

Evidence for Lipid Packaging in the Crystal Structure of the GM2-Activator Complex with Platelet Activating Factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Christine S.; Mi, Li-Zhi; Rastinejad, Fraydoon

2010-11-16

GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2 {angstrom} crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement ofmore » two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.« less

On estimation of time-dependent attributable fraction from population-based case-control studies.

PubMed

Zhao, Wei; Chen, Ying Qing; Hsu, Li

2017-09-01

Population attributable fraction (PAF) is widely used to quantify the disease burden associated with a modifiable exposure in a population. It has been extended to a time-varying measure that provides additional information on when and how the exposure's impact varies over time for cohort studies. However, there is no estimation procedure for PAF using data that are collected from population-based case-control studies, which, because of time and cost efficiency, are commonly used for studying genetic and environmental risk factors of disease incidences. In this article, we show that time-varying PAF is identifiable from a case-control study and develop a novel estimator of PAF. Our estimator combines odds ratio estimates from logistic regression models and density estimates of the risk factor distribution conditional on failure times in cases from a kernel smoother. The proposed estimator is shown to be consistent and asymptotically normal with asymptotic variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimator performs well in finite sample sizes. Finally, the method is illustrated by a population-based case-control study of colorectal cancer. © 2017, The International Biometric Society.

S-nitrosylation of VASP at cysteine 64 mediates the inflammation-stimulated increase in microvascular permeability.

PubMed

Zamorano, Patricia; Marín, Natalie; Córdova, Francisco; Aguilar, Alejandra; Meininger, Cynthia; Boric, Mauricio P; Golenhofen, Nikola; Contreras, Jorge E; Sarmiento, José; Durán, Walter N; Sánchez, Fabiola A

2017-07-01

We tested the hypothesis that platelet-activating factor (PAF) induces S -nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S -nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S -nitrosylation of VASP in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Reconstitution of VASP knockout myocardial endothelial cells with cysteine mutants of VASP demonstrated that S -nitrosylation of cysteine 64 is associated with PAF-induced hyperpermeability. We propose that regulation of VASP contributes to endothelial cell barrier integrity and to the onset of hyperpermeability. S -nitrosylation of VASP inhibits its function in barrier integrity and leads to endothelial monolayer hyperpermeability in response to PAF, a representative proinflammatory agonist. NEW & NOTEWORTHY Here, we demonstrate that S -nitrosylation of vasodilator-stimulated phosphoprotein (VASP) on C64 is a mechanism for the onset of platelet-activating factor-induced hyperpermeability. Our results reveal a dual role of VASP in endothelial permeability. In addition to its well-documented function in barrier integrity, we show that S -nitrosylation of VASP contributes to the onset of endothelial permeability. Copyright © 2017 the American Physiological Society.

Novel enzymatic method for assaying Lp-PLA2 in serum.

PubMed

Yamaura, Saki; Sakasegawa, Shin-Ichi; Koguma, Emisa; Ueda, Shigeru; Kayamori, Yuzo; Sugimori, Daisuke; Karasawa, Ken

2018-06-01

Measurement of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) can be used as an adjunct to traditional cardiovascular risk factors for identifying individuals at higher risk of cardiovascular events. This can be performed by quantification of the protein concentration using an ELISA platform or by measuring Lp-PLA 2 activity using platelet-activating factor (PAF) analog as substrate. Here, an enzymatic Lp-PLA 2 activity assay method using 1-O-Hexadecyl-2-acetyl-rac-glycero-3-phosphocholine (rac C 16 PAF) was developed. The newly revealed substrate specificity of lysoplasmalogen-specific phospholipase D (lysophospholipase D (LysoPLD)) was exploited. Lp-PLA 2 hydrolyzes 1-O-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C 16 PAF) to 1-O-Hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (LysoPAF). LysoPLD acted on LysoPAF, and the hydrolytically released choline was detected by choline oxidase. Regression analysis of Lp-PLA 2 activity measured by the enzymatic Lp-PLA 2 activity assay vs. two chemical Lp-PLA 2 activity assays, i.e. LpPLA 2 FS and PLAC® test, and ELISA, gave the following correlation coefficients: 0.990, 0.893 and 0.785, respectively (n = 30). Advantages of this enzymatic Lp-PLA 2 activity assay compared with chemical Lp-PLA 2 methods include the following; (i) only requires two reagents enabling a simple two-point linear calibration method with one calibrator (ii) no need for inhibitors of esterase-like activity in serum. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk factors for stillbirth in developing countries: a systematic review of the literature.

PubMed

Di Mario, Simona; Say, Lale; Lincetto, Ornella

2007-07-01

To identify risk factors for stillbirth in developing countries and to measure their impact by calculating the population attributable fraction (PAF) for each risk factor. Systematic review of published studies on risk factors for stillbirth within 3 broadly defined categories: infections, other clinical conditions, and context-dependent conditions such as socioeconomic status, maternal literacy, and receipt of antenatal care. Where statistically significant associations were found between a risk factor and occurrence of stillbirth, the PAF (the proportion of cases occurring in the total population that would be avoided if the exposure was removed) was calculated. A total of 33 studies, conducted in 31 developing countries, were included in the review. The definition of stillbirth varied widely in these studies. Risk factors for stillbirth having a PAF higher than 50% were maternal syphilis, chorioamnionitis, maternal malnutrition, lack of antenatal care, and maternal socioeconomic disadvantage. Maternal syphilis prevention, screening and treatment together with other interventions targeting universal use of antenatal care (that includes screening for syphilis) and improving the socioeconomic conditions including nutritional status of the mother, could effectively contribute towards reducing the unacceptably high burden due to stillbirth in developing countries.

Mutants of the Paf1 Complex Alter Phenotypic Expression of the Yeast Prion [PSI+

PubMed Central

Strawn, Lisa A.; Lin, Changyi A.; Tank, Elizabeth M.H.; Osman, Morwan M.; Simpson, Sarah A.

2009-01-01

The yeast [PSI+] prion is an epigenetic modifier of translation termination fidelity that causes nonsense suppression. The prion [PSI+] forms when the translation termination factor Sup35p adopts a self-propagating conformation. The presence of the [PSI+] prion modulates survivability in a variety of growth conditions. Nonsense suppression is essential for many [PSI+]-mediated phenotypes, but many do not appear to be due to read-through of a single stop codon, but instead are multigenic traits. We hypothesized that other global mechanisms act in concert with [PSI+] to influence [PSI+]-mediated phenotypes. We have identified one such global regulator, the Paf1 complex (Paf1C). Paf1C is conserved in eukaryotes and has been implicated in several aspects of transcriptional and posttranscriptional regulation. Mutations in Ctr9p and other Paf1C components reduced [PSI+]-mediated nonsense suppression. The CTR9 deletion also alters nonsense suppression afforded by other genetic mutations but not always to the same extent as the effects on [PSI+]-mediated read-through. Our data suggest that the Paf1 complex influences mRNA translatability but not solely through changes in transcript stability or abundance. Finally, we demonstrate that the CTR9 deletion alters several [PSI+]-dependent phenotypes. This provides one example of how [PSI+] and genetic modifiers can interact to uncover and regulate phenotypic variability. PMID:19225160

Complexity and spectral analysis of the heart rate variability dynamics for distant prediction of paroxysmal atrial fibrillation with artificial intelligence methods.

PubMed

Chesnokov, Yuriy V

2008-06-01

Paroxysmal atrial fibrillation (PAF) is a serious arrhythmia associated with morbidity and mortality. We explore the possibility of distant prediction of PAF by analyzing changes in heart rate variability (HRV) dynamics of non-PAF rhythms immediately before PAF event. We use that model for distant prognosis of PAF onset with artificial intelligence methods. We analyzed 30-min non-PAF HRV records from 51 subjects immediately before PAF onset and at least 45min distant from any PAF event. We used spectral and complexity analysis with sample (SmEn) and approximate (ApEn) entropies and their multiscale versions on extracted HRV data. We used that features to train the artificial neural networks (ANNs) and support vector machine (SVM) classifiers to differentiate the subjects. The trained classifiers were further tested for distant PAF event prognosis on 16 subjects from independent database on non-PAF rhythm lasting from 60 to 320 min before PAF onset classifying the 30-min segments as distant or leading to PAF. We found statistically significant increase in 30-min non-PAF HRV recordings from 51 subjects in the VLF, LF, HF bands and total power (p<0.0001) before PAF event compared to PAF distant ones. The SmEn and ApEn analysis provided significant decrease in complexity (p<0.0001 and p<0.001) before PAF onset. For training ANN and SVM classifiers the data from 51 subjects were randomly split to training, validation and testing. ANN provided better results in terms of sensitivity (Se), specificity (Sp) and positive predictivity (Pp) compared to SVM which became biased towards positive case. The validation results of the ANN classifier we achieved: Se 76%, Sp 93%, Pp 94%. Testing ANN and SVM classifiers on 16 subjects with non-PAF HRV data preceding PAF events we obtained distant prediction of PAF onset with SVM classifier in 10 subjects (58+/-18 min in advance). ANN classifier provided distant prediction of PAF event in 13 subjects (62+/-21 min in advance). From the results of distant PAF prediction we conclude that ANN and SVM classifiers learned the changes in the HRV dynamics immediately before PAF event and successfully identified them during distant PAF prognosis on independent database. This confirms the reported in the literature results that corresponding changes in the HRV data occur about 60 min before PAF onset and proves the possibility of distant PAF prediction with ANN and SVM methods.

Functional significance of differential eNOS translocation

PubMed Central

Sánchez, Fabiola A.; Savalia, Nirav B.; Durán, Ricardo G.; Lal, Brajesh K.; Boric, Mauricio P.; Durán, Walter N.

2006-01-01

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation. PMID:16679407

HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

PubMed

Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

2007-02-19

To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

Picomolar platelet-activating factor mobilizes Ca to change platelet shape without activating phospholipase C or protein kinase C; simultaneous fluorometric measurement of intracellular free Ca concentration and aggregation.

PubMed

James-Kracke, M R; Sexe, R B; Shukla, S D

1994-11-01

The purpose of this study was to investigate signal transduction mechanisms activated by low and high concentrations of platelet-activating factor (PAF) in rabbit platelets and to contrast the responses to those induced by thrombin. We measured changes in intracellular free calcium ([Ca++]i) with fura2, while monitoring light scatter simultaneously as a measure of shape change and aggregation in a dual-excitation dual-emission spectrofluorometer. An abrupt 20% fall in light scatter, coincident with the peak of the [Ca++]i, indicated shape change in Ca-containing or Ca-free medium and was blocked by BAPTA loading and 10 microM cytochalasin B. A secondary decline in light scatter, indicating aggregation, occurred only in Ca-containing medium and only under conditions favoring protein kinase C (PKC) activation. PAF at 10(-12) M did not increase 1,4,5-inositol triphosphate content, which suggested PKC would not be activated. However, PAF at 10(-12) rapidly increased [Ca++]i to 900 nM in 7 sec seemingly by Ca influx through receptor-operated channels inducing shape change. PAF at 10(-9) and 10(-8) M increased [Ca++]i to 2 microM in 12 sec and induced both shape change and aggregation. However, in platelets pretreated with 100 nM staurosporine to inhibit protein kinases, 10(-9) M PAF did not cause aggregation even though [Ca++]i still rose to 2 microM, which indicated that PKC plays a role in aggregation but not in Ca++ mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate.

PubMed

Violi, F; Alessandri, C; Praticò, D; Guzzo, A; Ghiselli, A; Balsano, F

1989-06-15

The effect of acetylsalicylic acid (ASA) on platelet aggregation (PA) and thromboxane A2 (TxA2) formation was investigated in vitro and ex vivo after 1 g or 300 mg ASA administration to healthy subjects. 50-100 microM ASA inhibited PA by single aggregating agent such as platelet aggregating factor (PAF) or epinephrine and reduced to less than or equal to 5% of control platelet TxB2 formation, but did not influence PA by epinephrine plus PAF. The latter was inhibited by increasing ASA concentration. In samples incubated with 100 microM ASA and stimulated with epinephrine plus PAF, PA could be inhibited by the addition of 100-300 microM sodium salicylate. After 300 mg-1 g ASA administration to healthy subjects, the inhibition of PA by epinephrine plus PAF was more marked by highest doses of ASA. This study suggests that aspirin inhibits PA with a cyclooxygenase-independent mechanism; this effect is mediated, at least in vitro, by salicylic acid.

TGF-β1/FGF-2 signaling mediates the 15-HETE-induced differentiation of adventitial fibroblasts into myofibroblasts.

PubMed

Zhang, Li; Chen, Yan; Li, Guixia; Chen, Minggang; Huang, Wei; Liu, Yanrui; Li, Yumei

2016-01-05

Pulmonary adventitial fibroblasts (PAFs) are activated under stress stimuli leading to their differentiation into myofibroblasts, which is involved in vessel remodeling. 15-HETE is known as an important factor in vessel remodeling under hypoxia; however, the role of 15-HETE in PAF phenotypic alteration is not clear. The effect of 15-HETE on PAF phenotypic alterations was investigated in the present study. PAFs were treated with 15-HETE (0.5 μM) for 24 h, and the myofibroblast marker α-smooth muscle actin (α-SMA) was analyzed. The 15-HETE induced α-SMA expression and cell morphology. 15-HETE upregulated FGF-2 levels in PAFs, and knockdown FGF-2 by siRNAs blocked the enhanced α-SMA expression induced by 15-HETE. p38 kinase was activated, and blocked depressed 15-HETE-induced FGF-2 expression. The downstream of p38 pathway, Egr-1 activation, was also raised by 15-HETE treatment, and silenced Egr-1 suppressed the 15-HETE-induced upregulation of FGF-2. TGF-β1 was upregulated with FGF-2 treatment, and α-SMA expression induced by FGF-2 was inhibited after the cell was transferred with TGF-β1 siRNA. Meanwhile, FGF-2 increased α-SMA expression and improved proliferation, which was associated with p27(kip1) and cyclin E variation. The above results suggest that p38/Egr-1 pathway-mediated FGF-2 is involved in 15-HETE-induced differentiation of PAFs into myofibroblasts and cell proliferation.

Independent regulation of periarteriolar and perivenular nitric oxide mechanisms in the in vivo hamster cheek pouch microvasculature

PubMed Central

Kim, David D.; Kanetaka, Takehito; Durán, Ricardo G.; Sánchez, Fabiola A.; Bohlen, H Glenn; Durán, Walter N.

2011-01-01

Objective We tested the hypothesis that differential stimulation of nitric oxide (NO) production can be induced in pre- and postcapillary segments of the microcirculation in the hamster cheek pouch. Methods We applied acetylcholine (ACh) or platelet-activating factor (PAF) topically and measured perivascular NO concentration ([NO]) with NO-sensitive microelectrodes in arterioles and venules of the hamster cheek pouch. We also measured NO in cultured coronary endothelial cells (CVEC) after ACh or PAF. Results ACh increased periarteriolar [NO] significantly in a dose-dependent manner. ACh at 1 μM increased [NO] from 438.1±43.4 nM at baseline to 647.9±66.3 nM, while 10 μM ACh increased [NO] from baseline to 1035.0±59.2 nM (P < 0.05). Neither 1 μM nor 10 μM ACh changed perivenular [NO] in the hamster cheek pouch. PAF, at 100 nM, increased perivenular [NO] from 326.6±50.8 nM to 622.8±41.5 nM. Importantly, 100 nM PAF did not increase periarteriolar [NO]. PAF increased [NO] from 3.6 ± 2.1 to 455.5 ± 19.9 in CVEC, while ACh had no effect. Conclusions We conclude that NO production can be stimulated in a differential manner in preand postcapillary segments in the hamster cheek pouch. ACh selectively stimulates the production of NO only in arterioles, while PAF stimulates the production of NO only in venules. PMID:19235626

KF19514, a phosphodieterase 4 and 1 inhibitor, inhibits PAF-induced lung inflammatory responses by inhaled administration in guinea pigs.

PubMed

Manabe, H; Akuta, K; Okamura, K; Ohmori, K

1997-12-01

Phosphodiesterase (PDE) 4 inhibitors are well known for their inhibitory effect on bronchoconstriction and inflammation and may be promising anti-asthma drugs. Platelet-activating factor (PAF) has been proposed as an inflammatory mediator to be relevant to asthma. It causes bronchoconstriction, airway microvascular leakage, inflammatory cell accumulation in the lung and hyperresponsiveness. In this study, we therefore have investigated the anti-asthmatic effects of the inhaled KF19514 [5-phenyl-3'-(3-pyridyl)methyl-3H-imidazo(4,5-c)(1,8) naphthyridin-4(5H)-one], a PDE 4 and 1 inhibitor, on PAF-induced lung inflammatory responses in guinea pigs. The inhaled KF19514 (0.0001-0.01%) significantly inhibited PAF-induced eosinophil and neutrophil accumulation into the airway and hyperresponsiveness in guinea pigs. The IC50 value of KF19514 against eosinophil accumulation was 14.8 microM (0.00063%). Moreover, the effect of KF19514 on the electrical field stimulation-induced bronchial contraction was examined using the main bronchi of guinea pigs in vitro. KF19514 inhibited both cholinergic and tachykininergic contraction and, in particular, produced a potent inhibitory effect on tachykininergic contraction (IC50 = 0.49 microM). The mechanism by which KF19514 inhibited the PAF-induced hyperresponsiveness may in part be the suppression of the tachykinin release. Based on these results, it was demonstrated that the inhaled KF19514 might have a significant potential effect on the inflammatory cell accumulation and hyperresponsiveness induced by PAF.

High population attributable fractions of myocardial infarction associated with waist–hip ratio

PubMed Central

Igland, Jannicke; Vollset, Stein Emil; Sulo, Gerhard; Eide, Geir Egil; Tell, Grethe S.

2016-01-01

Objective To estimate population attributable fractions (PAF) of acute myocardial infarction (AMI) associated with anthropometric measures by sex and age. Methods The Cohort of Norway study identified 140,790 participants free of cardiovascular disease, 1994‐2003. Participants were followed for AMI through 2009 by record linkages through the Cardiovascular Disease in Norway Project. PAFs were adjusted for age, smoking, systolic blood pressure, diabetes, and the ratio of total cholesterol to high‐density lipoprotein cholesterol. Results The PAFs associated with a waist–hip ratio (WHR) in the top two quintiles were 26.1% (95% confidence interval, CI 14.6–36.1) for middle‐aged women (<60 years, mean of 41 years) and 9.3% (95% CI 3.0–15.1) for similarly aged men after adjustment for body mass index (BMI) and conventional risk factors. However, PAFs associated with anthropometric measures in elderly participants (≥ 60 years, mean of 70 years) were non‐significant in multivariable analyses. Also, WHR was a significant predictor of AMI among men and women without an enlarged waist circumference (<102 cm for men and < 88 cm for women) in adjusted analyses. Conclusions WHR measurements could improve identification of at‐risk individuals above and beyond that of conventional risk factors, BMI, or an enlarged waist circumference. PMID:27030172

Attributable causes of cancer in Japan in 2005--systematic assessment to estimate current burden of cancer attributable to known preventable risk factors in Japan.

PubMed

Inoue, M; Sawada, N; Matsuda, T; Iwasaki, M; Sasazuki, S; Shimazu, T; Shibuya, K; Tsugane, S

2012-05-01

To contribute to evidence-based policy decision making for national cancer control, we conducted a systematic assessment to estimate the current burden of cancer attributable to known preventable risk factors in Japan in 2005. We first estimated the population attributable fractions (PAFs) of each cancer attributable to known risk factors from relative risks derived primarily from Japanese pooled analyses and large-scale cohort studies and the prevalence of exposure in the period around 1990. Using nationwide vital statistics records and incidence estimates, we then estimated the attributable cancer incidence and mortality in 2005. In 2005, ≈ 55% of cancer among men was attributable to preventable risk factors in Japan. The corresponding figure was lower among women, but preventable risk factors still accounted for nearly 30% of cancer. In men, tobacco smoking had the highest PAF (30% for incidence and 35% for mortality, respectively) followed by infectious agents (23% and 23%). In women, in contrast, infectious agents had the highest PAF (18% and 19% for incidence and mortality, respectively) followed by tobacco smoking (6% and 8%). In Japan, tobacco smoking and infections are major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan.

Leading Process Branch Instability in Lis1+/− Nonradially Migrating Interneurons

PubMed Central

Gopal, Pallavi P.; Simonet, Jacqueline C.; Shapiro, William

2010-01-01

Mammalian forebrain development requires extensive migration, yet the mechanisms through which migrating neurons sense and respond to guidance cues are not well understood. Similar to the axon growth cone, the leading process and branches of neurons may guide migration, but the cytoskeletal events that regulate branching are unknown. We have previously shown that loss of microtubule-associated protein Lis1 reduces branching during migration compared with wild-type neurons. Using time-lapse imaging of Lis1+/− and Lis1+/+ cells migrating from medial ganglionic eminence explant cultures, we show that the branching defect is not due to a failure to initiate branches but a defect in the stabilization of new branches. The leading processes of Lis1+/− neurons have reduced expression of stabilized, acetylated microtubules compared with Lis1+/+ neurons. To determine whether Lis1 modulates branch stability through its role as the noncatalytic β regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b, exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type neurons phenocopies the branch instability observed in Lis1+/− neurons, and a PAF antagonist rescues leading process branching in Lis1+/− neurons. These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization. PMID:19861636

Role of lecithin-cholesterol acyltransferase in the metabolism of oxidized phospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma.

PubMed

Subramanian, V S; Goyal, J; Miwa, M; Sugatami, J; Akiyama, M; Liu, M; Subbaiah, P V

1999-07-09

To determine the relative importance of platelet-activating factor-acetylhydrolase (PAF-AH) and lecithin-cholesterol acyltransferase (LCAT) in the hydrolysis of oxidized phosphatidylcholines (OXPCs) to lyso-phosphatidylcholine (lyso-PC), we studied the formation and metabolism of OXPCs in the plasma of normal and PAF-AH-deficient subjects. Whereas the loss of PC following oxidation was similar in the deficient and normal plasmas, the formation of lyso-PC was significantly lower, and the accumulation of OXPC was higher in the deficient plasma. Isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation, and stimulated adhesion molecule synthesis in endothelial cells, more than the normal LDL. Oxidation of 16:0-[1-14C]-18:2 PC, equilibrated with plasma PC, resulted in the accumulation of labeled short- and long-chain OXPCs, in addition to the labeled aqueous products. The formation of the aqueous products decreased by 80%, and the accumulation of short-chain OXPC increased by 110% in the deficient plasma, compared to the normal plasma, showing that PAF-AH is predominantly involved in the hydrolysis of the truncated OXPCs. Labeled sn-2-acyl group from the long-chain OXPC was not only hydrolyzed to free fatty acid, but was preferentially transferred to diacylglycerol, in both the normal and deficient plasmas. In contrast, the acyl group from unoxidized PC was transferred only to cholesterol, showing that the specificity of LCAT is altered by OXPC. It is concluded that, while PAF-AH carries out the hydrolysis of mainly truncated OXPCs, LCAT hydrolyzes and transesterifies the long-chain OXPCs.

Undifferentiated HL-60 cells internalize an antitumor alkyl ether phospholipid more rapidly than resistant K562 cells.

PubMed

Tsutsumi, T; Tokumura, A; Kitazawa, S

1998-02-05

In this study, we confirmed a previous finding that 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (methyl-PAF) expresses higher antineoplastic activity against the promyelocytic leukemia cell line HL-60, than against the erythroleukemic cell line K562, and intended to clarify the reason for this. Using an albumin back-exchange method, we measured the rates of binding and internalization of [3H]methyl-PAF by HL-60 and K562 cells. We found that methyl-PAF associated very rapidly and to similar extents with the two types of cells at low concentrations of extracellular bovine serum albumin, but that when bound to the cell surface, it was internalized into HL-60 cells faster than into K562 cells. The internalization of methyl-PAF by HL-60 cells was concentration-independent, intracellular ATP-independent and susceptible to thiol group-modifying reagents and cytochalasin B. Thus the inward transbilayer movement of methyl-PAF seems to occur by cytochalasin B-sensitive protein-mediated mechanism based on passive diffusion not requiring energy, in which SH-groups of protein play a critical role. We also found that the internalization of 1-hexadecanoyl-2-(4,4-difluoro-5,7- dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoyl)-sn-glycero-3-phosphocholine (Bodipy-C5-PC), whose structure resembles that of methyl-PAF, into HL-60 cells was faster than that into K562 cells. Using a combination of an albumin back-exchange method and observation by confocal laser scanning microscopy, we next examined the intracellular distribution of this fluorescent phospholipid probe after its internalization. Intracellular membranes, especially those peripheral to nuclei, were fluorescence-labeled in both HL-60 and K562 cells, but fluorescence of the nuclear membranes was weak, suggesting that this probe seems mainly to accumulate in intracellular granules, and may interact directly with several key enzymes for phospholipid metabolism, leading to cell injury. Because the difference between the internalization rates of methyl-PAF in HL-60 and K562 cells was correlated with their different susceptibilities to the cytotoxic effect of methyl-PAF, we suggest that the capacities for uptake of methyl-PAF and its accumulation in intracellular membranes are critical factor for its induction of apoptosis. (c) 1998 Elsevier Science B.V.

Banning Fisheries Discards Abruptly Has a Negative Impact on the Population Dynamics of Charismatic Marine Megafauna.

PubMed

Fondo, Esther N; Chaloupka, Milani; Heymans, Johanna J; Skilleter, Greg A

2015-01-01

Food subsidies have the potential to modify ecosystems and affect the provision of goods and services. Predictable Anthropogenic Food Subsidies (PAFS) modify ecosystems by altering ecological processes and food webs. The global concern over the effects of PAFS in ecosystems has led to development of environmental policies aimed at curbing the production or ultimately banning of PAFS. However, the effects of reducing or banning PAFS are not known. We explore the consequences of PAFS removal in a marine ecosystem under two scenarios: 1) gradual reduction, or 2) an abrupt ban, using a mass balance model to test these hypotheses-The reduction or loss of PAFS will: i) modify trophic levels and food webs through effects on foraging by opportunistic species, ii) increase the resilience of opportunistic species to food shortages, and iii) modify predator-prey interactions through shifts in prey consumption. We found that PAFS lower the trophic levels of opportunistic scavengers and increase their food pathways. Scavengers are able to switch prey when PAFS are reduced gradually but they decline when PAFS are abruptly banned. PAFS reduction to a certain minimal level causes a drop in the ecosystem's stability. We recommend gradual reduction of PAFS to a minimal level that would maintain the ecosystem's stability and allow species exploiting PAFS to habituate to the food subsidy reduction.

Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

PubMed

Francescangeli, Ermelinda; Grassi, Silvarosa; Pettorossi, Vito E; Goracci, Gianfrancesco

2002-11-01

LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.

Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions.

PubMed

Häkkinen, T; Luoma, J S; Hiltunen, M O; Macphee, C H; Milliner, K J; Patel, L; Rice, S Q; Tew, D G; Karkola, K; Ylä-Herttuala, S

1999-12-01

We studied the expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in human atherosclerotic lesions. In addition, approximately 6-fold higher Lp-PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA(2), which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA(2) activity could lead to antiatherogenic effects in the vessel wall.

Platelet-Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory Signaling in Experimental Uveitis.

PubMed

Elison, Jasmine R; Weinstein, Jessica E; Sheets, Kristopher G; Regan, Cornelius E; Lentz, Jennifer J; Reinoso, Maria; Gordon, William C; Bazan, Nicolas G

2018-04-11

The phospholipid mediator platelet-activating factor (PAF) activates an inflammatory response that includes arachidonic acid release and prostaglandin production in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU-0901, a novel PAF receptor antagonist, on experimental uveitis. Uveitis was induced in Lewis rats by lipopolysaccharide treatment. LAU-0901 was then delivered systemically in different concentrations at plus 4 and 16 hours, or vehicle injected as controls. Additional animals were used for histological analyses of untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological and immunohistochemical methods were employed. A slit lamp and Spectral Domain-Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU-0901 injection in this 24-hour model. Aqueous humor was collected and quantified, and also analyzed for tumor necrosis factor alpha (TNF-α). Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration, and an increase in aqueous protein and TNF-α levels. LAU-0901 treatment resulted in a dose-dependent reduction in inflammation, reflected by reduced total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented, leukocytes were absent in vitreous and aqueous humor, and TNF-α levels were reduced by 91%. The PAF receptor antagonist LAU-0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner, suggesting that use of this molecule may provide a means to attenuate inflammation onset and offer a future alternative or adjunctive treatment for ocular inflammation.

Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients.

PubMed Central

Shindo, K.; Koide, K.; Hirai, Y.; Sumitomo, M.; Fukumura, M.

1996-01-01

BACKGROUND: Eosinophils from asthmatic patients are known to release greater amounts of leukotrienes than normal eosinophils when stimulated by the calcium ionophore A23187. The effect of platelet activating factor (PAF) in priming eosinophils was investigated. METHODS: Eosinophils were obtained from 18 asthmatic patients and 18 healthy donors. Cells separated by the Percoll gradients were incubated with PAF (C-18) for 30 minutes and then stimulated with the calcium ionophore A23187 (2.5 microM) for 15 minutes. The amount of leukotriene C4 (LTC4) in supernatants was measured using a combination of high pressure liquid chromatography and radioimmunoassay. RESULTS: The mean (SD) amount of LTC4 released by eosinophils from asthmatic patients upon stimulation with the calcium ionophore A23187 alone was 27.9 (9.9) ng/10(6) cells (n = 6). The amount of LTC4 released following stimulation with the calcium ionophore A23187 after pretreatment with PAF (1, 5, and 10 microM) was 57.2 (8.9), 75.1 (14.3), and 52.6 (10.7) ng/10(6) cells (n = 6), respectively. Trace amounts of LTC4 (0.9 (0.02) ng/10(6) cells, n = 6) were detected in the supernatant of the cells after stimulation by PAF alone (5 microM). The amount of LTC4 released upon stimulation by calcium ionophore A23187 alone in eosinophils from healthy donors was 10.3 (3.7) ng/10(6) cells (n = 4). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with PAF at concentrations of 1, 5, and 10 microM were 11.9 (3.5), 17.8 (5.6), and 12.7 (5.1) ng/10(6) cells (n = 4), respectively. Trace amounts of LTC4 (0.6 (0.02) ng/10(6) cells, n = 4) were detected in the supernatant of the cells upon stimulation with PAF alone (5 microM). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with lyso-PAF at concentrations of 1, 5, and 10 microM (n = 4 or 6) were 30.8 (5.2), 22.9 (5.1), and 27.3 (4.3) ng/10(6) cells (n = 6) from the eosinophils of asthmatic patients and 13.7 (3.3), 15.2 (4.9), and 14.7 (3.8) ng/10(6) cells (n = 4) from the eosinophils of healthy donors. CONCLUSIONS: The results indicated that PAF enhanced LTC4 formation by eosinophils obtained from asthmatic patients stimulated with the calcium ionophore A23187, but not those obtained from normal subjects. PMID:8711647

Permanent atrial fibrillation in heart failure patients as another condition with increased reverse triiodothyronine concentration.

PubMed

Jakowczuk, Maciej; Zalas, Dominika; Owecki, Maciej

2016-09-01

To fully investigate the thyroid hormonal function in patients with the most common arrhythmia - atrial fibrillation. 120 patients (aged 55-85 yrs) with symptoms of congestive heart failure exacerbation and no other concomitant disorders (inclusion criteria: normal cardiac troponin T at admission and 12 hours after, normal renal, hepatic and respiratory function; exclusion criteria: inflammatory state, history of myocardial infarction). Depending on the presence of permanent atrial fibrillation (PAF), patients were divided into two groups: PAF (34 females, 26 males) and regular sinus heart rhythm (43 females, 17 males), the groups did not differ in terms of heart rate, blood pressure, presence of overt/subclinical thyroid dysfunction, and medical therapy used. In all subjects thyroid stimulating hormone, free thyroxine, free triiodothyronine, reverse triiodothyronine were measured; echocardiography was performed. PAF group showed higher FT4 and rT3 (1.41 vs. 1.27 ng/dl, p=0.0007; 0.61 vs. 0.32 ng/ml, p<0.0001, respectively). With ROC curve analysis the biochemical thyroid related factor of the highest prognostic value for PAF occurrence (with the highest sensitivity and specificity: 77% and 72%, respectively) was rT3 with the cut-off of above 0.3 ng/ml. Also, a positive correlation between rT3 levels and left ventricular posterior wall diameter was observed (Spearman's correlation coefficient 0.33, p=0.0093). PAF is another condition where an increase in rT3 is observed. rT3 concentration above 0.3 ng/ml may be a novel biochemical sign associated with the presence of PAF in patients with chronic heart failure.

S-nitrosation of β-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability

PubMed Central

Marín, N.; Zamorano, P.; Carrasco, R.; Mujica, P.; González, FG.; Quezada, C.; Meininger, CJ.; Boric, MP.; Durán, WN.; Sánchez, FA.

2014-01-01

Rationale Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of eNOS to cytosol and stimulation of eNOS-derived NO signaling cascade. The mechanisms by which NO signaling regulates permeability at adherens junctions are still incompletely understood. Objective We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins. Methods and Results We measured PAF-stimulated S-nitrosation of β-catenin and p120-catenin (p120) in three cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein) and CVEC (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. TNF-α increased NO production and caused similar increase in S-nitrosation as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosation of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of NO production and of S-nitrosation blocked PAF-induced S-nitrosation and hyperpermeability whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with VE-cadherin. Conclusions Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. PMID:22777005

Permeability of ferret trachea in vitro to {sup 99m}{Tc}-DTPA and [{sup 14}C]antipyrine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanafi, Z.; Webber, S.E.; Widdicombe, J.G.

1994-09-01

Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of {sup 99m}{Tc}-diethylenetriamine pentaacetic acid ({sup 99m}{Tc}-DTPA; hydrophilic) and [{sup 14}C]antipyrine ([{sup 14}C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either {sup 99m}{Tc}-DTPA or [{sup 14}C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline {sup 99m}{Tc}-DTPA and [{sup 14}C]AP permeability coefficients were - 4.7 {+-} 0.6 (SE) x 10{sup {minus}7} and -2.2 {+-} 0.1 x 10{sup {minus}5} cm/s, respectively. PAF (10 {mu}M) increased permeability tomore » {sup 99m}{Tc}-DTPA to -35.3 {+-} 7.6 x 10{sup {minus}7} cm/s (P < 0.05), but permeability to [{sup 14}C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 {mu}M), phenylephrine (PE, 100 {mu}M), and albuterol (Alb, 100 {mu}M) caused no change in permeability to {sup 99m}{Tc}-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 {mu}M) significantly increased permeability. Abluminal Hist decreased permeability to [{sup 14}C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to {sup 99m}{Tc}-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent. 37 refs., 11 figs., 1 tab.« less

/sup 3/H-PAF-acether displacement and inhibition of binding in intact human platelets by BN 52021

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korth, R.; Le Couedic, J.P.; Benveniste, J.

1986-03-05

Intact washed human platelets incubated at 20/sup 0/C in Tyrode's buffer containing 0.25% (w/v) bovine serum albumin bound /sup 3/H paf-acether in a concentration (0-6.5 nM) and time (0-60 min) dependent manner (n=3). BN 52021 (60 ..mu..M) a chemically defined extract from Ginkgo biloba inhibited the binding of increasing concentrations of /sup 3/H paf-acether. Calculated differences between /sup 3/H paf-acether binding in the presence or absence of BN 52021 (60 ..mu..M) reached nearly a plateau in concentrations higher than 0.65 nM /sup 3/H paf-acether. Increasing concentrations of BN 52021 (0-60 ..mu..M) as well as of unlabelled paf-acether (0-50 nM) preventedmore » within 15 min /sup 3/H paf-acether binding (0.65 nM) to platelets in a concentration-dependent way. Increasing BN 52021 concentrations (0-60 ..mu..M) also displaced platelet-bound /sup 3/H paf-acether (0.65 nM) in a concentration-dependent way. Displacement increased with the time length of platelet incubation with BN 52021 and reached a plateau at 15 min. Platelet-bound /sup 3/H paf-acether displacement of 28.3 +/- 6.3%, 31.1 +/- 4.0% and 26.7 +/- 5.6% was observed using 50 nM unlabelled paf-acether, 60 ..mu..M BN 52021 or both substances together (vs 4.3 +/- 7.2% for vehicle alone). No degradation of /sup 3/H paf-acether occurred as assessed by high pressure liquid chromatography. These results demonstrate that BN 52021 competes directly with paf-acether binding sites on human platelets.« less

In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palicz, Zoltán; Jenes, Ágnes; Gáll, Tamás

2013-05-15

The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg{sup −1} daily, for 2 weeks. Even at the highest concentration – a concentration highly toxic in vitro for all affected molds – used, animals neither died due tomore » the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. - Highlights: • PAF, the antifungal protein of Penicillium chrysogenum, was not toxic in mice. • Its intranasal application didn't induce pathological reactions in the lung. • PAF retained its antifungal activity in lung extracts. • Its application on the skin did not cause inflammation.« less

Electrocardiographic left ventricular hypertrophy predicts recurrence of atrial arrhythmias after catheter ablation of paroxysmal atrial fibrillation.

PubMed

Li, Song-Nan; Wang, Lu; Dong, Jian-Zeng; Yu, Rong-Hui; Long, De-Yong; Tang, Ri-Bo; Sang, Cai-Hua; Jiang, Chen-Xi; Liu, Nian; Bai, Rong; Du, Xin; Ma, Chang-Sheng

2018-06-01

Left ventricular hypertrophy (LVH) is an independent predictor of new-onset atrial fibrillation. Whether LVH can predict the recurrence of arrhythmia after radiofrequency catheter ablation (RFCA) in patients with paroxysmal atrial fibrillation (PAF) remains unclear. PAF patients with baseline-electrocardiographic LVH has a higher recurrence rate after RFCA procedure compared with those without LVH. A total of 436 patients with PAF undergoing first RFCA were consecutively enrolled and clustered into 2 groups based on electrocardiogram (ECG) findings: non-ECG LVH (218 patients) and ECG LVH (218 patients). LVH was characterized by the Romhilt-Estes point score system; the score ≥5points were defined as LVH. At 42 months' (interquartile range, 18.0-60.0 months) follow-up after RFCA, 151 (69.3%) patients in the non-ECG LVH group and 108 (49.5%) patients in the ECG LVH group maintained sinus rhythm without using antiarrhythmic drugs (P < 0.001). Patients with ECG LVH tended to experience a much higher prevalence of stroke and recurrence of atrial arrhythmia episodes compared with those without ECG LVH (log-rank P < 0.001). Multivariate analysis found the presence of ECG LVH and left atrial diameter to be independent risk factors for recurrence after adjusting for confounding factors. The presence of ECG LVH was a strong and independent predictor of recurrence in patients with PAF following RFCA. © 2018 Wiley Periodicals, Inc.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

PubMed Central

Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

2016-01-01

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

PubMed

Benjamin, Laura A; Corbett, Elizabeth L; Connor, Myles D; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C A; Bryer, Alan; Faragher, Brian; Heyderman, Robert S; Allain, Theresa J; Solomon, Tom

2016-01-26

To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4(+) T-lymphocyte count (92 vs 375 cells/mm(3), p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. © 2015 American Academy of Neurology.

Yangambin, a lignan obtained from Ocotea duckei, differentiates putative PAF receptor subtypes in the gastrointestinal tract of rats.

PubMed

Jesus-Morais, C M; Assis, E F; Cordeiro, R S; Barbosa-Filho, J M; Lima, W T; Silva, Z L; Bozza, P T; Castro-Faria-Neto, H C

2000-04-01

We investigated the presence of PAF receptor subtypes in the tissues of the gastrointestinal tract, airways, blood vessels and in murine macrophages. For this purpose we have used a competitive PAF receptor antagonist, yangambin (YAN), extracted from the Brazilian plant "louro de cheiro" (Ocotea duckei Vattimo). Rat duodenum, jejunum, ileum, colon, stomach fundus, trachea and bronchia were removed and 1.5-2 cm muscle segments from those regions were mounted in a 10 ml organ bath with aerated physiological solution at 37 degrees C. PAF evoked a contraction of the rat jejunum, ileum, colon and stomach fundus. The contraction was slow and resistant to wash and was followed by desensitization to further doses of PAF. Contractions induced by PAF (10(-6) M) were inhibited by YAN (10(-7) to M-2 x 10(-5) M) and WEB 2086 (10(-6) m to M-5 M) in rat jejunum, ileum and colon but not in the stomach fundus. In the rat stomach fundus only WEB 2086 (5 x 10(-6) M) was able to block PAF-induced contraction. The contractions induced by acetylcholine, histamine, 5-hydroxytryptamine and vasopressin were not inhibited by prior administration of YAN. Yangambin also significantly inhibited PAF-induced vascular permeability in rat duodenum, jejunum, ileum, colon, and mesentery. Yangambin significantly inhibited PAF-induced lipid body formation in mice peritoneal macrophages. We suggest that YAN is a selective PAF antagonist which is able to discriminate putative PAF receptors subtypes present in the stomach fundus.

Population-based analysis of Alzheimer's disease risk alleles implicates genetic interactions.

PubMed

Ebbert, Mark T W; Ridge, Perry G; Wilson, Andrew R; Sharp, Aaron R; Bailey, Matthew; Norton, Maria C; Tschanz, JoAnn T; Munger, Ronald G; Corcoran, Christopher D; Kauwe, John S K

2014-05-01

Reported odds ratios and population attributable fractions (PAF) for late-onset Alzheimer's disease (LOAD) risk loci (BIN1, ABCA7, CR1, MS4A4E, CD2AP, PICALM, MS4A6A, CD33, and CLU) come from clinically ascertained samples. Little is known about the combined PAF for these LOAD risk alleles and the utility of these combined markers for case-control prediction. Here we evaluate these loci in a large population-based sample to estimate PAF and explore the effects of additive and nonadditive interactions on LOAD status prediction performance. 2419 samples from the Cache County Memory Study were genotyped for APOE and nine LOAD risk loci from AlzGene.org. We used logistic regression and receiver operator characteristic analysis to assess the LOAD status prediction performance of these loci using additive and nonadditive models and compared odds ratios and PAFs between AlzGene.org and Cache County. Odds ratios were comparable between Cache County and AlzGene.org when identical single nucleotide polymorphisms were genotyped. PAFs from AlzGene.org ranged from 2.25% to 37%; those from Cache County ranged from .05% to 20%. Including non-APOE alleles significantly improved LOAD status prediction performance (area under the curve = .80) over APOE alone (area under the curve = .78) when not constrained to an additive relationship (p < .03). We identified potential allelic interactions (p values uncorrected): CD33-MS4A4E (synergy factor = 5.31; p < .003) and CLU-MS4A4E (synergy factor = 3.81; p < .016). Although nonadditive interactions between loci significantly improve diagnostic ability, the improvement does not reach the desired sensitivity or specificity for clinical use. Nevertheless, these results suggest that understanding gene-gene interactions may be important in resolving Alzheimer's disease etiology. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Regional blood flow volume in the eustachian tube.

PubMed

Minami, T; Kubo, N; Tomoda, K; Yamashita, T; Kumazawa, T

1993-01-01

Measurements of regional blood flow around the pharyngeal orifice of the Eustachian tube were carried out after topical administration of various inflammatory mediators in 14 mongrel dogs by the hydrogen clearance method. Histamine and platelet-activating factor (PAF) resulted in a significant alteration of blood flow volume. Histamine was found to induce a dose-response related increase, whereas blood flow volume tended to decrease in each concentration range in the series of PAF administration. There was no significant difference in blood flow between topical application of leukotriene C4 and leukotriene D4. It is likely that in upper respiratory tract inflammation, such as in otitis media and in nasal allergy, activated histamine and PAF affect the microcirculation of the tubal orifice. These results suggest that disturbance of the microcirculatory system in the Eustachian tube mucosa could be involved in the pathogenesis of chronic otitis media with effusion.

Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate.

PubMed

Emanuele, Michael J; Ciccia, Alberto; Elia, Andrew E H; Elledge, Stephen J

2011-06-14

The anaphase-promoting complex/cyclosome (APC/C) is a cell cycle-regulated E3 ubiquitin ligase that controls the degradation of substrate proteins at mitotic exit and throughout the G1 phase. We have identified an APC/C substrate and cell cycle-regulated protein, KIAA0101/PAF15. PAF15 protein levels peak in the G2/M phase of the cell cycle and drop rapidly at mitotic exit in an APC/C- and KEN-box-dependent fashion. PAF15 associates with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation. Following irradiation, PAF15 colocalized with γH2AX foci at sites of DNA damage through its interaction with PCNA. Finally, PAF15 depletion led to an increase in homologous recombination-mediated DNA repair, and overexpression caused sensitivity to UV-induced DNA damage. We conclude that PAF15 is an APC/C-regulated protein involved in both cell cycle progression and the DNA damage response.

Differences in skin sympathetic involvements between two chronic autonomic disorders: multiple system atrophy and pure autonomic failure.

PubMed

Asahina, Masato; Akaogi, Yuichi; Yamanaka, Yoshitaka; Koyama, Yu; Hattori, Takamichi

2009-06-01

Certain stimuli evoke increased sweat secretion (sympathetic sweat response; SSwR) and reduced skin blood flow (skin vasomotor reflex; SkVR) in the palm/sole. We evaluated SSwR and SkVR in patients with multiple system atrophy (MSA) and pure autonomic failure (PAF). SSwR and SkVR on the palm in response to deep inspiration and mental arithmetic were recorded in 11 MSA patients, 11 PAF patients, and 11 healthy controls. In addition, the head-up tilt test was performed, and the coefficient of variation of R-R intervals (CV(R-R)) was obtained. SSwR amplitudes were significantly lower in the MSA and PAF patients than the controls. SkVR amplitudes in the PAF patients were significantly lower than the controls, but preserved in the MSA patients. In head-up tilt tests, all MSA and PAF patients showed orthostatic hypotension, with similar severity. CV(R-R) was low in the MSA and PAF patients, but a significant difference was found only between the PAF and control groups. In the MSA patients, SkVR was preserved, but SSwR was diminished. In the PAF patients, both SkVR and SSwR were attenuated. The combination of SkVR and SSwR tests may differentiate MSA and PAF.

D19S Mutation of the Cationic, Cysteine-Rich Protein PAF: Novel Insights into Its Structural Dynamics, Thermal Unfolding and Antifungal Function

PubMed Central

Burtscher, Laura; Hajdu, Dorottya; Muñoz, Alberto; Gáspári, Zoltán; Read, Nick D.; Batta, Gyula; Marx, Florentine

2017-01-01

The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research. To understand its mode of action, we started to investigate the surface-exposed loops of PAF and replaced one aspartic acid at position 19 in loop 2 that is potentially involved in PAF active or binding site, with a serine (Asp19 to Ser19). We analysed the overall effects, such as unfolding, electrostatic changes, sporadic conformers and antifungal activity when substituting this specific amino acid to the fairly indifferent amino acid serine. Structural analyses revealed that the overall 3D solution structure is virtually identical with that of PAF. However, PAFD19S showed slightly increased dynamics and significant differences in the surface charge distribution. Thermal unfolding identified PAFD19S to be rather a two-state folder in contrast to the three-state folder PAF. Functional comparison of PAFD19S and PAF revealed that the exchange at residue 19 caused a dramatic loss of antifungal activity: the binding and internalization of PAFD19S by target cells was reduced and the protein failed to trigger an intracellular Ca2+ response, all of which are closely linked to the antifungal toxicity of PAF. We conclude that the negatively charged residue Asp19 in loop 2 is essential for full function of the cationic protein PAF. PMID:28072824

Monoclonal antibodies to alphaVbeta3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor.

PubMed

Kaul, D K; Tsai, H M; Liu, X D; Nakada, M T; Nagel, R L; Coller, B S

2000-01-15

Abnormal interaction of sickle red blood cells (SS RBC) with the vascular endothelium has been implicated as a factor in the initiation of vasoocclusion in sickle cell anemia. Both von Willebrand factor (vWf) and thrombospondin (TSP) play important roles in mediating SS RBC-endothelium interaction and can bind to the endothelium via alphaVbeta3 receptors. We have used monoclonal antibodies (MoAb) directed against alphaVbeta3 and alphaIIbbeta3 (GPIIb/IIIa) integrins to dissect the role of these integrins in SS RBC adhesion. The murine MoAb 7E3 inhibits both alphaVbeta3 and alphaIIbbeta3 (GPIIb/IIIa), whereas MoAb LM609 selectively inhibits alphaVbeta3, and MoAb 10E5 binds only to alphaIIbbeta3. In this study, we have tested the capacity of these MoAbs to block platelet-activating factor (PAF)-induced SS RBC adhesion in the ex vivo mesocecum vasculature of the rat. Infusion of washed SS RBC in preparations treated with PAF (200 pg/mL), with or without a control antibody, resulted in extensive adhesion of these cells in venules, accompanied by frequent postcapillary blockage and increased peripheral resistance units (PRU). PAF also caused increased endothelial surface and interendothelial expression of endothelial vWf. Importantly, pretreatment ofthe vasculature with either MoAb 7E3 F(ab')(2) or LM609, but not 10E5 F(ab')(2), after PAF almost completely inhibited SS RBC adhesion in postcapillary venules, the sites of maximal adhesion and frequent blockage. The inhibition of adhesion with 7E3 or LM609 was accompanied by smaller increases in PRU and shorter pressure-flow recovery times. Thus, blockade of alphaVbeta3 may constitute a potential therapeutic approach to prevent SS RBC-endothelium interactions under flow conditions. (Blood. 2000;95:368-374)

The Impact of Transforming Growth Factor-β1 Level on Outcome After Catheter Ablation in Patients With Atrial Fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2017-04-01

Transforming growth factor-β 1 (TGF-β 1 ) is an important factor that induces atrial fibrosis and atrial fibrillation (AF). The purpose of this study was to evaluate the association between TGF-β 1 level and clinical factors before catheter ablation (CA), and to investigate the impact of TGF-β 1 level on the outcome after CA for AF. This prospective study included 151 patients (persistent AF group: n = 59, paroxysmal AF [PAF] group: n = 54, and control group: n = 38). All patients who underwent CA for AF were followed up for 12 months. The PAF group had the highest TGF-β 1 levels in all patients. An early recurrence of AF (ERAF: defined as episodes of atrial tachyarrhythmia within a 3-month blanking period) was detected in 60 patients (53%). Recurrent AF after the blanking period was detected in 36 patients (32%). On multivariate analysis, low TGF-β 1 level was the only independent factor associated with recurrent AF. Moreover, the AF recurrence ratio was higher in the low TGF-β 1 group (< 12.56 ng/mL) than in the high TGF-β 1 group (16 of 29 patients, 55% vs. 20 of 84 patients, 24%, P = 0.002 by log-rank test). PAF was associated with a higher TGF-β 1 level. Moreover, lower TGF-β 1 level in AF patients could be a cause of recurrent AF after CA. © 2017 Wiley Periodicals, Inc.

25 CFR 170.220 - What is the Population Adjustment Factor?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false What is the Population Adjustment Factor? 170.220 Section... ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor § 170.220 What is the Population Adjustment Factor? The Population Adjustment Factor (PAF) is a special portion of the...

25 CFR 170.220 - What is the Population Adjustment Factor?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false What is the Population Adjustment Factor? 170.220 Section... ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor § 170.220 What is the Population Adjustment Factor? The Population Adjustment Factor (PAF) is a special portion of the...

25 CFR 170.220 - What is the Population Adjustment Factor?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What is the Population Adjustment Factor? 170.220 Section... ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor § 170.220 What is the Population Adjustment Factor? The Population Adjustment Factor (PAF) is a special portion of the...

25 CFR 170.220 - What is the Population Adjustment Factor?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false What is the Population Adjustment Factor? 170.220 Section... ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor § 170.220 What is the Population Adjustment Factor? The Population Adjustment Factor (PAF) is a special portion of the...

25 CFR 170.220 - What is the Population Adjustment Factor?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true What is the Population Adjustment Factor? 170.220 Section... ROADS PROGRAM Indian Reservation Roads Program Funding Population Adjustment Factor § 170.220 What is the Population Adjustment Factor? The Population Adjustment Factor (PAF) is a special portion of the...

A Porous Aromatic Framework Constructed from Benzene Rings Has a High Adsorption Capacity for Perfluorooctane Sulfonate

PubMed Central

Luo, Qin; Zhao, Changwei; Liu, Guixia; Ren, Hao

2016-01-01

A low-cost and easily constructed porous aromatic framework (PAF-45) was successfully prepared using the Scholl reaction. PAF-45 was, for the first time, used to remove perfluorooctane sulfonate (PFOS) from aqueous solution. Systematic experiments were performed to determine the adsorption capacity of PAF-45 for PFOS and to characterize the kinetics of the adsorption process. The adsorption of PFOS onto PAF-45 reached equilibrium in 30 min, and the adsorption capacity of PAF-45 for PFOS was excellent (5847 mg g−1 at pH 3). The amount of PFOS adsorbed by PAF-45 increased significantly as the cation (Na+, Mg2+, or Fe3+) concentration increased, which probably occurred because the cations enhanced the interactions between the negatively charged PFOS molecules and the positively charged PAF-45 surface. The cations Na+, Mg2+, and Fe3+ were found to form complexes with PFOS anions in solution. Density functional theory was used to identify the interactions between PFOS and Na+, Mg2+, and Fe3+. We expect that materials of the same type as PAF-45 could be useful adsorbents for removing organic pollutants from industrial wastewater and contaminated surface water. PMID:26843015

Spectral and Temporal Processing in Rat Posterior Auditory Cortex

PubMed Central

Pandya, Pritesh K.; Rathbun, Daniel L.; Moucha, Raluca; Engineer, Navzer D.; Kilgard, Michael P.

2009-01-01

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex. PMID:17615251

A Porous Aromatic Framework Constructed from Benzene Rings Has a High Adsorption Capacity for Perfluorooctane Sulfonate.

PubMed

Luo, Qin; Zhao, Changwei; Liu, Guixia; Ren, Hao

2016-02-04

A low-cost and easily constructed porous aromatic framework (PAF-45) was successfully prepared using the Scholl reaction. PAF-45 was, for the first time, used to remove perfluorooctane sulfonate (PFOS) from aqueous solution. Systematic experiments were performed to determine the adsorption capacity of PAF-45 for PFOS and to characterize the kinetics of the adsorption process. The adsorption of PFOS onto PAF-45 reached equilibrium in 30 min, and the adsorption capacity of PAF-45 for PFOS was excellent (5847 mg g(-1) at pH 3). The amount of PFOS adsorbed by PAF-45 increased significantly as the cation (Na(+), Mg(2+), or Fe(3+)) concentration increased, which probably occurred because the cations enhanced the interactions between the negatively charged PFOS molecules and the positively charged PAF-45 surface. The cations Na(+), Mg(2+), and Fe(3+) were found to form complexes with PFOS anions in solution. Density functional theory was used to identify the interactions between PFOS and Na(+), Mg(2+), and Fe(3+). We expect that materials of the same type as PAF-45 could be useful adsorbents for removing organic pollutants from industrial wastewater and contaminated surface water.

Pneumolysin mediates heterotypic aggregation of neutrophils and platelets in vitro.

PubMed

Nel, Jan G; Durandt, Chrisna; Theron, Annette J; Tintinger, Gregory R; Pool, Roger; Richards, Guy A; Mitchell, Timothy J; Feldman, Charles; Anderson, Ronald

2017-06-01

Platelets orchestrate the inflammatory activities of neutrophils, possibly contributing to pulmonary and myocardial damage during severe pneumococcal infection. This study tested the hypothesis that the pneumococcal toxin, pneumolysin (Ply), activates production of platelet-activating factor (PAF) and thromboxane A 2 (TxA 2 ) by neutrophils, these bioactive lipids being potential mediators of neutrophil:platelet (NP) networking. The effects of recombinant Ply (10-80 ng mL -1 ) on the production of PAF and TxA 2 by isolated neutrophils were measured using ELISA procedures, and NP aggregation by flow cytometry. Exposure of neutrophils to Ply induced production of PAF and, to a lesser extent, TxA 2 , achieving statistical significance at ≥20 ng mL -1 of the toxin. In the case of NP interactions, Ply promoted heterotypic aggregation which was dependent on upregulation of P-selectin (CD62P) and activation of protease-activated receptor 1 (PAR1), attaining statistical significance at ≥10 ng mL -1 of the toxin, but did not involve either PAF or TxA 2 . Ply induces synthesis of PAF and TxA 2, by human neutrophils, neither of which appears to contribute to the formation of NP heterotypic aggregates in vitro, a process which is seemingly dependent on CD62P and PAR1. These pro-inflammatory activities of Ply may contribute to the pathogenesis of pulmonary and myocardial injury during severe pneumococcal infection. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Cancers attributable to excess body weight in Canada in 2010.

PubMed

Zakaria, Dianne; Shaw, Amanda

2017-07-01

Excess body weight (body mass index [BMI] ≥ 25.00 kg/m2) is an established risk factor for diabetes, hypertension and cardiovascular disease, but its relationship to cancer is lesser-known. This study used population attributable fractions (PAFs) to estimate the cancer burden attributable to excess body weight in Canadian adults (aged 25+ years) in 2010. We estimated PAFs using relative risk (RR) estimates from the World Cancer Research Fund International Continuous Update Project, BMI-based estimates of overweight (25.00 kg/m2-29.99 kg/m2) and obesity (30.00+ kg/m2) from the 2000-2001 Canadian Community Health Survey, and cancer case counts from the Canadian Cancer Registry. PAFs were based on BMI corrected for the bias in self-reported height and weight. In Canada in 2010, an estimated 9645 cancer cases were attributable to excess body weight, representing 5.7% of all cancer cases (males 4.9%, females 6.5%). When limiting the analysis to types of cancer associated with high BMI, the PAF increased to 14.9% (males 17.5%, females 13.3%). Types of cancer with the highest PAFs were esophageal adenocarcinoma (42.2%), kidney (25.4%), gastric cardia (20.7%), liver (20.5%), colon (20.5%) and gallbladder (20.2%) for males, and esophageal adenocarcinoma (36.1%), uterus (35.2%), gallbladder (23.7%) and kidney (23.0%) for females. Types of cancer with the greatest number of attributable cases were colon (1445), kidney (780) and advanced prostate (515) for males, and uterus (1825), postmenopausal breast (1765) and colon (675) for females. Irrespective of sex or type of cancer, PAFs were highest in the Prairies (except Alberta) and the Atlantic region and lowest in British Columbia and Quebec. The cancer burden attributable to excess body weight is substantial and will continue to rise in the near future because of the rising prevalence of overweight and obesity in Canada.

PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation

PubMed Central

Yang, Yan; Li, Wencheng; Hoque, Mainul; Hou, Liming; Shen, Steven; Tian, Bin; Dynlacht, Brian D.

2016-01-01

The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and RNA polymerase II (PolII) elongation. Here, we provide the first genome-wide profiles for the distribution of the entire complex in mammalian cells using chromatin immunoprecipitation and high throughput sequencing. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3’ ends, a profile that sharply contrasted with the yeast complex. Remarkably, we identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription using RNAi coupled with deep sequencing of the 3’ ends of transcripts. Moreover, we found that depletion of Paf1C subunits resulted in the accumulation of PolII over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits led to global loss of histone H2B ubiquitylation, although there was little impact of Paf1C depletion on other histone modifications, including tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with yeast, while unifying observations that link Paf1C with PolII elongation and RNA processing, and indicate that Paf1C subunits could play roles in controlling transcript length through suppression of PolII accumulation at transcription start site (TSS)-proximal pA sites and regulating pA site choice in 3’UTRs. PMID:26765774

Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer

PubMed Central

Damiani, Elisabetta; Ullrich, Stephen E.

2016-01-01

Lipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome. PMID:27073146

Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer.

PubMed

Damiani, Elisabetta; Ullrich, Stephen E

2016-07-01

Lipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome. Copyright © 2016 Elsevier B.V. All rights reserved.

The impact of delayed maternity on foetal growth in Spain: An assessment by population attributable fraction.

PubMed

Varea, Carlos; Terán, José Manuel; Bernis, Cristina; Bogin, Barry

2017-09-18

Delayed childbearing is considered a risk factor for maternal-foetal health. As in other higher-income countries, in Spain age at maternity has steadily increased during the last two decades. To quantify the impact of the delay in the age at maternity on small for gestational age (SGA) categories of <3rd, 3rd-5th and 5th-10th percentiles. 2,672,350 singleton live births born to Spanish mothers in 2007-2015 were analysed. Adjusted relative risk was calculated to estimate the adjusted partial population attributable fractions (PAF p ) for mothers aged 35-39 and ≥40 years for each category of SGA considering the interaction between age at maternity and parity. Primipara 35-39 years old mothers have the highest PAF p in the three categories of SGA, with the maximum value for SGA <3rd percentile (2.57%, 95% CI 2.25, 2.88). PAF p for both primipara and multipara ≥40 years old mothers were less than 1%. PAF p for primipara older mothers increased significantly in 2007-2015 for the three categories of SGA, more clearly among those aged 35-39 years. The contribution of multipara mothers of both age groups did not increase significantly during the period. Delayed maternity is a significant adjusted risk factor for SGA, contributing to the increase of its prevalence. However, results also suggest a limited clinical impact of delayed maternity on foetal growth. Positive changes in maternal profile associated with the shift in maternal age might contribute to explain the limited impact of mothers aged 35 years and older on negative birth outcome in Spain. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS.

PubMed

Bayrak, Tulin; Dursun, Polat; Bayrak, Ahmet; Gültekin, Murat; Kolusarı, Ali; Cakır, Erdinç; Ozyurt, Merve; Zeyneloğlu, Hulusi B

2012-11-01

Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor-acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO) synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS patients with a BMI matched control group using the following characteristics: serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. 77 women with PCOS and 25 healthy subject were recruited for this study, The controls were non-obese BMI and age matched with the patients. There were no significant differences with respect to age, BMI, FSH, free testosterone, DHEA, androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total testosterone and fasting glucose levels were significantly higher in the PCOS group (p < 0.05). On the other hand, PON1-HTLase levels (39.6 ± 5.77 vs. 33.8 ± 8.2, p = 0.02) were significantly lower in the PCOS group while ADMA levels (1.14 ± 0.6 vs. 3.37 ± 6.4, p = 0.004) were significantly higher in the PCOS group. However, there was no significant difference in PAF-AH activity among the groups. Decreased PON1-HTLase and increased ADMA levels might be a relevant marker for the development of future atherosclerotic heart disease (AHD) in non-obese PCOS patients. Further studies are needed to confirm our results.

Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca²⁺]i, nitric oxide, and gap formation in intact venules.

PubMed

Zhou, Xueping; He, Pingnian

2011-11-01

We have previously demonstrated that platelet-activating factor (PAF)-induced increases in microvessel permeability were associated with endothelial gap formation and that the magnitude of peak endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)) and nitric oxide (NO) production at the single vessel level determines the degree of the permeability increase. This study aimed to examine whether the magnitudes of PAF-induced peak endothelial [Ca(2+)](i), NO production, and gap formation are correlated at the individual endothelial cell level in intact rat mesenteric venules. Endothelial gaps were quantified by the accumulation of fluorescent microspheres at endothelial clefts using confocal imaging. Endothelial [Ca(2+)](i) was measured on fura-2- or fluo-4-loaded vessels, and 4,5-diaminofluorescein (DAF-2) was used for NO measurements. The results showed that increases in endothelial [Ca(2+)](i), NO production, and gap formation occurred in all endothelial cells when vessels were exposed to PAF but manifested a spatial heterogeneity in magnitudes among cells in each vessel. PAF-induced peak endothelial [Ca(2+)](i) preceded the peak NO production by 0.6 min at the cellular level, and the magnitudes of NO production and gap formation linearly correlated with that of the peak endothelial [Ca(2+)](i) in each cell, suggesting that the initial levels of endothelial [Ca(2+)](i) determine downstream NO production and gap formation. These results provide direct evidence from intact venules that inflammatory mediator-induced increases in microvessel permeability are associated with the generalized formation of endothelial gaps around all endothelial cells. The spatial differences in the molecular signaling that were initiated by the heterogeneous endothelial Ca(2+) response contribute to the heterogeneity in permeability increases along the microvessel wall during inflammation.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

PubMed

Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, Sandrine

2016-05-11

Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.

Which Complications Matter Most? Prioritizing Quality Improvement in Emergency General Surgery

PubMed Central

Scarborough, John E; Schumacher, Jessica; Pappas, Theodore N; McCoy, Christopher C; Englum, Brian R; Agarwal, Suresh K; Greenberg, Caprice C

2016-01-01

BACKGROUND Because preoperative risk factor modification is generally not possible in the emergency setting, complication prevention represents an important focus for quality improvement in emergency general surgery (EGS). The objective of our study was to determine the overall impact that specific postoperative complications have in this patient population. STUDY DESIGN Our study sample consisted of patients from the 2012–2013 ACS-NSQIP database who underwent an EGS procedure. We used population attributable fractions (PAFs) to estimate the overall impact that each of 8 specific complications had on 30-day physiologic and resource use outcomes in our study population. The PAF represents the percentage reduction in a given outcome that would be anticipated if a complication were able to be completely prevented in our study population. Both unadjusted and risk-adjusted PAFs were calculated. RESULTS There were 79,183 patients included for analysis. The most common complications in these patients were bleeding (6.2%), incisional surgical site infection (SSI) (3.4%), pneumonia (2.7%), and organ/space SSI (2.6%). Bleeding was the complication with the greatest overall impact on mortality and end-organ dysfunction, demonstrating an adjusted PAF of 10.7% (95% CI 8.2%,13.1%, p < 0.001) and 15.9% (95% CI 13.9%, 16.7%, p < 0.001) for these respective outcomes. The only other complication with a sizeable impact on these outcomes was pneumonia (adjusted PAF of 7.9% for mortality and 13.2% for pneumonia). In contrast, complications such as urinary tract infection, venous thromboembolism, myocardial infarction, and incisional SSI had negligible impacts on these outcomes. CONCLUSIONS Our study provides a framework for the development of high-value quality initiatives in EGS. PMID:26916129

Population-attributable fraction of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the Central Provinces of Iran.

PubMed

Mohammadi, Masoud; Mirzaei, Masoud

2017-03-01

The prevalence of obesity has been increasing in Iran over the past decade. This study aimed to determine the population-attributable fraction (PAF) of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the central provinces of Iran. Prevalence of hypertension was extracted from the Iranian Ministry of Health Non-Communicable Disease Risk Factor InfoBase 2009. Measure of association between obesity and hypertension was extracted from Tehran Lipid and Glucose Study, for males and females, in order to calculate the PAF of hypertension associated with obesity. Age standardization of the reported prevalence of obesity was done using the World Health Organization method. The PAF of hypertension associated with the joint effect of obesity and abdominal obesity in females was highest in Semnan Province: 22.7 [95% confidence interval (CI): 4.2-35.6], followed by Qom 21.09 (95% CI: 3.7-33.1), and Yazd 20.3 (95% CI: 3.5-32.1). In males, the highest PAF was observed in Qom Province 31.07 (95% CI: 16.7-41.1), followed by Semnan 29.6 (95% CI: 15.9-39.3), Qazvin 25.9 (95% CI: 13.7-34.5), Tehran 24.2 (95% CI: 12.7-32.3), and Isfahan 20.4 (95% CI: 3.5-27.4). Prevalence of hypertension is higher in more developed provinces. PAFs suggest that a sizable share of hypertension in these provinces is associated with obesity. It is recommended that health promotion programs focus on obesity in the provinces with a higher share of hypertension due to obesity. Copyright © 2016 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature.

PubMed

Kaul, D K; Liu, X; Nagel, R L

2001-11-15

In sickle cell (SS) vaso-occlusion, the culminating event is blockage of blood vessels by sickled red blood cells (SS RBCs). As shown in animal models, SS RBC-induced vaso-occlusion is often partial, allowing for a residual flow, hence oxygen delivery to partially occluded vessels could reduce vaso-occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emulsion (PFE) was tested for its anti-vaso-occlusive effects in the ex vivo mesocecum vasculature of the rat. Microvascular obstruction was induced by the infusion of deoxygenated SS RBCs into ex vivo preparations with or without pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC-endothelium interactions, leading to greater vaso-occlusion. Microvascular blockage resulted in increased peripheral resistance units (PRU). Deoxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated preparations and approximately a 2-fold PRU increase in PAF-treated preparations. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated PFE, resulted in PRU decreases to baseline values in both groups of experiments (with or without PAF). The PRU decrease caused by oxygenated PFE infusion was caused by unsickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravital microscopy. PFE had no effect on vascular tone. The efficacy of PFE appears to result from its greater capacity to dissolve oxygen (10-fold higher than plasma). The dislodgement of trapped SS RBCs and an increase in wall shear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further development of this approach is advisable.

Morphologies of the atria and pulmonary veins in relation to lone atrial fibrillation progression: a dual-source computed tomography scan study.

PubMed

Liu, Xing-Peng; Xu, Xia; Tian, Ying; Tang, Ri-Bo; Yu, Rong-Hui; Long, De-Yong; Sang, Cai-Hua; Jiang, Chen-Xi; Ning, Man; Dong, Jian-Zeng; Ma, Chang-Sheng

2012-11-01

Atrial Remodeling and Lone Atrial Fibrillation. We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (<3 months) lone persistent AF (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF, all of whom had a history of paroxysmal AF (PAF). The control group consisted of 33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more extensive atrial anatomic remodeling than the PAF group as shown by ∼40% higher spot biatrial volume, even though the mean duration of continuous AF was only 6 weeks. In contrast, the DSCT variables in the recently developed PsAF group and the short-lasting PsAF group were comparable, despite the fact that the mean duration of continuous AF in the latter group was 8 months. Series of cross-sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the only independent factor associated with the progression of lone PAF to PsAF (OR: 1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. Prominent anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of recent progression of lone paroxysmal AF to the persistent variety. © 2012 Wiley Periodicals, Inc.

PLANT HOMOLOGOUS TO PARAFIBROMIN is a component of the PAF1 complex and assists in regulating expression of genes within H3K27ME3-enriched chromatin.

PubMed

Park, Sunchung; Oh, Sookyung; Ek-Ramos, Julissa; van Nocker, Steven

2010-06-01

The human Paf1 complex (Paf1C) subunit Parafibromin assists in mediating output from the Wingless/Int signaling pathway, and dysfunction of the encoding gene HRPT2 conditions specific cancer-related disease phenotypes. Here, we characterize the organismal and molecular roles of PLANT HOMOLOGOUS TO PARAFIBROMIN (PHP), the Arabidopsis (Arabidopsis thaliana) homolog of Parafibromin. PHP resides in an approximately 670-kD protein complex in nuclear extracts, and physically interacts with other known Paf1C-related proteins in vivo. In striking contrast to the developmental pleiotropy conferred by mutation in other plant Paf1C component genes in Arabidopsis, loss of PHP specifically conditioned accelerated phase transition from vegetative growth to flowering and resulted in misregulation of a very limited subset of genes that included the flowering repressor FLOWERING LOCUS C. Those genes targeted by PHP were distinguished from the bulk of Arabidopsis genes and other plant Paf1C targets by strong enrichment for trimethylation of lysine-27 on histone H3 (H3K27me3) within chromatin. These findings suggest that PHP is a component of a plant Paf1C protein in Arabidopsis, but has a more specialized role in modulating expression of a subset of Paf1C targets.

Rate and pattern of interproximal dental attrition.

PubMed

Sarig, Rachel; Hershkovitz, Israel; Shpack, Nir; May, Hila; Vardimon, Alexander D

2015-08-01

Although occlusal and interproximal attrition occur because of diverse etiology and present dissimilar features, both progress with age. The objectives of this study were to reveal the rate and pattern of development of interproximal attrition facets (PAF) with age and to compare those with occlusal attrition (OA) changes. Five-hundred and ninety-four teeth were collected from 198 skulls (of adults, 20-71 yr of age). Three mandibular teeth [first premolar (P1), second premolar (P2), and first molar (M1)] were examined for PAF size and OA rate. Interproximal attrition and OA followed similar patterns of development until subjects reached 40-45 yr of age, after which they took different paths: PAF did not increase in size and were not as large as in younger groups, regardless of facet location, whereas OA continued to progress. The PAF changes with age differed between premolars and molars, unlike OA, which presented a similar rate for all teeth studied. Although OA scores presented significantly moderate correlations with age, PAF area size demonstrated low correlations with age. Low, but significant, correlations were found between the rate of OA and that of PAF. However, PAF and OA exhibited different patterns of development with age. Premolars and molars presented dissimilar development of PAF, which is probably caused by a unique attrition pattern in the molar teeth, different morphology, and force vectors. © 2015 Eur J Oral Sci.

PAF-derived nitrogen-doped 3D Carbon Materials for Efficient Energy Conversion and Storage.

PubMed

Xiang, Zhonghua; Wang, Dan; Xue, Yuhua; Dai, Liming; Chen, Jian-Feng; Cao, Dapeng

2015-06-05

Owing to the shortage of the traditional fossil fuels caused by fast consumption, it is an urgent task to develop the renewable and clean energy sources. Thus, advanced technologies for both energy conversion (e.g., solar cells and fuel cells) and storage (e.g., supercapacitors and batteries) are being studied extensively. In this work, we use porous aromatic framework (PAF) as precursor to produce nitrogen-doped 3D carbon materials, i.e., N-PAF-Carbon, by exposing NH3 media. The "graphitic" and "pyridinic" N species, large surface area, and similar pore size as electrolyte ions endow the nitrogen-doped PAF-Carbon with outstanding electronic performance. Our results suggest the N-doping enhance not only the ORR electronic catalysis but also the supercapacitive performance. Actually, the N-PAF-Carbon obtains ~70 mV half-wave potential enhancement and 80% increase as to the limiting current after N doping. Moreover, the N-PAF-Carbon displays free from the CO and methanol crossover effect and better long-term durability compared with the commercial Pt/C benchmark. Moreover, N-PAF-Carbon also possesses large capacitance (385 F g(-1)) and excellent performance stability without any loss in capacitance after 9000 charge-discharge cycles. These results clearly suggest that PAF-derived N-doped carbon material is promising metal-free ORR catalyst for fuel cells and capacitor electrode materials.

Short-term risk of liver and renal injury in hospitalized patients using micafungin: a multicentre cohort study.

PubMed

Schneeweiss, Sebastian; Carver, Peggy L; Datta, Kausik; Galar, Alicia; Johnson, Melissa D; Johnson, Matthew G; Marty, Francisco M; Nagel, Jerod; Najdzinowicz, Maryann; Saul, Melissa; Shoham, Shmuel; Silveira, Fernanda P; Varughese, Christy A; Wilck, Marissa; Weatherby, Lisa; Auton, Tim; Walker, Alexander M

2016-10-01

Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Amino Acid Residues Critical for Endoplasmic Reticulum Export and Trafficking of Platelet-activating Factor Receptor*

PubMed Central

Hirota, Nobuaki; Yasuda, Daisuke; Hashidate, Tomomi; Yamamoto, Teruyasu; Yamaguchi, Satoshi; Nagamune, Teruyuki; Nagase, Takahide; Shimizu, Takao; Nakamura, Motonao

2010-01-01

Several residues are conserved in the transmembrane domains (TMs) of G-protein coupled receptors. Here we demonstrate that a conserved proline, Pro247, in TM6 of platelet-activating factor receptor (PAFR) is required for endoplasmic reticulum (ER) export and trafficking after agonist-induced internalization. Alanine-substituted mutants of the conserved residues of PAFRs, including P247A, were retained in the ER. Because a PAFR antagonist, Y-24180, acted as a pharmacological chaperone to rescue ER retention, this retention is due to misfolding of PAFR. Methylcarbamyl (mc)-PAF, a PAFR agonist, did not increase the cell surface expression of P247A, even though another ER-retained mutant, D63A, was effectively trafficked. Signaling and accumulation of the receptors in the early endosomes were observed in the mc-PAF-treated P247A-expressing cells, suggesting that P247A was trafficked to the cell surface by mc-PAF, and thereafter disappeared from the surface due to aberrant trafficking, e.g. enhanced internalization, deficiency in recycling, and/or accelerated degradation. The aberrant trafficking was confirmed with a sortase-A-mediated method for labeling cell surface proteins. These results demonstrate that the conserved proline in TM6 is crucial for intracellular trafficking of PAFR. PMID:20007715

Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

PubMed

Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

2011-08-01

Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

Beneficial effects of losartan for prevention of paroxysmal atrial fibrillation in patients with sick sinus syndrome: analysis with memory function of pacemaker.

PubMed

Takii, Eiichi; Inage, Tomohito; Yoshida, Teruhisa; Ohe, Masatsugu; Gondo, Takeki; Haraguchi, Go; Ito, Shogo; Kumanomido, Jun; Imaizumi, Tsutomu; Fukuomoto, Yoshihiro

2016-03-01

Renin-angiotensin system (RAS) inhibitors may be useful in preventing the occurrence of paroxysmal atrial fibrillation (PAF). However, evaluation of such effect is difficult because many PAF episodes are asymptomatic and not all episodes are detected by intermittent electrocardiographic monitoring. A pacemaker has been developed with dedicated functions for AF detection and electrocardiogram storage. Accordingly, we examined the effect of losartan, an angiotensin receptor blocker on PAF occurrence using this new modality. We enrolled 70 consecutive patients who had undergone dual-chamber pacemaker implantation for sick sinus syndrome. Finally, 62 patients participated in the study. Thirty patients were randomized to the losartan group (mean 43 ± 12 mg/day) and 32 patients to the control group. They were followed up for 3 months. The frequency, the maximum duration and the total duration of PAF recorded by the stored electrocardiograms for the last 1 month during the observation period and study period were compared between the two groups. The change in the frequency of PAF from the observation period in the losartan and control groups was similar (-35 ± 25 vs. -67 ± 62 times; NS). However, the change in the maximum duration and the total duration of PAF was significantly shorter in the losartan group than in the control group (-493 ± 158 vs. -10 ± 69 min; p < 0.05, and -4007 ± 2334 vs. 1119 ± 714 min; p < 0.05, respectively). Losartan suppressed the maximum duration and the total duration of PAF in patients with sick sinus syndrome without hemodynamic changes. This is the first study to show the effect of a renin-angiotensin system inhibitor on the secondary prevention of PAF using the dedicated functions of a pacemaker for PAF detection and electrocardiogram storage.

Evaluation of Parallel Analysis Methods for Determining the Number of Factors

ERIC Educational Resources Information Center

Crawford, Aaron V.; Green, Samuel B.; Levy, Roy; Lo, Wen-Juo; Scott, Lietta; Svetina, Dubravka; Thompson, Marilyn S.

2010-01-01

Population and sample simulation approaches were used to compare the performance of parallel analysis using principal component analysis (PA-PCA) and parallel analysis using principal axis factoring (PA-PAF) to identify the number of underlying factors. Additionally, the accuracies of the mean eigenvalue and the 95th percentile eigenvalue criteria…

Pathogenesis of vascular leak in dengue virus infection.

PubMed

Malavige, Gathsaurie Neelika; Ogg, Graham S

2017-07-01

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

Premenstrual Assessment Form Typological Categories: Classification of Self-Defined Premenstrually Symptomatic and Asymptomatic Women.

ERIC Educational Resources Information Center

Youdale, J. Valda M.; Freeman, Richard J.

1987-01-01

Investigated use of newly developed assessment instrument for premenstrual syndrome, the Premenstrual Assessment Form (PAF), as a retrospective assessment instrument, and the PAF subtypes as accurate reflectors of subjective premenstrual symptomatology. Severely premenstrually symptomatic and asymptomatic women completed the PAF. Results partially…

Effects of altered gravity on the swimming behaviour of fish

NASA Astrophysics Data System (ADS)

Hilbig, R.; Anken, R. H.; Sonntag, G.; Höhne, S.; Henneberg, J.; Kretschmer, N.; Rahmann, H.

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness-phenomena (SMS, a kinetosis). It has been argued that SMS during PAFs might not be based on microgravity alone but rather on changing accelerations from 0g to 2g. We test here the hypothesis that PAF-induced kinetosis is based on asymmetric statoliths (i.e., differently weighed statoliths on the right and the left side of the head), with asymmetric inputs to the brain being disclosed at microgravity. Since fish frequently reveal kinetotic behaviour during PAFs (especially so-called spinning movements and looping responses), we investigated (1) whether or not kinetotically swimming fish at microgravity would have a pronounced inner ear otolith asymmetry and (2) whether or not slow translational and continuously changing linear (vertical) acceleration on ground induced kinetosis. These latter accelerations were applied using a specially developed parabel-animal-container (PAC) to stimulate the cupular organs. The results suggest that the fish tested on ground can counter changing accelerations successfully without revealing kinetotic swimming patterns. Kinetosis could only be induced by PAFs. This finding suggests that it is indeed microgravity rather than changing accelerations, which induces kinetosis. Moreover, we demonstrate that fish swimming kinetotically during PAFs correlates with a higher otolith asymmetry in comparison to normally behaving animals in PAFs.

Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States

PubMed Central

Meester, Reinier G.S.; Doubeni, Chyke A.; Lansdorp-Vogelaar, Iris; Goede, S.L.; Levin, Theodore R.; Quinn, Virginia P.; van Ballegooijen, Marjolein; Corley, Douglas A.; Zauber, Ann G.

2015-01-01

Purpose Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the U.S., but is underutilized. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. Methods The established MISCAN-colon microsimulation model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake; PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. Results There were an estimated 51,500 CRC deaths in 2010, about 63% (N∼32,200) of which were attributable to non-screening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N∼23,600) for 2010. Conclusions The majority of current U.S. CRC deaths are attributable to non-screening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches. PMID:25721748

Decreased importance of environmental risk factors for childhood asthma from 1996 to 2006.

PubMed

Bjerg, A; Hedman, L; Perzanowski, M; Wennergren, G; Lundbäck, B; Rönmark, E

2015-01-01

The large increase in asthma prevalence continues in several, but not all areas. Despite the individual risk factors that have been identified, the reasons for the observed trends in prevalence are largely unknown. This study sought to characterize what trends in risk factors accompanied trends in asthma prevalence. Two population-based cohorts of 7- to 8-year-old children from the same Swedish study areas examined by expanded International Study of Asthma and Allergy in Childhood questionnaires were compared 10 years apart. In 1996 and 2006, 3430 (97% participation) and 2585 (96% participation) questionnaires were completed, respectively. A subset was skin-prick-tested: in 1996 and 2006, 2148 (88% participation) and 1700 (90% participation) children, respectively. The adjusted population-attributable fraction (aPAF) was calculated using the prevalence and multivariate odds ratio of each risk factor. The prevalence of current asthma and wheeze was similar in 1996 and 2006. Allergic sensitization, however, increased from 21% to 30%. The prevalence of parental asthma increased from 17% to 24%, while respiratory infections and maternal smoking decreased (60% to 29% and 32% to 16%, respectively). The aPAFs of non-environmental risk factors for current asthma increased in 1996-2006: allergic sensitization from 35% to 41%, parental asthma from 27% to 45% and male sex from 20% to 25%. Conversely, the aPAFs of environmental risk factors decreased: respiratory infections from 36% to 32% and damp home and maternal smoking from 14% and 19%, respectively, to near zero in 2006. From 1996 to 2006, the non-environmental risk factors parental asthma, allergic sensitization and male sex had an increasing or constant importance for current asthma in 7- to 8-year-old children. The importance of the environmental exposures damp home, respiratory infections and maternal smoking decreased. This counterbalancing in risk factors may explain the level of prevalence of current asthma. © 2014 John Wiley & Sons Ltd.

Effect of protopine on cytosolic Ca2+ in rabbit platelets.

PubMed

Shen, Z Q; Chen, Z H; Duan, L

1999-04-01

To study the influence of protopine (Pro) on the cytoplasmic free Ca2+ concentration ([Ca2+]i) in rabbit platelets. Measurement of [Ca2+]i of platelets in vitro by Fura 2-AM fluorescence technique. In the presence of CaCl2 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 attenuated the rise in [Ca2+]i evoked by ADP from (420 +/- 57) to (320 +/- 26), (264 +/- 21), and (180 +/- 14) nmol.L-1, respectively, by arachidonic acid (AA) from (280 +/- 36) to (210 +/- 17), (184 +/- 21), and (143 +/- 16) nmol.L-1, respectively, and by platelet-activating factor (PAF) from (350 +/- 42) to (282 +/- 31), (223 +/- 30), and (165 +/- 15) nmol.L-1, respectively. In the presence of egtazic acid 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 reduced the Ca2+ release induced by ADP, AA, and PAF, respectively. Pro 10, 20, and 40 mumol.L-1 also decreased ADP-, AA-, and PAF-induced Ca2+ influx. Pro inhibited not only Ca2+ release but also the influx of Ca2+.

Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? A 3.0 Tesla magnetic resonance study.

PubMed

Messner, Alina; Stelzeneder, David; Trattnig, Stefan; Welsch, Götz H; Schinhan, Martina; Apprich, Sebastian; Brix, Martin; Windhager, Reinhard; Trattnig, Siegfried

2017-03-01

Indicating lumbar disc herniation via magnetic resonance imaging (MRI) T2 mapping in the posterior annulus fibrosus (AF). Sagittal T2 maps of 313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla (3T). The discs were rated according to disc herniation and bulging. Region of interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were compared. A significant increase in the T2 values of discs with herniations affecting the imaged area, compared to bulging discs and discs with lateral herniation, was shown in the PAF-10, where no association to the NP was apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus (NP). High T2 values in the PAF-10 suggest the presence of disc herniation (DH). The results indicate that T2 values in the PAF-20 correspond more to changes in the NP.

Spatial and annual variation in fecundity and oocyte atresia of yellowtail flounder, Limanda ferruginea, in U.S. waters

NASA Astrophysics Data System (ADS)

McElroy, W. David; Wuenschel, Mark J.; Towle, Emilee K.; McBride, Richard S.

2016-01-01

Potential annual fecundity (PAF) was estimated over three years (2010-2012) for yellowtail flounder with individuals from the three stocks off the northeast U.S. coast. Down-regulation of PAF, the resorption of oocytes during development, was evident as the vitellogenic cohort advanced, so we directly measured atresia of vitellogenic oocytes using stereological techniques. PAF models including relative fish condition, stock area, year, and oocyte diameter of the leading cohort explained more variation than models with just size alone based on Akaike information criteria. In a given year, Gulf of Maine females had lower PAF at size than southern New England females. Interannual differences were evident: PAF of both stocks was higher in 2010 and lower in 2012, with 2011 showing less synchronization between these stocks. Differences in size at age and relative condition suggested that energy available for somatic and reproductive growth was lower in some years in the Gulf of Maine and Georges Bank, especially in 2011. Georges Bank PAF and condition were intermediate to the other stocks or more similar to the Gulf of Maine, varying annually. A latitudinal gradient in PAF is evident based on our results and relative to earlier studies that included Canadian stocks. The magnitude of down-regulation was variable across stocks and typically 3-25% of PAF. This can be accounted for in fecundity estimates, by the seasonal schedule of sampling and use of an oocyte diameter term in the fecundity model. Theoretical models of atresia patterns suggested variable rates over the later portion of clutch development. The timing of down-regulation varied among years, and its intensity was influenced by female relative condition. Fecundity was related to fish size, but was also affected by fish condition and oocyte diameter (a proxy for time until spawning), and spatial and temporal effects. A longer time series of PAF may identify environmental drivers that modulate annual stock reproductive potential.

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

PubMed Central

Piedimonte, G; McDonald, D M; Nadel, J A

1991-01-01

Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. PMID:1711545

Structural basis for signal recognition and transduction by platelet-activating-factor receptor.

PubMed

Cao, Can; Tan, Qiuxiang; Xu, Chanjuan; He, Lingli; Yang, Linlin; Zhou, Ye; Zhou, Yiwei; Qiao, Anna; Lu, Minmin; Yi, Cuiying; Han, Gye Won; Wang, Xianping; Li, Xuemei; Yang, Huaiyu; Rao, Zihe; Jiang, Hualiang; Zhao, Yongfang; Liu, Jianfeng; Stevens, Raymond C; Zhao, Qiang; Zhang, Xuejun C; Wu, Beili

2018-06-01

Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal structures of human PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491 at 2.8-Å and 2.9-Å resolution, respectively. The structures, supported by molecular docking of PAF, provide insights into the signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an unusual conformation showing that the intracellular tips of helices II and IV shift outward by 13 Å and 4 Å, respectively, and helix VIII adopts an inward conformation. The PAFR structures, combined with single-molecule FRET and cell-based functional assays, suggest that the conformational change in the helical bundle is ligand dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.

Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism.

PubMed

Entman, M L; Youker, K; Shappell, S B; Siegel, C; Rothlein, R; Dreyer, W J; Schmalstieg, F C; Smith, C W

1990-05-01

Cardiac myocytes were isolated from adult dogs and incubated with isolated canine neutrophils (PMN). Intercellular adhesion was low and unchanged by stimulation of the PMN with zymosan activated serum or platelet activating factor (PAF) at concentrations that significantly enhance PMN adhesion to protein-coated glass and canine endothelial cell monolayers. Intercellular adhesion was significantly increased only when both myocytes and PMN were stimulated (e.g., myocytes incubated with IL-1, tumor necrosis factor, or phorbol myristate acetate, and PMN were chemotactically stimulated). Inhibitors of protein synthesis diminished the IL-1 beta-induced effect by greater than 80%. The IL-1 beta, PAF-stimulated PMN-myocyte adhesion was associated with substantial H2O2 production. Under conditions with low PMN-myocyte adhesion (i.e., IL-1 beta alone, PAF alone, or no stimulus) H2O2 production was generally less than 5% of that occurring with high adhesion. An anti-CD18 monoclonal antibody (R15.7) inhibited stimulated PMN-myocyte adhesion by greater than 95% and reduced H2O2 production by greater than 90%. Control isotype-matched, binding, and nonbinding antibodies were without effect on adherence or H2O2 production. The results indicate that cytokine stimulation of adult myocytes induces expression of a ligand involved in CD18-dependent adherence of canine neutrophils.

Lysophosphatidylcholine acyltransferase1 overexpression promotes oral squamous cell carcinoma progression via enhanced biosynthesis of platelet-activating factor.

PubMed

Shida-Sakazume, Tomomi; Endo-Sakamoto, Yosuke; Unozawa, Motoharu; Fukumoto, Chonji; Shimada, Ken; Kasamatsu, Atsushi; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2015-01-01

The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs. We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression. LPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemistry showed significantly (p<0.05) elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis. In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05); cellular migration was inhibited compared with control cells. Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression. LPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration. LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.

Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers.

PubMed

Gale, Trevor V; Horton, Timothy M; Grant, Donald S; Garry, Robert F

2017-09-01

Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

Effects of intracerebroventricular injections of free fatty acids, lysophospholipids, or platelet activating factor in a mouse model of orofacial pain.

PubMed

Vahidy, Wajiha H; Ong, Wei-Yi; Farooqui, Akhlaq A; Yeo, Jin-Fei

2006-10-01

The present study was carried out to determine the effects of central nervous free fatty acids, lysophospholipids, or platelet activating factor (PAF), in a mouse facial carrageenan injection model of orofacial pain. Mice that received intracerebroventricular (I.C.V.) injection of arachidonic acid or oleic acid showed significantly reduced allodynia and behavioral responses to von Frey hair stimulation of a carrageenan-injected area of the face, at 8 h post-injection, compared to controls that received I.C.V. injection of vehicle. In contrast to free fatty acids, increased responses were observed in mice at 72 h after I.C.V. lysophosphatidic acid or lysophosphatidylcholine injection, and at 8 and 24 h after PAF injection, compared vehicle injected controls. Information regarding pro-nociceptive effect of specific brain lipids may be a useful basis for further studies to explore mechanism.

Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers

PubMed Central

Gale, Trevor V.; Horton, Timothy M.; Grant, Donald S.

2017-01-01

Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients. PMID:28922385

Prediction equation for estimating total daily energy requirements of special operations personnel.

PubMed

Barringer, N D; Pasiakos, S M; McClung, H L; Crombie, A P; Margolis, L M

2018-01-01

Special Operations Forces (SOF) engage in a variety of military tasks with many producing high energy expenditures, leading to undesired energy deficits and loss of body mass. Therefore, the ability to accurately estimate daily energy requirements would be useful for accurate logistical planning. Generate a predictive equation estimating energy requirements of SOF. Retrospective analysis of data collected from SOF personnel engaged in 12 different SOF training scenarios. Energy expenditure and total body water were determined using the doubly-labeled water technique. Physical activity level was determined as daily energy expenditure divided by resting metabolic rate. Physical activity level was broken into quartiles (0 = mission prep, 1 = common warrior tasks, 2 = battle drills, 3 = specialized intense activity) to generate a physical activity factor (PAF). Regression analysis was used to construct two predictive equations (Model A; body mass and PAF, Model B; fat-free mass and PAF) estimating daily energy expenditures. Average measured energy expenditure during SOF training was 4468 (range: 3700 to 6300) Kcal·d- 1 . Regression analysis revealed that physical activity level ( r  = 0.91; P  < 0.05) and body mass ( r  = 0.28; P  < 0.05; Model A), or fat-free mass (FFM; r  = 0.32; P  < 0.05; Model B) were the factors that most highly predicted energy expenditures. Predictive equations coupling PAF with body mass (Model A) and FFM (Model B), were correlated ( r  = 0.74 and r  = 0.76, respectively) and did not differ [mean ± SEM: Model A; 4463 ± 65 Kcal·d - 1 , Model B; 4462 ± 61 Kcal·d - 1 ] from DLW measured energy expenditures. By quantifying and grouping SOF training exercises into activity factors, SOF energy requirements can be predicted with reasonable accuracy and these equations used by dietetic/logistical personnel to plan appropriate feeding regimens to meet SOF nutritional requirements across their mission profile.

Orthopedic, ophthalmic, and psychiatric diseases primarily affect activity limitation for Japanese males and females: Based on the Comprehensive Survey of Living Conditions.

PubMed

Myojin, Tomoya; Ojima, Toshiyuki; Kikuchi, Keiko; Okada, Eisaku; Shibata, Yosuke; Nakamura, Mieko; Hashimoto, Shuji

2017-02-01

Healthy life expectancy (HLE) is used as one of the primary objectives of fundamental health promotion plans and social development plans. Activity limitation is used to calculate HLE, but little study has been done to identify determinants of activity limitation in order to extend HLE. The purpose of this study is to identify diseases and injuries that commonly lead to activity limitation to prioritize countermeasures against activity limitation. We used anonymous data from the 2007 "Comprehensive Survey of Living Conditions," collected by the Ministry of Health, Labour and Welfare of Japan according to the Statistics Act, Article 36. We used logistic regression analyses and calculated odds ratios (ORs) after adjusting for age and sex. Limitation in daily activities was applied as the dependent variable, and each disease/injury was applied as an independent variable in this analysis. Furthermore, population attributable fractions (PAFs) were calculated. The provided data included 98,789 subjects. We used data for 75,986 valid subjects aged 12 years or older. The following diseases showed high PAF: backache (PAF 13.27%, OR 3.88), arthropathia (PAF 7.61%, OR 4.82), eye and optical diseases (PAF 6.39%, OR 2.01), and depression and other mental diseases (PAF 5.70%, OR 11.55). PAFs of cerebrovascular diseases, hypertension, and diabetes were higher for males than for females; on the other hand, PAFs of orthopedic diseases were higher among females. Our results indicate that orthopedic diseases, ophthalmic diseases, and psychiatric diseases particularly affect activity limitation. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Transfusion of irradiated red blood cell units with a potassium adsorption filter: A randomized controlled trial.

PubMed

Cid, Joan; Villegas, Vanessa; Carbassé, Gloria; Alba, Cristina; Perea, Dolores; Lozano, Miguel

2016-05-01

The irradiation of red blood cells (RBCs) causes damage of the RBC membrane with increased potassium (K) leak during storage compared with nonirradiated RBC units of similar age. A previous in vitro study showed a mean reduction of K of 94 ± 5% with a potassium adsorption filter (PAF). A prospective, single-center, nonblinded, randomized controlled trial (RCT) was designed to evaluate the safety and efficacy of transfusing irradiated RBC units with the PAF. Patients 18 years of age or older who received irradiated RBC units due to chemotherapy-induced anemia were randomly assigned to receive irradiated RBC units with the PAF (PAF group) or with the standard blood infusion set (control group). Primary outcome measures were safety and efficacy of the PAF (absolute change in hemoglobin [Hb] and K, respectively, in patient's blood values after transfusing the irradiated RBC units with or without the PAF). A total of 63 irradiated RBC units were transfused to 17 patients in the control group, and a total of 56 irradiated RBC units were transfused to 13 patients in the PAF group. The absolute change of Hb (9.3 ± 6.3 g/L vs. 8.1 ± 5.8 g/L; p = 0.3) and the absolute change of K (-0.01 ± 0.4 mmol/L vs. -0.01 ± 0.3 mmol/L; p = 0.2) were comparable between the two groups of the trial. The transfusion of 1 irradiated RBC unit with the PAF was as safe and efficacious as the transfusion of 1 irradiated RBC unit with the standard blood infusion set in patients with chemotherapy-induced anemia. © 2016 AABB.

Phosphorylation of SPT5 by CDKD;2 Is Required for VIP5 Recruitment and Normal Flowering in Arabidopsis thaliana[OPEN

PubMed Central

Lu, Chengyuan; Tian, Yongke; Wang, Shiliang; Su, Yanhua; Mao, Ting; Chen, Qingqing; Xu, Zuntao

2017-01-01

The elongation factor suppressor of Ty 5 homolog (Spt5) is a regulator of transcription and histone methylation. In humans, phosphorylation of SPT5 by P-TEFb, a protein kinase composed of Cyclin-dependent kinase 9 (CDK9) and cyclin T, interacts with the RNA polymerase II-associated factor1 (PAF1) complex. However, the mechanism of SPT5 phosphorylation is not well understood in plants. Here, we examine the function of SPT5 in Arabidopsis thaliana and find that spt5 mutant flowers early under long-day and short-day conditions. SPT5 interacts with the CDK-activating kinase 4 (CAK4; CDKD;2) and is specifically phosphorylated by CDKD;2 at threonines. The phosphorylated SPT5 binds VERNALIZATION INDEPENDENCE5 (VIP5), a subunit of the PAF1 complex. Genetic analysis showed that VIP5 acts downstream of SPT5 and CDKD;2. Loss of SPT5 or CDKD;2 function results in early flowering because of decreased amounts of FLOWERING LOCUS C (FLC) transcript. Importantly, CDKD;2 and SPT5 are required for the deposition of VIP5 and the enhancement of trimethylation of histone 3 lysine 4 in the chromatin of the FLC locus. Together, our results provide insight into the mechanism by which the Arabidopsis elongation factor SPT5 recruits the PAF1 complex via the posttranslational modification of proteins and suggest that the phosphorylation of SPT5 by CDKD;2 enables it to recruit VIP5 to regulate chromatin and transcription in Arabidopsis. PMID:28188267

Integrating public risk perception into formal natural hazard risk assessment

NASA Astrophysics Data System (ADS)

Plattner, Th.; Plapp, T.; Hebel, B.

2006-06-01

An urgent need to take perception into account for risk assessment has been pointed out by relevant literature, its impact in terms of risk-related behaviour by individuals is obvious. This study represents an effort to overcome the broadly discussed question of whether risk perception is quantifiable or not by proposing a still simple but applicable methodology. A novel approach is elaborated to obtain a more accurate and comprehensive quantification of risk in comparison to present formal risk evaluation practice. A consideration of relevant factors enables a explicit quantification of individual risk perception and evaluation. The model approach integrates the effective individual risk reff and a weighted mean of relevant perception affecting factors PAF. The relevant PAF cover voluntariness of risk-taking, individual reducibility of risk, knowledge and experience, endangerment, subjective damage rating and subjective recurrence frequency perception. The approach assigns an individual weight to each PAF to represent its impact magnitude. The quantification of these weights is target-group-dependent (e.g. experts, laypersons) and may be effected by psychometric methods. The novel approach is subject to a plausibility check using data from an expert-workshop. A first model application is conducted by means of data of an empirical risk perception study in Western Germany to deduce PAF and weight quantification as well as to confirm and evaluate model applicbility and flexibility. Main fields of application will be a quantification of risk perception by individual persons in a formal and technical way e.g. for the purpose of risk communication issues in illustrating differing perspectives of experts and non-experts. For decision making processes this model will have to be applied with caution, since it is by definition not designed to quantify risk acceptance or risk evaluation. The approach may well explain how risk perception differs, but not why it differs. The formal model generates only "snap shots" and considers neither the socio-cultural nor the historical context of risk perception, since it is a highly individualistic and non-contextual approach.

Quinidine, but Not Eicosanoid Antagonists or Dexamethasone, Protect the Gut from Platelet Activating Factor-Induced Vasoconstriction, Edema and Paralysis

PubMed Central

Lautenschläger, Ingmar; Frerichs, Inéz; Dombrowsky, Heike; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martin; Weiler, Norbert; Uhlig, Stefan

2015-01-01

Intestinal circulatory disturbances, atony, edema and swelling are of great clinical relevance, but the related mechanisms and possible therapeutic options are poorly characterized, in part because of the difficulties to comprehensively analyze these conditions. To overcome these limitations we have developed a model of the isolated perfused rat small intestine where all of these symptoms can be studied simultaneously. Here we used this model to study the role of eicosanoids, steroids and quinidine in platelet-activating factor (PAF)-induced intestinal disorders. A vascular bolus of PAF (0.5 nmol) triggered release of thromboxane and peptidoleukotrienes into the vascular bed (peak concentration 35 nM and 0.8 nM) and reproduced all symptoms of intestinal failure: mesenteric vasoconstriction, translocation of fluid and macromolecules from the vasculature to the lumen and lymphatics, intestinal edema formation, loss of intestinal peristalsis and decreased galactose uptake. All effects of PAF were abolished by the PAF-receptor antagonist ABT491 (2.5 μM). The COX and LOX inhibitors ASA and AA861 (500 μM, 10 μM) did not exhibit barrier-protective effects and the eicosanoid antagonists SQ29548 and MK571 (10 μM, each) only moderately attenuated the loss of vascular fluid, the redistribution to the lumen and the transfer of FITC dextran to the lumen. The steroid dexamethasone (10 μM) showed no barrier-protective properties and failed to prevent edema formation. Quinidine (100 μM) inhibited the increase in arterial pressure, stabilized all the intestinal barriers, and reduced lymph production and the transfer of FITC dextran to the lymph. While quinidine by itself reduced peristalsis, it also obviated paralysis, preserved intestinal functions and prevented edema formation. We conclude that quinidine exerts multiple protective effects against vasoconstriction, edema formation and paralysis in the intestine. The therapeutic use of quinidine for intestinal ailments deserves further study. PMID:25793535

Examining Parents' Ratings of Middle-School Students' Academic Self-Regulation Using Principal Axis Factoring Analysis

ERIC Educational Resources Information Center

Chen, Peggy P.; Cleary, Timothy J.; Lui, Angela M.

2015-01-01

This study examined the reliability and validity of a parent rating scale, the "Self-Regulation Strategy Inventory: Parent Rating Scale" ("SRSI-PRS"), using a sample of 451 parents of sixth- and seventh-grade middle-school students. Principal axis factoring (PAF) analysis revealed a 3-factor structure for the 23-item SRSI-PRS:…

The Histone Modification Domain of Paf1 Complex Subunit Rtf1 Directly Stimulates H2B Ubiquitylation through an Interaction with Rad6

DOE PAGES

Van Oss, S. Branden; Shirra, Margaret K.; Bataille, Alain R.; ...

2016-11-10

The five-subunit yeast Paf1 Complex (Paf1C) regulates all stages of transcription and is critical for the monoubiquitylation of histone H2B (H2Bub), a modification that broadly influences chromatin structure and eukaryotic transcription. Here we show that the histone modification domain (HMD) of Paf1C subunit Rtf1 directly interacts with the ubiquitin conjugase Rad6 and stimulates H2Bub independently of transcription. We present the crystal structure of the Rtf1 HMD and use site-specific, in vivo crosslinking to identify a conserved Rad6 interaction surface. Utilizing ChIP-exo analysis, we define the localization patterns of the H2Bub machinery at high resolution and demonstrate the importance of Paf1Cmore » in targeting the Rtf1 HMD, and thereby H2Bub, to its appropriate genomic locations. Finally, we observe HMD-dependent stimulation of H2Bub in a transcription-free, reconstituted in vitro system. Taken together, our results argue for an active role for Paf1C in promoting H2Bub and ensuring its proper localization in vivo.« less

Predictive assimilation framework to support contaminated site understanding and remediation

NASA Astrophysics Data System (ADS)

Versteeg, R. J.; Bianchi, M.; Hubbard, S. S.

2014-12-01

Subsurface system behavior at contaminated sites is driven and controlled by the interplay of physical, chemical, and biological processes occurring at multiple temporal and spatial scales. Effective remediation and monitoring planning requires an understanding of this complexity that is current, predictive (with some level of confidence) and actionable. We present and demonstrate a predictive assimilation framework (PAF). This framework automatically ingests, quality controls and stores near real-time environmental data and processes these data using different inversion and modeling codes to provide information on the current state and evolution of the subsurface system. PAF is implemented as a cloud based software application which has five components: (1) data acquisition, (2) data management, (3) data assimilation and processing, (4) visualization and result deliver and (5) orchestration. Access to and interaction with PAF is done through a standard browser. PAF is designed to be modular so that it can ingest and process different data streams dependent on the site. We will present an implementation of PAF which uses data from a highly instrumented site (the DOE Rifle Subsurface Biogeochemistry Field Observatory in Rifle, Colorado) for which PAF automatically ingests hydrological data and forward models groundwater flow in the saturated zone.

Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy.

PubMed

Saborido, C Martin; Hockenhull, J; Bagust, A; Boland, A; Dickson, R; Todd, D

2010-06-01

Atrial fibrillation (AF) is a tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of impairment of atrial function and a rapid, irregular heartbeat. The annual incidence rate of paroxysmal AF (PAF) has been estimated at 1.0 per 1000 person-years (95% confidence interval 0.9 to 1.1), and reported prevalence rates show wide variations depending on age and country. Conventional treatment strategies for PAF focus on the suppression of paroxysms of AF and return to normal sinus rhythm. To summarise the results of the rapid reviews of the clinical effectiveness and cost-effectiveness literature describing the pill-in-the-pocket (PiP) approach for the treatment of patients with PAF; and to develop an economic model to assess the cost-effectiveness of PiP compared with in-hospital treatment (IHT) or continuous antiarrhythmic drugs (AADs) for the treatment of patients with PAF. Ovid MEDLINE and Ovid OLDMEDLINE 1950 to present with Daily Update were searched. The following electronic databases were searched for ongoing trials: Health Services Research Projects in Progress, ClinicalTrials.gov, metaRegister of Current Controlled Trials, BioMed Central, World Health Organization International Clinical Trials Registry Platform, ClinicalStudyResults.org and the National Library of Medicine Gateway. Inclusion criteria, which included patients suffering from PAF, were independently applied to all identified references by two reviewers (JH and CMS). Electronic searches were conducted to identify clinical effectiveness and cost-effectiveness evidence describing the use of a PiP strategy for the treatment of PAF, published since the release of the Royal College of Physicians' national guidelines on AF in June 2006. A Markov model was constructed to examine differences between three PAF strategies (PiP, AAD and IHT) in terms of cost per quality-adjusted life-year (QALY). A Markov model structure was chosen because it is assumed that PAF is a condition that causes patients to move between a limited number of relevant health states during their lives. The search strategies for clinical studies identified 201 randomised controlled trials (RCTs). Of the 201 RCTs identified, 12 were deemed to be relevant to the decision problem as they included drugs used to treat PAF; summary data were abstracted from these studies in order to inform the development of the economic model only. The model results indicate that the PiP strategy is slightly less effective than the other two strategies, but also less costly (incremental cost-effectiveness ratio of 45,916 pounds per QALY when compared to AAD, and 12,424 pounds per QALY when compared to IHT). The one-way sensitivity analyses performed do not show substantial changes in relative cost-effectiveness except in relation to the age of patients, where PiP dominates AAD in men over 65 years and in women over 70 years. At a threshold of 25,000 pounds per QALY, IHT has the maximum probability of being cost-effective at this threshold. For threshold values between 0 pounds and 9266 pounds per QALY, PiP is the option exhibiting the maximum probability of being cost-effective. The AAD strategy has a very poor probability of being cost-effective under any threshold. However, none of the strategies considered has more than a 40% probability of being cost-effective at a threshold of 25,000 pounds per QALY at any threshold level. This demonstrates the uncertainty around the parameters and its effect on the decision to choose any one strategy over the others. Most of the data used to populate the model have been taken from studies with populations that do not match the patient population specified in the decision problem. Populating the model in this way was unavoidable as there was a paucity of published clinical effectiveness and cost-effectiveness data describing a PiP strategy for this highly specific group of patients. Overall, a PiP strategy seems to be slightly less effective (i.e. fewer QALYs gained) than AAD and IHT, but is associated with cost savings. A PiP strategy seems to be more efficacious and cost-effective than an AAD strategy in men over 65 years and women over 70 years, but this is principally due to a very slight difference in QALY gained by the PiP strategy. A change in clinical practice that includes the introduction of PiP may save costs, but also involves a reduction in clinical effectiveness compared to existing approaches used to treat patients with PAF. Uncertainty in the available clinical data means there was insufficient evidence to support a recommendation for the use of PiP strategy in patients with PAF. Further research should identify outcomes of interest such as adverse events and recurrent AF episodes in an RCT setting because the only clinical study addressing these issues, even partially, is not an RCT but a descriptive analysis. Patient preferences also need to be considered in any future research designs.

Assessing the Structure of the Ways of Coping Questionnaire in Fibromyalgia Patients Using Common Factor Analytic Approaches.

PubMed

Van Liew, Charles; Santoro, Maya S; Edwards, Larissa; Kang, Jeremy; Cronan, Terry A

2016-01-01

The Ways of Coping Questionnaire (WCQ) is a widely used measure of coping processes. Despite its use in a variety of populations, there has been concern about the stability and structure of the WCQ across different populations. This study examines the factor structure of the WCQ in a large sample of individuals diagnosed with fibromyalgia. The participants were 501 adults (478 women) who were part of a larger intervention study. Participants completed the WCQ at their 6-month assessment. Foundational factoring approaches were performed on the data (i.e., maximum likelihood factoring [MLF], iterative principal factoring [IPF], principal axis factoring (PAF), and principal components factoring [PCF]) with oblique oblimin rotation. Various criteria were evaluated to determine the number of factors to be extracted, including Kaiser's rule, Scree plot visual analysis, 5 and 10% unique variance explained, 70 and 80% communal variance explained, and Horn's parallel analysis (PA). It was concluded that the 4-factor PAF solution was the preferable solution, based on PA extraction and the fact that this solution minimizes nonvocality and multivocality. The present study highlights the need for more research focused on defining the limits of the WCQ and the degree to which population-specific and context-specific subscale adjustments are needed.

Assessing the Structure of the Ways of Coping Questionnaire in Fibromyalgia Patients Using Common Factor Analytic Approaches

PubMed Central

Edwards, Larissa; Kang, Jeremy

2016-01-01

The Ways of Coping Questionnaire (WCQ) is a widely used measure of coping processes. Despite its use in a variety of populations, there has been concern about the stability and structure of the WCQ across different populations. This study examines the factor structure of the WCQ in a large sample of individuals diagnosed with fibromyalgia. The participants were 501 adults (478 women) who were part of a larger intervention study. Participants completed the WCQ at their 6-month assessment. Foundational factoring approaches were performed on the data (i.e., maximum likelihood factoring [MLF], iterative principal factoring [IPF], principal axis factoring (PAF), and principal components factoring [PCF]) with oblique oblimin rotation. Various criteria were evaluated to determine the number of factors to be extracted, including Kaiser's rule, Scree plot visual analysis, 5 and 10% unique variance explained, 70 and 80% communal variance explained, and Horn's parallel analysis (PA). It was concluded that the 4-factor PAF solution was the preferable solution, based on PA extraction and the fact that this solution minimizes nonvocality and multivocality. The present study highlights the need for more research focused on defining the limits of the WCQ and the degree to which population-specific and context-specific subscale adjustments are needed. PMID:28070160

Modulation of Gardos channel activity by cytokines in sickle erythrocytes.

PubMed

Rivera, Alicia; Jarolim, Petr; Brugnara, Carlo

2002-01-01

It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using (86)Rubidium ((86)Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation normal T cells expressed and secreted (RANTES) on the Gardos channel activity in human normal and sickle red cells. It was found that PAF (EC(50): 15 +/- 7 nM), RANTES (EC(50), 9 +/- 6 ng/mL [1.2 +/- 0.8 nM]), IL-10 (EC(50), 11 +/- 8 ng/mL [204 +/- 148 nM]), and ET-1 (EC(50), 123 +/- 34 nM) induce a significant increase in Gardos channel activity-between 28% and 84%-over the control. In addition, these agents modify the Gardos channel affinity for internal Ca(++) (K(0.5)) by 2- to 6-fold. Biochemical evidence is provided for the presence of ET receptor subtype B in sickle and normal red cells. Furthermore, it was found that ET-1, PAF, RANTES, and IL-10 induce a significant increase in red cell density (P <.05). These data suggest that activation of the Gardos channel is functionally coupled to receptor motifs such as C-X-C (PAF), C-C (RANTES), and ET receptor subtype B. Thus, cell volume regulation or erythrocyte hydration states might be altered by activation of the Gardos channel by cytokines in vivo. The role of these mediators in promoting sickle cell dehydration in vivo is under investigation.

Trichinella spiralis infection enhances protein kinase C phosphorylation in guinea pig alveolar macrophages.

PubMed

Dzik, J M; Zieliński, Z; Cieśla, J; Wałajtys-Rode, E

2010-03-01

To learn more about the signalling pathways involved in superoxide anion production in guinea pig alveolar macrophages, triggered by Trichinella spiralis infection, protein level and phosphorylation of mitogen activated protein (MAP) kinases and protein kinase C (PKC) were investigated. Infection with T. spiralis, the nematode having 'lung phase' during colonization of the host, enhances PKC phosphorylation in guinea pig alveolar macrophages. Isoenzymes beta and delta of PKC have been found significantly phosphorylated, although their location was not changed as a consequence of T. spiralis infection. Neither in macrophages from T. spiralis-infected guinea pig nor in platelet-activating factor (PAF)-stimulated macrophages from uninfected animals, participation of MAP kinases in respiratory burst activation was statistically significant. The parasite antigens seem to act through macrophage PAF receptors, transducing a signal for enhanced NADPH oxidase activity, as stimulating effect of newborn larvae homogenate on respiratory burst was abolished by specific PAF receptor antagonist CV 6209. A suppressive action of T. spiralis larvae on host alveolar macrophage innate immunological response was reflected by diminished protein level of ERK2 kinase and suppressed superoxide anion production, in spite of high level of PKC phosphorylation.

Multiple receptors mobilize calcium through a pertussis toxin (PT) sensitive GTP-binding protein in human neutrophils (PMN's)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lad, P.M.; Olson, C.V.; Grewal, I.S.

1986-03-05

Treatment of PMN's with PT causes an abolition of chemotaxis, enzyme release, superoxide generation and aggregation caused by f-met-leu-phe (FMLP),C5a and platelet activating factor (PAF). Lectin (Con-A) induced capping and receptor induced shape change are abolished, but phagocytosis is unaltered. In whole cells, calcium mobilization induced by FMLP, PAF and Con-A inhibited by PT although the FMLP-mediated effect is more susceptible to PT's effects. Treatment of PMN's with phorbol 12-myristate 13 acetate (PMA) causes an abolition of calcium mobilization by all agents in a range which also inhibits cap formation. Investigation of calcium uptake reveals PT sensitive and insensitive components.more » Reciprocal interactions between Ns and Ni proteins are also observed since pretreatment with FMLP and PAF causes a stimulation of Ns-mediated cyclic AMP enhancement while pretreatment with Ns linked receptors (PGE/sub 1/ and beta receptor agonists) inhibits calcium mobilization. Comparative peptide mapping studies indicate substantial similarity between Ni proteins in PMN's, platelets and human erythrocytes. The authors results suggest that the Ni linked calcium mobilization sensitive to PMA is important to the regulation of the human neutrophil.« less

When Antimicrobial Stewardship Isn′t Watching: The Educational Impact of Critical Care Prospective Audit and Feedback

PubMed Central

Fleming, Dimitra; Ali, Karim F.; Matelski, John; D'Sa, Ryan; Powis, Jeff

2016-01-01

Prospective audit and feedback (PAF) is an effective strategy to optimize antimicrobial use in the critical care setting, yet whether skills gained during PAF influence future antimicrobial prescribing is uncertain. This multisite study demonstrates that knowledge learned during PAF is translated and incorporated into the practice of critical care physicians even when not supported by an antimicrobial stewardship program. PMID:27382599

Reorganization in processing of spectral and temporal input in the rat posterior auditory field induced by environmental enrichment

PubMed Central

Jakkamsetti, Vikram; Chang, Kevin Q.

2012-01-01

Environmental enrichment induces powerful changes in the adult cerebral cortex. Studies in primary sensory cortex have observed that environmental enrichment modulates neuronal response strength, selectivity, speed of response, and synchronization to rapid sensory input. Other reports suggest that nonprimary sensory fields are more plastic than primary sensory cortex. The consequences of environmental enrichment on information processing in nonprimary sensory cortex have yet to be studied. Here we examine physiological effects of enrichment in the posterior auditory field (PAF), a field distinguished from primary auditory cortex (A1) by wider receptive fields, slower response times, and a greater preference for slowly modulated sounds. Environmental enrichment induced a significant increase in spectral and temporal selectivity in PAF. PAF neurons exhibited narrower receptive fields and responded significantly faster and for a briefer period to sounds after enrichment. Enrichment increased time-locking to rapidly successive sensory input in PAF neurons. Compared with previous enrichment studies in A1, we observe a greater magnitude of reorganization in PAF after environmental enrichment. Along with other reports observing greater reorganization in nonprimary sensory cortex, our results in PAF suggest that nonprimary fields might have a greater capacity for reorganization compared with primary fields. PMID:22131375

Comparison of Prolonged Atrial Electromechanical Delays with Different Definitions in the Discrimination of Patients with Non-Valvular Paroxysmal Atrial Fibrillation

PubMed Central

Lee, Dong Hyun; Choi, Sun Young; Seo, Jeong-Min; Choi, Jae-Hyuk; Cho, Young-Rak; Park, Kyungil; Kim, Moo Hyun; Kim, Young-Dae

2015-01-01

Background and Objectives Previous studies have evaluated atrial electromechanical delays (AEMDs) with a number of different definitions to discriminate patients with paroxysmal atrial fibrillation (PAF) from controls without PAF. However, their discriminative values for PAF have not previously been directly compared. Subjects and Methods A total of 65 PAF patients and 130 control subjects matched for age, sex, history of hypertension, and diabetes mellitus were selected. The AEMDi and AEMDp were defined as the time intervals from the initiation of the P wave on the surface electrocardiogram to the initiation and peak of the late diastolic transmitral inflow on pulsed wave Doppler images, respectively. The AEMDim and AEMDpm were defined as the time intervals from the initiation of the P wave on the surface electrocardiogram to the initiation and peak of the late diastolic lateral mitral annular motion on tissue Doppler images, respectively. Results There were no significant differences in the clinical characteristics between the two groups. All 4 AEMDs were consistently longer in the PAF group, and proven effective to differentiate the PAF patients from the controls. The AEMDi measurement had a larger area under the curve (AUC) than the other AEMDs, left atrial volume index, and P wave amplitude. However, the AEMDp, AEMDim, and AEMDpm measurements had AUCs similar to those of the left atrial volume index and P wave amplitude. Conclusion The findings suggest that the AEMDi is better than the other AEMDs for the discrimination of PAF patients from the controls. PMID:26617650

Inositol-C2-PAF down-regulates components of the antigen presentation machinery in a 2D-model of epidermal inflammation.

PubMed

Semini, Geo; Hildmann, Annette; Klein, Andreas; Lucka, Lothar; Schön, Margarete; Schön, Michael P; Shmanai, Vadim; Danker, Kerstin

2014-02-01

In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells modulate keratinocyte function via the secretion of pro-inflammatory cytokines. Keratinocytes then produce mediators that recruit and activate immune cells and amplify the inflammatory response. These pathophysiological tissue changes are caused by altered gene expression and the proliferation and maturation of dermal and epidermal cells. We recently demonstrated that the glycosidated phospholipid Ino-C2-PAF down-regulates a plethora of gene products associated with innate and acquired immune responses and inflammation in the HaCaT keratinocyte cell line. To further evaluate the influence of Ino-C2-PAF we established an in vitro 2D-model of epidermal inflammation. The induction of inflammation and the impact of Ino-C2-PAF were assessed in this system using a genome-wide microarray analysis. In addition, the expression of selected genes was validated using qRT-PCR and flow cytometry. Treatment of the keratinocytes with a mix of proinflammatory cytokines resulted in transcriptional effects on a variety of genes involved in cutaneous inflammation and immunity, while additional treatment with Ino-C2-PAF counteracted the induction of many of these genes. Remarkably, Ino-C2-PAF suppressed the expression of a group of targets that are implicated in antigen processing and presentation, including MHC molecules. Thus, it is conceivable that Ino-C2-PAF possess therapeutic potential for inflammatory skin disorders, such as psoriasis and allergic contact dermatitis. Copyright © 2013 Elsevier Inc. All rights reserved.

The RNA Polymerase-Associated Factor 1 Complex Is Required for Plant Touch Responses

PubMed Central

Jensen, Gregory S.; Fal, Kateryna; Hamant, Olivier

2017-01-01

Abstract Thigmomorphogenesis is a stereotypical developmental alteration in the plant body plan that can be induced by repeatedly touching plant organs. To unravel how plants sense and record multiple touch stimuli we performed a novel forward genetic screen based on the development of a shorter stem in response to repetitive touch. The touch insensitive (ths1) mutant identified in this screen is defective in some aspects of shoot and root thigmomorphogenesis. The ths1 mutant is an intermediate loss-of-function allele of VERNALIZATION INDEPENDENCE 3 (VIP3), a previously characterized gene whose product is part of the RNA polymerase II-associated factor 1 (Paf1) complex. The Paf1 complex is found in yeast, plants and animals, and has been implicated in histone modification and RNA processing. Several components of the Paf1 complex are required for reduced stem height in response to touch and normal root slanting and coiling responses. Global levels of histone H3K36 trimethylation are reduced in VIP3 mutants. In addition, THS1/VIP3 is required for wild type histone H3K36 trimethylation at the TOUCH3 (TCH3) and TOUCH4 (TCH4) loci and for rapid touch-induced upregulation of TCH3 and TCH4 transcripts. Thus, an evolutionarily conserved chromatin-modifying complex is required for both short- and long-term responses to mechanical stimulation, providing insight into how plants record mechanical signals for thigmomorphogenesis. PMID:28204553

Understanding the disparity: predictors of virologic failure in women using highly active antiretroviral therapy vary by race and/or ethnicity.

PubMed

McFall, Allison M; Dowdy, David W; Zelaya, Carla E; Murphy, Kerry; Wilson, Tracey E; Young, Mary A; Gandhi, Monica; Cohen, Mardge H; Golub, Elizabeth T; Althoff, Keri N

2013-11-01

Stark racial/ethnic disparities in health outcomes exist among those living with HIV in the United States. One of 3 primary goals of the National HIV/AIDS Strategy is to reduce HIV-related disparities and health inequities. Using data from HIV-infected women participating in the Women's Interagency HIV Study from April 2006 to March 2011, we measured virologic failure (HIV RNA >200 copies/mL) after suppression (HIV RNA < 80 copies/mL) on highly active antiretroviral therapy. We identified predictors of virologic failure using discrete time survival analysis and calculated racial/ethnic-specific population-attributable fractions (PAFs). Of 887 eligible women, 408 (46%) experienced virologic failure during the study period. Hispanic and white women had significantly lower hazards of virologic failure than African American women [Hispanic hazard ratio, (HR) = 0.8, 95% confidence interval: (0.6 to 0.9); white HR = 0.7 (0.5 to 0.9)]. The PAF of virologic failure associated with low income was higher in Hispanic [adjusted hazard ratios (aHR) = 2.2 (0.7 to 6.5), PAF = 49%] and African American women [aHR = 1.8 (1.1 to 3.2), PAF = 38%] than among white women [aHR = 1.4 (0.6 to 3.4), PAF = 16%]. Lack of health insurance compared with public health insurance was associated with virologic failure only among Hispanic [aHR = 2.0 (0.9 to 4.6), PAF = 22%] and white women [aHR = 1.9 (0.7 to 5.1), PAF = 13%]. By contrast, depressive symptoms were associated with virologic failure only among African-American women [aHR = 1.6 (1.2 to 2.2), PAF = 17%]. In this population of treated HIV-infected women, virologic failure was common, and correlates of virologic failure varied by race/ethnicity. Strategies to reduce disparities in HIV treatment outcomes by race/ethnicity should address racial/ethnic-specific barriers including depression and low income to sustain virologic suppression.

Morphological variability of the P-wave for premature envision of paroxysmal atrial fibrillation events.

PubMed

Martínez, Arturo; Alcaraz, Raul; Rieta, Jose J

2014-01-01

The present work introduces the first study on the P-wave morphological variability two hours preceding the onset of paroxysmal atrial fibrillation (PAF). The development of non-invasive methods able to track P-wave alterations over time is a clinically relevant tool to anticipate as much as possible the envision of a new PAF episode. This information is essential for further improvement of preventive and patient-tailored treatment strategies, which could avert the loss of sinus rhythm. In this way, risks for the patients could be minimized and their quality of life improved. Recently, the P-wave morphological analysis is drawing increasing attention because differences in morphology can reflect different atrial activation patterns. Indeed, the P-wave morphology study has recently proved to be useful for determining the presence of an underlying pathophysiological condition in patients prone to atrial fibrillation. However, the P-wave morphology variability over time has not been studied yet. In this respect, the present work puts forward some parameters related to the P-wave shape and energy with the ability to quantify non-invasively the notable atrial conduction alterations preceding the onset of PAF. Results showed that P-wave fragmentation and area presented higher variability over time as the onset of PAF approximates. By properly combining these indices, an average global accuracy of 86.33% was achieved to discern between electrocardiogram segments from healthy subjects, far from a PAF episode and less than one hour close to a PAF episode. As a consequence, the P-wave morphology long-term analysis seems to be a useful tool for the non-invasive envision of PAF onset with a reasonable anticipation. Nonetheless, further research is required to corroborate this finding and to validate the capability of the proposed P-wave metrics in the earlier prediction of PAF onset.

Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation.

PubMed

Mandyam, Mala C; Vedantham, Vasanth; Scheinman, Melvin M; Tseng, Zian H; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Gerstenfeld, Edward P; Olgin, Jeffrey E; Marcus, Gregory M

2012-08-01

Alcohol and vagal activity may be important triggers for paroxysmal atrial fibrillation (PAF), but it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies. We compared self-reported frequency of these triggers in patients with PAF to those with other supraventricular tachycardias (SVTs). Consecutive consenting patients presenting for electrophysiology procedures at a single university medical center underwent a structured interview regarding arrhythmia triggers. Two hundred twenty-three patients with a documented arrhythmia (133 with PAF and 90 with SVT) completed the survey. After multivariable adjustment, patients with PAF had a 4.42 greater odds (95% confidence interval [CI] 1.35 to 14.44) of reporting alcohol consumption (p = 0.014) and a 2.02 greater odds (95% CI 1.02 to 4.00) of reporting vagal activity (p = 0.044) as an arrhythmia trigger compared to patients with SVT. In patients with PAF, drinking primarily beer was associated with alcohol as a trigger (odds ratio [OR] 4.49, 95% CI 1.41 to 14.28, p = 0.011), whereas younger age (OR 0.68, 95% CI 0.49 to 0.95, p = 0.022) and a family history of AF (OR 5.73, 95% CI 1.21 to 27.23, p = 0.028) each were independently associated with having vagal activity provoke an episode. Patients with PAF and alcohol triggers were more likely to have vagal triggers (OR 10.32, 95% CI 1.05 to 101.42, p = 0.045). In conclusion, alcohol consumption and vagal activity elicit PAF significantly more often than SVT. Alcohol and vagal triggers often were found in the same patients with PAF, raising the possibility that alcohol may precipitate AF by vagal mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of the P-wave high frequency energy and duration as noninvasive cardiovascular predictors of paroxysmal atrial fibrillation.

PubMed

Alcaraz, Raúl; Martínez, Arturo; Rieta, José J

2015-04-01

A normal cardiac activation starts in the sinoatrial node and then spreads throughout the atrial myocardium, thus defining the P-wave of the electrocardiogram. However, when the onset of paroxysmal atrial fibrillation (PAF) approximates, a highly disturbed electrical activity occurs within the atria, thus provoking fragmented and eventually longer P-waves. Although this altered atrial conduction has been successfully quantified just before PAF onset from the signal-averaged P-wave spectral analysis, its evolution during the hours preceding the arrhythmia has not been assessed yet. This work focuses on quantifying the P-wave spectral content variability over the 2h preceding PAF onset with the aim of anticipating as much as possible the arrhythmic episode envision. For that purpose, the time course of several metrics estimating absolute energy and ratios of high- to low-frequency power in different bands between 20 and 200Hz has been computed from the P-wave autoregressive spectral estimation. All the analyzed metrics showed an increasing variability trend as PAF onset approximated, providing the P-wave high-frequency energy (between 80 and 150Hz) a diagnostic accuracy around 80% to discern between healthy subjects, patients far from PAF and patients less than 1h close to a PAF episode. This discriminant power was similar to that provided by the most classical time-domain approach, i.e., the P-wave duration. Furthermore, the linear combination of both metrics improved the diagnostic accuracy up to 88.07%, thus constituting a reliable noninvasive harbinger of PAF onset with a reasonable anticipation. The information provided by this methodology could be very useful in clinical practice either to optimize the antiarrhythmic treatment in patients at high-risk of PAF onset and to limit drug administration in low risk patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Aquatic community structure in Mediterranean edge-of-field waterbodies as explained by environmental factors and the presence of pesticide mixtures.

PubMed

Pereira, Ana Santos; Dâmaso-Rodrigues, Maria Luísa; Amorim, Ana; Daam, Michiel A; Cerejeira, Maria José

2018-06-16

Studies addressing the predicted effects of pesticides in combination with abiotic and biotic factors on aquatic biota in ditches associated with typical Mediterranean agroecosystems are scarce. The current study aimed to evaluate the predicted effects of pesticides along with environmental factors and biota interactions on macroinvertebrate, zooplankton and phytoplankton community compositions in ditches adjacent to Portuguese maize and tomato crop areas. Data was analysed with the variance partitioning procedure based on redundancy analysis (RDA). The total variance in biological community composition was divided into the variance explained by the multi-substance potentially affected fraction [(msPAF) arthropods and primary producers], environmental factors (water chemistry parameters), biotic interactions, shared variance, and unexplained variance. The total explained variance reached 39.4% and the largest proportion of this explained variance was attributed to msPAF (23.7%). When each group (phytoplankton, zooplankton and macroinvertebrates) was analysed separately, biota interactions and environmental factors explained the largest proportion of variance. Results of this study indicate that besides the presence of pesticide mixtures, environmental factors and biotic interactions also considerably influence field freshwater communities. Subsequently, to increase our understanding of the risk of pesticide mixtures on ecosystem communities in edge-of-field water bodies, variations in environmental and biological factors should also be considered.

Suicidal Ideation Among Korean Elderly: Risk Factors and Population Attributable Fractions.

PubMed

Park, Jong-Il; Yang, Jong-Chul; Han, Changsu; Park, Tae Won; Chung, Sang-Keun

2016-01-01

The objective of this study was to investigate the risk factors of suicidal ideation and their population attributable fraction (PAF) in a representative sample of the elderly population in Korea. We examined the data set from the Survey of Living Conditions and Welfare Needs of Korean Older Persons, which was conducted by the Korea Institute for Health and Social Affairs (KIHASA) in 2011. In that survey, 10,674 participants were randomly selected from those older than age 65. Simultaneous multivariate logistic regression was used to investigate the risk factors of suicidal ideation in terms of their sociodemographic and health-related variables. Subsequently, the PAF was calculated with adjustment for other risk factors. The weighted prevalences of depression and suicidal ideation were 30.3% and 11.2%, respectively. In multivariate analysis, factors significantly associated with decreased risk of suicidal ideation included old-old age (odds ratio [OR] = 0.66 for 75 to 79 years, OR = 0.52 for 80 to 84 years, OR = 0.32 for older than 85 years), economic status (OR = 0.59 for 5th quintile; more than US$25,700 per year), whereas those associated with increased risk included poor social support (OR = 1.28), currently smoking (OR = 1.42), sleep problems (OR = 1.74), chronic illness (OR = 1.40), poor subjective health (OR = 1.56), functional impairment (OR = 1.45), and depression (OR = 4.36). Depression was associated with a fully adjusted PAF of 45.7%, followed by chronic illness (19.4%), poor subjective health status (18.9%), sleep problems (14.1%), functional impairment (4.9%), poor social support (4.2%), and currently smoking (3.6%). Preventive strategies focused particularly on depression might reduce the impact of suicidal ideation in the elderly population. Also, specific mental health centers focused on the specific needs of the elderly population should be established to manage suicidal risk.

Perinatal Risk Factors Associated with Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000-2012): A Record Linkage Cohort Study.

PubMed

Fathima, Parveen; Snelling, Thomas Laurence; de Klerk, Nicholas; Lehmann, Deborah; Blyth, Christopher Charles; Waddington, Claire Shelley; Moore, Hannah Catherine

2018-03-31

Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions (PAFs) associated with childhood gastroenteritis-related hospitalizations. We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia (WA) 2000-2012. We identified hospital admissions up to age <15 years pertaining to these children, with a principal diagnosis code for infectious gastroenteritis. Cox regression was used to obtain the adjusted hazard ratios with 95% confidence intervals (CIs) and the PAFs associated with each risk factor in Aboriginal and non-Aboriginal children for their first gastroenteritis hospital admission. There were a total of 15,888 gastroenteritis-related hospital admissions (25.7% occurring among Aboriginal children). The overall gastroenteritis hospitalization rate for children aged <15 years was 4.6/1000 child-years for non-Aboriginal children and 21.5/1000 child-years for Aboriginal children. Male gender, maternal age <20 years, pre-term birth, low birth weight, residence in remote regions of WA and birth in the pre-rotavirus vaccine era were significant independent risk factors for gastroenteritis hospitalization in both Aboriginal and non-Aboriginal children. Additionally, birth by caesarean section and low socio-economic status were identified as being associated with gastroenteritis hospitalization in non-Aboriginal children. PAFs suggest that 39% of all gastroenteritis hospitalizations in non-Aboriginal children (38% in Aboriginal children) could be averted if all children receive the rotavirus vaccine. Given the beneficial effect of infant rotavirus vaccination in preventing all-cause gastroenteritis hospitalization, efforts should be taken to optimize rotavirus vaccine coverage in those at highest risk.

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists.

PubMed

Curtin, M L; Davidsen, S K; Heyman, H R; Garland, R B; Sheppard, G S; Florjancic, A S; Xu, L; Carrera, G M; Steinman, D H; Trautmann, J A; Albert, D H; Magoc, T J; Tapang, P; Rhein, D A; Conway, R G; Luo, G; Denissen, J F; Marsh, K C; Morgan, D W; Summers, J B

1998-01-01

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.

Effects of garlic extract on platelet aggregation: a randomized placebo-controlled double-blind study.

PubMed

Morris, J; Burke, V; Mori, T A; Vandongen, R; Beilin, L J

1995-01-01

1. Studies of the effects of garlic on platelet aggregation have produced inconsistent results possibly related to variations in study design and in the garlic preparations used. 2. The present study examined the effects on platelet aggregation and serum thromboxane and lyso-platelet activating factor, of feeding garlic extract to healthy men using a placebo-controlled, double-blind design. The effects of the same garlic preparation on platelet aggregation in vitro were also investigated. 3. There were no significant differences in platelet aggregation with adenosine diphosphate, platelet activating factor (PAF) or collagen according to treatment group. Serum thromboxane and lysoPAF also showed no change related to garlic supplements. 4. In vitro aggregation with collagen decreased linearly with increasing amounts of garlic extract, but concentrations were higher than those attainable in vivo. Gastrointestinal side effects prevented the use of higher doses of garlic which must be considered to be pharmacological as they exceed changes achievable by dietary modification.

Porous Aromatic Framework 48/Gel Hybrid Material Coated Solid-Phase Microextraction Fiber for the Determination of the Migration of Styrene from Polystyrene Food Contact Materials.

PubMed

Jin, Yuanyuan; Li, Zhongyue; Yang, Lei; Xu, Jun; Zhao, Le; Li, Zhonghao; Niu, Jiajia

2017-01-17

A novel solid-phase microextraction (SPME) fiber was fabricated by a porous aromatic framework 48 (PAF-48)/gel hybrid material through a sol-gel process. PAF-48 is a porous organic framework (POF) material that was polymerized from 1,3,5-triphenylbenzene. The uniform pore structure, high surface area, continuous conjugate network, and hydrophobicity make PAF-48 expected to have special abilities to absorb and extract styrene as well as some other harmful volatile aromatic compounds (VACs). The PAF-48/gel-coated fiber was explored for the extraction of styrene and six VACs (benzene, toluene, ethylbenzene, and xylenes) from aqueous food simulants followed by gas chromatography (GC) separation. The fiber was found to be very sensitive for the determination of the target molecules with wide linear ranges (0.1-200 or 500 μg·kg -1 ), low limits of detection (LODs, 0.003-0.060 μg·kg -1 ), acceptable precisions (intraday relative standard deviation, RSD < 5.9%, interday RSD < 7.3%), and long lifetime (>200 times). Particularly for styrene, the PAF-48/gel-coated fiber exhibited a much lower LOD (0.006 μg·kg -1 ) compared with most of the reported fibers. Moreover, the PAF-48/gel-coated fiber had a high extraction selectivity for styrene and VACs over alcohols, phenols, aromatic amines, and alkanes and show a molecular sieving effect for the different molecule sizes. Finally, the PAF-48/gel-coated SPME fiber was successfully applied in GC for the determination of the specific migrations of styrene and VACs from polystyrene (PS) plastic food contact materials (FCMs).

Delayed right atrial lateral electromechanical coupling relative to the septal one can be associated with paroxysmal atrial fibrillation.

PubMed

Karapinar, H; Acar, G; Kirma, C; Kaya, Z; Karavelioglu, Y; Kucukdurmaz, Z; Esen, O; Alizade, E; Dasli, T; Sirma, D; Esen, A M

2013-08-01

Non-invasive prediction of paroxysmal atrial fibrillation (PAF) is one of the most recent interests of cardiology. The current study investigates the relationship between the atrial electromechanical coupling time (EMCT) and PAF. A group of 35 patients with PAF was compared with a group of 37 subjects without PAF. Pulsed wave tissue Doppler evaluations of atrial walls were performed from apical four chambers view under ECG monitoring. The time intervals from the onset of P wave to the onset of late diastolic wave (A') at right atrial wall (P-RA), interatrial septum (P-IAS), and left atrial wall (P-LA, maximum EMCT) were measured. The right atrial EMCT (P-RA minus P-IAS), left atrial EMCT (P-LA minus P-IAS) and interatrial EMCT (P-LA minus P-RA) were computed. A' wave velocities were measured from each atrial wall. RA (16.0±13.1 vs. -8.7±18.6 ms, p < 0.001) and maximum (91.5±32.6 vs. 72.0±23.1 ms, p = 0.001) EMCT were longer, RA A' velocity was higher in the patient group. There were no differences between the groups in LA and interatrial EMCT, and septal and LA A' velocities. Regression analysis revealed that only RA [OR: 1.148 (1.041-1.267), p = 0.006] and maximum [OR: 1.099 (1.009-1.197), p = 0.031] EMCT were independent variables for PAF. In order to predict patients with PAF, we have chosen +7.5 msn for the RA EMCT which yielded 69% sensitivity and 71.4% specificity to predict patients. Delayed RA lateral EMCT relative to septal one and delayed maximum EMCT detected by tissue Doppler could be a valuable method for identifying patients with PAF.

The population attributable fraction of low education for mortality in South Korea with improvement in educational attainment and no improvement in mortality inequalities.

PubMed

Lim, Dohee; Kong, Kyoung Ae; Lee, Hye Ah; Lee, Won Kyung; Park, Su Hyun; Baik, Sun Jung; Park, Hyesook; Jung-Choi, Kyunghee

2015-03-31

The educational attainment of Koreans has greatly increased, which was expected to reduce the magnitude of the population attributable fraction (PAF) of mortality associated with low education levels. However, increase in the relative risk (RR) of mortality among those with lower educational levels actually increased the PAF. The purpose of this study was to examine the change in the PAF of lower educational levels for mortality in Korea, where educational attainment has improved and is associated with the exacerbation of inequalities in mortality levels. National census data were used to derive educational levels. The mortality-associated RR of lower educational levels was calculated by reference to national census and death certificate data from 1995, 2000, 2005, and 2010. PAFs were calculated for all-cause mortality, malignant neoplasms, cerebrovascular disease, heart disease, and suicide by gender and age group (30-44 and 45-59 years). The PAF of low educational level in terms of total mortality has decreased since 1995 in both genders. This trend was more prominent among those aged 30-44 years. However, the PAFs of suicide in younger females (30-44 years) and of cerebrovascular disease in older males (45-59 years) have increased. The RRs of all-cause mortality and those of the four leading causes of death in those with the lowest educational levels have increased, especially in females aged 30-44 years. The consistent and sharp increase in the attainment of education has contributed to the reduction in the PAFs of lower education for mortality, despite the fact that mortality inequalities have not improved. Efforts to reduce health inequalities must promote healthy public policy and address public health policies.

Effects of photoperiod on wheat growth, development and yield in CELSS

NASA Astrophysics Data System (ADS)

Yunze, Shen; Shuangsheng, Guo

2014-12-01

A Controlled Ecological Life Support System (CELSS) is a sealed system used in spaceflight in order to provide astronauts with food and O2 by plants. It is of great significance to increase the energy-using efficiency because energy is extremely deficient in the space. Therefore, the objective of this research was to increase the energy-using efficiency of wheat by regulating the photoperiod. Sixteen treatments were set in total: four photoperiods before flowering (PBF) combined with four photoperiods after flowering (PAF) of 12 h, 16 h, 20 h and 24 h. The light source was red-blue LED (90% red+10% blue). As a result, the growth period of wheat was largely extended by shorter PBF, particularly the number of days from tillering to jointing and from jointing to heading. The period from flowering to maturity was extended by shorter PAF. Shorter PBF and longer PAF could increase not only the yield but also the energy-using efficiency of wheat. As for the nutritional quality, longer photoperiod (both PBF and PAF) increased starch concentration as well as decreased protein concentration of seeds. The effects of PBF and PAF were interactional. The lighting strategy with PBF of 12 h and PAF of 24 h was proved to be the optimum photoperiod for wheat cultivation in CELSS. The mechanisms of photoperiod effect contain two aspects. Firstly, photoperiod is a signal for many processes in plant growth, particularly the process of ear differentiation. Shorter PBF promoted the ear differentiation of wheat, increasing the spikelet number, floret number and seed number and thus enhancing the yield. Secondly, longer photoperiod leads to more light energy input and longer time of photosynthesis, so that longer PAF provided more photosynthate and increased seed yield.

Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest.

PubMed

Nir, Rony-Reuven; Sinai, Alon; Raz, Einat; Sprecher, Elliot; Yarnitsky, David

2010-07-16

Recordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Behavioral toxicity of selected radioprotectors

NASA Astrophysics Data System (ADS)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

Analysis of the Postoperative Periarticular Environment and Influence on Sustained Drug Delivery from a Gel Formulation.

PubMed

Svirskis, Darren; Martis, Waldron; Bhusal, Prabhat; Sharma, Manisha; Stowers, Renus; Young, Simon W

2018-05-16

Regional intraarticular delivery of local anaesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients and the composition and physicochemical properties determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p<0.05) and higher buffer capacity (p<0.05) were observed in the biological fluid. We demonstrated the solubility of lidocaine is almost double in PO-PAF compared to PBS (p<0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and non-sink conditions. Collectively, these data indicate PBS is inappropriate for the in-vitro evaluation of intraarticular drug delivery systems. The presented data describes PO-PAF and will support the future development of biorelevant media to ultimately improve in-vivo in-vitro correlation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Racial/Ethnic Differences in Gestational Diabetes Prevalence and Contribution of Common Risk Factors.

PubMed

Pu, Jia; Zhao, Beinan; Wang, Elsie J; Nimbal, Vani; Osmundson, Sarah; Kunz, Liza; Popat, Rita A; Chung, Sukyung; Palaniappan, Latha P

2015-09-01

The White House, the American Heart Association, the Agency for Healthcare Research and Quality, and the National Heart, Lung and Blood Institute have all recently acknowledged the need to disaggregate Asian American subgroups to better understand this heterogeneous racial group. This study aims to assess racial/ethnic differences in relative contribution of risk factors of gestational diabetes mellitus (GDM) among Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese), Hispanics, non-Hispanic blacks, and non-Hispanic whites. Pregnant women in 2007-2012 were identified through California state birth certificate records and linked to the electronic health records in a large mixed-payer ambulatory care organisation in Northern California (n = 24 195). Relative risk and population attributable fraction (PAF) for specific racial/ethnic groups were calculated to assess the contributions of advanced maternal age, overweight/obesity (Centers for Disease Control and Prevention (CDC) standards and World Health Organization (WHO)/American Diabetes Association (ADA) body mass index cut-offs for Asians), family history of type 2 diabetes, and foreign-born status. GDM was most prevalent among Asian Indians (19.3%). Relative risks were similar across all race/ethnic groups. Advanced maternal age had higher PAFs in non-Hispanic whites (22.5%) and Hispanics (22.7%). Meanwhile family history (Asian Indians 22.6%, Chinese 22.9%) and foreign-borne status (Chinese 40.2%, Filipinos 30.2%) had higher PAFs in Asian subgroups. Overweight/obesity was the most important GDM risk factor for non-Hispanic whites, Hispanics, Asian Indians, and Filipinos when the WHO/ADA cut-off points were applied. Advanced maternal age was the only risk factor studied that was modified by race/ethnicity, with non-Hispanic white and Hispanic women being more adversely affected than other racial/ethnic groups. Overweight/obesity, advanced maternal age, family history of type 2 diabetes, and foreign-borne status are important risk factors for GDM. The relative contributions of these risk factors differ by race/ethnicity, mainly due to differences in population prevalence of these risk factors. © 2015 John Wiley & Sons Ltd.

Febuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial dysfunction.

PubMed

Li, YanGuang; Chen, FuKun; Deng, Long; Lin, Kun; Shi, Xiangmin; Zhaoliang, Shan; Wang, YuTang

2017-01-01

Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear. We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO). Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups. Group P and group FP received rapid atrial pacing (RAP). Group FP was administered febuxostat (FX) for 7days before RAP. Post-procedure, blood samples were collected from the LA, right atrium (RA) and peripheral circulation. Tissues from the LA and RA were obtained. Endothelial dysfunction (thrombomodulin [TM], von Willebrand factor [VWF], asymmetric dimethylarginine [ADMA]), and indirect thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1.2]) and oxidative stress in atrial tissue (xanthine oxidase [XO], superoxide dismutase [SOD], malondialdehyde [MDA]) were measured using an Enzyme-linked immunosorbent assay. Atrial endothelial expression of TM and VWF was measured by histology/western blotting. Endothelial dysfunction (TM, VWF, ADMA), TAT generation and oxidative stress (XO, SOD, MDA) in group P were more significant compared with that in group S (p<0.05, respectively). In group P, all of these changes occurred to a greater extent in the LA compared with those in the RA or peripheral circulation. In group FP, FX attenuated endothelial dysfunction and reduced TAT levels by inhibition of XO-mediated oxidative stress. PAF can lead to endothelial dysfunction and TAT generation by XO-mediated oxidative stress. The LA is more susceptible to these effects. FX can attenuate these changes by inhibition XO and XO-mediated oxidative stress. Copyright © 2016. Published by Elsevier Ltd.

Performance of a Highly Sensitive, 19-element, Dual-polarization, Cryogenic L-band Phased-array Feed on the Green Bank Telescope

NASA Astrophysics Data System (ADS)

Roshi, D. Anish; Shillue, W.; Simon, B.; Warnick, K. F.; Jeffs, B.; Pisano, D. J.; Prestage, R.; White, S.; Fisher, J. R.; Morgan, M.; Black, R.; Burnett, M.; Diao, J.; Ruzindana, M.; van Tonder, V.; Hawkins, L.; Marganian, P.; Chamberlin, T.; Ray, J.; Pingel, N. M.; Rajwade, K.; Lorimer, D. R.; Rane, A.; Castro, J.; Groves, W.; Jensen, L.; Nelson, J. D.; Boyd, T.; Beasley, A. J.

2018-05-01

A new 1.4 GHz, 19-element, dual-polarization, cryogenic phased-array feed (PAF) radio astronomy receiver has been developed for the Robert C. Byrd Green Bank Telescope (GBT) as part of the Focal L-band Array for the GBT (FLAG) project. Commissioning observations of calibrator radio sources show that this receiver has the lowest reported beam-formed system temperature (T sys) normalized by aperture efficiency (η) of any phased-array receiver to date. The measured T sys/η is 25.4 ± 2.5 K near 1350 MHz for the boresight beam, which is comparable to the performance of the current 1.4 GHz cryogenic single-feed receiver on the GBT. The degradation in T sys/η at ∼4‧ (required for Nyquist sampling) and ∼8‧ offsets from the boresight is, respectively, ∼1% and ∼20% of the boresight value. The survey speed of the PAF with seven formed beams is larger by a factor between 2.1 and 7 compared to a single-beam system, depending on the observing application. The measured performance, both in frequency and offset from the boresight, qualitatively agrees with predictions from a rigorous electromagnetic model of the PAF. The astronomical utility of the receiver is demonstrated by observations of the pulsar B0329+54 and an extended H II region, the Rosette Nebula. The enhanced survey speed with the new PAF receiver will enable the GBT to carry out exciting new science, such as more efficient observations of diffuse, extended neutral hydrogen emission from galactic inflows and searches for fast radio bursts.

Use of steroidal antiinflammatory drug provides further evidence for a potential role of PAF-acether in bronchial anaphylaxis.

PubMed

Chignard, M; Le Còuedic, J P; Andersson, P; Brange, C

1986-01-01

We presently demonstrate that PAF-acether (1-O-alkyl-2-O-acetyl-sn-glycerol-3-phosphoryl-choline) is formed by sensitized guinea pig lungs upon in vitro antigenic challenge. Pretreatment of the animals with a steroidal antiinflammatory drug, budesonide, almost totally suppresses this biosynthesis. Since budesonide inhibits the anaphylactic bronchoconstriction in actively sensitized guinea pigs, these data strongly support the assumption that PAF-acether is a mediator of bronchial anaphylaxis.

Assessment of left atrial mechanical function and synchrony in paroxysmal atrial fibrillation with two-dimensional speckle tracking echocardiography.

PubMed

Shang, Zhijuan; Su, Dechun; Cong, Tao; Sun, Yinghui; Liu, Yan; Chen, Na; Yang, Jun

2017-02-01

The aim of this study was to investigate left atrial (LA) function and synchrony in paroxysmal atrial fibrillation (PAF) patients using two-dimensional speckle tracking echocardiography (STE). Forty-five PAF patients and 30 healthy controls were enrolled. LA peak ventricular systolic longitudinal strain (LA S -S ) and strain rate (LA SR -S ) and left atrial longitudinal strain (LA S -A ) and strain rate (LA SR -A ) during late diastole were determined using STE, and the standard deviation of the time to peak (TPSD) of the regional strains was calculated to quantify LA dyssynchrony. TPSD during ventricular systole and late diastole were named SDs and SDa, respectively. Left atrial peak longitudinal strain during ventricular systole (LA S -S ) (29.34±8.57 vs 36.73±6.13), LA SR -S (1.27±0.311 vs 1.57±0.25), LA S -A (13.11±4.91 vs 17.86±3.57), and LA SR -A (-1.51±0.58 vs -1.90±0.30) were reduced in the PAF group compared with the controls (P<.05 for all). SDs (8.11±3.00% vs 4.67±1.48%) and SDa (5.57±2.26% vs 3.11±1.13%) were greater in PAF patients than in the controls (P<.05 for both). Furthermore, PAF patients with normal LA sizes exhibited lower LA S -S (P<.05), LA SR -S (P<.05), LA S -A (P<.05), and LA SR -A (P<.05) values and increased SDs (P<.05) and SDa (P<.05) values compared with the controls. Multivariate regression confirmed that SDs and SDa were powerful parameters for differentiating PAF patients from controls (SDs: sensitivity, 83%; specificity, 72%; SDa: sensitivity, 81%; specificity, 76%). Left atrial (LA) dysfunction and dyssynchrony in PAF patients can be detected with STE even in the absence of LA enlargement. STE-derived SDs and SDa were powerful parameters for identifying PAF patients. © 2017, Wiley Periodicals, Inc.

Plasma phospholipase, γ-CEHC and antioxidant capacity in fibromyalgia.

PubMed

Fais, Antonella; Cacace, Enrico; Atzori, Luigi; Era, Benedetta; Ruggiero, Valeria

2017-05-01

Recent studies have suggested a possible role of high levels of plasma lysophosphocholines (lysoPCs) in fibromyalgia syndrome (FMS). The aim of this study was to evaluate the content of plasma phospholipases (e.g., Platelet Activating Factor Acetyl Hydrolase [PAF-AH], secretory Phospholipase A 2 [sPLA 2 ], Total Antioxidant Capacity [TAOC] and 2,7,8-trimethyl-2-(2-carboxyethyl)-6-hydroxy chroman [γ-CEHC]) in FMS patients and their association with clinical status and quality of life. Thirty-six females meeting the 2011 American College of Rheumatology criteria for the classification of FMS and thirty-four healthy females were enrolled for the study. Plasma enzyme levels were quantified using commercial enzyme-linked-immunosorbent-assay (ELISA). In order to assess the disease severity and the functional status of patients, the Fibromyalgia Impact Questionnarie (FIQ) was used. Higher levels of sPLA 2 and lower PAF-AH and γ-CEHC were observed in the plasma of FMS patients compared to the controls. A decrease in PAF-AH and TAOC levels were found in severe FMS (S-FMS) compared to mild/slight (MS-FMS) forms. The results of the study indicate a possible involvement of phospholipases and γ-CEHC in fibromyalgia syndrome. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

The Latest Results from the Focal L-Band Array for the Green Bank Telescope (FLAG), the World's (Current) Most Sensitive Phased Array Feed

NASA Astrophysics Data System (ADS)

Pingel, Nickolas; Pisano, D. J.

2018-01-01

Phased Array Feeds (PAFs) represent the next revolution in radio astronomy instrumentation. I will present results from the latest commissioning run from the Focal L-Band Array for the Green Bank telescope (FLAG), which holds the current world record for PAF sensitivity. Since we are able to operate at system temperatures comparable with the traditional GBT single pixel L-Band feed, the increase in the field-of-view provided by the beamforming capabilities of PAFs results in a dramatic (a factor of 5) increase in survey speeds. In particular, FLAG can probe similar neutral hydrogen column density regimes over a 4 sq. deg region in 24.6 minutes as opposed to 4.1 hours in an equivalent single pixel map (excluding observing overhead). In addition to comparisons between data taken with FLAG and the single-pixel L-Band feed, I will also discuss the technical aspects of the observing procedure, data reduction, and the transition path for FLAG from an instrument that is principle-investigator run to one that is general use. These FLAG results provide a very encouraging outlook on how the GBT will continue to compete with current and planned radio telescope facilities.

Lipid effects on neutrophil calcium signaling induced by opsonized particles: platelet activating factor is only part of the story.

PubMed

Wanten, Geert; Kusters, Anneke; van Emst-de Vries, Sjenet E; Tool, Anton; Roos, Dirk; Naber, Ton; Willems, Peter

2004-08-01

Total parenteral nutrition is frequently used in clinical practice to improve the nutritional status of patients. However, the risk for infectious complications remains a drawback in which immune-modulating effects of the lipid component may play a role. To characterize these lipid effects we investigated neutrophil activation by opsonized yeast particles under influence of lipid emulsions derived from fish oil (VLCT), olive oil (LCT-MUFA), soybean oil (LCT), and a physical mixture of coconut and soybean oil (LCT-MCT). Serum-treated zymosan (STZ) evoked a biphasic increase in cytosolic Ca2+ concentration ([Ca2+]c) with an initial slow rise that turned into a second fast rise until a plateau was reached. LCT-MCT (5 mM) pretreatment markedly increased the rate of [Ca2+]c rise during the initial phase, abolished the second phase and lowered the plateau. These effects of LCT-MCT were mimicked by the protein kinase C (PKC) activating phorbol ester PMA. LCT, LCT-MUFA and VLCT, on the other hand, decreased the rate of [Ca2+]c rise during both phases and lowered the plateau. The platelet-activating factor (PAF) receptor antagonist WEB 2086 inhibited the second phase, demonstrating that PAF acts as an intercellular messenger in STZ-induced Ca2+ mobilization, but did not interfere with the stimulatory effect of LCT-MCT or PMA on the initial rate of [Ca2+]c rise. Structurally different lipids act only in part through PAF to distinctively modulate neutrophil calcium signaling in response to activation by opsonized particles. Copyright 2003 Elsevier Ltd.

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

PubMed

Carlioglu, Ayse; Kaygusuz, Ikbal; Karakurt, Feridun; Gumus, Ilknur Inegol; Uysal, Aysel; Kasapoglu, Benan; Armutcu, Ferah; Uysal, Sema; Keskin, Esra Aktepe; Koca, Cemile

2014-11-01

To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients. Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis. PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group. In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

Ecological significance of hazardous concentrations in a planktonic food web.

PubMed

De Laender, Frederik; Soetaert, Karline; De Schamphelaere, Karel A C; Middelburg, Jack J; Janssen, Colin R

2010-03-01

Species sensitivity distributions (SSDs) are statistical distributions that are used to estimate the potentially affected fraction (PAF) of species at a given toxicant concentration, the hazardous concentration for that fraction of species (HC(PAF)). Here, we use an aquatic food web model that includes 14 phytoplankton and 6 zooplankton species to estimate the number of species experiencing a biomass reduction when the food web is exposed to the HC(PAF) and this for 1000 hypothetical toxicants and for PAF=5-30%. When choosing a 20% decrease as a cut-off to categorize a species' biomass as affected, 0-1 and 2-5 out of the 20 species were affected at the HC(5) and HC(30), respectively. From this, it can be concluded that the PAF is a relatively good estimator of the number of affected species. However, when phytoplankton species experiencing >or=20% biomass increase were also classified as affected, the number of affected species predicted by the food web model varied strongly among toxicants for PAF >5, with 2-16 out of 20 species affected at the HC(30). Phytoplankton species with extreme (both high and low) values for uptake rates and light limitation constants experienced smaller effects on their biomass than phytoplankton species with more average parameter values. We conclude that, next to measures of toxicity, ecological characteristics of species may help understanding ecological effects occurring in ecosystems also. (c) 2009 Elsevier Inc. All rights reserved.

Novel conjugative plasmids from the natural isolate Lactococcus lactis subspecies cremoris DPC3758: a repository of genes for the potential improvement of dairy starters.

PubMed

Fallico, V; Ross, R P; Fitzgerald, G F; McAuliffe, O

2012-07-01

A collection of 17 natural lactococcal isolates from raw milk cheeses were studied in terms of their plasmid distribution, content, and diversity. All strains in the collection harbored an abundance of plasmids, including Lactococcus lactis ssp. cremoris DPC3758, whose 8-plasmid complement was selected for sequencing. The complete sequences of pAF22 (22,388 kb), pAF14 (14,419 kb), pAF12 (12,067 kb), pAF07 (7,435 kb), and pAF04 (3,801 kb) were obtained, whereas gene functions of technological interest were mapped to pAF65 (65 kb) and pAF45 (45 kb) by PCR. The plasmids of L. lactis DPC3758 were found to encode many genes with the potential to improve the technological properties of dairy starters. These included 3 anti-phage restriction/modification (R/M) systems (1 of type I and 2 of type II) and genes for immunity/resistance to nisin, lacticin 481, cadmium, and copper. Regions encoding conjugative/mobilization functions were present in 6 of the 8 plasmids, including those containing the R/M systems, thus enabling the food-grade transfer of these mechanisms to industrial strains. Using cadmium selection, the sequential stacking of the R/M plasmids into a plasmid-free host provided the recipient with increased protection against 936- and c2-type phages. The association of food-grade selectable markers and mobilization functions on L. lactis DPC3758 plasmids will facilitate their exploitation to obtain industrial strains with enhanced phage protection and robustness. These natural plasmids also provide another example of the major role of plasmids in contributing to host fitness and preservation within its ecological niche. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Efficient estimation of the attributable fraction when there are monotonicity constraints and interactions.

PubMed

Traskin, Mikhail; Wang, Wei; Ten Have, Thomas R; Small, Dylan S

2013-01-01

The PAF for an exposure is the fraction of disease cases in a population that can be attributed to that exposure. One method of estimating the PAF involves estimating the probability of having the disease given the exposure and confounding variables. In many settings, the exposure will interact with the confounders and the confounders will interact with each other. Also, in many settings, the probability of having the disease is thought, based on subject matter knowledge, to be a monotone increasing function of the exposure and possibly of some of the confounders. We develop an efficient approach for estimating logistic regression models with interactions and monotonicity constraints, and apply this approach to estimating the population attributable fraction (PAF). Our approach produces substantially more accurate estimates of the PAF in some settings than the usual approach which uses logistic regression without monotonicity constraints.

Effects of high pressure freezing (HPF) on denaturation of natural actomyosin extracted from prawn (Metapenaeus ensis).

PubMed

Cheng, Lina; Sun, Da-Wen; Zhu, Zhiwei; Zhang, Zhihang

2017-08-15

Effects of protein denaturation caused by high pressure freezing, involving Pressure-Factors (pressure, time) and Freezing-Factors (temperature, phase transition, recrystallization, ice crystal types), are complicated. In the current study, the conformation and functional changes of natural actomyosin (NAM) under pressure assisted freezing (PAF, 100,150,300,400,500MPa P -20°C/25min ), pressure shift freezing (PSF, 200MPa P -20°C/25min ), and immersion freezing ( 0.1MPa P -20°C/5min ) after pressure was released to 0.1MPa, as compared to normal immersion freezing process (IF, 0.1MPa P -20°C/30min ). Results indicated that PSF ( 200MPa P -20°C/30min ) could reduce the denaturation of frozen NAM and a pressure of 300MPa was the critical point to induce such a denaturation. During the periods of B→D in PSF or B→C→D in PAF, the generation and growth of ice crystals played an important role on changing the secondary and tertiary structure of the treated NAM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disentangling polydispersity in the PCNA−p15PAF complex, a disordered, transient and multivalent macromolecular assembly

PubMed Central

Cordeiro, Tiago N.; Chen, Po-chia; De Biasio, Alfredo; Sibille, Nathalie; Blanco, Francisco J.; Hub, Jochen S.; Crehuet, Ramon

2017-01-01

Abstract The intrinsically disordered p15PAF regulates DNA replication and repair when interacting with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp. As many interactions between disordered proteins and globular partners involved in signaling and regulation, the complex between p15PAF and trimeric PCNA is of low affinity, forming a transient complex that is difficult to characterize at a structural level due to its inherent polydispersity. We have determined the structure, conformational fluctuations, and relative population of the five species that coexist in solution by combining small-angle X-ray scattering (SAXS) with molecular modelling. By using explicit ensemble descriptions for the individual species, built using integrative approaches and molecular dynamics (MD) simulations, we collectively interpreted multiple SAXS profiles as population-weighted thermodynamic mixtures. The analysis demonstrates that the N-terminus of p15PAF penetrates the PCNA ring and emerges on the back face. This observation substantiates the role of p15PAF as a drag regulating PCNA processivity during DNA repair. Our study reveals the power of ensemble-based approaches to decode structural, dynamic, and thermodynamic information from SAXS data. This strategy paves the way for deciphering the structural bases of flexible, transient and multivalent macromolecular assemblies involved in pivotal biological processes. PMID:28180305

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

PubMed Central

Gao, Lu; Rabbitt, Elizabeth H.; Condon, Jennifer C.; Renthal, Nora E.; Johnston, John M.; Mitsche, Matthew A.; Chambon, Pierre; Xu, Jianming; O’Malley, Bert W.; Mendelson, Carole R.

2015-01-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2–deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2–deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2–deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2–dependent production of SP-A and PAF is crucial for this process. PMID:26098214

Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis.

PubMed

Vilela, Márcia Carvalho; Lima, Graciela Kunrath; Rodrigues, David Henrique; Lacerda-Queiroz, Norinne; Pedroso, Vinicius Sousa Pietra; de Miranda, Aline Silva; Rachid, Milene Alvarenga; Kroon, Erna Geessien; Campos, Marco Antônio; Teixeira, Mauro Martins; Teixeira, Antonio Lucio

2016-12-01

Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR -/- ) mice were inoculated intracranially with 10 4 plaque-forming units (PFU) of HSV-1. Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR -/- mice, there was delayed lethality but no difference in viral load. Histopathological analysis of infected PAFR -/- mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR -/- mice showed less TCD4 + , TCD8 + and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling and adhesion. PAFR -/- mice also presented a reduction of the chemokine CXCL9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation.

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.

PubMed

Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C; Renthal, Nora E; Johnston, John M; Mitsche, Matthew A; Chambon, Pierre; Xu, Jianming; O'Malley, Bert W; Mendelson, Carole R

2015-07-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A-deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2-deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2-deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2-deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process.

Fetal-to-maternal signaling to initiate parturition

PubMed Central

Reinl, Erin L.; England, Sarah K.

2015-01-01

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions.

PubMed

Tachibana, A; Kato, M; Kimura, H; Fujiu, T; Suzuki, M; Morikawa, A

2002-12-01

Agonists at beta2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed beta2-adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O2-) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of beta2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O2- was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O2- generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O2- generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O2- generation was not reversed by ICI-118551, a selective beta2-adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O2- generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via beta2 adrenoceptors.

Risk Factors of Typhoid Infection in the Indonesian Archipelago

PubMed Central

Alba, Sandra; Bakker, Mirjam I.; Hatta, Mochammad; Scheelbeek, Pauline F. D.; Dwiyanti, Ressy; Usman, Romi; Sultan, Andi R.; Sabir, Muhammad; Tandirogang, Nataniel; Amir, Masyhudi; Yasir, Yadi; Pastoor, Rob; van Beers, Stella; Smits, Henk L.

2016-01-01

Background Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. Methods We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post-recruitment: cases were individuals with a culture or serology positive result (n = 449); controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484). Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF) of removing each risk significant independent behavioural risk factor. Results Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often). These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5). Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score). Conclusions Major gains could potentially be achieved in reducing the incidence of typhoid by ensuring adherence to adequate hand-washing practices alone. This confirms that there is a pivotal role for ‘software’ related interventions to encourage behavior change and create demand for goods and services, alongside development of water and sanitation infrastructure. PMID:27281311

Ecological risk assessment in legislation on contaminated soil in The Netherlands.

PubMed

Boekhold, Alexandra E

2008-12-01

Recently the Dutch soil policy was revised including new rules for the relocation of contaminated soil and dredged soil material. With these rules, new methods for ecotoxicological risk assessment were implemented. One of the new methods is the assessment of the local toxic pressure of mixtures, also known as the ms-PAF- method, based on the Species Sensitivity Distribution concept. The ms-PAF method is applied for risk assessment of spreading of dredged soil material on adjacent land. Its application will possibly be extended to the derivation of local soil quality standards relevant in the context of soil relocation. The application of the local toxic pressure will probably increase the reuse of contaminated soil and dredged soil material and hence will reduce the amounts considered to be unfit for use. With this method, local ecological risk limits are derived using pore water concentrations and effects on water organisms. Pore water concentrations are subsequently transferred to total soil concentrations using empirical relationships. The methodology does not impose upper limits for total soil concentrations. In soils with a high sorption capacity, total soil concentrations that are considered to be acceptable may be several times higher than the current Dutch intervention values. The possible introduction of the ms-PAF method will open the door to local soil relocation with soils containing large amounts of (semi-permanently soil bound) contaminants. Since the ms-PAF method is not yet properly validated, the lack of evidence of ecological effects using models like the ms-PAF method cannot be regarded as an indication for the absence of effects in reality. The Dutch soil quality decree would gain environmental ambition when the ms-PAF method was combined with a realistic upper limit on total soil concentrations. This would prevent contamination of land by means of soil relocation.

FLO11 Gene Is Involved in the Interaction of Flor Strains of Saccharomyces cerevisiae with a Biofilm-Promoting Synthetic Hexapeptide

PubMed Central

Bou Zeidan, Marc; Carmona, Lourdes

2013-01-01

Saccharomyces cerevisiae “flor” yeasts have the ability to form a buoyant biofilm at the air-liquid interface of wine. The formation of biofilm, also called velum, depends on FLO11 gene length and expression. FLO11 encodes a cell wall mucin-like glycoprotein with a highly O-glycosylated central domain and an N-terminal domain that mediates homotypic adhesion between cells. In the present study, we tested previously known antimicrobial peptides with different mechanisms of antimicrobial action for their effect on the viability and ability to form biofilm of S. cerevisiae flor strains. We found that PAF26, a synthetic tryptophan-rich cationic hexapeptide that belongs to the class of antimicrobial peptides with cell-penetrating properties, but not other antimicrobial peptides, enhanced biofilm formation without affecting cell viability in ethanol-rich medium. The PAF26 biofilm enhancement required a functional FLO11 but was not accompanied by increased FLO11 expression. Moreover, fluorescence microscopy and flow cytometry analyses showed that the PAF26 peptide binds flor yeast cells and that a flo11 gene knockout mutant lost the ability to bind PAF26 but not P113, a different cell-penetrating antifungal peptide, demonstrating that the FLO11 gene is selectively involved in the interaction of PAF26 with cells. Taken together, our data suggest that the cationic and hydrophobic PAF26 hexapeptide interacts with the hydrophobic and negatively charged cell wall, favoring Flo11p-mediated cell-to-cell adhesion and thus increasing biofilm biomass formation. The results are consistent with previous data that point to glycosylated mucin-like proteins at the fungal cell wall as potential interacting partners for antifungal peptides. PMID:23892742

Prediction of paroxysmal atrial fibrillation using recurrence plot-based features of the RR-interval signal.

PubMed

Mohebbi, Maryam; Ghassemian, Hassan

2011-08-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of stroke. Predicting the onset of paroxysmal AF (PAF), based on noninvasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic intervention and to minimize risks for the patients. In this paper, we propose an effective PAF predictor which is based on the analysis of the RR-interval signal. This method consists of three steps: preprocessing, feature extraction and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the RR-interval signal is extracted. In the next step, the recurrence plot (RP) of the RR-interval signal is obtained and five statistically significant features are extracted to characterize the basic patterns of the RP. These features consist of the recurrence rate, length of longest diagonal segments (L(max )), average length of the diagonal lines (L(mean)), entropy, and trapping time. Recurrence quantification analysis can reveal subtle aspects of dynamics not easily appreciated by other methods and exhibits characteristic patterns which are caused by the typical dynamical behavior. In the final step, a support vector machine (SVM)-based classifier is used for PAF prediction. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database (AFPDB) which consists of both 30 min ECG recordings that end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, positive predictivity and negative predictivity were 97%, 100%, 100%, and 96%, respectively. The proposed methodology presents better results than other existing approaches.

Sympathetically mediated hypertension in autonomic failure

NASA Technical Reports Server (NTRS)

Shannon, J. R.; Jordan, J.; Diedrich, A.; Pohar, B.; Black, B. K.; Robertson, D.; Biaggioni, I.; Roberton, D. (Principal Investigator)

2000-01-01

BACKGROUND: Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could be driven by residual sympathetic activity. METHODS AND RESULTS: In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg. min; P=0.022). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+/-9.5%, respectively (P=0. 0015). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan were correlated (r=0.98; P=0.001). CONCLUSIONS: Residual sympathetic activity drives supine hypertension in MSA. It contributes to, but does not completely explain, supine hypertension in PAF.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat.

PubMed

Miao, F J; Benowitz, N L; Heller, P H; Levine, J D

1997-01-01

1. In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. 2. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective beta 2-adrenoceptor blocker) (30 micrograms ml-1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg-1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 microgram kg-1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that beta 2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg-1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. 3. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg-1, s.c.), and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg-1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. 4. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg-1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. 5. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat

PubMed Central

Jia-Pei Miao, Frederick; Benowitz, Neal L; Heller, Philip H; Levine, Jon D

1997-01-01

In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective β2-adrenoceptor blocker) (30 μg ml−1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg−1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 μg kg−1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that β2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg−1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg−1, s.c.) and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg−1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg−1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone. PMID:9117123

Poison prevention practices and medically attended poisoning in young children: multicentre case-control study.

PubMed

Kendrick, Denise; Majsak-Newman, Gosia; Benford, Penny; Coupland, Carol; Timblin, Clare; Hayes, Mike; Goodenough, Trudy; Hawkins, Adrian; Reading, Richard

2017-04-01

Childhood poisonings are common, placing a substantial burden on health services. Case-control studies have found inconsistent evidence about modifiable risk factors for poisonings among children aged 0-4 years. This study quantifies associations between poison prevention practices and medically attended poisonings in children aged 0-4 years. Multicentre case-control study conducted at hospitals, minor injury units and family practices from four study centres in England between 2010 and 2013. Participants comprised 567 children presenting with unintentional poisoning occurring at home and 2320 community control participants matched on age, sex, date of event and study centre. Parents/caregivers provided data on safety practices, safety equipment use, home hazards and potential confounders by means of self-completion questionnaires. Data were analysed using conditional logistic regression. Compared with community controls, parents of poisoned children were significantly more likely not to store medicines out of reach (adjusted OR (AOR) 1.59; 95% CI 1.21 to 2.09; population attributable fraction (PAF) 15%), not to store medicines safely (locked or out of reach (AOR 1.83; 95% CI 1.38 to 2.42; PAF 16%) and not to have put all medicines (AOR 2.11; 95% CI 1.54 to 2.90; PAF 20%) or household products (AOR 1.79, 95% CI 1.29 to 2.48; PAF 11%) away immediately after use. Not storing medicines out of reach or locked away and not putting medicines and household products away immediately after use increased the odds of secondary care attended poisonings in children aged 0-4 years. If associations are causal, implementing these poison prevention practices could each prevent between 11% and 20% of poisonings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Group sparse multiview patch alignment framework with view consistency for image classification.

PubMed

Gui, Jie; Tao, Dacheng; Sun, Zhenan; Luo, Yong; You, Xinge; Tang, Yuan Yan

2014-07-01

No single feature can satisfactorily characterize the semantic concepts of an image. Multiview learning aims to unify different kinds of features to produce a consensual and efficient representation. This paper redefines part optimization in the patch alignment framework (PAF) and develops a group sparse multiview patch alignment framework (GSM-PAF). The new part optimization considers not only the complementary properties of different views, but also view consistency. In particular, view consistency models the correlations between all possible combinations of any two kinds of view. In contrast to conventional dimensionality reduction algorithms that perform feature extraction and feature selection independently, GSM-PAF enjoys joint feature extraction and feature selection by exploiting l(2,1)-norm on the projection matrix to achieve row sparsity, which leads to the simultaneous selection of relevant features and learning transformation, and thus makes the algorithm more discriminative. Experiments on two real-world image data sets demonstrate the effectiveness of GSM-PAF for image classification.

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Increased Risk of Paroxysmal Atrial Fibrillation Episodes Associated with Acute Increases in Ambient Air Pollution

PubMed Central

Rich, David Q.; Mittleman, Murray A.; Link, Mark S.; Schwartz, Joel; Luttmann-Gibson, Heike; Catalano, Paul J.; Speizer, Frank E.; Gold, Diane R.; Dockery, Douglas W.

2006-01-01

Objectives: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. Design: We performed a case–crossover study. Participants: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n = 203) were followed until July 2002. Evaluations/Measurements: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. Results: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio = 2.08; 95% confidence interval = 1.22, 3.54; p = 0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. Conclusions: Increased ambient O3 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events. PMID:16393668

Effects of Pharmacologic Intervention on Oxygenation, Lung Water and Protein Leak in the Pseudomonas ARDS Porcine Model

DTIC Science & Technology

1989-07-01

model indicate that Pseudomonas primes these cells to produce superoxide anion at a much higher rate post-injury than pre-injury, thus implicating...as oxygen free radicals, the neutrophils, platelets, monocytes and lymphocytes can release a number of other factors which have an affect on...mediator in the lung injury seen with endotoxin induced ARDS is the inappropriately named platelet activating factor (PAF). This phospholipid, which is

Chromatin signaling to kinetochores: Trans-regulation of Dam1 methylation by histone H2B ubiquitination

PubMed Central

Latham, John A.; Chosed, Renée J.; Wang, Shanzhi; Dent, Sharon Y.R.

2011-01-01

Summary Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory cross-talk in trans between a histone modification and modification on a non-histone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries. PMID:21884933

Exploration of the (Interrater) Reliability and Latent Factor Structure of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) in a Sample of Dutch Probationers.

PubMed

Hildebrand, Martin; Noteborn, Mirthe G C

2015-01-01

The use of brief, reliable, valid, and practical measures of substance use is critical for conducting individual (risk and need) assessments in probation practice. In this exploratory study, the basic psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) are evaluated. The instruments were administered as an oral interview instead of a self-report questionnaire. The sample comprised 383 offenders (339 men, 44 women). A subset of 56 offenders (49 men, 7 women) participated in the interrater reliability study. Data collection took place between September 2011 and November 2012. Overall, both instruments have acceptable levels of interrater reliability for total scores and acceptable to good interrater reliabilities for most of the individual items. Confirmatory factor analyses (CFA) indicated that the a priori one-, two- and three-factor solutions for the AUDIT did not fit the observed data very well. Principal axis factoring (PAF) supported a two-factor solution for the AUDIT that included a level of alcohol consumption/consequences factor (Factor 1) and a dependence factor (Factor 2), with both factors explaining substantial variance in AUDIT scores. For the DUDIT, CFA and PAF suggest that a one-factor solution is the preferred model (accounting for 62.61% of total variance). The Dutch language versions of the AUDIT and the DUDIT are reliable screening instruments for use with probationers and both instruments can be reliably administered by probation officers in probation practice. However, future research on concurrent and predictive validity is warranted.

Inhibition by fenoterol of human eosinophil functions including β2-adrenoceptor-independent actions

PubMed Central

TACHIBANA, A; KATO, M; KIMURA, H; FUJIU, T; SUZUKI, M; MORIKAWA, A

2002-01-01

Agonists at β2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed β2-adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O2−) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of β2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O2− was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O2− generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O2− generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O2− generation was not reversed by ICI-118551, a selective β2-adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O2− generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via β2 adrenoceptors. PMID:12452831

Effects of ZCR-2060 on allergic airway inflammation and cell activation in guinea-pigs.

PubMed

Abe, T; Yoshida, K; Omata, T; Segawa, Y; Matsuda, K; Nagai, H

1994-11-01

The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg-1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10(-6)-10(-4) M) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10(-6)-10(-4) M). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.

Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants.

PubMed

Kaul, Dhananjay K; Liu, Xiao-du; Zhang, Xiaoqin; Ma, Li; Hsia, Carleton J C; Nagel, Ronald L

2006-07-01

In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and transient vasoocclusive) events result in chronic endothelial activation. In addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal interaction with the vascular endothelium, which is considered to have an important role in initiation of vasoocclusion. Upregulation of endothelial adhesion molecules caused by oxidants (and cytokines) may lead to increased SS red cell adhesion. We hypothesize that endothelial activation is indispensable in SS red cell adhesion to the endothelium and that antioxidants will have an inhibitory effect on this interaction. We examined the effect of selected antioxidants in ex vivo mesocecum vasculature, a well-established model that allows measurement of hemodynamic parameters and, by intravital microscopy, can allow quantification of adhesion. We tested antioxidant enzymes (SOD and catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the presence of platelet-activating factor (PAF); the latter causes endothelial oxidant generation and endothelial activation, which characterize SCA. In ex vivo preparations, PAF not only induced marked endothelial oxidant generation, it also enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter venules. The adhesion, inversely related to venular diameter, and vasoocclusion were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA, the most effective antioxidant, also abolished SS red cell adhesion in non-PAF-activated preparations. Thus SS red cell adhesion and related vasoocclusion may be ameliorated by antioxidant therapy with a stable and long-acting molecule (e.g., PNA).

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

Attributable causes of colorectal cancer in China.

PubMed

Gu, Meng-Jia; Huang, Qiu-Chi; Bao, Cheng-Zhen; Li, Ying-Jun; Li, Xiao-Qin; Ye, Ding; Ye, Zhen-Hua; Chen, Kun; Wang, Jian-Bing

2018-01-05

Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the burden of colorectal cancer incidence and mortality attributable to the known risk factors in China. We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies and meta-analyses. Among 245,000 new cases and 139,000 deaths of colorectal cancer in China in 2012, we found that 115,578 incident cases and 63,102 deaths of colorectal cancer were attributable to smoking, alcohol drinking, overweight and obesity, physical inactivity and dietary factors. Low vegetable intake was the main risk factor for colorectal cancer with a PAF of 17.9%. Physical inactivity was responsible for 8.9% of colorectal cancer incidence and mortality. The remaining factors, including high red and processed meat intake, low fruit intake, alcohol drinking, overweight/obesity and smoking, accounted for 8.6%, 6.4%, 5.4%, 5.3% and 4.9% of colorectal cancer, respectively. Overall, 45.5% of colorectal cancer incidence and mortality were attributable to the joint effects of these seven risk factors. Tobacco smoking, alcohol drinking, overweight or obesity, physical inactivity, low vegetable intake, low fruit intake, and high red and processed meat intake were responsible for nearly 46% of colorectal cancer incidence and mortality in China in 2012. Our findings could provide a basis for developing guidelines of colorectal cancer prevention and control in China.

Paroxysmal atrial fibrillation recognition based on multi-scale Rényi entropy of ECG.

PubMed

Xin, Yi; Zhao, Yizhang; Mu, Yuanhui; Li, Qin; Shi, Caicheng

2017-07-20

Atrial fibrillation (AF) is a common type of arrhythmia disease, which has a high morbidity and can lead to some serious complications. The ability to detect and in turn prevent AF is extremely significant to the patient and clinician. Using ECG to detect AF and develop a robust and effective algorithm is the primary objective of this study. Some studies show that after AF occurs, the regulatory mechanism of vagus nerve and sympathetic nerve will change. Each R-R interval will be absolutely unequal. After studying the physiological mechanism of AF, we will calculate the Rényi entropy of the wavelet coefficients of heart rate variability (HRV) in order to measure the complexity of PAF signals, as well as extract the multi-scale features of paroxysmal atrial fibrillation (PAF). The data used in this study is obtained from MIT-BIH PAF Prediction Challenge Database and the correct rate in classifying PAF patients from normal persons is 92.48%. The results of this experiment proved that AF could be detected by using this method and, in turn, provide opinions for clinical diagnosis.

Antiplatelet effects of protopine isolated from Corydalis tubers.

PubMed

Ko, F N; Wu, T S; Lu, S T; Wu, Y C; Huang, T F; Teng, C M

1989-10-15

Protopine inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, PAF, collagen and ionophore A23187. Although the platelet aggregation caused by thrombin was not inhibited by protopine (100 micrograms/ml), the release reaction was partially suppressed. In rabbit platelet-rich plasma, protopine also inhibited the platelet aggregation caused by ADP, arachidonic acid, PAF and collagen. The thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, ionophore A23187 and thrombin was suppressed by protopine. Protopine inhibited the intracellular calcium increase caused by arachidonic acid in quin-2/AM loaded rabbit platelets. In the presence of indomethacin, the intracellular calcium increase caused by collagen and PAF was completely suppressed by protopine, and the intracellular calcium increase caused by thrombin was partially inhibited. The phosphoinositides breakdown caused by collagen and PAF was inhibited by protopine, but that by thrombin was not affected significantly. Protopine did not cause the elevation of cyclic AMP level of platelets. It is concluded that the antiplatelet effects of protopine is due to inhibition on thromboxane formation and phosphoinositides breakdown and then lead to the decrease of intracellular calcium concentration.

Anti-thrombotic and anti-inflammatory activities of protopine.

PubMed

Saeed, S A; Gilani, A H; Majoo, R U; Shah, B H

1997-07-01

The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (microM) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen; 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A2 (TXA2) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg-1) protected rabbits from the lethal effects of AA (2 mg kg-1) or PAF (11 micrograms kg-1) in dose-dependent fashion. Protopine (50-100 mg kg-1) also inhibited carrageenan-induced rat paw oedema with a potency of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties.

Fragmented QRS and prediction of paroxysmal atrial fibrillation episodes

PubMed Central

Temiz, Ahmet; Gazi, Emine; Güngör, Ömer; Altun, Burak; Barutcu, Ahmet; Bekler, Adem; Tan, Yusuf Ziya; Ozcan, Sedat; Yener, Ali Ümit; Kurt, Tolga

2014-01-01

Objective: Prior studies have demonstrated the relationship between cardiovascular diseases and fragmented QRS (fQRS). fQRS was also associated with ventricular arrhythmias. Our objective was to find out the relationship between fQRS and paroxysmal atrial fibrillation (PAF). Method: A total of 301 patients without overt structural heart disease were prospectively included in the study. Patients were divided in to 2 groups according to presence of fQRS. Multivariate logistic regression analysis was used to assess the predictive value of fQRS for predicting PAF. Results: One hundred and three patients had fQRS. Patients with fQRS were older (53±16.8 vs 45.3±17.2, p<0.001), with larger left atrium (LA) (33.2±5.9 vs 30.1±5.9 mm, p=0.001), with thicker interventricular septum (IVS) (10.2±1.9 vs 9.5±2.3 mm, p=0.032), more diabetic (19.8 vs 10.6%, p=0.029) and have more PAF episodes (22.3 vs 4.1%, p<0.001) in comparison with patients without fQRS. fQRS was an independent predictor of detecting PAF episode (odds ratio, 9.69; 95% confidence interval, 2.46-38.15, p=0.001). Hypertension and diabetes mellitus were also predictive. Conclusion: The presence of fQRS independently predicted PAF episodes in holter monitoring (HM). Further studies are needed to clarify the clinical implications of this finding. PMID:25097533

Clinical impact of rotor ablation in atrial fibrillation: a systematic review.

PubMed

Parameswaran, Ramanathan; Voskoboinik, Aleksandr; Gorelik, Alexandra; Lee, Geoffrey; Kistler, Peter M; Sanders, Prashanthan; Kalman, Jonathan M

2018-01-11

Rotor mapping and ablation have gained favour over the recent years as an emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their efficacy, however, has been a topic of great debate with variable outcomes across centres. The aim of this study was to systematically review the recent medical literature to determine the medium-term outcomes of rotor ablation in patients with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF). A systematic search of the contemporary scientific literature (PubMed and EMBASE) was performed in August 2017. Only studies assessing arrhythmia-free survival from rotor ablation of AF were included. We used the random-effects model to assess the primary outcome of pooled medium-term single-procedure AF-free survival for both PAF and PeAF. Success rates from multiple procedures and complication rates were also examined. We included 11 observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence interval 5.6-86.3%] at a mean follow-up period of 13.8 ± 1.8 months for PAF and 59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 ± 6 months for PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and 88.3% for PeAF). The mean complication rate of rotor ablation among the reported studies was 3.4%. The wide variability in success rate between different centres performing rotor ablations suggests that the optimal ablation strategy, particularly targeting rotors, is unclear. Results from randomized studies are necessary before this technique can be considered as an established clinical tool. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

The P Wave Time-Frequency Variability Reflects Atrial Conduction Defects before Paroxysmal Atrial Fibrillation.

PubMed

Alcaraz, Raúl; Martínez, Arturo; Rieta, José J

2015-09-01

The study of atrial conduction defects associated with the onset of paroxysmal atrial fibrillation (PAF) can be addressed by analyzing the P wave from the surface electrocardiogram (ECG). Traditionally, signal-averaged ECGs have been mostly used for this purpose. However, this alternative hinders the possibility to quantify every single P wave, its variability over time, as well as to obtain complimentary and evolving information about the arrhythmia. This work analyzes the time progression of several time and frequency P wave features as potential indicators of atrial conduction variability several hours preceding the onset of PAF. The longest sinus rhythm interval from 24-hour Holter recordings of 46 PAF patients was selected. Next, the 2 hours before the onset of PAF were extracted and divided into two 1-hour periods. Every single P wave was automatically delineated and characterized by 16 time and frequency metrics, such as its duration, absolute energy in several frequency bands and high-to-low-frequency energy ratios. Finally, the P wave variability over each 1-hour period was estimated from the 16 features making use of a least-squares linear fitting. As a reference, the same parameters were also estimated from a set of 1-hour ECG segments randomly chosen from a control group of 53 healthy subjects age-, gender-, and heart rate-matched. All the analyzed metrics provided an increasing P wave variability trend as the onset of PAF approximated, being P wave duration and P wave high-frequency energy the most significant individual metrics. The linear fitting slope α associated with P wave duration was (2.48 ± 1.98)×10(-2) for healthy subjects, (23.8 ± 14.1)×10(-2) for ECG segments far from PAF and for (81.8 ± 48.7)×10(-2) ECG segments close to PAF p = 6.96×10(-22) . Similarly, the P wave high-frequency energy linear fitting slope was (2.42 ± 4.97)×10(-9) , (54.2 ± 107.1)×10(-9) and (274.2 ± 566.1)×10(-9) , respectively (p = 2.85×10(-20) ). A univariate discriminant analysis provided that both P wave duration and P wave high-frequency energy could discern among the three ECG sets with diagnostic ability around 80%, which was improved up to 88% by combining these metrics in a multivariate discriminant analysis. Alterations in atrial conduction can be successfully quantified several hours before the onset of PAF by estimating variability over time of several time and frequency P wave features. © 2014 Wiley Periodicals, Inc.

Neural Responses to Injury: Prevention, Protection, and Repair. Neurochemical Protection of the Brain, Neural Plasticity and Repair

DTIC Science & Technology

1998-10-01

can be displaced by BN-52021, a terpenoid extracted from the leaf of the Ginkgo biloba tree, which binds preferentially to the synaptosomal site...lyso PAF (22-24). Presynaptic membranes display PAF binding that can be displaced by BN 52021, a terpenoid extracted from the leaf of the Ginkgo

Proportion of cancer in a Middle eastern country attributable to established risk factors.

PubMed

Charafeddine, Maya A; Olson, Sara H; Mukherji, Deborah; Temraz, Sally N; Abou-Alfa, Ghassan K; Shamseddine, Ali I

2017-05-18

Providing an estimate of the percentage of cancer in Lebanon by 2018 that is due to the exposure to risk factors in 2008. Factors include: smoking, body mass index (BMI), physical inactivity, dietary factors, alcohol consumption, infections, and air pollution in adults. Population Attributable Fraction (PAF) was calculated using the proportion of the population exposed and relative risks for each risk factor from meta-analyses. The PAF estimates the proportion of cases in which exposure may have played a causal role. Smoking caused most cancer cases, and it will further add a total of 1800 new cases by 2018. Among many other cancers, lung cancer had the largest proportion attributable of around 75%. BMI is expected to increase colorectal, liver and gastric cardia carcinoma specifically in males. High physical activity has a an average of 15% protection rate on cancer on colorectal cancer. Minimal adherence to Mediterranean diet will affect gastric cancer incidence by 7%. Cases of oropharyngeal and esophageal cancer will be the result of alcohol consumption mainly in males. H.Pylori infection is expected to result in half of the gastric cases by 2018. The high exposure to air pollution is expected to contribute by 13% to lung cancer cases in 2018. The highest benefits can be achieved by controlling tobacco smoking. Interrelated and small changes in weight, physical activity and healthy diet with limited alcohol consumption can protect against several GI cancers in the long run. These results can be used to determine public health interventions that target important risk factors in the general population.

Exploring Time Perspective in Greek Young Adults: Validation of the Zimbardo Time Perspective Inventory and Relationships with Mental Health Indicators

ERIC Educational Resources Information Center

Anagnostopoulos, Fotios; Griva, Fay

2012-01-01

In this article we examine the factorial structure of the Greek version of the Zimbardo Time Perspective Inventory (ZTPI; Zimbardo and Boyd in "J Personal Soc Psychol" 77:1271-1288, 1999), in a sample of 337 university students, using principal axis factoring (PAF) with oblique rotation, and its dimensionality using parallel analysis.…

Cholesterol ester hydrolase inhibitors reduce the production of synaptotoxic amyloid-β oligomers.

PubMed

McHale-Owen, Harriet; Bate, Clive

2018-03-01

The production of amyloid-β (Aβ) is the key factor driving pathogenesis in Alzheimer's disease (AD). Increasing concentrations of Aβ within the brain cause synapse degeneration and the dementia that is characteristic of AD. Here the factors that affect the release of disease-relevant forms Aβ were studied in a cell model. 7PA2 cells expressing the human amyloid precursor protein released soluble Aβ oligomers that caused synapse damage in cultured neurons. Supernatants from 7PA2 cells treated with the cholesterol synthesis inhibitor squalestatin contained similar concentrations of Aβ 42 to control cells but did not cause synapse damage in neuronal cultures. These supernatants contained reduced concentrations of Aβ 42 oligomers and increased concentrations of Aβ 42 monomers. Treatment of 7PA2 cells with platelet-activating factor (PAF) antagonists had similar effects; it reduced concentrations of Aβ 42 oligomers and increased concentrations of Aβ 42 monomers in cell supernatants. PAF activated cholesterol ester hydrolases (CEH), enzymes that released cholesterol from stores of cholesterol esters. Inhibition of CEH also reduced concentrations of Aβ 42 oligomers and increased concentrations of Aβ 42 monomers in cell supernatants. The Aβ monomers produced by treated cells protected neurons against Aβ oligomer-induced synapse damage. These studies indicate that pharmacological manipulation of cells can alter the ratio of Aβ monomer:oligomer released and consequently their effects on synapses. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnostic work-up for detection of paroxysmal atrial fibrillation after acute ischemic stroke: cross-sectional survey on German stroke units.

PubMed

Rizos, Timolaos; Quilitzsch, Anika; Busse, Otto; Haeusler, Karl Georg; Endres, Matthias; Heuschmann, Peter; Veltkamp, Roland

2015-06-01

Multiple methods to detect paroxysmal atrial fibrillation (pAF) in patients with acute stroke are available. However, it is unknown which approaches are currently used in clinical routine and guidelines remain vague to the extent of cardiac monitoring. We characterize diagnostic efforts for pAF detection on German stroke units (SU). A standardized anonymous questionnaire was sent to all clinical leads of certified SUs in Germany. The questionnaire focused on basic characteristics of SUs, procedures to detect AF, and estimates on AF detection. One hundred seventy-nine SU leads participated (response rate 71.6%). All patients undergo continuous bedside ECG monitoring. A percentage of 77.6 SUs initiate additional 24-hour Holter ECG in >50% of patients without known AF. Patients with transient ischemic attack are monitored significantly shorter than patients with ischemic stroke. Independent of SU type or size, 67.6% of leads assumed to fail detecting pAF in 5% to 20% of patients. In cryptogenic stroke, additional ECG monitoring is recommended by 90.2% but only 13.8% of SUs perform routine ECG follow-up visits. The use of implanted event recorders is low (1-10 patients/y by 60.7% of SUs; 28.1%: no use). A percentage of 83.9 do not use external event recorders. Our survey demonstrates substantial heterogeneity among German SUs on diagnostic work-up for pAF. Future prospective multicenter studies should systematically evaluate the impact of different methods to uncover pAF. © 2015 American Heart Association, Inc.

Structures of the recurrence plot of heart rate variability signal as a tool for predicting the onset of paroxysmal atrial fibrillation.

PubMed

Mohebbi, Maryam; Ghassemian, Hassan; Asl, Babak Mohammadzadeh

2011-05-01

This paper aims to propose an effective paroxysmal atrial fibrillation (PAF) predictor which is based on the analysis of the heart rate variability (HRV) signal. Predicting the onset of PAF, based on non-invasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic interventions and to minimize the risks for the patients. This method consists of four steps: Preprocessing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In the next step, the recurrence plot (RP) of HRV signal is obtained and six features are extracted to characterize the basic patterns of the RP. These features consist of length of longest diagonal segments, average length of the diagonal lines, entropy, trapping time, length of longest vertical line, and recurrence trend. In the third step, these features are reduced to three features by the linear discriminant analysis (LDA) technique. Using LDA not only reduces the number of the input features, but also increases the classification accuracy by selecting the most discriminating features. Finally, a support vector machine-based classifier is used to classify the HRV signals. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database which consists of both 30-minutes ECG recordings end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, and positive predictivity were 96.55%, 100%, and 100%, respectively.

Patterns of recurrence after trimodality therapy for esophageal cancer.

PubMed

Dorth, Jennifer A; Pura, John A; Palta, Manisha; Willett, Christopher G; Uronis, Hope E; D'Amico, Thomas A; Czito, Brian G

2014-07-15

Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes. © 2014 American Cancer Society.

Tuberculosis and poverty: why are the poor at greater risk in India?

PubMed

Oxlade, Olivia; Murray, Megan

2012-01-01

Although poverty is widely recognized as an important risk factor for tuberculosis (TB) disease, the specific proximal risk factors that mediate this association are less clear. The objective of our study was to investigate the mechanisms by which poverty increases the risk of TB. Using individual level data from 198,754 people from the 2006 Demographic Health Survey (DHS) for India, we assessed self-reported TB status, TB determinants and household socioeconomic status. We used these data to calculate the population attributable fractions (PAF) for each key TB risk factor based on the prevalence of determinants and estimates of the effect of these risk factors derived from published sources. We conducted a mediation analysis using principal components analysis (PCA) and regression to demonstrate how the association between poverty and TB prevalence is mediated. The prevalence of self-reported TB in the 2006 DHS for India was 545 per 100,000 and ranged from 201 in the highest quintile to 1100 in the lowest quintile. Among those in the poorest population, the PAFs for low body mass index (BMI) and indoor air pollution were 34.2% and 28.5% respectively. The PCA analysis also showed that low BMI had the strongest mediating effect on the association between poverty and prevalent TB (12%, p = 0.019). TB control strategies should be targeted to the poorest populations that are most at risk, and should address the most important determinants of disease--specifically low BMI and indoor air pollution.

The economic burden of physical inactivity: a systematic review and critical appraisal.

PubMed

Ding, Ding; Kolbe-Alexander, Tracy; Nguyen, Binh; Katzmarzyk, Peter T; Pratt, Michael; Lawson, Kenny D

2017-10-01

To summarise the literature on the economic burden of physical inactivity in populations, with emphases on appraising the methodologies and providing recommendations for future studies. Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number CRD42016047705). Electronic databases for peer-reviewed and grey literature were systematically searched, followed by reference searching and consultation with experts. Studies that examined the economic consequences of physical inactivity in a population/population-based sample, with clearly stated methodologies and at least an abstract/summary written in English. Of the 40 eligible studies, 27 focused on direct healthcare costs only, 13 also estimated indirect costs and one study additionally estimated household costs. For direct costs, 23 studies used a population attributable fraction (PAF) approach with estimated healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of national healthcare expenditure; 17 studies used an econometric approach, which tended to yield higher estimates than those using a PAF approach. For indirect costs, 10 studies used a human capital approach, two used a friction cost approach and one used a value of a statistical life approach. Overall, estimates varied substantially, even within the same country, depending on analytical approaches, time frame and other methodological considerations. Estimating the economic burden of physical inactivity is an area of increasing importance that requires further development. There is a marked lack of consistency in methodological approaches and transparency of reporting. Future studies could benefit from cross-disciplinary collaborations involving economists and physical activity experts, taking a societal perspective and following best practices in conducting and reporting analysis, including accounting for potential confounding, reverse causality and comorbidity, applying discounting and sensitivity analysis, and reporting assumptions, limitations and justifications for approaches taken. We have adapted the Consolidated Health Economic Evaluation Reporting Standards checklist as a guide for future estimates of the economic burden of physical inactivity and other risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Whey Peptide-Based Formulas With ω-3 Fatty Acids Are Protective in Lipopolysaccharide-Mediated Sepsis.

PubMed

Tsutsumi, Rie; Horikawa, Yousuke T; Kume, Katsuyoshi; Tanaka, Katsuya; Kasai, Asuka; Kadota, Takako; Tsutsumi, Yasuo M

2015-07-01

Sepsis and septic shock syndrome are among the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon may translocate across a compromised epithelium, leading to oxidative stress, inflammation, sepsis, and eventually death. We examined the effects of a whey-based enteral formula high in cysteine (antioxidant precursor) and the addition of ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against a mouse model of LPS-induced sepsis. Mice were fed either a whey-based diet with EPA-DHA (PAF), a whey-based diet without EPA-DHA (PSTD), or a casein-based control diet (CONT). Mice fed PAF or PSTD were protected against LPS-induced weight loss. Whey-based diets suppressed inflammatory cytokine release and oxidative stress damage. Furthermore, PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles. These anti-inflammatory and antioxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microbiota within the intestines. These data suggest a clinical role for whey peptide-based diets in promoting healing and recovery in critically ill patients. © 2014 American Society for Parenteral and Enteral Nutrition.

Job dissatisfaction and the older worker: baseline findings from the Health and Employment After Fifty study

PubMed Central

D’Angelo, Stefania; Coggon, David; Harris, E Clare; Linaker, Cathy; Sayer, Avan Aihie; Gale, Catharine R; Evandrou, Maria; van Staa, Tjeerd; Cooper, Cyrus; Walker-Bone, Karen; Palmer, Keith T

2016-01-01

Objectives Demographic changes are requiring people to work longer. Labour force participation might be promoted by tackling sources of job dissatisfaction. We aimed to describe the epidemiology of job dissatisfaction in older British workers, to explore which perceptions of work contribute most importantly, and to assess possible impacts on health. Methods Subjects aged 50-64 years were recruited from 24 English general practices. At baseline, those currently in work (N=5,437) reported on their demographic and employment circumstances, overall job satisfaction, perceptions of their work that might contribute to dissatisfaction, and their general health, mood and well-being. Associations of job dissatisfaction with risk factors and potential health outcomes were assessed cross-sectionally by logistic regression and the potential contributions of different negative perceptions to overall dissatisfaction were summarised by population attributable fractions (PAFs). Results Job dissatisfaction was more common among men, below age 60 years, those living in London and the South East, in the more educated and in those working for larger employers. The main contributors to job dissatisfaction among employees were feeling unappreciated and/or lacking a sense of achievement (PAF 55%-56%), while in the self-employed, job insecurity was the leading contributor (PAF 79%). Job dissatisfaction was associated with all of the adverse health outcomes examined (odds ratios of 3-5), as were most of the negative perceptions of work that contributed to overall dissatisfaction. Conclusions Employment policies aimed at improving job satisfaction in older workers may benefit from focussing particularly on relationships in the workplace, fairness, job security and instilling a sense of achievement. PMID:27152012

Amifostine, a reactive oxigen species scavenger with radiation- and chemo-protective properties, inhibits in vitro platelet activation induced by ADP, collagen or PAF.

PubMed

Porta, C; Maiolo, A; Tua, A; Grignani, G

2000-08-01

Reactive oxygen species (ROS) generation has been suggested to represent an important regulatory mechanism of platelet reactivity in both physiologic and pathologic conditions; consistent with this hypothesis is the observation that free-radical scavengers may inhibit platelet activation, thus contributing to the regulation of their reactivity. The purpose of the present study is to study the in vitro effects of amifostine (WR-2721, ethyol ), a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and radiation, on platelet activation induced by the physiologic agonists ADP, collagen and PAF. The effect of amifostine, added to the experimental system at final concentrations ranging from 10(-7) M to 10(-5) M, was studied on platelet aggregation induced by the following physiologic agonists at the given concentrations: ADP (1 microM), collagen (2 microg/mL), and PAF (0.1 microg/mL). Platelet aggregation was investigated using a platelet ionized calcium aggregometer and was expressed as the percentage change in light transmission. Furthermore, thromboxane B((2)) (TxB((2))) levels and nitric oxide (NO) production were determined by radioimmunoassay and by evaluating the total nitrite/nitrate concentration using a commercially available colorimetric kit, respectively, both in the control system and after the addition of amifostine. Amifostine inhibited both platelet aggregation and TxB((2)) production induced by ADP, collagen and PAF, in a dose-dependent manner. Amifostine proved to be an effective inhibitor of platelet function and the effect was more pronounced if platelets were stimulated with ADP, intermediate when collagen was the chosen agonist, and less evident, though present, when PAF was used. Platelets stimulated with ADP, collagen or PAF produced significant amounts of NO over the baseline. When amifostine was added at a final concentration of 5 microM, it significantly increased ADP, collagen and PAF-induced NO production, which suggests that NO release by activated platelets was involved in the inhibitory effect of amifostine. Amifostine proved to be an effective inhibitor of platelet activation induced in vitro by physiologic inducers. This previously unrecognized effect was more evident with the weak agonist ADP and was related to reduced NO consumption by free radicals generated during platelet activation. Amifostine proved to be not only a powerful cytoprotectant, but, more generally, a therapeutic agent endowed with several relevant, though largely unknown, biological effects. Finally, our data once again support the concept that oxidative balance is of crucial importance in regulating platelet reactivity in both health and disease.

Usefulness of left ventricular speckle tracking echocardiography and novel measures of left atrial structure and function in diagnosing paroxysmal atrial fibrillation in ischemic stroke and transient ischemic attack patients.

PubMed

Skaarup, Kristoffer Grundtvig; Christensen, Hanne; Høst, Nis; Mahmoud, Masti Mahdy; Ovesen, Christian; Olsen, Flemming Javier; Jensen, Jan Skov; Biering-Sørensen, Tor

2017-12-01

Asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of cryptogenic ischemic strokes (IS) and transient ischemic attacks (TIA). We examined the usefulness of measures obtained by 2D speckle tracking echocardiography and novel left atrial measurements, in the diagnosis of PAF in patients with IS and TIA. We retrospectively included 205 patients who after acute IS or TIA underwent an echocardiogram in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. None of the conventional echocardiographic parameters were significantly associated with PAF. Of the speckle tracking measurements, only early diastolic strain rate (0.7±0.2 s -1 vs. 0.8±0.3 s -1 , p = 0.048) and global longitudinal displacement (GLD) (3.15 ± 1.40 mm vs. 3.87 ± 1.56 mm, p = 0.007) proved significantly different. Of the left atrial parameters both minimal and maximal left atrium volume divided by left ventricular length (min LAV/LVL and max LAV/LVL, respectively) were significantly impaired (min LAV/LVL: 3.7 ± 2.1 cm 2 vs. 2.8 ± 1.11 cm 2 , p = 0.012; max LAV/LVL: 6.6 ± 3.1 cm 2 vs. 5.6 ± 1.7 cm 2 , p = 0.012). GLD, min max LAV/LVL proved significant after adjustment for age, gender, CHA 2 DS 2 -VASc and NIHSS. By combining information regarding age, GLD, min and max LAV/LVL the diagnostic accuracy of PAF improved, resulting in a significantly increased area under the curve (p = 0.037). In patients with IS and TIA GLD, min and max LAV/LVL were independently associated with the presence of PAF.

Improvement in quality of life after catheter ablation for paroxysmal versus long-standing persistent atrial fibrillation: a prospective study with 3-year follow-up.

PubMed

Bulková, Veronika; Fiala, Martin; Havránek, Stěpán; Simek, Jan; Skňouřil, Libor; Januška, Jaroslav; Spinar, Jindřich; Wichterle, Dan

2014-07-18

Changes in quality of life (QoL) after catheter ablation for long-standing persistent atrial fibrillation (LSPAF) are not well described. We sought to compare QoL improvement after catheter ablation of paroxysmal atrial fibrillation (PAF) versus that after LSPAF. A total of 261 PAF and 126 LSPAF ablation recipients were prospectively followed for arrhythmia recurrence, QoL, hospital stay, and sick leave. In PAF versus LSPAF groups, 1.3±0.6 versus 1.6±0.7 procedures were performed per patient (P<0.00001) during a 3-year follow-up. Good arrhythmia control was achieved in 86% versus 87% of patients (P=0.69) and in 69% versus 69% of patients not receiving antiarrhythmic drugs (P=0.99). The baseline QoL was better in the PAF than in the LSPAF group (European Quality of Life Group instrument self-report questionnaire visual analog scale: 66.4±14.2 versus 61.0±14.2, P=0.0005; European Quality of Life Group 3-level, 5-dimensional descriptive system: 71.4±9.2 versus 67.7±13.8, P=0.002). Postablation 3-year increase in QoL was significant in both groups (all P<0.00001) and significantly lower in PAF versus LSPAF patients (visual analog scale: +5.0±14.5 versus +10.2±12.8, P=0.001; descriptive system: +5.9±14.3 versus +9.3±13.9, P=0.03). In multivariate analysis, LSPAF, less advanced age, shorter history of AF and good arrhythmia control were consistently associated with postablation 3-year improvement in QoL. Days of hospital stay for cardiovascular reasons and days on sick leave per patient/year were significantly reduced in both groups. Patients with LSPAF had worse baseline QoL. The magnitude of QoL improvement after ablation of LSPAF was significantly greater compared with after ablation of PAF, particularly when good arrhythmia control was achieved without the use of antiarrhythmic drugs. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Paroxysmal atrial fibrillation prediction method with shorter HRV sequences.

PubMed

Boon, K H; Khalil-Hani, M; Malarvili, M B; Sia, C W

2016-10-01

This paper proposes a method that predicts the onset of paroxysmal atrial fibrillation (PAF), using heart rate variability (HRV) segments that are shorter than those applied in existing methods, while maintaining good prediction accuracy. PAF is a common cardiac arrhythmia that increases the health risk of a patient, and the development of an accurate predictor of the onset of PAF is clinical important because it increases the possibility to stabilize (electrically) and prevent the onset of atrial arrhythmias with different pacing techniques. We investigate the effect of HRV features extracted from different lengths of HRV segments prior to PAF onset with the proposed PAF prediction method. The pre-processing stage of the predictor includes QRS detection, HRV quantification and ectopic beat correction. Time-domain, frequency-domain, non-linear and bispectrum features are then extracted from the quantified HRV. In the feature selection, the HRV feature set and classifier parameters are optimized simultaneously using an optimization procedure based on genetic algorithm (GA). Both full feature set and statistically significant feature subset are optimized by GA respectively. For the statistically significant feature subset, Mann-Whitney U test is used to filter non-statistical significance features that cannot pass the statistical test at 20% significant level. The final stage of our predictor is the classifier that is based on support vector machine (SVM). A 10-fold cross-validation is applied in performance evaluation, and the proposed method achieves 79.3% prediction accuracy using 15-minutes HRV segment. This accuracy is comparable to that achieved by existing methods that use 30-minutes HRV segments, most of which achieves accuracy of around 80%. More importantly, our method significantly outperforms those that applied segments shorter than 30 minutes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contribution of the Mission in Afghanistan to the Burden of Past-Year Mental Disorders in Canadian Armed Forces Personnel, 2013

PubMed Central

Zamorski, Mark A.

2016-01-01

Objective: The purpose of this study was to estimate the contribution of the mission in Afghanistan to the burden of mental health problems in the Canadian Armed Forces (CAF). Methods: Data were obtained from the 2013 Canadian Forces Mental Health Survey, which assessed mental disorders using the World Health Organization’s Composite International Diagnostic Interview. The sample consisted of 6696 Regular Force (RegF) personnel, 3384 of whom had deployed in support of the mission. We estimated the association of past-year mental health problems with Afghanistan deployment status, adjusting for covariates using logistic regression; population attributable fractions (PAFs) were also calculated. Results: Indication of a past-year mental disorder was identified in 18.4% (95% confidence interval [CI], 17.0% to 19.7%) of Afghanistan deployers compared with 14.6% (95% CI, 13.3% to 15.8%) in others. Afghanistan-related deployments contributed to the burden of a past-year disorder (PAF = 8.7%; 95% CI, 3.0% to 14.2%), with the highest PAFs being seen for panic disorder (34.7%) and posttraumatic stress disorder (32.1%). The PAFs for individual alcohol use disorders and suicide ideation were not different from zero. Child abuse, however, had a much greater PAF for any past-year disorder (28.7%; 95% CI, 23.4% to 33.7%) than did the Afghanistan mission. Conclusions: The mission in Afghanistan contributed significantly to the burden of mental disorders in the CAF RegF in 2013. However, the much stronger contribution of child abuse highlights the need for strong military mental health systems, even in peacetime, and the need to target the full range of determinants of mental health in prevention and control efforts. PMID:27270744

Structures of the Recurrence Plot of Heart Rate Variability Signal as a Tool for Predicting the Onset of Paroxysmal Atrial Fibrillation

PubMed Central

Mohebbi, Maryam; Ghassemian, Hassan; Asl, Babak Mohammadzadeh

2011-01-01

This paper aims to propose an effective paroxysmal atrial fibrillation (PAF) predictor which is based on the analysis of the heart rate variability (HRV) signal. Predicting the onset of PAF, based on non-invasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic interventions and to minimize the risks for the patients. This method consists of four steps: Preprocessing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In the next step, the recurrence plot (RP) of HRV signal is obtained and six features are extracted to characterize the basic patterns of the RP. These features consist of length of longest diagonal segments, average length of the diagonal lines, entropy, trapping time, length of longest vertical line, and recurrence trend. In the third step, these features are reduced to three features by the linear discriminant analysis (LDA) technique. Using LDA not only reduces the number of the input features, but also increases the classification accuracy by selecting the most discriminating features. Finally, a support vector machine-based classifier is used to classify the HRV signals. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database which consists of both 30-minutes ECG recordings end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, and positive predictivity were 96.55%, 100%, and 100%, respectively. PMID:22606666

Paroxysmal atrial fibrillation prediction based on HRV analysis and non-dominated sorting genetic algorithm III.

PubMed

Boon, K H; Khalil-Hani, M; Malarvili, M B

2018-01-01

This paper presents a method that able to predict the paroxysmal atrial fibrillation (PAF). The method uses shorter heart rate variability (HRV) signals when compared to existing methods, and achieves good prediction accuracy. PAF is a common cardiac arrhythmia that increases the health risk of a patient, and the development of an accurate predictor of the onset of PAF is clinical important because it increases the possibility to electrically stabilize and prevent the onset of atrial arrhythmias with different pacing techniques. We propose a multi-objective optimization algorithm based on the non-dominated sorting genetic algorithm III for optimizing the baseline PAF prediction system, that consists of the stages of pre-processing, HRV feature extraction, and support vector machine (SVM) model. The pre-processing stage comprises of heart rate correction, interpolation, and signal detrending. After that, time-domain, frequency-domain, non-linear HRV features are extracted from the pre-processed data in feature extraction stage. Then, these features are used as input to the SVM for predicting the PAF event. The proposed optimization algorithm is used to optimize the parameters and settings of various HRV feature extraction algorithms, select the best feature subsets, and tune the SVM parameters simultaneously for maximum prediction performance. The proposed method achieves an accuracy rate of 87.7%, which significantly outperforms most of the previous works. This accuracy rate is achieved even with the HRV signal length being reduced from the typical 30 min to just 5 min (a reduction of 83%). Furthermore, another significant result is the sensitivity rate, which is considered more important that other performance metrics in this paper, can be improved with the trade-off of lower specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and testing of a new framework for rapidly assessing legal and managerial protection afforded by marine protected areas: Mediterranean Sea case study.

PubMed

Rodríguez-Rodríguez, D; Rodríguez, J; Abdul Malak, D

2016-02-01

The Convention on Biological Diversity (CBD) states the need to effectively conserve at least 10% of coastal and marine areas of particular importance for biodiversity by 2020. Here, a new indicator-based methodological framework to assess biodiversity protection afforded by marine protected areas' (MPA) was developed as a quick surrogate for MPAs' potential conservation effectiveness: the Marine Protected Area Protection Assessment Framework (MaPAF). The MaPAF consists of a limited number of headline indicators that are integrated in two indexes: Legal protection and Management effort, which eventually integrate in the overall MPA Protection super-index. The MaPAF was then tested in the Mediterranean MPA network as a case study. Spatial analyses were performed at three meaningful scales: the whole Mediterranean Sea, Mediterranean ecoregions and countries. The results of this study suggest that: 1) The MaPAF can serve as a useful tool for consistent, adaptive, quick and cost-effective MPA effectiveness assessments of MPAs and MPA networks in virtually any marine region, as the headline indicators used are commonly compiled and easy to retrieve; 2) The MaPAF proved usable and potentially relevant in the Mediterranean Sea where most indicators in the framework can be publicly accessed through the MAPAMED database and are planned to be regularly updated; 3) Protection afforded by MPAs is low across the whole Mediterranean, with only few MPAs having relatively high legal and managerial protection; and 4) Most Mediterranean countries need to devote substantially more work to improve MPA effectiveness mainly through increased management effort. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using reference values to define disease based on the lower limit of normal biased the population attributable fraction, but not the population excess risk: the example of chronic airflow obstruction.

PubMed

Burney, Peter; Minelli, Cosetta

2018-01-01

The impact of disease on population health is most commonly estimated by the population attributable fraction (PAF), or less commonly by the excess risk, an alternative measure that estimates the absolute risk of disease in the population that can be ascribed to the exposure. Using chronic airflow obstruction as an example, we examined the impact on these estimates of defining disease based on different "normal" values. We estimated PAF and the excess risk in scenarios in which the true rate of disease was 10% in the exposed and 5% in the unexposed, and where either 50% or 20% of the population was exposed. Disease definition was based on a "lower limit of normal", using the 5th, 1st and 0.2nd centile of values in a "normal" population as thresholds to define normality. Where normality is defined by centiles of values in a "normal" population, PAF is strongly influenced by which centile is selected to define normality. This is not true for the population excess risk. Care should be taken when interpreting estimates of PAF when disease is defined from a centile of a normal population. Copyright © 2017 Elsevier Inc. All rights reserved.

What proportion of cancer deaths in the contemporary United States is attributable to cigarette smoking?

PubMed

Jacobs, Eric J; Newton, Christina C; Carter, Brian D; Feskanich, Diane; Freedman, Neal D; Prentice, Ross L; Flanders, W Dana

2015-03-01

The proportion of cancer deaths in the contemporary United States caused by cigarette smoking (the population attributable fraction [PAF]) is not well documented. The PAF of all cancer deaths due to active cigarette smoking among adults 35 years and older in the United States in 2010 was calculated using age- and sex-specific smoking prevalence from the National Health Interview Survey (NHIS) and age- and sex-specific relative risks from the Cancer Prevention Study-II (for ages 35-54 years) and from the Pooled Contemporary Cohort data set (for ages 55 years and older). The PAF for active cigarette smoking was 28.7% when estimated conservatively, including only deaths from the 12 cancers currently formally established as caused by smoking by the US Surgeon General. The PAF was 31.7% when estimated more comprehensively, including excess deaths from all cancers. These estimates do not include additional potential cancer deaths from environmental tobacco smoke or other type of tobacco use such as cigars, pipes, or smokeless tobacco. Cigarette smoking causes a large proportion of cancer deaths in the contemporary United States. Reducing smoking prevalence as rapidly as possible should be a top priority for the US public health efforts to prevent cancer deaths. Copyright © 2015 Elsevier Inc. All rights reserved.

Origins of thalamic and cortical projections to the posterior auditory field in congenitally deaf cats.

PubMed

Butler, Blake E; Chabot, Nicole; Kral, Andrej; Lomber, Stephen G

2017-01-01

Crossmodal plasticity takes place following sensory loss, such that areas that normally process the missing modality are reorganized to provide compensatory function in the remaining sensory systems. For example, congenitally deaf cats outperform normal hearing animals on localization of visual stimuli presented in the periphery, and this advantage has been shown to be mediated by the posterior auditory field (PAF). In order to determine the nature of the anatomical differences that underlie this phenomenon, we injected a retrograde tracer into PAF of congenitally deaf animals and quantified the thalamic and cortical projections to this field. The pattern of projections from areas throughout the brain was determined to be qualitatively similar to that previously demonstrated in normal hearing animals, but with twice as many projections arising from non-auditory cortical areas. In addition, small ectopic projections were observed from a number of fields in visual cortex, including areas 19, 20a, 20b, and 21b, and area 7 of parietal cortex. These areas did not show projections to PAF in cats deafened ototoxically near the onset of hearing, and provide a possible mechanism for crossmodal reorganization of PAF. These, along with the possible contributions of other mechanisms, are considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Anger in the UK Armed Forces: strong association with mental health, childhood antisocial behavior, and combat role.

PubMed

Rona, Roberto J; Jones, Margaret; Hull, Lisa; MacManus, Deirdre; Fear, Nicola T; Wessely, Simon

2015-01-01

We assessed the strength of the association of several mental health problems, childhood difficulties, and combat role with anger, as well as the contribution of these factors to explain anger assessed by population attributable fraction (PAF). A total of 9885 UK service personnel, some of them deployed to Iraq and Afghanistan, participated in the study. There was a strong or intermediate association between cases and subthreshold cases of symptoms of posttraumatic stress disorder, psychological distress, multiple physical symptoms and alcohol misuse, having a combat role, childhood adversity, and childhood antisocial behavior with anger. The PAF for any mental health problem and combat role and childhood difficulties was 0.64 (95% confidence interval [CI], 0.56-0.70) and increased to 0.77 (95% CI, 0.69-0.83) if subthreshold cases were included. Anger is a frequent component of mental disorders; health care professionals need to be aware of the interference of anger in the management of mental illness and that anger infrequently presents as an isolated phenomenon.

Tannase production by Penicillium purpurogenum PAF6 in solid state fermentation of tannin-rich plant residues following OVAT and RSM.

PubMed

Jana, Arijit; Maity, Chiranjit; Halder, Suman Kumar; Mondal, Keshab Chandra; Pati, Bikash Ranjan; Mohapatra, Pradeep Kumar Das

2012-07-01

Tannase production by newly isolated Penicillium purpurogenum PAF6 was investigated by 'one variable at a time' (OVAT) approach followed by response surface methodology (RSM). Tannin-rich plant residues were used as supporting solid substrate and sole carbon source and, among them, tamarind seed was found to be the most favorable substrate than haritaki, pomegranate, tea leaf waste and arjun fruit. Physicochemical parameters were initially optimized using OVAT methodology and some important factors like incubation time, incubation temperature, substrate:moisture ratio as well as carbon, nitrogen and phosphate concentrations were verified with Box-Behken design of response surface methodology. Phosphate source, nitrogen source and temperature were found as the most favorable variables in the maximization of production. Tannase production was enhanced from 1.536 U/g to 5.784 U/g using tamarind seed OVAT optimization and further enhancement up to 6.15 U/g following RSM. An overall 3.76- and 4.0-fold increases in tannase production were achieved in OVAT and RSM, respectively.

Job dissatisfaction and the older worker: baseline findings from the Health and Employment After Fifty study.

PubMed

D'Angelo, Stefania; Coggon, David; Harris, E Clare; Linaker, Cathy; Sayer, Avan Aihie; Gale, Catharine R; Evandrou, Maria; van Staa, Tjeerd; Cooper, Cyrus; Walker-Bone, Karen; Palmer, Keith T

2016-08-01

Demographic changes are requiring people to work longer. Labour force participation might be promoted by tackling sources of job dissatisfaction. We aimed to describe the epidemiology of job dissatisfaction in older British workers, to explore which perceptions of work contribute most importantly, and to assess possible impacts on health. Participants aged 50-64 years were recruited from 24 English general practices. At baseline, those currently in work (N=5437) reported on their demographic and employment circumstances, overall job satisfaction, perceptions of their work that might contribute to dissatisfaction, and their general health, mood and well-being. Associations of job dissatisfaction with risk factors and potential health outcomes were assessed cross-sectionally by logistic regression, and the potential contributions of different negative perceptions to overall dissatisfaction were summarised by population attributable fractions (PAFs). Job dissatisfaction was more common among men, below age 60 years, those living in London and the South East, in the more educated and in those working for larger employers. The main contributors to job dissatisfaction among employees were feeling unappreciated and/or lacking a sense of achievement (PAF 55-56%), while in the self-employed, job insecurity was the leading contributor (PAF 79%). Job dissatisfaction was associated with all of the adverse health outcomes examined (ORs of 3-5), as were most of the negative perceptions of work that contributed to overall dissatisfaction. Employment policies aimed at improving job satisfaction in older workers may benefit from focussing particularly on relationships in the workplace, fairness, job security and instilling a sense of achievement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Co-incubation of PMN and CaCo-2 cells modulates inflammatory potential.

PubMed

Schaefer, M B; Schaefer, C A; Hecker, M; Morty, R E; Witzenrath, M; Seeger, W; Mayer, K

2017-05-20

Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only. Human neutrophil elastase (HNE) and respiratory Burst were measured. To evaluate the modulation of inflammatory crosstalk we applied inhibitors of COX (acetyl salicylic acid; ASA), NO-synthase (N-monomethyl-L-arginin; L-NMMA), and the PAF-receptor (WEB2086). Unstimulated, co-incubation of CaCo-2 cells and PMN led to significantly reduced Burst and elevated HNE as compared to PMN. After stimulation with A23187, co-incubation resulted in an inhibition of Burst and HNE. Using fMLP co-incubation failed to modulate Burst but increased HNE. Without stimulation, all three inhibitors abolished the effect of co-incubation on Burst but did not change HNE.  ASA partly prevented modulation of Burst L-NMMA and WEB2086 did not change Burst but abolished mitigation of HNE. Without stimulation, co-incubation reduced Burst and elevated HNE. Activation of PMN and CaCo-2 cells by fMLP as compared to A23187 resulted in a completely different pattern of Burst and HNE, possibly due to single vs. dual cell activation. Anti-inflammatory effect of co-incubation might in part be due to due to COX-signalling governing Burst whereas NO- and PAF-dependent signalling seemed to control HNE release.

Risk of cancer among HIV-infected individuals compared to the background population: impact of smoking and HIV.

PubMed

Helleberg, Marie; Gerstoft, Jan; Afzal, Shoaib; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Court; Bojesen, Stig E; Nordestgaard, Børge G; Obel, Niels

2014-06-19

The relative impact of immune deficiency and lifestyle-related factors on risk of cancer in the HIV-infected population is controversial. We aimed to estimate the population-attributable fractions (PAFs) associated with smoking, being HIV-infected and with immune deficiency. In a Danish, nationwide, population-based cohort study (1995-2011), incidences of cancer were compared between an HIV-infected cohort and a population-based matched cohort in analyses stratified on cancer category, smoking status and for HIV patients: low CD4 cell count. We included 3503 HIV patients [baseline CD4+ 450 cells/μl (inter-quartile range 310-630)] and 12,979 population controls. Smoking-related and virological cancers accounted for 23 and 43% of cancers in the HIV-infected population. The risk of these cancers were higher among HIV patients compared to controls [incidence rate ratio (IRR) 2.8, 95% confidence interval (CI) 1.6-4.9; and IRR 11.5, 95% CI 6.5-20.5], whereas the risk of other cancers did not differ (IRR 1.0, 95% CI 0.7-1.3). Non-smoking HIV patients did not have increased risk of non-virological cancers compared to non-smoking controls (IRR 1.2, 95% CI 0.7-2.1). The PAFs of cancer associated with smoking and with being HIV-infected were 27 and 49%, respectively. For cancers not strongly related to smoking or viral infections, the PAFs associated with being HIV-infected and with immune deficiency were 0%. The risk of cancer is increased in HIV patients compared to the background population. In absence of smoking, the increase in risk is confined to cancers related to viral infections, whereas the risk of other cancers is not elevated and does not seem to be associated with immune deficiency.

Influence of propofol and volatile anaesthetics on the inflammatory response in the ventilated lung.

PubMed

Kalimeris, K; Christodoulaki, K; Karakitsos, P; Batistatou, A; Lekka, M; Bai, M; Kitsiouli, E; Nakos, G; Kostopanagiotou, G

2011-07-01

The immunomodulatory effects of volatile anaesthetics in vitro and the protective effect of propofol in lung injury spurred us to study the effects of volatile anaesthetics and propofol on lung tissue in vivo. Twenty-seven pigs were randomized to 4-h general anaesthesia with propofol (8 mg/kg/h, group P, n=9), sevoflurane [minimum alveolar concentration (MAC)=1.0, group S, n=9) or desflurane (MAC=1.0, group D, n=9). Four healthy animals served as the no-ventilation group. Bronchoalveolar lavage fluid (BALF) was obtained to measure the cell counts, platelet-activating factor acetylhydrolase (PAF-AcH), phospholipase A(2) (PLA(2)) and superoxide dismutase (SOD) activity. Lung tissues were evaluated histologically and for caspase-3 expression. Volatile anaesthetics reduced PAF-AcH levels without affecting PLA(2) activity and resulted in decreased alveolar macrophage and increased lymphocyte counts in BALF (sevoflurane: 29 ± 23%; desflurane: 26 ± 6%, both P<0.05 compared with 4 ± 2% in the no-ventilation group). These findings were accompanied by atelectasis and inflammatory cells' infiltration in the inhalational anaesthetics groups. Also, sevoflurane reduced SOD activity and both sevoflurane and desflurane induced significant caspase-3 expression. In contrast, propofol resulted in a minor degree of inflammation and preserved BALF cells' composition without triggering apoptosis. Halogenated anaesthetics seem to trigger an immune lymphocytic response in the lung, inducing significant apoptosis and impairment of PAF-AcH. In contrast, propofol preserves anti-inflammatory and anti-oxidant defences during mechanical ventilation, thus preventing the emergence of apoptosis. © 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

Diabetes mellitus in Jamaica: sex differences in burden, risk factors, awareness, treatment and control in a developing country.

PubMed

Cunningham-Myrie, Colette; Younger-Coleman, Novie; Tulloch-Reid, Marshall; McFarlane, Shelly; Francis, Damian; Ferguson, Trevor; Gordon-Strachan, Georgiana; Wilks, Rainford

2013-11-01

The objective of this study was to provide valid estimates of the burden of and risk factors for diabetes mellitus by sex in Jamaica, a predominantly Black, middle-income and developing country. The Jamaica Health and Lifestyle Survey 2008 examined a nationally representative sample of 2848 Jamaicans aged 15-74. Parameter estimates and 95% confidence intervals [CI] were weighted for non-response as well as age and sex of the source population. Sex differences in risk factors and diabetes prevalence, awareness, treatment and control were estimated in multivariable models. Population-attributable fractions (PAFs) of obesity on diabetes mellitus were estimated in both sexes. The prevalence of diabetes mellitus was 7.9% (95% CI: 6.7-9.1%), significantly higher in women than men 9.3% vs. 6.4% (P = 0.02) and increasing with age. Seventy-six percentage of persons with diabetes mellitus were aware of their status; urban women and rural men were less likely to be aware. Diabetes control (43% overall) was less common in higher-income men, but more common in higher-income women. Persons without health insurance were less likely to control their diabetes. The prevalence of diabetes risk factors was higher in women than men. Increased waist circumference (≥94 cm [men]/≥80 cm [women]), overweight/obesity (body mass index ≥ 25 kg/m(2)) and low physical activity/inactivity were associated with PAFs for diabetes mellitus of 27%, 37% and 15%, respectively, in men and 77%, 54% and 24%, respectively, in women. Prevalence of diabetes mellitus and its risk factors is high in Jamaica, especially among women, and national programmes to stem the diabetes mellitus epidemic should take these sex differences into consideration. © 2013 John Wiley & Sons Ltd.

Prognostic factors of clinical endpoints in elderly patients with atrial fibrillation during a 2-year follow-up in China

PubMed Central

Wang, Hao; Wang, Hai-Jun; Chen, Ya-Dong; Tao, Tao; Guo, Yu-Tao; Zhao, Xiao-Ning; Liu, Hong-Bin; Wang, Yu-Tang

2017-01-01

Abstract This study aimed to reveal the incidence of clinical endpoints in elderly patients with atrial fibrillation (AF) during a 2-year follow-up and evaluate the related prognostic factors of these endpoints. In total, 200 elderly patients with AF and 400 age- and sex-matched patients without AF were enrolled in this prospective observational cohort study. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, during the 2-year follow-up was analyzed. Other follow-up data, including disease history, laboratory examinations, medication status, and other clinical endpoints, were collected. The prognostic factors of these clinical endpoints were then evaluated by Cox-survival analysis. In addition, the predicative role of C-reactive protein (CRP) and platelet-activating factor (PAF) on these clinical endpoints was analyzed. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, was significantly higher in patients with AF than in those without AF (27.8% vs 9.8%, 29.4% vs 12.7%, and 28.7% vs 11.6%, respectively; all P < .001). Antithrombotic therapy significantly reduced the incidences of all-cause deaths (P < .05). Body mass index (BMI) and digoxin were prognostic risk factors of thromboembolism; age, massive hemorrhage history, and digoxin were prognostic risk factors of hemorrhage and age, renal insufficiency history, massive hemorrhage history, and digoxin were prognostic risk factors of all-cause death (P < .05). Further, both CRP and PAF were prognostic risk factors of thromboembolism and massive hemorrhage (P < .05). Age, BMI, massive hemorrhage history, and digoxin appear to be prognostic risk factors of clinical endpoints in elderly patients with AF. Appropriate drug use during follow-up may be beneficial in preventing the occurrence of clinical endpoints in elderly patients with AF. Trial registration number: ChiCTR-OCH-13003479. PMID:28816946

Left atrial appendage function in prediction of paroxysmal atrial fibrilation in patients with untreated hypertension.

PubMed

Tenekecioglu, Erhan; Agca, Fahriye Vatansever; Karaagac, Kemal; Ozluk, Ozlem Arican; Peker, Tezcan; Kuzeytemiz, Mustafa; Senturk, Muhammed; Yılmaz, Mustafa

2014-01-01

Abstract The onset of AF results in a significant increase in mortality rates and morbidity in hypertensive patients and this rhythm disorder exposes patients to a significantly increased risk of cerebral or peripheral embolisms. Tissue Doppler imaging was found to be useful in early detection of myocardial dysfunction in several diseases. It was shown that tissue Doppler analysis of the walls of the left atrial appendage (LAA) can give accurate information about the function of the LAA in hypertensive patients. In this study, we aimed to investigate and identify the specific predictive parameters for the onset of AF in patients with hypertension with tissue Doppler imaging of LAA. We studied age and sex matched 57 untreated hypertensive patients with paroxysmal atrial fibrillation (PAF) and 27 untreated hypertensive subjects without PAF. With transthoracic echocardiography, diastolic mitral A-velocity and LA maximal volume index which reflects reservoir function of left atrium was measured, with transesophageal echocardiography, LAA emptying velocity (LAA-PW D2) and tissue Doppler contracting velocity of LAA (LAA-TDI-D2) were measured. LA maximal volume index of the groups (22.28 ± 3.59 mL/m(2) in Group 1 versus 20.37 ± 3.97 mL/m(2) in Group 2, p = 0.07) and diastolic mitral A-velocity [0.93 (0.59-1.84) m/s in patients with PAF versus 0.90 (0.62-1.76) m/s in patients without PAF, p = 0.26] was not significantly different between study groups, during TEE, LAA-PW D2 (0.31 ± 0.04 m/s in Group 1 versus 0.33 ± 0.03 m/s in Group 2, p = 0.034) and LAA-TDI-D2 (0.18 ± 0.04 m/s in Group 1 versus 0.21 ± 0.05 m/s in Group 2, p = 0.014) were significantly decreased in Group 1. In this study, we found that in hypertensive PAF patients despite normal global LA functions, LAA contracting function was deteriorated. Tissue Doppler analysis of LAA is clinically usefull approach to detect the risk of developing PAF in hypertensives.

Russia-specific relative risks and their effects on the estimated alcohol-attributable burden of disease.

PubMed

Shield, Kevin D; Rehm, Jürgen

2015-05-10

Alcohol consumption is a major risk factor for the burden of disease globally. This burden is estimated using Relative Risk (RR) functions for alcohol from meta-analyses that use data from all countries; however, for Russia and surrounding countries, country-specific risk data may need to be used. The objective of this paper is to compare the estimated burden of alcohol consumption calculated using Russia-specific alcohol RRs with the estimated burden of alcohol consumption calculated using alcohol RRs from meta-analyses. Data for 2012 on drinking indicators were calculated based on the Global Information System on Alcohol and Health. Data for 2012 on mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years (DALYs) lost by cause were obtained by country from the World Health Organization. Alcohol Population-Attributable Fractions (PAFs) were calculated based on a risk modelling methodology from Russia. These PAFs were compared to PAFs calculated using methods applied for all other countries. The 95% Uncertainty Intervals (UIs) for the alcohol PAFs were calculated using a Monte Carlo-like method. Using Russia-specific alcohol RR functions, in Russia in 2012 alcohol caused an estimated 231,900 deaths (95% UI: 185,600 to 278,200) (70,800 deaths among women and 161,100 deaths among men) and 13,295,000 DALYs lost (95% UI: 11,242,000 to 15,348,000) (3,670,000 DALYs lost among women and 9,625,000 DALYs lost among men) among people 0 to 64 years of age. This compares to an estimated 165,600 deaths (95% UI: 97,200 to 228,100) (29,700 deaths among women and 135,900 deaths among men) and 10,623,000 DALYs lost (95% UI: 7,265,000 to 13,754,000) (1,783,000 DALYs lost among women and 8,840,000 DALYs lost among men) among people 0 to 64 years of age caused by alcohol when non-Russia-specific alcohol RRs were used. Results indicate that if the Russia-specific RRs are used when estimating the health burden attributable to alcohol consumption in Russia, then the total estimated burden will be more than if RRs from meta-analyses are used. Furthermore, additional research is needed to understand which aspects of the Russian style of drinking cause the most harm.

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

PubMed

de Bernardis, E; Leonardi, G; Caruso, A; Cutuli, V M; Amico-Roxas, M

1994-08-01

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Wenxin Keli versus Sotalol for Paroxysmal Atrial Fibrillation Caused by Hyperthyroidism: A Prospective, Open Label, and Randomized Study

PubMed Central

Meng, Zhaowei; Tan, Jian; He, Qing; Zhu, Mei; Li, Xue; Zhang, Jianping; Jia, Qiang; Wang, Shen; Zhang, Guizhi; Zheng, Wei

2015-01-01

We aimed to compare effectiveness of Wenxin Keli (WK) and sotalol in assisting sinus rhythm (SR) restoration from paroxysmal atrial fibrillation (PAF) caused by hyperthyroidism, as well as in maintaining SR. We randomly prescribed WK (18 g tid) or sotalol (80 mg bid) to 91 or 89 patients. Since it was not ethical not to give patients antiarrhythmia drugs, no control group was set. Antithyroid drugs were given to 90 patients (45 in WK group, 45 in sotalol group); 131I was given to 90 patients (46 in WK group, 44 in sotalol group). Three months later, SR was obtained in 83/91 or 80/89 cases from WK or sotalol groups (P = 0.762). By another analysis, SR was obtained in 86/90 or 77/90 cases from 131I or ATD groups (P = 0.022). Then, we randomly assigned the successfully SR-reverted patients into three groups: WK, sotalol, and control (no antiarrhythmia drug was given) groups. After twelve-month follow-up, PAF recurrence happened in 1/54, 2/54, and 9/55 cases, respectively. Log-Rank test showed significant higher PAF recurrent rate in control patients than either treatment (P = 0.06). We demonstrated the same efficacies of WK and sotalol to assist SR reversion from hyperthyroidism-caused PAF. We also showed that either drug could maintain SR in such patients. PMID:26074982

Immediately modifiable risk factors attributable to colorectal cancer in Malaysia.

PubMed

Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

2017-08-04

This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal limits and avoid alcohol intake are recommended. Future studies with other site-specific cancers and additional risk factors are needed.

Autonomous cloud based site monitoring through hydro geophysical data assimilation, processing and result delivery

NASA Astrophysics Data System (ADS)

Versteeg, R.; Johnson, D. V.; Rodzianko, A.; Zhou, H.; Dafflon, B.; Leger, E.; de Kleine, M.

2017-12-01

Understanding of processes in the shallow subsurface requires that geophysical, biogeochemical, hydrological and remote sensing datasets are assimilated, processed and interpreted. Multiple enabling software capabilities for process understanding have been developed by the science community. These include information models (ODM2), reactive transport modeling (PFLOTRAN, Modflow, CLM, Landlab), geophysical inversion (E4D, BERT), parameter estimation (PEST, DAKOTA), visualization (ViSiT, Paraview, D3, QGIS) as well as numerous tools written in python and R for petrophysical mapping, stochastic modeling, data analysis and so on. These capabilities use data collected using sensors and analytical tools developed by multiple manufacturers which produce many different measurements. While scientists obviously leverage tools, capabilities and lessons learned from one site at other sites, the current approach to site characterization and monitoring is very labor intensive and does not scale well. Our objective is to be able to monitor many (hundreds - thousands) of sites. This requires that monitoring can be done in a near time, affordable, auditable and essentially autonomous manner. For this we have developed a modular vertically integrated cloud based software framework which was designed from the ground up for effective site and process monitoring. This software framework (PAF - Predictive Assimilation Framework) is multitenant software and provides automation of data ingestion, processing and visualization of hydrological, geochemical and geophysical (ERT/DTS) data. The core organizational element of PAF is a project/user one in which capabilities available to users are controlled by a combination of available data and access permissions. All PAF capabilities are exposed through APIs, making it easy to quickly add new components. PAF is fully integrated with newly developed autonomous electrical geophysical hardware and thus allows for automation of electrical geophysical ingestion and processing and the ability for co analysis and visualization of the raw and processed data with other data of interest (e.g. soil temperature, soil moisture, precipitation). We will demonstrate current PAF capabilities and discuss future efforts.

Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily

PubMed Central

2016-01-01

Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme’s cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >107-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active-site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes from existing promiscuous templates. More generally, comparative enzymology and analysis of catalytic promiscuity can provide mechanistic and evolutionary insights. PMID:27670607

Global burden of cancer attributable to high body-mass index in 2012: a population-based study

PubMed Central

Byrnes, Graham; Renehan, Prof Andrew G; Stevens, Gretchen A; Ezzati, Prof Majid; Ferlay, Jacques; Miranda, J. Jaime; Romieu, Isabelle; Dikshit, Rajesh; Forman, David; Soerjomataram, Isabelle

2015-01-01

Background Excess body mass index (BMI) is associated with increased risk of cancer. To inform public health policyand future research, we estimated the global burden of cancer attributable to excess BMI. Methods Population attributable fractions (PAFs) were derived using relative risks and BMI estimates in adults by age, sex and country. Assuming a10-year lag-period, PAFs were calculated using BMI estimates in 2002. GLOBOCAN2012 was used to compute numbers of new cancer cases attributable to excess BMI. In an alternative scenario, we computed the proportion of potentially avoidable cancers assuming that populations maintained their BMI-level observed in 1982. Secondary analyses were performed to test the model and estimate the impactof hormone replacement therapy (HRT) and smoking. Findings Worldwide, we estimated that 481,000 or 3·6% of all new cancer cases in 2012 were attributable to excess BMI. PAFs were greater in women compared with men (5·4% versus 1·9%). The burden was concentrated in countries with very high and high human development index (HDI, PAF: 5·3% and 4·8%) compared with countries with moderate and low HDI (PAF: 1·6% and 1·0%). Corpus uteri, post-menopausal breast and colon cancers accounted for approximately two-thirds (64%) of excess BMI attributable cancers. One fourth (~118,000) of all cases related to excess BMI in 2012 could be attributed to the rising BMI since 1982. Interpretation These findings further underpin the need for a global effort to abate the rising trends in population-level excess weight. Assuming that the relationship between excess BMI and cancer is causal and the current pattern of population weight gain continues, this will likely augment the future burden of cancer. Funding World Cancer Research Fund, Marie Currie Fellowship, the National Health and Medical Research Council Australia and US NIH. PMID:25467404

The influence of uncertainty and location-specific conditions on the environmental prioritisation of human pharmaceuticals in Europe.

PubMed

Oldenkamp, Rik; Huijbregts, Mark A J; Ragas, Ad M J

2016-05-01

The selection of priority APIs (Active Pharmaceutical Ingredients) can benefit from a spatially explicit approach, since an API might exceed the threshold of environmental concern in one location, while staying below that same threshold in another. However, such a spatially explicit approach is relatively data intensive and subject to parameter uncertainty due to limited data. This raises the question to what extent a spatially explicit approach for the environmental prioritisation of APIs remains worthwhile when accounting for uncertainty in parameter settings. We show here that the inclusion of spatially explicit information enables a more efficient environmental prioritisation of APIs in Europe, compared with a non-spatial EU-wide approach, also under uncertain conditions. In a case study with nine antibiotics, uncertainty distributions of the PAF (Potentially Affected Fraction) of aquatic species were calculated in 100∗100km(2) environmental grid cells throughout Europe, and used for the selection of priority APIs. Two APIs have median PAF values that exceed a threshold PAF of 1% in at least one environmental grid cell in Europe, i.e., oxytetracycline and erythromycin. At a tenfold lower threshold PAF (i.e., 0.1%), two additional APIs would be selected, i.e., cefuroxime and ciprofloxacin. However, in 94% of the environmental grid cells in Europe, no APIs exceed either of the thresholds. This illustrates the advantage of following a location-specific approach in the prioritisation of APIs. This added value remains when accounting for uncertainty in parameter settings, i.e., if the 95th percentile of the PAF instead of its median value is compared with the threshold. In 96% of the environmental grid cells, the location-specific approach still enables a reduction of the selection of priority APIs of at least 50%, compared with a EU-wide prioritisation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Higher serum 25-hydroxyvitamin D concentrations are related to a reduced risk of depression.

PubMed

Jääskeläinen, Tuija; Knekt, Paul; Suvisaari, Jaana; Männistö, Satu; Partonen, Timo; Sääksjärvi, Katri; Kaartinen, Niina E; Kanerva, Noora; Lindfors, Olavi

2015-05-14

Vitamin D has been suggested to protect against depression, but epidemiological evidence is scarce. The present study investigated the relationship of serum 25-hydroxyvitamin D (25(OH)D) with the prevalence of depressive and anxiety disorders. The study population consisted of a representative sample of Finnish men and women aged 30-79 years from the Health 2000 Survey. The sample included 5371 individuals, of which 354 were diagnosed with depressive disorder and 222 with anxiety disorder. Serum 25(OH)D concentration was determined from frozen samples. In a cross-sectional study, a total of four indicators of depression and one indicator of anxiety were used as dependent variables. Serum 25(OH)D was the risk factor of interest, and logistic models used further included sociodemographic and lifestyle variables as well as indicators of metabolic health as confounding and/or effect-modifying factors. The population attributable fraction (PAF) was estimated. Individuals with higher serum 25(OH)D concentrations showed a reduced risk of depression. The relative odds between the highest and lowest quartiles was 0.65 (95% CI 0.46, 0.93; P for trend = 0.006) after adjustment for sociodemographic, lifestyle and metabolic factors. Higher serum 25(OH)D concentrations were associated with a lower prevalence of depressive disorder especially among men, younger, divorced and those who had an unhealthy lifestyle or suffered from the metabolic syndrome. The PAF was estimated to be 19% for depression when serum 25(OH)D concentration was at least 50 nmol/l. These results support the hypothesis that higher serum 25(OH)D concentrations protect against depression even after adjustment for a large number of sociodemographic, lifestyle and metabolic factors. Large-scale prospective studies are needed to confirm this finding.

Anaemia in infancy in rural Bangladesh: contribution of iron deficiency, infections and poor feeding practices.

PubMed

Rawat, Rahul; Saha, Kuntal Kumar; Kennedy, Andrew; Rohner, Fabian; Ruel, Marie; Menon, Purnima

2014-01-14

Few data exist on the aetiology of anaemia and Fe deficiency (ID) during early infancy in South Asia. The present study aimed to determine the contribution of ID, infections and feeding practices to anaemia in Bangladeshi infants aged 6-11 months. Baseline data from 1600 infants recruited into a cluster-randomised trial testing the effectiveness of micronutrient powder sales by frontline health workers on the prevalence of anaemia were used. Multivariate logistic regression was used to identify risk factors for anaemia and ID, and population attributable fractions (PAF) were computed to estimate the proportion of anaemia that might be prevented by the elimination of individual risk factors. It was found that 68 % of the infants were anaemic, 56 % were Fe deficient, and one-third had evidence of subclinical infections. The prevalence of anaemia and ID increased rapidly, until 8-9 months of age, while that of subclinical infections was constant. ID (adjusted OR (AOR) 2·6-5·0; P< 0·001) and subclinical infections (AOR 1·4-1·5; P< 0·01) were major risk factors for anaemia, in addition to age and male sex. Similarly, subclinical infections, age and male sex were significant risk factors for ID. Previous-day consumption of Fe-rich foods was very low and not associated with anaemia or ID. The PAF of anaemia attributable to ID was 67 % (95 % CI 62, 71) and that of subclinical infections was 16 % (95 % CI 11, 20). These results suggest that a multipronged strategy that combines improvements in dietary Fe intake alongside infection control strategies is needed to prevent anaemia during infancy in Bangladesh.

Embryo-endometrial interactions during early development after embryonic diapause in the marsupial tammar wallaby.

PubMed

Renfree, Marilyn B; Shaw, Geoff

2014-01-01

The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal. Reproduction in the tammar is seasonal, regulated by photoperiod and also lactation. Reactivation is triggered by falling daylength after the austral summer solstice in December. Young are born late January and commence a 9-10-month lactation. Females mate immediately after birth. The resulting conceptus develops over 6- 7 days to form a unilaminar blastocyst of 80-100 cells and enters lactationally, and later seasonally, controlled diapause. The proximate endocrine signal for reactivation is an increase in progesterone which alters uterine secretions. Since the diapausing blastocyst is surrounded by the zona and 2 other acellular coats, the mucoid layer and shell coat, the uterine signals that maintain or terminate diapause must involve soluble factors in the secretions rather than any direct cellular interaction between uterus and embryo. Our studies suggest involvement of a number of cytokines in the regulation of diapause in tammars. The endometrium secretes platelet activating factor (PAF) and leukaemia inhibitory factor, which increase after reactivation. Receptors for PAF are low on the blastocyst during diapause but are upregulated at reactivation. Conversely, there is endometrial expression of the muscle segment homeobox gene MSX2 throughout diapause, but it is rapidly downregulated at reactivation. These patterns are consistent with those observed in diapausing mice and mink after reactivation, despite the very different patterns of endocrine control of diapause in these 3 divergent species. These common patterns suggest a similar underlying mechanism for diapause, perhaps common to all mammals, but which is activated in only a few.

Recent advances and plans in processing and geocoding of SAR data at the DFD

NASA Technical Reports Server (NTRS)

Noack, W.

1993-01-01

Because of the needs of future projects like ENVISAT and the experiences made with the current operational ERS-1 facilities, a radical change in the synthetic aperture radar (SAR) processing scenarios can be predicted for the next years. At the German PAF several new developments were initialized which are driven mainly either by user needs or by system and operational constraints ('lessons learned'). At the end there will be a major simplification and uniformation of all used computer systems. Especially the following changes are likely to be implemented at the German PAF: transcription before archiving, processing of all standard products with high throughput directly at the receiving stations, processing of special 'high-valued' products at the PAF, usage of a single type of processor hardware, implementation of a large and fast on-line data archive, and improved and unified fast data network between the processing and archiving facilities. A short description of the current operational SAR facilities as well as the future implementations are given.

“Invisible” Conformers of an Antifungal Disulfide Protein Revealed by Constrained Cold and Heat Unfolding, CEST-NMR Experiments, and Molecular Dynamics Calculations

PubMed Central

Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

2015-01-01

Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20–40 % at 298 K in a disulfide-rich protein. In addition, sensitive 15N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR “dark matter”. Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. PMID:25676351

[Masculinity and femininity scales: current state of the art].

PubMed

Fernández, Juan; Quiroga, María A; Del Olmo, Isabel; Rodríguez, Antonio

2007-08-01

A theoretical and empirical review of masculinity and femininity scales was carried out after 30 years of their existence. Hypotheses to be tested were: (a) muldimensionality versus bidimensionality; (b) inadequate percentage of variance accounted for (less than 50%); (c) inconsistency between factor structure and the dualistic model. 618, 200 and 287 students took part in each of the three studies that were carried out. Factorial analyses (PAF) were performed. Results support multidimensionality, unsatisfactory percentage of variance accounted for, and lack of congruence between obtained factors and the dualistic model. All these data were analysed within the context of the twofold sex and gender reality model.

Evaluation of anti-allergic properties of caffeic acid phenethyl ester in a murine model of systemic anaphylaxis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sae-Gwang; Lee, Da-Young; Seo, Su-Kil

Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. It has several positive effects, including anti-inflammatory, anti-oxidation, anti-cancer, anti-bacterial, anti-viral, anti-fungal, and immunomodulatory effects. In particular, the suppressive effect of NF-{kappa}B may disrupt a component of allergic induction. The principal objective of this experimental study was to evaluate the effects of CAPE on the active systemic anaphylaxis induced by ovalbumin (OVA) challenge in mice. Mice were intraperitoneally sensitized and intravenously challenged with OVA. Histopathological analysis, nuclear factor (NF)-{kappa}B activation, and the plasma levels of histamine and total IgE after allergen challenge were evaluated. After challenges, allmore » of the sham-treated mice developed anaphylactic symptoms, increased plasma levels of histamine and OVA-specific IgE, marked vascular leakage, NF-{kappa}B activation, platelet-activating factor (PAF) production, and histological changes including pulmonary edema and hemorrhage in the renal medullae within 20 min. By way of contrast, a reduction in the plasma levels of histamine and OVA-specific IgE and an inhibition of NF-{kappa}B activation and PAF release were observed in the CAPE-treated mice. In addition, a significant prevention of hemoconcentration and OVA-induced pathological changes were noted. These results indicate that CAPE demonstrates an anti-allergic effect, which may be the result of its protective effects against IgE-mediated allergy.« less

An essential role for platelet-activating factor in activating mast cell migration following ultraviolet irradiation

PubMed Central

Chacón-Salinas, Rommel; Chen, Limo; Chávez-Blanco, Alma D.; Limón-Flores, Alberto Y.; Ma, Ying; Ullrich, Stephen E.

2014-01-01

The UVB (290–320 nm) radiation in sunlight is responsible for inducing skin cancer. Exposure to UV radiation is also immunosuppressive, and the systemic immune suppression induced by UV is a well-recognized risk factor for cancer induction. As UVB radiation is absorbed within the upper layers of the skin, indirect mechanisms must play a role in activating systemic immune suppression. One prominent example is mast cell migration, which from the skin to the draining LN is an essential step in the cascade of events leading to immune suppression. What triggers mast cell migration is not entirely clear. Here, we tested the hypothesis that PAF, a lipid mediator of inflammation produced by the skin in response to UV exposure, is involved. Mast cell-deficient mice (KitW-sh/W-sh) are resistant to the suppressive effect of UV radiation, and reconstituting mast cell-deficient mice with normal bone marrow-derived mast cells restores susceptibility to immunosuppression. However, when mast cells from PAFR−/− mice were used, the reconstituted mice were not susceptible to the suppressive effects of UV. Furthermore, PAFR−/− mice showed impaired UV-induced mast cell migration when compared with WT mice. Finally, injecting PAF into WT mice mimicked the effect of UV irradiation and induced mast cell migration but not in PAFR−/− mice. Our findings indicate that PAFR binding induces mast cells to migrate from the skin to the LNs, where they mediate immune suppression. PMID:24009177

A Cloud Based Framework For Monitoring And Predicting Subsurface System Behaviour

NASA Astrophysics Data System (ADS)

Versteeg, R. J.; Rodzianko, A.; Johnson, D. V.; Soltanian, M. R.; Dwivedi, D.; Dafflon, B.; Tran, A. P.; Versteeg, O. J.

2015-12-01

Subsurface system behavior is driven and controlled by the interplay of physical, chemical, and biological processes which occur at multiple temporal and spatial scales. Capabilities to monitor, understand and predict this behavior in an effective and timely manner are needed for both scientific purposes and for effective subsurface system management. Such capabilities require three elements: Models, Data and an enabling cyberinfrastructure, which allow users to use these models and data in an effective manner. Under a DOE Office of Science funded STTR award Subsurface Insights and LBNL have designed and implemented a cloud based predictive assimilation framework (PAF) which automatically ingests, controls quality and stores heterogeneous physical and chemical subsurface data and processes these data using different inversion and modeling codes to provide information on the current state and evolution of subsurface systems. PAF is implemented as a modular cloud based software application with five components: (1) data acquisition, (2) data management, (3) data assimilation and processing, (4) visualization and result delivery and (5) orchestration. Serverside PAF uses ZF2 (a PHP web application framework) and Python and both open source (ODM2) and in house developed data models. Clientside PAF uses CSS and JS to allow for interactive data visualization and analysis. Client side modularity (which allows for a responsive interface) of the system is achieved by implementing each core capability of PAF (such as data visualization, user configuration and control, electrical geophysical monitoring and email/SMS alerts on data streams) as a SPA (Single Page Application). One of the recent enhancements is the full integration of a number of flow and mass transport and parameter estimation codes (e.g., MODFLOW, MT3DMS, PHT3D, TOUGH, PFLOTRAN) in this framework. This integration allows for autonomous and user controlled modeling of hydrological and geochemical processes. In our presentation we will discuss our software architecture and present the results of using these codes and the overall developed performance of our framework using hydrological, geochemical and geophysical data from the LBNL SFA2 Rifle field site.

Hemodynamic and proinflammatory actions of endothelin-1 in guinea pig small intestine submucosal microcirculation.

PubMed

King-VanVlack, C E; Mewburn, J D; Chapler, C K; MacDonald, P H

2003-06-01

The hemodynamic and proinflammatory effects of endothelin-1 (ET-1) in proximal (1st/2nd order) and terminal (3rd/4th order) arterioles and venules were examined in small intestine submucosa of anesthetized guinea pigs. Vessel diameter (D), red blood cell velocity, and blood flow (Q) were determined in eight proximal and eight terminal microvessels before and at 20 min of ET-1 suffusion (10(-10), 10(-9), and 10(-8) M) and then with endothelin-A (ET(A))-receptor blockade with BQ-123 (10(-5) M). This protocol was repeated with platelet-activating factor (PAF) inhibition (WEB-2086, 1.0 mg/kg iv; n = 16). The ET-1-mediated microvascular responses were also examined with endothelin-B (ET(B))-receptor blockade using BQ-788 (10(-5) M; n = 11) alone or with ET(A+B)-receptor blockade with BQ-123 + BQ-788 (n = 10). Microvascular permeability was assessed by FITC-albumin (25 mg/kg iv) extravasation in seven series: 1) buffered modified Krebs solution suffusion (n = 6), 2) histamine suffusion (HIS; 10(-3) M, n = 5), 3) ET-1 suffusion (10(-8) M, n = 5), 4) BQ-123 (10(-5) M) plus ET-1 suffusion (n = 5), 5) PAF inhibition before ET-1 suffusion (n = 5), 6) histamine-1 (H1)-receptor blockade (diphenhydramine, 20 mg/kg iv) before ET-1 suffusion (n = 5), and 7) ET(B)-receptor blockade before (BQ-788 10(-5) M; n = 3) or with ET-1 suffusion (n = 3). D and Q decreased at 10(-8) M ET-1 and returned to control values with BQ-123 and BQ-123+BQ788 but not with BQ-788 in proximal microvessels. D did not change in terminal microvessels with ET-1 (10(-8) M) but decreased with BQ-788 and increased with BQ-123. PAF inhibition did not affect the D and Q responses of proximal microvessels to ET-1 but prevented the fall in Q in terminal microvessels with ET-1. ET-1 increased vascular permeability to approximately 1/3 of that with HIS; this response was prevented with BQ-123 and WEB-2086 but not with H1-receptor blockade. This is the first evidence that submucosal terminal microvessel flow is reduced with ET-1 independent of vessel diameter changes and that this response is associated with increased microvascular permeability mediated via ET(A)-receptor stimulation and PAF activation.

PAF involvement in dermal extravasation in the reverse passive Arthus reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deacon, R.W.; Melden, M.K.; Saunders, R.N.

The reverse passive erthus reaction (RPAR) is characterized by PMN infiltration, increased vascular permeability leading to plasma extravasation and vessel damage. In the skin RPAR is an inflammatory response initiated by deposition of immune complexes and attributed to complement activation. As PAF can elicit similar dermal reactions, they examined the PAF antagonist SRI 63-072 in the RPAR. Guinea pigs were given an i.v. injection of /sup 125/I-BSA (Ag-20 mg/kg with 20 mg/kg Evan's blue as a permeability tracer), followed by intradermal (i.d.) injections (0.1 ml/site) of anti-BSA antibodies (Ab). After 30 min, dermal sites (2 cm diam.) were removed, countedmore » and the ..mu..l plasma/site (over background counts) calculated from plasma radioactivity measurements. The plasma leakage (..mu..l plasma/site) was dose-dependent upon Ab dose (6-200 ..mu..g/site). At the ultrastructural level, the presence of neutrophils and eosinophils were observed in the extravascular spaces. The luminal endothelium exhibited cytotoxic characteristics and loss of junctional integrity. SRI 63-072 exhibited 50% maximal inhibition when given i.d. with the Ab (0.1 ..mu..g/site) but only 5-10% when given at 3.0 mg/kg i.v. with Ag. No further inhibition of dermal extravasation was observed using SRI 63-441, a competitive receptor antagonist with 3-30 fold the in vivo potency of SRI 63-072. As dermal extravasation in RPAR is only partially inhibited by a PAF antagonist, it appears that other vasoactive mediators, possibly histamine, may be influencing vessel permeability as well.« less

Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase.

PubMed

Wagner, Christopher; Goldmann, Torsten; Rohmann, Kristina; Rupp, Jan; Marwitz, Sebastian; Rotta Detto Loria, Johannes; Limmer, Stefan; Zabel, Peter; Dalhoff, Klaus; Drömann, Daniel

2015-01-01

Inhaled corticosteroids (ICS) are widely used in the treatment of obstructive lung diseases. Recent data suggest a higher pneumonia risk in chronic obstructive pulmonary disease (COPD) patients treated with ICS. Since non-typeable Haemophilus influenzae (NTHi) is the most common pathogen associated with acute exacerbations of COPD, we investigated the effects of budesonide (BUD) on NTHi-induced inflammation and invasive infection. The alveolar epithelial cell line A549 and specimens of human lung tissue (HLT) were used in our experiments. Intracellular infection was determined by a lysis/culture assay of infected cells. Activated p38 mitogen-associated protein kinase (MAPK) was assessed using Western blotting and immunohistochemistry, expression of toll-like receptor 2 (TLR2) was determined by PCR, and CXCL-8 levels were measured using ELISA. Immunohistochemistry was used for detection of CXCL-8, platelet-activating factor receptor (PAF-R) and NTHi. BUD significantly reduced CXCL-8 secretion in A549 cells and lung tissue infected with NTHi. Furthermore, BUD decreased the expression of PAF-R in HLT and A549 cells. In A549 cells and HLT, BUD inhibited intracellular infection and - synergistically with NTHi - increased the expression of TLR2 (in A549 cells). TLR2 stimulation did not influence the intracellular infection of A549 cells, but p38 MAPK inhibition resulted in a significant reduction of infection. The present study adds new insights into the effects of glucocorticoids on pulmonary host defence after NTHi infection. Although the inflammatory response to infection is suppressed by BUD, interestingly, the intracellular infection is also inhibited. This effect seems to depend on the inhibition of p38 MAPK - a key enzyme in many pro-inflammatory pathways - as well as of PAF-R expression. © 2015 S. Karger AG, Basel.

Effects of two novel tachykinin antagonists, FK224 and FK888, on neurogenic airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo.

PubMed Central

Hirayama, Y.; Lei, Y. H.; Barnes, P. J.; Rogers, D. F.

1993-01-01

1. We compared the effects of two novel tachykinin receptor antagonists, FK888 (selective at the tachykinin NK1 receptor) and FK224 (dual antagonist at NK1 and NK2 tachykinin receptors) on stimulus-evoked airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo. Plasma exudation was induced by substance P (SP), synthetic tachykinin receptor agonists, platelet activating factor (PAF), electrical stimulation of the cervical vagus nerves or by inhalation of cigarette smoke. Changes in airway tone and in carotid artery blood pressure (BP) were induced by synthetic tachykinin agonists, PAF and vagal stimulation. 2. Both FK224 and FK888 dose-dependently inhibited SP-induced plasma exudation in the lower trachea and main bronchi (ID50 values respectively of 1.1 and 0.1 mumol kg-1 in lower trachea, and of 0.5 and 0.1 mumol kg-1 in main bronchi) with complete inhibition at both airway levels at 10 mumol kg-1 for FK224 and at 2 mumol kg-1 for FK888. 3. The NK1-selective tachykinin receptor agonist, [Sar9,Met(O2)11]substance P ([Sar]SP), induced plasma exudation, a response which was blocked by both FK888 and FK224. The NK2-selective agonist, [beta-Ala8]neurokinin A-(4-10) ([beta-Ala]NKA), did not induce plasma exudation: neither FK888 nor FK224 affected this lack of response to [beta-Ala]NKA. 4. [beta-Ala]NKA induced bronchoconstriction, a response which was blocked by FK224 but which was completely unaffected by FK888. [Sar]SP induced a small but significant bronchoconstriction which was completely inhibited by both tachykinin antagonists. 5. In animals pretreated with capsaicin to deplete sensory neuropeptides, PAF induced both plasma exudation and bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682142

Population-attributable causes of cancer in Korea: obesity and physical inactivity.

PubMed

Park, Sohee; Kim, Yeonju; Shin, Hai-Rim; Lee, Boram; Shin, Aesun; Jung, Kyu-Won; Jee, Sun Ha; Kim, Dong Hyun; Yun, Young Ho; Park, Sue Kyung; Boniol, Mathieu; Boffetta, Paolo

2014-01-01

Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992-1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea.

Population-Attributable Causes of Cancer in Korea: Obesity and Physical Inactivity

PubMed Central

Shin, Hai-Rim; Lee, Boram; Shin, Aesun; Jung, Kyu-Won; Jee, Sun Ha; Kim, Dong Hyun; Yun, Young Ho; Park, Sue Kyung; Boniol, Mathieu; Boffetta, Paolo

2014-01-01

Background Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. Methodology/Principal Findings Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992–1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. Conclusions/Significance With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea. PMID:24722008

Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, China

PubMed Central

2010-01-01

Background There are growing concerns regarding inequities in health, with poverty being an important determinant of health as well as a product of health status. Within the People's Republic of China (P.R. China), disparities in socio-economic position are apparent, with the rural-urban gap of particular concern. Our aim was to compare direct and proxy methods of estimating household wealth in a rural and a peri-urban setting of Hunan province, P.R. China. Methods We collected data on ownership of household durable assets, housing characteristics, and utility and sanitation variables in two village-wide surveys in Hunan province. We employed principal components analysis (PCA) and principal axis factoring (PAF) to generate household asset-based proxy wealth indices. Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We compared the estimated household wealth for each approach. Asset-based proxy wealth indices were compared to those based on self-reported average annual income and savings at the household level. Results Spearman's rank correlation analysis revealed that PCA and PAF yielded similar results, indicating that either approach may be used for estimating household wealth. In both settings investigated, the two indices were significantly associated with self-reported average annual income and combined income and savings, but not with savings alone. However, low correlation coefficients between the proxy and direct measures of wealth indicated that they are not complementary. We found wide disparities in ownership of household durable assets, and utility and sanitation variables, within and between settings. Conclusion PCA and PAF yielded almost identical results and generated robust proxy wealth indices and categories. Pooled data from the rural and peri-urban settings highlighted structural differences in wealth, most likely a result of localized urbanization and modernization. Further research is needed to improve measurements of wealth in low-income and transitional country contexts. PMID:20813070

Factors attributable for the prevalence of dental caries in Queensland children.

PubMed

Do, Loc Giang; Ha, Diep Hong; Spencer, A John

2015-10-01

Dental caries is a multifactorial condition, prevention of which requires comprehensive understanding of both contextual and compositional determinants and their population impact. To investigate contextual and compositional factors associated with the prevalence of dental caries in children and to estimate the population impact of those factors. Children in one Australian state were selected through stratified random sampling selection in 2010-2011. Oral epidemiological examinations provided individual-level outcomes: prevalence of dental caries in the primary (among 5- to 8-year-olds) and permanent dentitions (9- to 14-year-olds). Socioeconomic status, oral health behaviours and practices and dietary patterns were explanatory factors at the individual-level, school-level and area-level fluoridation status. Three-level multilevel multivariable models were sequentially specified for the prevalence of dental caries to estimate prevalence ratios (PR) associated with explanatory factors, adjusting for covariates and between- and within-group variances. Population attributable fraction (PAF) was estimated as the population impact of the statistically significant explanatory factors. Data from 2214 5- to 8-year-olds and 3186 9- to 14-year-olds from 207 schools in 16 areas were analysed. The prevalence of dental caries in the primary and the permanent dentitions was 47.1% (43.9-50.4) and 38.8% (36.1-41.6), respectively. The highest prevalence of dental caries was observed in the nonfluoridated areas. In bivariate associations, factors at three levels were associated with prevalence of dental caries. In the full models, children in the nonfluoridated areas had significantly higher prevalence of dental caries [PR for the primary: 1.29 (1.11-1.50); PR for the permanent 1.49 (1.01-2.21)] compared with children in fluoridated areas, controlling for other factors. PAF estimates indicated that lack of water fluoridation attributed to 21% and 31% of primary and permanent dental caries, respectively in this child population. A multitude of factors had significant population impact on the prevalence of dental caries in children. Water fluoridation has a significant population impact on dental caries experience in this child population. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Processing methods for photoacoustic Doppler flowmetry with a clinical ultrasound scanner

NASA Astrophysics Data System (ADS)

Bücking, Thore M.; van den Berg, Pim J.; Balabani, Stavroula; Steenbergen, Wiendelt; Beard, Paul C.; Brunker, Joanna

2018-02-01

Photoacoustic flowmetry (PAF) based on time-domain cross correlation of photoacoustic signals is a promising technique for deep tissue measurement of blood flow velocity. Signal processing has previously been developed for single element transducers. Here, the processing methods for acoustic resolution PAF using a clinical ultrasound transducer array are developed and validated using a 64-element transducer array with a -6 dB detection band of 11 to 17 MHz. Measurements were performed on a flow phantom consisting of a tube (580 μm inner diameter) perfused with human blood flowing at physiological speeds ranging from 3 to 25 mm / s. The processing pipeline comprised: image reconstruction, filtering, displacement detection, and masking. High-pass filtering and background subtraction were found to be key preprocessing steps to enable accurate flow velocity estimates, which were calculated using a cross-correlation based method. In addition, the regions of interest in the calculated velocity maps were defined using a masking approach based on the amplitude of the cross-correlation functions. These developments enabled blood flow measurements using a transducer array, bringing PAF one step closer to clinical applicability.

Case-control study on risk factors for acute hepatitis E in Germany, 2012 to 2014.

PubMed

Faber, Mirko; Askar, Mona; Stark, Klaus

2018-05-01

BackgroundNotified cases of hepatitis E have increased 40-fold in the past 10 years in Germany. Food safety is a major concern as hepatitis E virus (HEV) RNA has been detected in ready-to-eat retail-level food products. The objective of this case-control study was to assess risk factors for autochthonous symptomatic hepatitis E and explore reasons for delays in diagnosis. Methods: Demographic, clinical and exposure data from notified hepatitis E cases and individually matched population controls were collected in semi-standardised telephone interviews. Conditional logistic regression analysis was used to calculate matched odds ratios (mOR) and population attributable fractions (PAF). Results: In total, 270 cases and 1,159 controls were included (mean age 53 years, 61% men in both groups). Associated with disease were: consumption of undercooked pork liver, pork, wild boar meat, frankfurters, liver sausage and raw vegetables; contact with waste water (occupational) and various host factors (mORs between 1.9 and 34.1, p value < 0.03). PAF for frankfurters and liver sausage were 17.6%, and 23.6%, respectively. There were statistically significant differences in the clinical presentation and hospitalisation proportion of acute hepatitis E in men and women. Diagnosis was preceded by more invasive procedures in 29.2% of patients, suggesting that hepatitis E was not immediately considered as a common differential diagnosis. Conclusions: Our study suggests that there are indeed sex-specific differences in disease development and lends important epidemiological evidence to specific ready-to-eat pork products as a major source for autochthonous hepatitis E. A review of existing consumer recommendations and production methods may be indicated.

Rural-to-urban migration and risk of hypertension: longitudinal results of the PERU MIGRANT study

PubMed Central

Bernabe-Ortiz, A; Sanchez, J F; Carrillo-Larco, R M; Gilman, R H; Poterico, J A; Quispe, R; Smeeth, L; Miranda, J J

2017-01-01

Urbanization can be detrimental to health in populations due to changes in dietary and physical activity patterns. The aim of this study was to determine the effect of migration on the incidence of hypertension. Participants of the PERU MIGRANT study, that is, rural, urban and rural-to-urban migrants, were re-evaluated after 5 years after baseline assessment. The outcome was incidence of hypertension; and the exposures were study group and other well-known risk factors. Incidence rates, relative risks (RRs) and population attributable fractions (PAFs) were calculated. At baseline, 201 (20.4%), 589 (59.5%) and 199 (20.1%) participants were rural, rural-to-urban migrant and urban subjects, respectively. Overall mean age was 47.9 (s.d.±12.0) years, and 522 (52.9%) were female. Hypertension prevalence at baseline was 16.0% (95% confidence interval (CI) 13.7–18.3), being more common in urban group; whereas pre-hypertension was more prevalent in rural participants (P<0.001). Follow-up rate at 5 years was 94%, 895 participants were re-assessed and 33 (3.3%) deaths were recorded. Overall incidence of hypertension was 1.73 (95%CI 1.36–2.20) per 100 person-years. In multivariable model and compared with the urban group, rural group had a greater risk of developing hypertension (RR 3.58; 95%CI 1.42–9.06). PAFs showed high waist circumference as the leading risk factor for the hypertension development in rural (19.1%), migrant (27.9%) and urban (45.8%) participants. Subjects from rural areas are at higher risk of developing hypertension relative to rural–urban migrant or urban groups. Central obesity was the leading risk factor for hypertension incidence in the three population groups. PMID:26865219

Hydrolysis of phosphatidylcholine during LDL oxidation is mediated by platelet-activating factor acetylhydrolase.

PubMed

Steinbrecher, U P; Pritchard, P H

1989-03-01

Degradation of phosphatidylcholine to lysophosphatidylcholine occurs during oxidative modification of low density lipoproteins (LDL). In this study, we have shown that this phospholipid hydrolysis is brought about by an LDL-associated phospholipase A2 that can hydrolyze oxidized but not intact LDL phosphatidylcholine. The chemical nature of the oxidized phospholipids that can act as substrates for this enzyme was not fully characterized, but we hypothesized that the specificity of the enzyme for oxidized LDL phosphatidylcholine might be explained by fragmentation of polyunsaturated sn-2 fatty acyl groups in LDL phosphatidylcholine during oxidation. To facilitate characterization of this enzyme, we therefore selected a fluorescent phosphatidylcholine substrate that had a short-chain, polar residue in the sn-2 position: 1-palmitoyl 2-(6-[7-nitrobenzoxadiazolyl]amino) caproyl phosphatidylcholine, (C6NBD PC). This substrate was efficiently hydrolyzed by LDL, but the dodecanoyl analogue of C6NBD PC, which differed only in that a 12-carbon rather than a 6-carbon acyl derivative was present in the sn-2 position, was not hydrolyzed. The phospholipase activity was heat-stable, calcium-independent, and was inhibited by the serine esterase inhibitors phenylmethylsulfonyl-fluoride and diisopropylfluorophosphate, but was resistant to p-bromophenacylbromide and dithiobisnitrobenzoic acid. The phospholipid hydrolysis could not be attributed to the action of lecithin:cholesterol acyltransferase or lipoprotein lipase. Nearly all of the activity in EDTA-anticoagulated normal plasma was physically associated with apoB-containing lipoproteins, but this apoprotein was not essential as enzyme activity was present in plasma from abetalipoproteinemic patients. These properties are very similar to those recently reported for human plasma platelet-activating factor (PAF) acetylhydrolase. In the present study, we found that acylhydrolase activity against C6NBD PC, PAF, and oxidized phosphatidylcholine copurfied through gel filtration and ion-exchange chromatography. Substrate competition was demonstrated between C6NBD PC, PAF, and oxidized 2-arachidonyl phosphatidylcholine, suggesting that a single enzyme was active against all three substrates. The enzyme had an apparent molecular weight of 40,000-45,000 by high pressure gel exclusion chromatography. Inhibition of this activity with disopropyfluorophosphate prior to oxidative modification of LDL prevented phospholipid hydrolysis but did not affect the production of thiobarbituric acid reactive compounds or the change in electrophoretic mobility. In addition, this inhibition of phospholipase did not prevent the rapid degradati

Feed-Forward Reciprocal Activation of PAFR and STAT3 Regulates Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer.

PubMed

Chen, Jie; Lan, Tian; Zhang, Weimin; Dong, Lijia; Kang, Nan; Zhang, Shumin; Fu, Ming; Liu, Bing; Liu, Kangtai; Zhan, Qimin

2015-10-01

Platelet-activating factor receptor (PAFR), a G-protein-coupled receptor, has been implicated in tumorigenesis, but its contributions to metastatic progression have not been investigated. Here, we show that PAFR is overexpressed in non-small cell lung cancer (NSCLC) as well as in breast, colorectal, and gastric carcinomas. Expression of PAFR correlates closely with clinical stages, survival time, and distant metastasis. In human NSCLC cells, activation of the PAF/PAFR signaling axis accentuated malignant character, including by stimulating epithelial-mesenchymal transition (EMT). In contrast, silencing PAFR in aggressive NSCLC cells inhibited these effects. Mechanistic investigations showed that PAFR stimulated EMT by activating STAT3 via upregulation of G-protein-dependent SRC or JAK2 kinase activity. Notably, STAT3 transcriptionally elevated PAFR expression. Thus, activation of PAFR in NSCLC cells initiated a forward feedback loop responsible for mediating the aggressive malignant character of NSCLC cells in vitro and in vivo. Reinforcing this reciprocal activation loop, PAF/PAFR signaling also upregulated IL6 expression and thereby STAT3 activation. Overall, our results elucidated an important role for PAFR dysregulation in the pathogenicity of NSCLC and unraveled a forward feedback loop between PAFR and STAT3 that acts to drive the malignant progression of NSCLC. ©2015 American Association for Cancer Research.

Modulation of leukocyte adhesion in rat mesenteric venules by aspirin and salicylate.

PubMed

Asako, H; Kubes, P; Wallace, J; Wolf, R E; Granger, D N

1992-07-01

Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and number of adherent and emigrated leukocytes were measured in postcapillary venules both before and during superfusion of rat mesentery with either aspirin or sodium salicylate. In some experiments, animals were treated with either a leukotriene (LT)-synthesis inhibitor (L-663,536), an LTD4 antagonist (MK-571), an LTB4 antagonist (SC-41930), misoprostol, or prostaglandin (PG) I2, then the aspirin protocol was repeated. Superfusion of aspirin but not sodium salicylate resulted in increased leukocyte adherence and a reduced leukocyte rolling velocity but did not affect leukocyte emigration. Aspirin-induced leukocyte adhesion was effectively prevented by the LT-synthesis inhibitor and LTB4 antagonist but not by the LTD4 antagonist. Misoprostol and PGI2 also prevented the aspirin-induced adhesion responses. Superfusion of the mesentery with either platelet-activating factor (PAF) or LTB4 enhanced leukocyte adherence and emigration while reducing leukocyte rolling velocity. Sodium salicylate prevented all of the adhesion responses elicited by LTB4. Although salicylate did not affect the PAF-induced leukocyte adherence and rolling responses, it completely prevented the increased leukocyte emigration. These results indicate that aspirin promotes, whereas sodium salicylate inhibits, leukocyte-endothelial cell adhesive interactions at therapeutically relevant concentrations.

Mortality in Mild Cognitive Impairment Diagnosed with DSM-5 Criteria and with Petersen's Criteria: A 17-Year Follow-Up in a Community Study.

PubMed

Santabárbara, Javier; Gracia-García, Patricia; Pírez, Guillermo; López-Antón, Raúl; De La Cámara, Concepcion; Ventura, Tirso; Pérez-Sastre, Marina; Lobo, Elena; Saz, Pedro; Marcos, Guillermo; Lobo, Antonio

2016-11-01

To explore the possibility that the mortality risk of mild cognitive impairment (MCI) as diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (DSM-5-MCI) will be higher than using Petersen's criteria (P-MCI) and to report the population-attributable fraction (PAF) of mortality due to MCI. A representative community sample of 4,803 individuals aged 55 or more years was interviewed and then followed for 17 years. Standardized instruments were used in the assessment, including the Geriatric Mental State-AGECAT, and research psychiatrists diagnosed P-MCI and DSM-5-MCI cases following operationalized criteria. Mortality information was obtained from the official population registry. Kaplan-Meier age-adjusted survival curves were built for the MCI diagnostic groups, and Cox proportional hazards regression models were used to calculate the hazard ratio of death in participants with MCI relative to those without. We also estimated the PAF of mortality due to specific MCI diagnostic groups. Compared with noncases, the mortality rate ratio was approximately double in DSM-5-MCI individuals (2.3) than in P-MCI individuals (1.2). In the multivariate statistical analysis, a significant association between each diagnostic category and mortality was observed but was only maintained in the final model in DSM-5-MCI cases (hazard ratio: 1.24). The PAF of mortality due to MCI was approximately 1% in both MCI categories. The mortality risk in comparison with noncases was higher in DSM-5-MCI than in P-MCI. The PAF of mortality in DSM-5-MCI individuals was ~ 1% over a 17-year period. Copyright © 2016. Published by Elsevier Inc.

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure.

PubMed

Goldstein, David S; Holmes, Courtney; Kaufmann, Horacio; Freeman, Roy

2004-12-01

Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. Plasma L-DOPS peaked at 1.9 microg/ml (9 micromol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.

Land application driven performance requirements for airborne imaging spectroscopy

NASA Astrophysics Data System (ADS)

Schaepman, M. E.; Schläpfer, D.; Kaiser, J. W.; Brazile, J.; Itten, K. I.

2003-04-01

Over the past few years, a joint Swiss/Belgium ESA initiative resulted in a project to build a precursor mission of future spaceborne imaging spectrometers, namely APEX (Airborne Prism Experiment). APEX is designed to be an airborne dispersive pushbroom imaging spectrometer operating in the solar reflected wavelength range between 400 and 2500 nm. The system is optimized for land applications including limnology, snow, soil, amongst others. The baseline for the requirements of APEX are built on various land requirements and subsequently modelled to at-sensor specific radiances. The model is based on existing biophysical and -chemical retrieval algorithms and assumes no physical limitation of the sensor system. Final technology limitations are discussed using system tradeoffs. The absolute radiance calibration of APEX includes the use of pre- and post-data acquisition internal calibration facility as well as a laboratory calibration and a performance model serving as a stable reference. We will discuss the instrument's present status in its breadboarding phase, including some new results with respect to the detector development and design optimization for imaging spectrometers. In the same framework of APEX, a complete processing and archiving facility (PAF) is developed. The PAF not only includes imaging spectrometer data processing up to physical units, but also geometric and atmospheric correction for each scene, as well as calibration data input. The PAF software includes an Internet based web-server and provides interfaces to data users as well as instrument operators and programmers. The software design, the tools and its life cycle is discussed as well. Further we will discuss particular instrument requirements (resampling, bad pixel treatment, etc.) in view of the operation of the PAF as well as their consequences on the product quality. Finally we will discuss a combined approach for geometric and atmospheric correction including BRDF (or view angle) related effects.

Component effect of stem cell-loaded thermosensitive polypeptide hydrogels on cartilage repair.

PubMed

Liu, He; Cheng, Yilong; Chen, Jinjin; Chang, Fei; Wang, Jincheng; Ding, Jianxun; Chen, Xuesi

2018-06-01

Biophysical properties of the desired biomimetic scaffolds, such as porosity and elasticity, have been proven associated with the efficacy of cartilage regeneration. In this work, the copolymers of poly(l-alanine)-block-poly(ethylene glycol)-block-poly(l-alanine) (PA-PEG-PA) and poly(l-alanine-co-l-phenylalanine)-block-poly(ethylene glycol)-block-poly(l-alanine-co-l-phenylalanine) (PAF-PEG-PAF) with different ratios of alanine to phenylalanine were synthesized. The introduction of a hydrophobic amino acid, i.e., phenylalanine, into polyalanine-based thermosensitive hydrogel led to the enhanced gelation behaviors and upregulated mechanical properties. Moreover, the increase of phenylalanine content resulted in the enlarged pore size and enhanced mechanical strength of PAF-PEG-PAF thermogel, followed by the regeneration of hyaline-like cartilage with reduced fibrous tissue formation in vivo. The findings indicated the great potential of thermosensitive polypeptide hydrogels in cartilage tissue engineering. Articular cartilage defect has limited self-repair ability due to the lack of blood supply and innervation, which may lead to knee osteoarthritis afterwards. Injectable hydrogels are demonstrated possessing outstanding properties as biomimetic scaffolds in cartilage tissue engineering, while the effect of biophysical properties on the efficacy of cartilage regeneration has not been revealed. Herein, the poly(ethylene glycol)-polypeptide triblock copolymers with different ratios of alanine to phenylalanine were synthesized. The sol-to-gel transition temperature and the critical gelation concentration decreased as the increased amount of phenylalanine unit, resulting in the enlarged pore size and enhanced mechanical strength. These features lead to better regeneration of hyaline-like cartilage with reduced fibrous tissue formation, indicating great potential of thermosensitive polypeptide hydrogels for efficient cartilage repair. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison of catheter ablation for paroxysmal atrial fibrillation between cryoballoon and radiofrequency: a meta-analysis.

PubMed

Chen, Chao-Feng; Gao, Xiao-Fei; Duan, Xu; Chen, Bin; Liu, Xiao-Hua; Xu, Yi-Zhou

2017-04-01

The present systematic review and meta-analysis aimed to assess and compare the safety and efficacy of radiofrequency (RF) and cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF). RF and CB ablation are two frequently used methods for pulmonary vein isolation in PAF, but which is a better choice for PAF remains uncertain. A systematic review was conducted in Medline, PubMed, Embase, and Cochrane Library. All trials comparing RF and CB ablation were screened and included if the inclusion criteria were met. A total of 38 eligible studies, 9 prospective randomized or randomized controlled trials (RCTs), and 29 non- RCTs were identified, adding up to 15,496 patients. Pool analyses indicated that CB ablation was more beneficial in terms of procedural time [standard mean difference = -0.58; 95% confidence interval (CI), -0.85 to -0.30], complications without phrenic nerve injury (PNI) [odds ratio (OR) = 0.79; 95% CI, 0.67-0.93; I 2  = 16%], and recrudescence (OR = 0.83; 95% CI, 0.70-0.97; I 2  = 63%) for PAF; however, the total complications of CB was higher than RF. The subgroup analysis found that, compared with non-contact force radiofrequency (non-CF-RF), both first-generation cryoballoon (CB1) and second-generation cryoballoon (CB2) ablation could reduce complications with PNI, procedural time, and recrudescence. However, the safety and efficacy of CB2 was similar to those of CF-RF. Available overall and subgroup data suggested that both CB1 and CB2 were more beneficial than RF ablation, and the main advantages were reflected in comparing them with non-CF-RF. However, CF-RF and CB2 showed similar clinical benefits.

Predictors of acute myocarditis in complicated scrub typhus: an endemic province in the Republic of Korea.

PubMed

Chin, Jung Yeon; Kang, Ki-Woon; Moon, Kyung Min; Kim, Jongwoo; Choi, Yu Jeong

2018-03-01

Scrub typhus is known as a self-limited infectious disease. Cardiac complication is uncommon and usually not life-threatening. Until now, few cases of fulminant myocarditis by scrub typhus have been reported. So, we investigated incidence and predictors of acute myocarditis in severe scrub typhus. We retrospectively reviewed 89 patients among 91 scrub typhus confirmed patients who examined an echocardiogram and cardiac biomarkers from 2005 to 2015 in the intensive care unit at our hospital. We excluded two patients who didn't have electrocardiography. Patients were divided into two groups and compared between scrub typhus with (n = 13) and without (n = 76) acute myocarditis. Age, sex, and underlying diseases were similar between the groups. The existence of eschar and duration of general ache and fever were similar between the groups. However, patients with acute myocarditis had more elevated total bilirubin, high incidence of ST elevations and paroxysmal atrial fibrillation (PAF) than those without acute myocarditis. Receiver operating characteristic analysis showed that the PAF was a predictor of myocarditis with a sensitivity of 70% and specificity of 84%. Predictive power of combination of ST-segment elevation and PAF was significantly associated with myocarditis in the multivariate analysis (odds ratio, 1.57; 95% confidence interval [CI], 1.21 to 11.7; p = 0.041) and area under the curve was 0.947 (95% CI, 0.878 to 0.983; p < 0.001). Acute myocarditis with scrub typhus may be more common than previously reported. Patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus. These patients warrant closer follow-up and echocardiogram would be needed.

Predictors of acute myocarditis in complicated scrub typhus: an endemic province in the Republic of Korea

PubMed Central

Chin, Jung Yeon; Kang, Ki-Woon; Moon, Kyung Min; Kim, Jongwoo; Choi, Yu Jeong

2018-01-01

Background/Aims Scrub typhus is known as a self-limited infectious disease. Cardiac complication is uncommon and usually not life-threatening. Until now, few cases of fulminant myocarditis by scrub typhus have been reported. So, we investigated incidence and predictors of acute myocarditis in severe scrub typhus. Methods We retrospectively reviewed 89 patients among 91 scrub typhus confirmed patients who examined an echocardiogram and cardiac biomarkers from 2005 to 2015 in the intensive care unit at our hospital. We excluded two patients who didn’t have electrocardiography. Patients were divided into two groups and compared between scrub typhus with (n = 13) and without (n = 76) acute myocarditis. Results Age, sex, and underlying diseases were similar between the groups. The existence of eschar and duration of general ache and fever were similar between the groups. However, patients with acute myocarditis had more elevated total bilirubin, high incidence of ST elevations and paroxysmal atrial fibrillation (PAF) than those without acute myocarditis. Receiver operating characteristic analysis showed that the PAF was a predictor of myocarditis with a sensitivity of 70% and specificity of 84%. Predictive power of combination of ST-segment elevation and PAF was significantly associated with myocarditis in the multivariate analysis (odds ratio, 1.57; 95% confidence interval [CI], 1.21 to 11.7; p = 0.041) and area under the curve was 0.947 (95% CI, 0.878 to 0.983; p < 0.001). Conclusions Acute myocarditis with scrub typhus may be more common than previously reported. Patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus. These patients warrant closer follow-up and echocardiogram would be needed. PMID:28226202

Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson’s Disease

PubMed Central

2016-01-01

Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson’s and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson’s disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications. PMID:27285482

Trends in educational inequalities in premature mortality in Belgium between the 1990s and the 2000s: the contribution of specific causes of deaths.

PubMed

Renard, Françoise; Gadeyne, Sylvie; Devleesschauwer, Brecht; Tafforeau, Jean; Deboosere, Patrick

2017-04-01

Reducing socioeconomic inequalities in mortality, a key public health objective may be supported by a careful monitoring and assessment of the contributions of specific causes of death to the global inequality. The 1991 and 2001 Belgian censuses were linked with cause-of-death data, each yielding a study population of over 5 million individuals aged 25-64, followed up for 5 years. Age-standardised mortality rates (ASMR) were computed by educational level (EL) and cause. Inequalities were measured through rate differences (RDs), rate ratios (RRs) and population attributable fractions (PAFs). We analysed changes in educational inequalities between the 1990s and the 2000s, and decomposed the PAF into the main causes of death. All-cause and avoidable ASMR decreased in all ELs and both sexes. Lung cancer, ischaemic heart disease (IHD), chronic obstructive pulmonary disease (COPD) and suicide in men, and IHD, stroke, lung cancer and COPD in women had the highest impact on population mortality. RDs decreased in men but increased in women. RRs and PAFs increased in both sexes, albeit more in women. In men, the impact of lung cancer and COPD inequalities on population mortality decreased while that of suicide and IHD increased. In women, the impact of all causes except IHD increased. Absolute inequalities decreased in men while increasing in women; relative inequalities increased in both sexes. The PAFs decomposition revealed that targeting mortality inequalities from lung cancer, IHD, COPD in both sexes, suicide in men and stroke in women would have the largest impact at population level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Changes in Left Atrial Transport Function in Patients Who Maintained Sinus Rhythm After Successful Radiofrequency Catheter Ablation for Atrial Fibrillation: A 1-Year Follow-Up Multislice Computed Tomography Study.

PubMed

Kim, Jin-Seok; Im, Sung Il; Shin, Seung Yong; Kang, Jun Hyuk; Na, Jin Oh; Choi, Cheol Ung; Kim, Seong Hwan; Kim, Eung Ju; Rha, Seung-Woon; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo; Hwang, Chun; Kim, Young-Hoon; Yong, Hwan Seok; Lim, Hong Euy

2017-02-01

Functional remodeling of left atrium (LA) after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has not been fully elucidated. This study aimed to determine the impact of RFCA on LA transport function in patients who maintained sinus rhythm (SR) after AF ablation. A total of 96 patients (paroxysmal AF [PAF] = 52) who maintained SR during 1 year after AF ablation were enrolled. Multislice computed tomography was performed to determine LA volume (LAV) and LA emptying fraction (LAEF) at pre-RFCA and 1-year post-RFCA. Creatine kinase-MB (CK-MB) and troponin-T levels were analyzed 1-day post-RFCA. At 1-year post-RFCA, mean LAV and LAEF decreased in overall patients. Based on LAEF change (ΔLAEF) cutoff of 5.0%, LAEF reduced in 41 patients (worsened group) and improved or showed no change in 55 patients (preserved group). Compared with preserved group, worsened group had a higher proportion of PAF, higher levels of CK-MB and troponin-T, and additional LA ablation. ΔLAEF was inversely correlated with CK-MB and troponin-T levels. Subgroup analysis showed that LAEF significantly decreased in PAF patients who underwent additional LA ablation. Multivariate analysis revealed that high baseline LAEF and additional LA ablation were independent predictors for worsened LAEF. Although SR was maintained for 1 year after AF ablation, LAEF as well as LAV decreased. The extent of LAEF deterioration was significantly associated with the amount of iatrogenic myocardial damage. Our data indicate that extensive atrial ablation may lead to LA functional deterioration, especially in patients with PAF. © 2016 Wiley Periodicals, Inc.

Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.

PubMed

Pemberton, Travis A; Chen, Mengbin; Harris, Golda G; Chou, Wayne K W; Duan, Lian; Köksal, Mustafa; Genshaft, Alex S; Cane, David E; Christianson, David W

2017-04-11

Terpenoid synthases catalyze isoprenoid cyclization reactions underlying the generation of more than 80,000 natural products. Such dramatic chemodiversity belies the fact that these enzymes generally consist of only three domain folds designated as α, β, and γ. Catalysis by class I terpenoid synthases occurs exclusively in the α domain, which is found with α, αα, αβ, and αβγ domain architectures. Here, we explore the influence of domain architecture on catalysis by taxadiene synthase from Taxus brevifolia (TbTS, αβγ), fusicoccadiene synthase from Phomopsis amygdali (PaFS, (αα) 6 ), and ophiobolin F synthase from Aspergillus clavatus (AcOS, αα). We show that the cyclization fidelity and catalytic efficiency of the α domain of TbTS are severely compromised by deletion of the βγ domains; however, retention of the β domain preserves significant cyclization fidelity. In PaFS, we previously demonstrated that one α domain similarly influences catalysis by the other α domain [ Chen , M. , Chou , W. K. W. , Toyomasu , T. , Cane , D. E. , and Christianson , D. W. ( 2016 ) ACS Chem. Biol. 11 , 889 - 899 ]. Here, we show that the hexameric quaternary structure of PaFS enables cluster channeling. We also show that the α domains of PaFS and AcOS can be swapped so as to make functional chimeric αα synthases. Notably, both cyclization fidelity and catalytic efficiency are altered in all chimeric synthases. Twelve newly formed and uncharacterized C 20 diterpene products and three C 25 sesterterpene products are generated by these chimeras. Thus, engineered αβγ and αα terpenoid cyclases promise to generate chemodiversity in the greater family of terpenoid natural products.

Smoking-attributable burden of lung cancer in the Philippines.

PubMed

Bilano, Ver Luanni Feliciano; Borja, Maridel P; Cruz, Eduardo L; Tan, Alvin G; Mortera, Lalaine L; Reganit, Paul Ferdinand M

2015-05-01

In the Philippines, smoking is highly prevalent and tobacco control policies fail to fully implement the WHO Framework Convention on Tobacco Control provisions. To aid in policy change, intervention implementation, monitoring and evaluation, this study aimed to provide the first internally consistent and latest Philippine estimates of the following: disability-adjusted life-years (DALYs) lost due to lung cancer; population-attributable fractions (PAFs) of smoking; and smoking-attributable lung cancer DALYs. This study applied the Global Burden of Disease and Comparative Risk Assessment frameworks to secondary data, supplemented by expert opinion. A comprehensive internally consistent assessment of disease epidemiology was conducted using DISMOD II and disease impact was quantified as DALYs. PAFs were calculated using the smoking impact ratio and Monte Carlo uncertainty analyses were conducted. For 2008, lung cancer incidence and mortality estimates were 10 871 cases and 9871 deaths respectively. Lung cancer accounted for an estimated 267 787 DALYs lost, 99% of which were due to years of life lost. Overall, the PAF of smoking was 65% and a total of 173 103 DALYs were smoking-attributable. There were increasing trends in incidence, mortality and DALY rates with age. The majority of incidence (72%), mortality (71%) and disease burden (72%) occurred among men, who also had higher PAF estimates. Considerable health gains could be achieved if smoking exposure were reduced in the Philippines. Strong enforcement of measures like increasing taxation to the WHO-endorsed rate, expanding smoke-free environments, and requiring large graphic warnings within a comprehensive tobacco control programme is recommended. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chronic elevation of phosphocholine containing lipids in mice exposed to Gulf War agents pyridostigmine bromide and permethrin.

PubMed

Abdullah, Laila; Evans, James E; Montague, Hannah; Reed, Jon M; Moser, Ann; Crynen, Gogce; Gonzalez, Ariel; Zakirova, Zuchra; Ross, Ivan; Mullan, Chris; Mullan, Michael; Ait-Ghezala, Ghania; Crawford, Fiona

2013-01-01

For two decades, 25% of the veterans who served in the 1991 Gulf War (GW) have been living with Gulf War Illness (GWI), a chronic multisymptom illness. Evidence suggests that brain structures involved in cognitive function may be affected in GWI. Gulf War agents such as the acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and the pesticide permethrin (PER) are considered key etiogenic factors in GWI. We therefore developed a mouse model of GW agent exposure by co-administering PB and PER and showed that this model exhibits cognitive impairment and anxiety, and increased astrogliosis at chronic post-exposure time-points. Since GW agents inhibit AChE, we hypothesized that PB+PER exposure will modulate phosphatidylcholine (PC) and sphingomyelin (SM), which are reservoirs of phosphocholine required for endogenous ACh synthesis. Lipidomic analyses showed that PC and SM were elevated in the brains of exposed compared to control mice. Brain ether PC (ePC) species were increased but lyso-platelet activating factors (lyso-PAF) that are products of ePC were decreased in exposed animals compared to controls. Catalase expression (a marker for peroxisomes) was increased in GW agent exposed mice compared to controls. Ether PC and lyso-PAF modulation was also evident in the plasma of GW agent exposed mice compared to controls. These studies suggest peroxisomal and lysosomal dysfunction in the brain at a chronic post-exposure timepoint following GW agent exposure. Our studies provide a new direction for GWI research, which will be useful for developing suitable therapies for treating GWI. © 2013 Elsevier Inc. All rights reserved.

Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs.

PubMed

Liu, Rui; Hu, Xiao-Hang; Wang, Shu-Ming; Guo, Si-Jia; Li, Zong-Yu; Bai, Xiao-Dong; Zhou, Fang-Qiang; Hu, Sen

2016-06-01

To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Dermal exposure to jet fuel suppresses delayed-type hypersensitivity: a critical role for aromatic hydrocarbons.

PubMed

Ramos, Gerardo; Limon-Flores, Alberto Yairh; Ullrich, Stephen E

2007-12-01

Dermal exposure to military (JP-8) and/or commercial (Jet-A) jet fuel suppresses cell-mediated immune reactions. Immune regulatory cytokines and biological modifiers, including platelet activating factor (PAF), prostaglandin E(2), and interleukin-10, have been implicated in the pathway of events leading to immune suppression. It is estimated that approximately 260 different hydrocarbons are found in jet fuel, and the exact identity of the active immunotoxic agent(s) is unknown. The recent availability of synthetic jet fuel (S-8), which is refined from natural gas, and is devoid of aromatic hydrocarbons, made it feasible to design experiments to address this problem. Here we tested the hypothesis that the aromatic hydrocarbons present in jet fuel are responsible for immune suppression. We report that applying S-8 to the skin of mice does not upregulate the expression of epidermal cyclooxygenase-2 (COX-2) nor does it induce immune suppression. Adding back a cocktail of seven of the most prevalent aromatic hydrocarbons found in jet fuel (benzene, toluene, ethylbenzene, xylene, 1,2,4-trimethlybenzene, cyclohexylbenzene, and dimethylnaphthalene) to S-8 upregulated epidermal COX-2 expression and suppressed a delayed-type hypersensitivity (DTH) reaction. Injecting PAF receptor antagonists, or a selective cycloozygenase-2 inhibitor into mice treated with S-8 supplemented with the aromatic cocktail, blocked suppression of DTH, similar to data previously reported using JP-8. These findings identify the aromatic hydrocarbons found in jet fuel as the agents responsible for suppressing DTH, in part by the upregulation of COX-2, and the production of immune regulatory factors and cytokines.

Impact of urbanisation and altitude on the incidence of, and risk factors for, hypertension

PubMed Central

Bernabé-Ortiz, Antonio; Carrillo-Larco, Rodrigo M; Gilman, Robert H; Checkley, William; Smeeth, Liam; Miranda, J Jaime

2017-01-01

Background Most of the data regarding the burden of hypertension in low-income and middle-income countries comes from cross-sectional surveys instead of longitudinal studies. We estimated the incidence of, and risk factors for, hypertension in four study sites with different degree of urbanisation and altitude. Methods Data from the CRONICAS Cohort Study, conducted in urban, semiurban and rural areas in Peru, was used. An age-stratified and sex-stratified random sample of participants was taken from the most updated census available in each site. Hypertension was defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or self-report physician diagnosis and current treatment. The exposures were study site and altitude as well as modifiable risk factors. Incidence, incidence rate ratios (IRRs), 95% CIs and population-attributable fractions (PAFs) were estimated using generalised linear models. Results Information from 3237 participants, mean age 55.8 (SD±12.7) years, 48.4% males, was analysed. Overall baseline prevalence of hypertension was 19.7% (95% CI 18.4% to 21.1%). A total of 375 new cases of hypertension were recorded, including 5266 person-years of follow-up, with an incidence of 7.12 (95% CI 6.44 to 7.88) per 100 person-years. Individuals from semiurban site were at higher risk of hypertension compared with highly urbanised areas (IRR=1.76; 95% CI 1.39 to 2.23); however, those from high-altitude sites had a reduced risk (IRR=0.74; 95% CI 0.58 to 0.95). Obesity was the leading risk factor for hypertension with a great variation according to study site with PAF ranging from 12.5% to 42.4%. Conclusions Our results suggest heterogeneity in the progression towards hypertension depending on urbanisation and site altitude. PMID:28115473

Impact of urbanisation and altitude on the incidence of, and risk factors for, hypertension.

PubMed

Bernabé-Ortiz, Antonio; Carrillo-Larco, Rodrigo M; Gilman, Robert H; Checkley, William; Smeeth, Liam; Miranda, J Jaime

2017-06-01

Most of the data regarding the burden of hypertension in low-income and middle-income countries comes from cross-sectional surveys instead of longitudinal studies. We estimated the incidence of, and risk factors for, hypertension in four study sites with different degree of urbanisation and altitude. Data from the CRONICAS Cohort Study, conducted in urban, semiurban and rural areas in Peru, was used. An age-stratified and sex-stratified random sample of participants was taken from the most updated census available in each site. Hypertension was defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or self-report physician diagnosis and current treatment. The exposures were study site and altitude as well as modifiable risk factors. Incidence, incidence rate ratios (IRRs), 95% CIs and population-attributable fractions (PAFs) were estimated using generalised linear models. Information from 3237 participants, mean age 55.8 (SD±12.7) years, 48.4% males, was analysed. Overall baseline prevalence of hypertension was 19.7% (95% CI 18.4% to 21.1%). A total of 375 new cases of hypertension were recorded, including 5266 person-years of follow-up, with an incidence of 7.12 (95% CI 6.44 to 7.88) per 100 person-years. Individuals from semiurban site were at higher risk of hypertension compared with highly urbanised areas (IRR=1.76; 95% CI 1.39 to 2.23); however, those from high-altitude sites had a reduced risk (IRR=0.74; 95% CI 0.58 to 0.95). Obesity was the leading risk factor for hypertension with a great variation according to study site with PAF ranging from 12.5% to 42.4%. Our results suggest heterogeneity in the progression towards hypertension depending on urbanisation and site altitude. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Arabidopsis thaliana VOZ (Vascular plant One-Zinc finger) transcription factors are required for proper regulation of flowering time

PubMed Central

Celesnik, Helena; Ali, Gul S.; Robison, Faith M.; Reddy, Anireddy S. N.

2013-01-01

Summary Transition to flowering in plants is tightly controlled by environmental cues, which regulate the photoperiod and vernalization pathways, and endogenous signals, which mediate the autonomous and gibberellin pathways. In this work, we investigated the role of two Zn2+-finger transcription factors, the paralogues AtVOZ1 and AtVOZ2, in Arabidopsis thaliana flowering. Single atvoz1-1 and atvoz2-1 mutants showed no significant phenotypes as compared to wild type. However, atvoz1-1 atvoz2-1 double mutant plants exhibited several phenotypes characteristic of flowering-time mutants. The double mutant displayed a severe delay in flowering, together with additional pleiotropic phenotypes. Late flowering correlated with elevated expression of FLOWERING LOCUS C (FLC), which encodes a potent floral repressor, and decreased expression of its target, the floral promoter FD. Vernalization rescued delayed flowering of atvoz1-1 atvoz2-1 and reversed elevated FLC levels. Accumulation of FLC transcripts in atvoz1-1 atvoz2-1 correlated with increased expression of several FLC activators, including components of the PAF1 and SWR1 chromatin-modifying complexes. Additionally, AtVOZs were shown to bind the promoter of MOS3/SAR3 and directly regulate expression of this nuclear pore protein, which is known to participate in the regulation of flowering time, suggesting that AtVOZs exert at least some of their flowering regulation by influencing the nuclear pore function. Complementation of atvoz1-1 atvoz2-1 with AtVOZ2 reversed all double mutant phenotypes, confirming that the observed morphological and molecular changes arise from the absence of functional AtVOZ proteins, and validating the functional redundancy between AtVOZ1 and AtVOZ2. PMID:23616927

[Perspectives of psychological aging research].

PubMed

Wahl, H-W; Diegelmann, M

2015-12-01

Psychological aging research (PAF) focuses on age-related changes and behavioral stability (e.g. structure of social relations), performance and competences (e.g. cognitive functioning) as well as experiences (e.g. well-being) in advanced age. Knowledge is based in particular on currently available longitudinal studies, which historically for the first time allow very long observational periods (nearly across the complete life span). Additionally, innovative statistical analytical methods co-developed in the PAF nowadays allow a better understanding of the dynamics of change than ever before. This results in a new picture of psychological aging that confirms the multifaceted strengths of human aging but also reveals new risks of the current "prolonged aging".

A weight-of-evidence approach to assessing the ecological impact of organotin pollution in Dutch marine and brackish waters; combining risk prognosis and field monitoring using common periwinkles (Littorina littorea).

PubMed

Schipper, Cor A; Smit, Mathijs G D; Kaag, Nicholas H B M; Dick Vethaak, A

2008-08-01

In the present study an integrated ecological risk assessment based on multiple lines of evidence (LOEs) was evaluated in order to better assess the risk from TBT in Dutch harbours and open coastal waters. On the basis of spatial distributions of measured tributyltin (TBT) concentrations in sediments and suspended matter, predictions of the intersex index (ISI) in Littorina littorea and the ecological risk expressed as the Potentially Affected Fraction (PAF) of species were made. The results were compared to actual ISI measurements and presence of L. littorea in the field. The PAF calculated on the basis of TBT levels for open coastal waters ranged from 4.2% to 15.3%; for harbours it ranged from 3.5% to 26.9%. Significant intersex levels were observed only in waters where the risk was calculated above 10% PAF. This study suggests that the absence of L. littorea from some harbours with high ecological risk values can be explained by high TBT concentrations. A call is made for the use of integrated approaches like weight-of-evidence (WOE) to help practitioners improve ecological risk assessment.

Cancers in Australia in 2010 attributable to overweight and obesity.

PubMed

Kendall, Bradley J; Wilson, Louise F; Olsen, Catherine M; Webb, Penelope M; Neale, Rachel E; Bain, Christopher J; Whiteman, David C

2015-10-01

To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity. We estimated the population attributable fraction (PAF) and number of cancers causally associated with overweight/obesity. We used standard formulae incorporating Australian prevalence data for body mass index (BMI), relative risks associated with BMI and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that the prevalence of overweight/obesity had remained at 1990 levels. An estimated 3,917 cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to overweight/obesity, including 1,101 colon cancers, 971 female post-menopausal breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%, respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%), endometrial cancer (26%) and kidney cancer (19%). If the prevalence of overweight/obesity in Australia had remained at levels prevailing in 1990, we estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%). Overweight/obesity causes a substantial number of cancers in Australia. Public health strategies to reduce the prevalence of overweight and obesity will reduce the incidence of cancer, particularly of the colon, breast and endometrium. © 2015 The Authors.

Occupational Lymphohematopoietic Cancer in Korea

PubMed Central

Lee, Won Jin; Son, Mia; Kang, Seong-Kyu

2010-01-01

The purpose of this study was to review the existing studies on lymphohematopoietic (LHP) cancer in Korea, estimate the prevalence of workers exposed to carcinogens, and determine the population attributable fraction (PAF) of leukemia. Two case series and 4 case reports were reviewed. Using official statistics, the prevalence of benzene exposure and ionizing radiation exposure was estimated. Based on the prevalence of exposure and the relative risk, The PAF of leukemia was calculated. Between 1996 and 2005, 51 cases of LHP cancer were reported from the compensation system. Greater than 50% of occupational LHP cancer was leukemia, and the most important cause was benzene. In a cohort study, the standardized incidence ratio was 2.71 (95% CI, 0.56-7.91). The prevalence of exposure was 2.5% and 2.2% in 1995 and 2000, respectively. Using the 1995 prevalence, 3.6-4.8% and 0.1% of cases with leukemia were attributable to benzene and ionizing radiation exposure, respectively, which resulted in 39.7-51.4 cases per year. Benzene is the most important cause of occupational leukemia in Korea. Considering the estimated PAF in this study, the annual number of occupational LHP cancer (51 cases during 10-yr period), might be underreported within the compensation system. PMID:21258598

Determining the best population-level alcohol consumption model and its impact on estimates of alcohol-attributable harms

PubMed Central

2012-01-01

Background The goals of our study are to determine the most appropriate model for alcohol consumption as an exposure for burden of disease, to analyze the effect of the chosen alcohol consumption distribution on the estimation of the alcohol Population- Attributable Fractions (PAFs), and to characterize the chosen alcohol consumption distribution by exploring if there is a global relationship within the distribution. Methods To identify the best model, the Log-Normal, Gamma, and Weibull prevalence distributions were examined using data from 41 surveys from Gender, Alcohol and Culture: An International Study (GENACIS) and from the European Comparative Alcohol Study. To assess the effect of these distributions on the estimated alcohol PAFs, we calculated the alcohol PAF for diabetes, breast cancer, and pancreatitis using the three above-named distributions and using the more traditional approach based on categories. The relationship between the mean and the standard deviation from the Gamma distribution was estimated using data from 851 datasets for 66 countries from GENACIS and from the STEPwise approach to Surveillance from the World Health Organization. Results The Log-Normal distribution provided a poor fit for the survey data, with Gamma and Weibull distributions providing better fits. Additionally, our analyses showed that there were no marked differences for the alcohol PAF estimates based on the Gamma or Weibull distributions compared to PAFs based on categorical alcohol consumption estimates. The standard deviation of the alcohol distribution was highly dependent on the mean, with a unit increase in alcohol consumption associated with a unit increase in the mean of 1.258 (95% CI: 1.223 to 1.293) (R2 = 0.9207) for women and 1.171 (95% CI: 1.144 to 1.197) (R2 = 0. 9474) for men. Conclusions Although the Gamma distribution and the Weibull distribution provided similar results, the Gamma distribution is recommended to model alcohol consumption from population surveys due to its fit, flexibility, and the ease with which it can be modified. The results showed that a large degree of variance of the standard deviation of the alcohol consumption Gamma distribution was explained by the mean alcohol consumption, allowing for alcohol consumption to be modeled through a Gamma distribution using only average consumption. PMID:22490226

Tuberculosis incidence in prisons: a systematic review.

PubMed

Baussano, Iacopo; Williams, Brian G; Nunn, Paul; Beggiato, Marta; Fedeli, Ugo; Scano, Fabio

2010-12-21

Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population. A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0-61.8) and 23.0 (IQR: 11.7-36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%-17.9%) and 6.3% (IQR: 2.7%-17.2%) in high- and middle/low-income countries, respectively. The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors' Summary.

Three new 7.3',8.5'-connected bicyclo[3.2.1]octanoids and other neolignans from leaves of Nectandra amazonum NEES. (Lauraceae).

PubMed

Coy Barrera, Ericsson David; Cuca Suárez, Luis Enrique

2009-06-01

Three new 7.3',8.5'-connected (macrophyllin-type) bicyclo[3.2.1]octanoid neolignans (nectamazins A-C, 1-3) were isolated from leaves of Nectandra amazonum NEES., along with seven known neolignans (4-10). The structures of 1-3 were characterized by spectroscopic methods (1D, 2D NMR) and the absolute configuration was assigned on the basis of circular dichroism (CD) spectra supported by nuclear Overhauser effect spectroscopy (NOESY) correlations. The new compounds showed inhibition activity against platelet activating factor (PAF)-induced aggregation of rabbit platelets.

Disease burden due to biomass cooking-fuel-related household air pollution among women in India.

PubMed

Sehgal, Meena; Rizwan, Suliankatchi Abdulkader; Krishnan, Anand

2014-01-01

Household air pollution (HAP) due to biomass cooking fuel use is an important risk factor for a range of diseases, especially among adult women who are primary cooks, in India. About 80% of rural households in India use biomass fuel for cooking. The aim of this study is to estimate the attributable cases (AC) for four major diseases/conditions associated with biomass cooking fuel use among adult Indian women. We used the population attributable fraction (PAF) method to calculate the AC of chronic bronchitis, tuberculosis (TB), cataract, and stillbirths due to exposure to biomass cooking fuel. A number of data sources were accessed to obtain population totals and disease prevalence rates. A meta-analysis was conducted to obtain adjusted pooled odds ratios (ORs) for strength of association. Using this, PAF and AC were calculated using a standard formula. Results were presented as number of AC and 95% confidence intervals (CI). The fixed effects pooled OR obtained from the meta-analysis were 2.37 (95% CI: 1.59, 3.54) for chronic bronchitis, 2.33 (1.65, 3.28) for TB, 2.16 (1.42, 3.26) for cataract, and 1.26 (1.12, 1.43) for stillbirths. PAF varied across conditions being maximum (53%) for chronic bronchitis in rural areas and least (1%) for cataract in older age and urban areas. About 2.4 (95% CI: 1.4, 3.1) of 5.6 m cases of chronic bronchitis, 0.3 (0.2, 0.4) of 0.76 m cases of TB, 5.0 (2.8, 6.7) of 51.4 m cases of cataract among adult Indian women and 0.02 (0.01, 0.03) of 0.15 m stillbirths across India are attributable to HAP due to biomass cooking fuel. These estimates should be cautiously interpreted in the light of limitations discussed which relate to exposure assessment, exposure characterization, and age-specific prevalence of disease. HAP due to biomass fuel has diverse and major impacts on women's health in India. Although challenging, incorporating the agenda of universal clean fuel access or cleaner technology within the broader framework of rural development will go a long way in reducing disease burden.

"Invisible" conformers of an antifungal disulfide protein revealed by constrained cold and heat unfolding, CEST-NMR experiments, and molecular dynamics calculations.

PubMed

Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

2015-03-23

Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20-40 % at 298 K in a disulfide-rich protein. In addition, sensitive (15) N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR "dark matter". Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A novel platelet activating factor receptor antagonist reduces cell infiltration and expression of inflammatory mediators in mice exposed to desiccating conditions after PRK.

PubMed

Esquenazi, Salomon; He, Jiucheng; Li, Na; Bazan, Nicolas G; Esquenazi, Isi; Bazan, Haydee E P

2009-01-01

To study the contribution of a novel PAF receptor antagonist LAU-0901 in the modulation of the increased inflammatory response in mice exposed to dessicating conditions (DE) after PRK. Eighty 13-14 week old female Balb/C mice were used. They were divided into two groups: One group was treated with LAU-0901 topical drops. The other group was treated with vehicle. In each group ten mice served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided in two additional groups: ten mice remained under normal conditions (NC) and the other ten were exposed to DE. After 1 week all animals underwent in vivo confocal microscopy, immunostaining and western blotting analysis. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-090). Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.

Stereochemistry- and concentration-dependent effects of phosphatidylserine enrichment on platelet function.

PubMed

Meyer, Audrey F; Gruba, Sarah M; Kim, Donghyuk; Meyer, Ben M; Koseoglu, Secil; Dalluge, Joseph J; Haynes, Christy L

2017-08-01

Platelets are small (1-2μm in diameter), circulating anuclear cell fragments with important roles in hemostasis and thrombosis that provide an excellent platform for studying the role of membrane components in cellular communication. Platelets use several forms of communication including exocytosis of three distinct granule populations, formation of bioactive lipid mediators, and shape change (allowing for adhesion). This work explores the role of stereochemistry and concentration of exogenous phosphatidylserine (PS) on platelet exocytosis and adhesion. PS, most commonly found in the phosphatidyl-l-serine (l-PS) form, is exposed on the outer leaflet of the cell membrane after the platelet is activated. Knowledge about the impact of exogenous phosphatidylserine on cell-to-cell communication is limited (particularly concentration and stereochemistry effects). This study found that platelets incubated in l-PS or phosphatidyl-d-serine (d-PS) are enriched to the same extent with their respective incubated PS. All levels of l-PS enrichment also showed an increase in platelet cholesterol, but only the 50μM d-PS incubation showed an increase in cholesterol. The uptake of d-PS induced the secretion of granules and manufactured platelet activating factor (PAF) in otherwise unstimulated platelets. The uptake of l-PS had a greater impact on platelet stimulation by decreasing both the amount of δ-granule secretion and the amount of PAF that was manufactured. Copyright © 2017 Elsevier B.V. All rights reserved.

Fetal-to-maternal signaling in the timing of birth.

PubMed

Mendelson, Carole R; Montalbano, Alina P; Gao, Lu

2017-06-01

Preterm birth remains the major cause of neonatal morbidity and mortality throughout the world. This is due, in part, to our incomplete understanding of the mechanisms that underlie the maintenance of pregnancy and the initiation of parturition at term. In this article, we review our current knowledge of the complex, interrelated and concerted mechanisms whereby progesterone maintains myometrial quiescence throughout most of pregnancy, as well as those that mediate the upregulation of the inflammatory response and decline in progesterone receptor function leading to parturition. Herein, we review findings that demonstrate a role of the fetus in the timing of birth. Specifically, we focus on our own studies indicating that maturation of the fetal lung and enhanced secretion of the surfactant components, surfactant protein A (SP-A) and the potent inflammatory glycerophospholipid, platelet-activating factor (PAF), initiate a signaling cascade culminating in parturition. Our studies suggest an essential role of steroid receptor coactivators, SRC-1 and SRC-2, which activate expression of genes encoding SP-A and LPCAT1. LPCAT1 is a key enzyme in the synthesis of PAF, as well as DPPC, a highly surface-active glycerophospholipid component of surfactant. Thus, we describe a novel pathway through which the fetus contributes to the initiation of labor by signaling the mother when its lungs have achieved sufficient maturity for survival in an aerobic environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

"Platelet-associated regulatory system (PARS)" with particular reference to female reproduction.

PubMed

Bódis, József; Papp, Szilárd; Vermes, István; Sulyok, Endre; Tamás, Péter; Farkas, Bálint; Zámbó, Katalin; Hatzipetros, Ioannis; Kovács, Gábor L

2014-01-01

Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface. Selected relevant literature and own views and experiences as clinical observations have been used. Considering that platelets are indispensable in numerous homeostatic endocrine functions, it is reasonable to suppose that a platelet-associated regulatory system (PARS) may exist; internal or external triggers and/or stimuli may complement and connect regulatory pathways aimed towards target tissues and/or cells. The signal (PAF, or other tissue/cell specific factors) comes from the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors, etc.) organs or cells, and activates platelets. Platelet activation means their aggregation, sludge formation, furthermore the release of the for-mentioned biologically very powerful factors, which can locally amplify and deepen the tissue specific cell reactions. If this process is impaired or inhibited for any reason, the specifically stimulated organ shows hypofunction. When PARS is upregulated, organ hyperfunction may occur that culminate in severe diseases. Based on clinical and experimental evidences we propose that platelets modulate the function of hypothalamo-hypophyseal-ovarian system. Specifically, hypothalamic GnRH releases FSH from the anterior pituitary, which induces and stimulates follicular and oocyte maturation and steroid hormone secretion in the ovary. At the same time follicular cells enhance PAF production. Through these pathways activated platelets are accumulated in the follicular vessels surrounding the follicle and due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase oocyte maturation and hormone secretion. Therefore we suggest that platelets are not only a small participant but may be the conductor or active mediator of this complex regulatory system which has several unrevealed mechanisms. In other words platelets are corpuscular messengers, or are more than a member of the family providing hemostasis.

Enhanced Antigen Retrieval of Amyloid β Immunohistochemistry

PubMed Central

Kai, Hideaki; Ogino, Koichi; Hatsuta, Hiroyuki; Murayama, Shigeo; Kitamoto, Tetsuyuki

2012-01-01

Senile plaques, extracellular deposits of amyloid β peptide (Aβ), are one of the pathological hallmarks of Alzheimer disease (AD). As the standard immunohistochemical detection method for Aβ deposits, anti-Aβ immunohistochemistry combined with antigen retrieval (AR) by formic acid (FA) has been generally used. Here, we present a more efficient AR for Aβ antigen. On brain sections of AD and its mouse model, a double combination of either autoclave heating in EDTA buffer or digestion with proteinase K plus FA treatment reinforced Aβ immunoreactivity. A further triple combination of digestion with proteinase K (P), autoclave heating in EDTA buffer (A), and FA treatment (F), when employed in this order, gave a more enhanced immunoreactivity. Our PAF method prominently visualized various forms of Aβ deposits in AD that have not been clearly detected previously and revealed numerous minute-sized plaques both in AD and the mouse model. Quantification of Aβ loads showed that the AR effect by the PAF method was 1.86-fold (in the aged human brain) and 4.64-fold (in the mouse brain) higher than that by the FA method. Thus, the PAF method could have the potential to be the most sensitive tool so far to study Aβ pathology in AD and its mouse model. PMID:22821668

Worldwide burden of gastric cancer in 2010 attributable to high sodium intake in 1990 and predicted attributable burden for 2030 based on exposures in 2010.

PubMed

Peleteiro, Bárbara; Barros, Susana; Castro, Clara; Ferro, Ana; Morais, Samantha; Lunet, Nuno

2016-08-01

Assessing the impact that patterns of Na intake may have on gastric cancer will provide a more comprehensive estimation of Na reduction as a primary prevention approach. We aimed to estimate the proportion of gastric cancer cases that are attributable to Na intake above the recommendation by the WHO (≤2 g/d) throughout the world in 2010, as well as expected values for 2030. Population attributable fractions (PAF) were computed for 187 countries, using Na intakes in 1990 and 2010 and estimates of the association between Na intake and gastric cancer, assuming a time lag of 20 years. Median PAF ranged from 10·1% in low to 22·5 % in very high Human Development Index (HDI) countries in men (P<0·001) and from 7·2 to 16·6 %, respectively, among women (P<0·001). An increase in median PAF until 2030 is expected in most settings, except for countries classified as low HDI, in both sexes. High Na intakes account for a large proportion of gastric cancer cases, and proportions are expected to increase in almost all of the countries. Intensified efforts to diminish Na intake in virtually all populations are needed to further reduce gastric cancer burden.

Differential Effects of AAV.BDNF and AAV.Ntf3 in the Deafened Adult Guinea Pig Ear

PubMed Central

Budenz, Cameron L.; Wong, Hiu Tung; Swiderski, Donald L.; Shibata, Seiji B.; Pfingst, Bryan E.; Raphael, Yehoash

2015-01-01

Cochlear hair cell loss results in secondary regression of peripheral auditory fibers (PAFs) and loss of spiral ganglion neurons (SGNs). The performance of cochlear implants (CI) in rehabilitating hearing depends on survival of SGNs. Here we compare the effects of adeno-associated virus vectors with neurotrophin gene inserts, AAV.BDNF and AAV.Ntf3, on guinea pig ears deafened systemically (kanamycin and furosemide) or locally (neomycin). AAV.BDNF or AAV.Ntf3 was delivered to the guinea pig cochlea one week following deafening and ears were assessed morphologically 3 months later. At that time, neurotrophins levels were not significantly elevated in the cochlear fluids, even though in vitro and shorter term in vivo experiments demonstrate robust elevation of neurotrophins with these viral vectors. Nevertheless, animals receiving these vectors exhibited considerable re-growth of PAFs in the basilar membrane area. In systemically deafened animals there was a negative correlation between the presence of differentiated supporting cells and PAFs, suggesting that supporting cells influence the outcome of neurotrophin over-expression aimed at enhancing the cochlear neural substrate. Counts of SGN in Rosenthal's canal indicate that BDNF was more effective than NT-3 in preserving SGNs. The results demonstrate that a transient elevation in neurotrophin levels can sustain the cochlear neural substrate in the long term. PMID:25726967

dbPAF: an integrative database of protein phosphorylation in animals and fungi.

PubMed

Ullah, Shahid; Lin, Shaofeng; Xu, Yang; Deng, Wankun; Ma, Lili; Zhang, Ying; Liu, Zexian; Xue, Yu

2016-03-24

Protein phosphorylation is one of the most important post-translational modifications (PTMs) and regulates a broad spectrum of biological processes. Recent progresses in phosphoproteomic identifications have generated a flood of phosphorylation sites, while the integration of these sites is an urgent need. In this work, we developed a curated database of dbPAF, containing known phosphorylation sites in H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, S. pombe and S. cerevisiae. From the scientific literature and public databases, we totally collected and integrated 54,148 phosphoproteins with 483,001 phosphorylation sites. Multiple options were provided for accessing the data, while original references and other annotations were also present for each phosphoprotein. Based on the new data set, we computationally detected significantly over-represented sequence motifs around phosphorylation sites, predicted potential kinases that are responsible for the modification of collected phospho-sites, and evolutionarily analyzed phosphorylation conservation states across different species. Besides to be largely consistent with previous reports, our results also proposed new features of phospho-regulation. Taken together, our database can be useful for further analyses of protein phosphorylation in human and other model organisms. The dbPAF database was implemented in PHP + MySQL and freely available at http://dbpaf.biocuckoo.org.

The Australian SKA Pathfinder: project update and initial operations

NASA Astrophysics Data System (ADS)

Schinckel, Antony E. T.; Bock, Douglas C.-J.

2016-08-01

The Australian Square Kilometre Array Pathfinder (ASKAP) will be the fastest dedicated cm-wave survey telescope, and will consist of 36 12-meter 3-axis antennas, each with a large chequerboard phased array feed (PAF) receiver operating between 0.7 and 1.8 GHz, and digital beamforming prior to correlation. The large raw data rates involved ( 100 Tb/sec), and the need to do pipeline processing, has led to the antenna incorporating a third axis to fix the parallactic angle with respect to the entire optical system (blockages and phased array feed). It also results in innovative technical solutions to the data transport and processing issues. ASKAP is located at the Murchison Radio-astronomy Observatory (MRO), a new observatory developed for the Square Kilometre Array (SKA), 315 kilometres north-east of Geraldton, Western Australia. The MRO also hosts the SKA low frequency pathfinder instrument, the Murchison Widefield Array and will host the initial low frequency instrument of the SKA, SKA1-Low. Commissioning of ASKAP using six antennas equipped with first-generation PAFs is now complete and installation of second-generation PAFs and digital systems is underway. In this paper we review technical progress and commissioning to date, and refer the reader to relevant technical and scientific publications.

Population attributable fractions of psychopathology and suicidal behaviour associated with childhood adversities in Northern Ireland.

PubMed

McLafferty, Margaret; O'Neill, Siobhan; Murphy, Sam; Armour, Cherie; Bunting, Brendan

2018-03-01

Childhood adversities are strong predictors of psychopathology and suicidality. However, specific adversities are associated with different outcomes, with cross-national variations reported. The current study examined rates of adversities reported in Northern Ireland (NI), and associations between adverse childhood experiences and psychopathology and suicidal behaviour were explored. Data was obtained from the Northern Ireland Study of Health and Stress (NISHS), conducted as part of the World Mental Health (WMH) survey initiative (2004-2008); response rate 68.4% (n = 1,986). The on-line survey used, the WHO Composite International Diagnostic Interview (CIDI) to examine psychopathology and associated risk factors in the NI population. Prevalence rates of retrospectively reported childhood adversities were calculated, with gender and age variations explored. Females were more likely to experience sexual abuse. Individuals who grew up during the worst years of the civil conflict in NI experienced elevated levels of childhood adversities. Participants who endured childhood adversities were more likely to have mental health problems but variations in risk factors were found for different disorders. Parental mental illness was associated with all disorders however, with ORs ranging from 2.20 for mood disorders to 4.07 for anxiety disorders. Population attributable fractions (PAF) estimated the reduction in psychopathology and suicidal behaviour in the population if exposure to adverse childhood events had not occurred. The highest PAF values were revealed for parental mental illness and sexual abuse. The findings indicate that a substantial proportion of psychopathology and suicide risk in NI are attributable to childhood adversities, providing support for early intervention and prevention initiatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of the lay-off length on +Gz tolerance.

PubMed

Mikuliszyn, Romuald; Kowalski, Wieslaw; Kowalczuk, Krzysztof

2002-07-01

There are many factors affecting pilots' +Gz-tolerance. Recently, attention of the aviation community has been focused on lay-off and it's impact on +Gz-tolerance. Pilots of the Polish Air Force (PAF) have dealt with that problem for several years now. The aim of the study was to provide insight on how lay-off periods with different duration impact +Gz-tolerance. 95 male jet pilots from the PAF participated in the study. Every one had at least two weeks lay-off period (non-medical reasons). Subjects were divided into four groups according to the length of lay-off period (2-4 weeks; 5-13 weeks; 14-26 weeks; 27-154 weeks), All pilots were subjected to a centrifuge exposure in GOR (0.1 G/s) or ROR (1.0 G/s) profiles, depending on the pre-lay-off exposure. Post-lay-off exposures were carried out directly after lay-off. 18 jet pilots without any lay-off constituted the control group. The difference between pre- and post-lay-off G-tolerance limit (-0,93 +/- 0,53) was statistically significant (p<0.01) only for one group, where lay-off period ranged between two and four weeks. No statistically significant differences were found where influence of other factors like total and yearly flight hours, heart rate gain (AHR) or physical activity measured as maximal oxygen intake were considered. 2-4 weeks of lay-off period decreases +Gz tolerance is statistically significant manner. Subsequent increase of lay-off period does not result in mean tolerance changes for group, however in certain individuals critical decrement of +Gz tolerance occurs. Total and last year flying hours, physical fitness does not modify impact of lay-off period on +Gz tolerance.

D-lactic acid interferes with the effects of platelet activating factor on bovine neutrophils.

PubMed

Alarcón, P; Conejeros, I; Carretta, M D; Concha, C; Jara, E; Tadich, N; Hidalgo, M A; Burgos, R A

2011-11-15

D-lactic acidosis occurs in ruminants, such as cattle, with acute ruminal acidosis caused by ingestion of excessive amounts of highly fermentable carbohydrates. Affected animals show clinical signs similar to those of septic shock, as well as acute laminitis and liver abscesses. It has been proposed that the inflammatory response and susceptibility to infection could both be caused by the inhibition of phagocytic mechanisms. To determine the effects of d-lactic acid on bovine neutrophil functions, we pretreated cells with different concentrations of D-lactic acid and measured intracellular pH using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and calcium flux using FLUO-3 AM-loaded neutrophils. Reactive oxygen species (ROS) production was measured using a luminol chemiluminescence assay, and MMP-9/gelatinase-B granule release was measured by zymography. CD11b and CD62L/l-selectin expression, changes in cell shape, superoxide anion production, phagocytosis of Escherichia coli-Texas red bioparticles, and apoptosis were all measured using flow cytometry. Our results demonstrated that D-lactic acid reduced ROS production, CD11b upregulation and MMP-9 release in bovine neutrophils treated with 100 nM platelet-activating factor (PAF). D-lactic acid induced MMP-9 release and, at higher concentrations, upregulated CD11b expression, decrease L-selectin expression, and induces late apoptosis. We concluded that D-lactic acid can interfere with neutrophil functions induced by PAF, leading to reduced innate immune responses during bacterial infections. Moreover, the increase of MMP-9 release and CD11b expression induced by 10mM D-lactic acid could promote an nonspecific neutrophil-dependent inflammatory reaction in cattle with acute ruminal acidosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Adaptive-servo ventilation combined with deep sedation is an effective strategy during pulmonary vein isolation.

PubMed

Murakami, Takashi; Yamaji, Hirosuke; Numa, Kenji; Kawamura, Hiroshi; Murakami, Masaaki; Higashiya, Shunichi; Kamikawa, Shigeshi; Hina, Kazuyoshi; Hirohata, Satoshi; Kusachi, Shozo

2013-07-01

Pulmonary vein isolation (PVI) by catheter ablation for atrial fibrillation (AF) requires suppression of patient restlessness by sufficient sedation in addition to maintaining stable respiration. We applied adaptive-servo ventilation (ASV) and examined the effects of ASV combined with deep propofol sedation on PVI using a NavX. We analysed 75 paroxysmal AF (PAF) patients (62 ± 11 years; 53 men and 22 women) who underwent PVI for treatment of PAF using an ASV system combined with deep sedation (ASV group). Control patients included 75 consecutive PAF patients (62 ± 11 years; 51 men and 24 women) who underwent PVI just before introduction of the ASV system. Deep sedation was defined as a Ramsay sedation score of 6. The ASV group had a lower frequency of restless body movements compared with the control group during PVI (1.5 ± 0.7 vs. 7.8 ± 1.4 times, P < 0.01). The frequency of respiratory compensation and EnGuide alignment of catheter position by the NavX was lower in the ASV (4.2 ± 3.3 and 8.8 ± 7.1 times) than control group (7.1 ± 5.1 and 15.2 ± 10.0 times, P < 0.05 and <0.01, respectively). Consequently, significantly lower total electrical energy supply (48.7 ± 6.0 KJ) was required in the ASV than control group (64.5 ± 24.9 KJ, P < 0.01). Further, significantly shorter fluoroscopy and procedural times were observed in the ASV (28 ± 5 and 109 ± 25 min) than the control group (33 ± 6 and 141 ± 38 min, respectively, P < 0.01) and the AF recurrence rate was significantly lower in the ASV than the control group (12 vs. 25%, P < 0.01). ASV combined with deep sedation is an effective strategy during PVI using the NavX in patients with PAF.

IMPACT OF SPECIFIC PHOBIA ON THE RISK OF ONSET OF MENTAL DISORDERS: A 10-YEAR PROSPECTIVE-LONGITUDINAL COMMUNITY STUDY OF ADOLESCENTS AND YOUNG ADULTS.

PubMed

Lieb, Roselind; Miché, Marcel; Gloster, Andrew T; Beesdo-Baum, Katja; Meyer, Andrea H; Wittchen, Hans-Ulrich

2016-07-01

The role of specific phobia as a potentially important psychopathological precursor condition to more severe mental disorders is understudied. We examined the prospective-longitudinal association of early childhood/adolescent phobia with subsequent mental disorders and the proportion of outcome disease incidence attributable to specific phobia simultaneously for a broad range of disorders. N = 2210 14- to 24-year-old community subjects were followed up for 10 years. DSM-IV-specific phobia as exposure and a broad range of DSM-IV mental disorders as outcomes were assessed with the DSM-IV/M-CIDI. Logistic regressions, adjusting for confounders, were used to estimate the associations of specific phobia with the subsequent onset of outcome disorders. Baseline specific phobia predicted the subsequent first onset of anxiety disorders [panic disorder: risk ratio (RR) = 4.38, 95% confidence interval (2.34, 8.21); generalized anxiety disorder: RR = 4.10 (2.19, 7.69); posttraumatic stress disorder: RR = 2.15 (1.13, 4.10); obsessive-compulsive disorder: RR = 3.79 (1.63, 8.82)], affective disorders [major depression: RR = 1.54 (1.16, 2.03); bipolar disorder: RR = 2.20 (1.10, 4.41); dysthymia: RR = 2.75 (1.48, 5.11)], pain disorder: RR = 1.52 (1.14, 2.02), and eating disorders: RR = 2.27 (1.14, 4.51). Population attributable fractions (PAFs; i.e., proportion of outcome disease incidence in the total population attributable to specific phobia) were highest for panic disorder (PAF = 22.9), generalized anxiety disorder (PAF = 32.3), and obsessive-compulsive disorders (PAF = 30.2). This study provides strong evidence that specific phobia is an early onset disorder predicting the subsequent onset of a range of disorders. Future studies should examine the underlying mechanisms and the potential of using specific phobia as a target for prevention of subsequent psychopathology. © 2016 Wiley Periodicals, Inc.

The feasibility of a Box isolation strategy for non-paroxysmal atrial fibrillation in elderly patients.

PubMed

Higuchi, Satoshi; Sohara, Hiroshi; Nakamura, Yoshinori; Ihara, Minoru; Yamaguchi, Yoshio; Shoda, Morio; Hagiwara, Nobuhisa; Satake, Shutaro

2016-06-01

Catheter ablation of non-paroxysmal atrial fibrillation (non-PAF) is a therapeutic challenge especially in elderly patients. This study describes the feasibility of a posterior left atrium isolation as a substrate modification in addition to pulmonary vein isolation, the so-called Box isolation, for elderly patients with non-PAF. Two hundred twenty-nine consecutive patients who underwent Box isolations for drug-refractory non-PAF were divided into two groups according to their age; younger group comprising 175 patients aged <75 years and elderly group comprising 54 patients aged ≥75 years. During 23.7±12.0 months of follow-up, the arrhythmia-free rates after one procedure were 53.1% in younger group versus 48.1% in elderly group (p=0.50). Following the second procedure, all patients had electrical conduction recoveries along the initial Box lesion. However, a complete Box re-isolation was highly established in both age groups (87.1% vs. 92.9%, respectively; p=1.00). Recurrence of macro-reentrant atrial tachycardia was mainly associated with the gaps through the initial Box lesion in both age groups (25.8% vs. 21.4%, p=1.00), but typical cavo-tricuspid isthmus (CTI) dependent atrial flutter was significantly observed in the elderly patients' group only (all events were observed within 6 months after the initial procedure; 3.2% vs. 28.6%, p=0.009). After two procedures, the arrhythmia-free rates increased to 73.1% in younger group versus 66.7% in elderly group (p=0.38). The occurrence rate of procedural-related complications did not differ between the two age groups, and there were no life-threatening complications even in elderly patients. Box isolation of non-PAF is effective and safe even in elderly patients. A prophylactic CTI ablation combined with Box isolation might be feasible to improve the long-term outcome.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

Panoramic autofluorescence: highlighting retinal pathology.

PubMed

Slotnick, Samantha; Sherman, Jerome

2012-05-01

Recent technological advances in fundus autofluorescence (FAF) are providing new opportunities for insight into retinal physiology and pathophysiology. FAF provides distinctly different imaging information than standard photography or color separation. A review of the basis for this imaging technology is included to help the clinician understand how to interpret FAF images. Cases are presented to illustrate image interpretation. Optos, which manufactures equipment for simultaneous panoramic imaging, has recently outfitted several units with AF capabilities. Six cases are presented in which panoramic autofluorescent (PAF) images highlight retinal pathology, using Optos' Ultra-Widefield technology. Supportive imaging technologies, such as Optomap® images and spectral domain optical coherence tomography (SD-OCT), are used to assist in the clinical interpretation of retinal pathology detected on PAF. Hypofluorescent regions on FAF are identified to occur along with a disruption in the photoreceptors and/or retinal pigment epithelium, as borne out on SD-OCT. Hyperfluorescent regions on FAF occur at the advancing zones of retinal degeneration, indicating impending damage. PAF enables such inferences to be made in retinal areas which lie beyond the reach of SD-OCT imaging. PAF also enhances clinical pattern recognition over a large area and in comparison with the fellow eye. Symmetric retinal degenerations often occur with genetic conditions, such as retinitis pigmentosa, and may impel the clinician to recommend genetic testing. Autofluorescent ophthalmoscopy is a non-invasive procedure that can detect changes in metabolic activity at the retinal pigment epithelium before clinical ophthalmoscopy. Already, AF is being used as an adjunct technology to fluorescein angiography in cases of age-related macular degeneration. Both hyper- and hypoautofluorescent changes are indicative of pathology. Peripheral retinal abnormalities may precede central retinal impacts, potentially providing early signs for intervention before impacting visual acuity. The panoramic image enhances clinical pattern recognition over a large area and in comparison between eyes. Optos' Ultra-Widefield technology is capable of capturing high-resolution images of the peripheral retina without requiring dilation.

Herd-level risk factors for bovine tuberculosis in French cattle herds.

PubMed

Marsot, Maud; Béral, Marina; Scoizec, Axelle; Mathevon, Yoann; Durand, Benoit; Courcoul, Aurélie

2016-09-01

Although officially free of bovine tuberculosis (bTB), France has been experiencing a slight increase in the incidence and geographical spread of the infection. Eradication of bTB requires determining the infection risk factors. Although several studies identifying bTB risk factors have been conducted in the United Kingdom and Spain, no information is currently available regarding bTB risk factors in French cattle. The objective of this work was thus to study the factors associated with the risk of bTB in cattle herds in three French administrative divisions (départements of Ardennes, Côte d'Or and Dordogne). A case-control study was conducted to compare herds having experienced a bTB outbreak between 2012 and early 2014 with randomly selected control herds of the three study départements. A questionnaire of farming practices, inter-herd contacts (e.g. at pasture or via vehicles or materials), and the presence of other domestic species was carried out in the selected herds. Data on other variables of interest included animal movements between farms and potential contacts between cattle and wildlife (e.g. badger and wild boar abundances) were also collected. Multivariable logistic regression and multimodel inference methods were used to assess risk factors related to bTB. A total of 216 herds (72 cases and 144 controls) were analyzed. The two main risk factors were the presence of a recent neighboring outbreak, being defined as a neighboring herd at pasture reported as infected in the past two years (odds ratio (OR)=3.6; population attributable fraction (PAF)=30.7%) and the presence of a farm building for cattle housing or for feed storage located at more than 300-m from inhabited areas (OR=2.3; PAF=27.6%). Another risk factor was related to sharing water points at pasture with a recent neighboring outbreak. Results illustrated the multifactorial nature of bTB dynamics. The risk factors related to recently infected neighboring herds could be attributable to between-herd contacts at pasture and/or to exposure to a common source of infection (environment or wildlife). Moreover, the use of remote farm buildings by wildlife may also play a role in the bTB spread in the French départements studied. The identification of the main risk factors help better understand bTB dynamics and are useful for implementing appropriate and targeted surveillance, biosecurity and control measures in France. Copyright © 2016 Elsevier B.V. All rights reserved.

Visualization of polarization state and its application in optics classroom teaching

NASA Astrophysics Data System (ADS)

Lei, Bing; Liu, Wei; Shi, Jianhua; Wang, Wei; Yao, Tianfu; Liu, Shugang

2017-08-01

Polarization of light and the related knowledge are key and difficult points in optical teaching, and they are difficult to be understood since they are very abstract concepts. To help students understand the polarization properties of light, some classroom demonstration experiments have been constructed by employing the optical source, polarizers, wave plates optical cage system and polarization axis finder (PAF). The PAF is a polarization indicating device with many linear polarizing components concentric circles, which can visualize the polarization axis's direction of linearly polarized light intuitively. With the help of these demonstration experiment systems, the conversion and difference between the linear polarized light and circularly polarized light have been observed directly by inserting or removing a quarter-wave plate. The rotation phenomenon of linearly polarized light's polarization axis when it propagates through an optical active medium has been observed and studied in experiment, and the strain distribution of some mounted and unmounted lenses have also been demonstrated and observed in experiment conveniently. Furthermore, some typical polarization targets, such as liquid crystal display (LCD), polarized dark glass and skylight, have been observed based on PAF, which is quite suitable to help students understand these targets' polarization properties and the related physical laws. Finally, these demonstration experimental systems have been employed in classroom teaching of our university in physical optics, optoelectronics and photoelectric detection courses, and they are very popular with teachers and students.

Mortality and Burden of Disease Attributable to Cigarette Smoking in Qingdao, China.

PubMed

Wang, Yani; Qi, Fei; Jia, Xiaorong; Lin, Peng; Liu, Hui; Geng, Meiyun; Liu, Yunning; Li, Shanpeng; Tan, Jibin

2016-09-09

In China, smoking is the leading preventable cause of deaths by a disease. Estimating the disease burden attributable to smoking contributes to an evaluation of the adverse impact of smoking. To aid in policy change and implementation, this study estimated the population-attributable fractions (PAFs) of smoking, the all-cause mortality and the loss of life expectancy attributable to smoking in 2014 of Qingdao. PAFs were calculated using the smoking impact ratio (SIR) or current smoking rate (P) and relative risk (RR). We determined the smoking-attributable mortality by multiplying the smoking-attributable fraction by the total mortality. This study used the method of an abridged life table to calculate the loss of life expectancy caused by smoking. Smoking caused about 8635 deaths (6883 males, 1752 females), and accounted for 16% of all deaths; 22% in males and 8% in females. The leading causes of deaths attributable to smoking were lung cancer (38%), ischemic heart disease (19%) and chronic obstructive pulmonary disease (COPD, 12%). The PAF for all causes was 22%; 30% in males and 10% in females. Tobacco use may cause a reduction of about 2.01 years of the loss of life expectancy; 3 years in males and 0.87 years in females. The findings highlight the need for taking effective measures to prevent initiation and induce cessation.

Mortality and Burden of Disease Attributable to Cigarette Smoking in Qingdao, China

PubMed Central

Wang, Yani; Qi, Fei; Jia, Xiaorong; Lin, Peng; Liu, Hui; Geng, Meiyun; Liu, Yunning; Li, Shanpeng; Tan, Jibin

2016-01-01

In China, smoking is the leading preventable cause of deaths by a disease. Estimating the disease burden attributable to smoking contributes to an evaluation of the adverse impact of smoking. To aid in policy change and implementation, this study estimated the population-attributable fractions (PAFs) of smoking, the all-cause mortality and the loss of life expectancy attributable to smoking in 2014 of Qingdao. PAFs were calculated using the smoking impact ratio (SIR) or current smoking rate (P) and relative risk (RR). We determined the smoking-attributable mortality by multiplying the smoking-attributable fraction by the total mortality. This study used the method of an abridged life table to calculate the loss of life expectancy caused by smoking. Smoking caused about 8635 deaths (6883 males, 1752 females), and accounted for 16% of all deaths; 22% in males and 8% in females. The leading causes of deaths attributable to smoking were lung cancer (38%), ischemic heart disease (19%) and chronic obstructive pulmonary disease (COPD, 12%). The PAF for all causes was 22%; 30% in males and 10% in females. Tobacco use may cause a reduction of about 2.01 years of the loss of life expectancy; 3 years in males and 0.87 years in females. The findings highlight the need for taking effective measures to prevent initiation and induce cessation. PMID:27618084

Impact of Catheter Ablation for Paroxysmal Atrial Fibrillation in Patients With Sick Sinus Syndrome　- Important Role of Non-Pulmonary Vein Foci.

PubMed

Hayashi, Kentaro; Fukunaga, Masato; Yamaji, Kyohei; An, Yoshimori; Nagashima, Michio; Hiroshima, Kenichi; Ohe, Masatsugu; Makihara, Yu; Yamashita, Kennosuke; Ando, Kenji; Iwabuchi, Masashi; Goya, Masahiko

2016-01-01

The clinical efficacy of catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) in patients with sick sinus syndrome (SSS) and the mechanism and predictors of recurrence are not yet completely elucidated. Of 963 consecutive patients who underwent PAF ablation during the study period, a total of 108 patients with SSS (SSS group) and 108 matched controls without SSS (non-SSS group) were followed up. During the follow-up period (mean, 32.8±17.5 months), the SSS group had significantly higher AF recurrence rate since the last procedure than the non-SSS group (26.9% vs. 12.0%; P=0.02). The SSS group had significantly higher prevalence of non-pulmonary vein (non-PV) foci than the non-SSS group (25.9% vs. 13.9%; P=0.027). On multivariate analysis congestive heart failure (HR, 13.7; 95% CI: 1.57-119; P=0.02) and non-PV foci (HR, 5.75; 95% CI: 1.69-19.6; P=0.005) were independent predictors of recurrence following CA in the SSS group. In the SSS group, 88 patients had bradycardia-tachycardia syndrome without prior permanent pacemaker implantation. Of these, 6 required pacemaker implantation because of AF and sinus pause recurrence. Patients with SSS are at higher risk of AF recurrence after CA. Non-PV foci are associated with AF recurrence following PAF with SSS.

Size and Cell Number of the Utricle in kinetotically swimming Fish: A parabolic Aircraft Flight Study

NASA Astrophysics Data System (ADS)

Baeuerle, A.; Anken, R.; Baumhauer, N.; Hilbig, R.; Rahmann, H.

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behaviour during PAFs (especially so-called spinning movements and looping responses), and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalisation of gravity in teleosteans) of fish swimming kinetotically during the μg-phases in the course of PAFs in comparison with animals from the same batch who swam normally. On the light microscopical level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100μm -μm), however, was reduced in kinetotic animals (p<0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in asymmetric inner ear otoliths as has been suggested earlier, but also in genetically predispositioned, malformed sensory epithelia. This work was financially supported by the German Aerospace Center (DLR) e.V. (FKZ: 50 WB 9997).

Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

PubMed Central

Fernandez, Christian A.; Smith, Colton; Karol, Seth E.; Ramsey, Laura B.; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E.; Finkelman, Fred D.

2015-01-01

A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10−13) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10−3) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10−5). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10−4). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell–derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity. PMID:25573198

The pressor response to water drinking in humans : a sympathetic reflex?

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Black, B. K.; Ali, Y.; Farley, M.; Costa, F.; Diedrich, A.; Robertson, R. M.; Biaggioni, I.; Robertson, D.

2000-01-01

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

PubMed

Uhlig, S; Nüsing, R; von Bethmann, A; Featherstone, R L; Klein, T; Brasch, F; Müller, K M; Ullrich, V; Wendel, A

1996-05-01

Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1.

Pharmacological modulation of lipopolysaccharide-induced pleural eosinophilia in the rat; a role for a newly generated protein.

PubMed

Bozza, P T; Castro-Faria-Neto, H C; Martins, M A; Larangeira, A P; Perales, J E; e Silva, P M; Cordeiro, R S

1993-06-01

Intrathoracic injection of endotoxin lipopolysaccharide, LPS into rats induced a dose-dependent increase in the number of eosinophils recovered from the pleural cavity. The pleural eosinophil accumulation peaked within 24-48 h, and returned to basal levels within 120 h. This phenomenon was accompanied by mononuclear cell infiltration, and preceded by massive neutrophil accumulation. Pretreatment with indomethacin, BW 755C (a dual cyclo/lipoxygenase inhibitor), BW A4C (a specific lipoxygenase inhibitor) or the platelet activating factor (PAF) antagonists WEB 2086 and PCA 4248 failed to inhibit the endotoxin-induced pleural eosinophilia, whilst dexamethasone (5-10 micrograms/cavity) or cycloheximide (14-28 micrograms/cavity) abolished this phenomenon. Transfer of the cell-free pleural washing from LPS-treated donor rats to normal recipient rats led to a two-fold increase in the eosinophil counts. Treatment of donors, but not recipients, with cycloheximide or dexamethasone inhibited the eosinophil accumulation induced by the pleural washings, indicating that the generation of the eosinophilotactic activity, but not its effects, depends on protein synthesis. This eosinophilotactic activity was maintained after lyophilization and heating (100 degrees C for 30 min), but was destroyed by trypsin. This substance has a molecular weight ranging between 10 and 50 kDa. The available data suggest that the late eosinophil accumulation induced by LPS is independent of arachidonic acid metabolites and PAF, and probably depends on a newly generated heat-stable soluble protein.

Importance of anticoagulation and postablation silent cerebral lesions: Subanalyses of REVOLUTION and reMARQable studies.

PubMed

Grimaldi, Massimo; Swarup, Vijay; DeVille, Brian; Sussman, Jonathan; Jaïs, Pierre; Gaita, Fiorenzo; Duytschaever, Mattias; Ng, G Andre; Daoud, Emile; Lakkireddy, Dhanunjaya Dj; Horton, Rodney; Wickliffe, Andrew; Ellis, Christopher; Geller, Laszlo

2017-12-01

Silent cerebral lesions (SCLs) are a potential complication of left atrial radiofrequency ablation (RFA) procedures for paroxysmal atrial fibrillation (PAF). We aimed to compare the incidence of SCLs in patients treated with irrigated RFA multielectrode catheters (nMARQ ® Catheter group) and irrigated focal RFA catheters (NAVISTAR ® THERMOCOOL ® Catheter; TC group) after PAF ablation from subpopulation neurological assessment (SNA) cohorts of the REVOLUTION and reMARQable studies. Data from SNA cohorts in the prospective, nonrandomized REVOLUTION study (March 2011-September 2013) and the prospective, randomized, controlled reMARQable study (October 2013-November 2015) were included. The incidence of SCLs was assessed pre- and postablation using magnetic resonance imaging. Neurological deficits were assessed using the National Institutes of Health Stroke Scale, modified Rankin Scale, and Montreal Cognitive Assessment. A total of 37 patients from REVOLUTION and 76 patients from reMARQable were included in the SNA cohort of each study. In the REVOLUTION SNA cohort, the incidence of SCLs was 21.1% (4/19) in the nMARQ ® Catheter group and 5.9% (1/17) in the TC group. Findings from REVOLUTION helped inform the reMARQable study protocol's stringent anticoagulation regimen. SCL incidence was subsequently reduced in both groups (nMARQ ® Catheter, 7.9%; TC, 3.3%). No permanent neurological deficits were observed. Adherence to a stringent anticoagulation regimen prior to and during ablation procedures appears to be an important factor in minimizing the risk of SCL. © 2017 Wiley Periodicals, Inc.

Examining parents' ratings of middle-school students' academic self-regulation using principal axis factoring analysis.

PubMed

Chen, Peggy P; Cleary, Timothy J; Lui, Angela M

2015-09-01

This study examined the reliability and validity of a parent rating scale, the Self-Regulation Strategy Inventory: Parent Rating Scale (SRSI-PRS), using a sample of 451 parents of sixth- and seventh-grade middle-school students. Principal axis factoring (PAF) analysis revealed a 3-factor structure for the 23-item SRSI-PRS: (a) Managing Behavior and Learning (α = .92), (b) Maladaptive Regulatory Behaviors (α = .76), and (c) Managing Environment (α = .84). The majority of the observed relations between these 3 subscales, and the SRSI-SR, student motivation beliefs, and student mathematics grades were statistically significant and in the small to medium range. After controlling for various student variables and motivation indices of parental involvement, 2 SRSI-PRS factors (Managing Behavior and Learning, Maladaptive Regulatory Behaviors) reliably predicted students' achievement in their mathematics course. This study provides initial support for the validity and reliability of the SRSI-PRS and underscores the advantages of obtaining parental ratings of students' SRL behaviors. (c) 2015 APA, all rights reserved).

Status report of the end-to-end ASKAP software system: towards early science operations

NASA Astrophysics Data System (ADS)

Guzman, Juan Carlos; Chapman, Jessica; Marquarding, Malte; Whiting, Matthew

2016-08-01

The Australian SKA Pathfinder (ASKAP) is a novel centimetre radio synthesis telescope currently in the commissioning phase and located in the midwest region of Western Australia. It comprises of 36 x 12 m diameter reflector antennas each equipped with state-of-the-art and award winning Phased Array Feeds (PAF) technology. The PAFs provide a wide, 30 square degree field-of-view by forming up to 36 separate dual-polarisation beams at once. This results in a high data rate: 70 TB of correlated visibilities in an 8-hour observation, requiring custom-written, high-performance software running in dedicated High Performance Computing (HPC) facilities. The first six antennas equipped with first-generation PAF technology (Mark I), named the Boolardy Engineering Test Array (BETA) have been in use since 2014 as a platform to test PAF calibration and imaging techniques, and along the way it has been producing some great science results. Commissioning of the ASKAP Array Release 1, that is the first six antennas with second-generation PAFs (Mark II) is currently under way. An integral part of the instrument is the Central Processor platform hosted at the Pawsey Supercomputing Centre in Perth, which executes custom-written software pipelines, designed specifically to meet the ASKAP imaging requirements of wide field of view and high dynamic range. There are three key hardware components of the Central Processor: The ingest nodes (16 x node cluster), the fast temporary storage (1 PB Lustre file system) and the processing supercomputer (200 TFlop system). This High-Performance Computing (HPC) platform is managed and supported by the Pawsey support team. Due to the limited amount of data generated by BETA and the first ASKAP Array Release, the Central Processor platform has been running in a more "traditional" or user-interactive mode. But this is about to change: integration and verification of the online ingest pipeline starts in early 2016, which is required to support the full 300 MHz bandwidth for Array Release 1; followed by the deployment of the real-time data processing components. In addition to the Central Processor, the first production release of the CSIRO ASKAP Science Data Archive (CASDA) has also been deployed in one of the Pawsey Supercomputing Centre facilities and it is integrated to the end-to-end ASKAP data flow system. This paper describes the current status of the "end-to-end" data flow software system from preparing observations to data acquisition, processing and archiving; and the challenges of integrating an HPC facility as a key part of the instrument. It also shares some lessons learned since the start of integration activities and the challenges ahead in preparation for the start of the Early Science program.

SU-D-19A-05: The Dosimetric Impact of Using Xoft Axxent® Electronic Brachytherapy Source TG-43 Dosimetry Parameters for Treatment with the Xoft 30 Mm Diameter Vaginal Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simiele, S; Micka, J; Culberson, W

2014-06-01

Purpose: A full TG-43 dosimetric characterization has not been performed for the Xoft Axxent ® electronic brachytherapy source (Xoft, a subsidiary of iCAD, San Jose, CA) within the Xoft 30 mm diameter vaginal applicator. Currently, dose calculations are performed using the bare-source TG-43 parameters and do not account for the presence of the applicator. This work focuses on determining the difference between the bare-source and sourcein- applicator TG-43 parameters. Both the radial dose function (RDF) and polar anisotropy function (PAF) were computationally determined for the source-in-applicator and bare-source models to determine the impact of using the bare-source dosimetry data. Methods:more » MCNP5 was used to model the source and the Xoft 30 mm diameter vaginal applicator. All simulations were performed using 0.84p and 0.03e cross section libraries. All models were developed based on specifications provided by Xoft. The applicator is made of a proprietary polymer material and simulations were performed using the most conservative chemical composition. An F6 collision-kerma tally was used to determine the RDF and PAF values in water at various dwell positions. The RDF values were normalized to 2.0 cm from the source to accommodate the applicator radius. Source-in-applicator results were compared with bare-source results from this work as well as published baresource results. Results: For a 0 mm source pullback distance, the updated bare-source model and source-in-applicator RDF values differ by 2% at 3 cm and 4% at 5 cm. The largest PAF disagreements were observed at the distal end of the source and applicator with up to 17% disagreement at 2 cm and 8% at 8 cm. The bare-source model had RDF values within 2.6% of the published TG-43 data and PAF results within 7.2% at 2 cm. Conclusion: Results indicate that notable differences exist between the bare-source and source-in-applicator TG-43 simulated parameters. Xoft Inc. provided partial funding for this work.« less

Characterization of airway and vascular responses in murine lungs

PubMed Central

Held, Heinz-Dieter; Martin, Christian; Uhlig, Stefan

1999-01-01

We characterized the responses of murine airways and pulmonary vessels to a variety of endogenous mediators in the isolated perfused and ventilated mouse lung (IPL) and compared them with those in precision-cut lung slices. Airways: The EC50 (μM) for contractions of airways in IPL/slices was methacholine (Mch), 6.1/1.5>serotonin, 0.7/2.0>U46619 (TP-receptor agonist), 0.1/0.06>endothelin-1, 0.1/0.05. In the IPL, maximum increase in airway resistance (RL) was 0.6, 0.4, 0.8 and 11 cmH2O s ml−1, respectively. Adenosine (⩽1 mM), bombesin (⩽100 μM), histamine (⩽10 mM), LTC4 (⩽1 μM), PAF (0.25 μM) and substance P (⩽100 μM) had only weak effects (<5% of Mch) on RL. Vessels: The EC50 (μM) for vasoconstriction in the IPL was LTC4, 0.06>U46619, 0.05

Disease burden due to biomass cooking-fuel-related household air pollution among women in India

PubMed Central

Sehgal, Meena; Rizwan, Suliankatchi Abdulkader; Krishnan, Anand

2014-01-01

Background Household air pollution (HAP) due to biomass cooking fuel use is an important risk factor for a range of diseases, especially among adult women who are primary cooks, in India. About 80% of rural households in India use biomass fuel for cooking. The aim of this study is to estimate the attributable cases (AC) for four major diseases/conditions associated with biomass cooking fuel use among adult Indian women. Methods We used the population attributable fraction (PAF) method to calculate the AC of chronic bronchitis, tuberculosis (TB), cataract, and stillbirths due to exposure to biomass cooking fuel. A number of data sources were accessed to obtain population totals and disease prevalence rates. A meta-analysis was conducted to obtain adjusted pooled odds ratios (ORs) for strength of association. Using this, PAF and AC were calculated using a standard formula. Results were presented as number of AC and 95% confidence intervals (CI). Results The fixed effects pooled OR obtained from the meta-analysis were 2.37 (95% CI: 1.59, 3.54) for chronic bronchitis, 2.33 (1.65, 3.28) for TB, 2.16 (1.42, 3.26) for cataract, and 1.26 (1.12, 1.43) for stillbirths. PAF varied across conditions being maximum (53%) for chronic bronchitis in rural areas and least (1%) for cataract in older age and urban areas. About 2.4 (95% CI: 1.4, 3.1) of 5.6 m cases of chronic bronchitis, 0.3 (0.2, 0.4) of 0.76 m cases of TB, 5.0 (2.8, 6.7) of 51.4 m cases of cataract among adult Indian women and 0.02 (0.01, 0.03) of 0.15 m stillbirths across India are attributable to HAP due to biomass cooking fuel. These estimates should be cautiously interpreted in the light of limitations discussed which relate to exposure assessment, exposure characterization, and age-specific prevalence of disease. Conclusions HAP due to biomass fuel has diverse and major impacts on women’s health in India. Although challenging, incorporating the agenda of universal clean fuel access or cleaner technology within the broader framework of rural development will go a long way in reducing disease burden. PMID:25373414

Public health importance of triggers of myocardial infarction: a comparative risk assessment.

PubMed

Nawrot, Tim S; Perez, Laura; Künzli, Nino; Munters, Elke; Nemery, Benoit

2011-02-26

Acute myocardial infarction is triggered by various factors, such as physical exertion, stressful events, heavy meals, or increases in air pollution. However, the importance and relevance of each trigger are uncertain. We compared triggers of myocardial infarction at an individual and population level. We searched PubMed and the Web of Science citation databases to identify studies of triggers of non-fatal myocardial infarction to calculate population attributable fractions (PAF). When feasible, we did a meta-regression analysis for studies of the same trigger. Of the epidemiologic studies reviewed, 36 provided sufficient details to be considered. In the studied populations, the exposure prevalence for triggers in the relevant control time window ranged from 0.04% for cocaine use to 100% for air pollution. The reported odds ratios (OR) ranged from 1.05 to 23.7. Ranking triggers from the highest to the lowest OR resulted in the following order: use of cocaine, heavy meal, smoking of marijuana, negative emotions, physical exertion, positive emotions, anger, sexual activity, traffic exposure, respiratory infections, coffee consumption, air pollution (based on a difference of 30 μg/m3 in particulate matter with a diameter <10 μm [PM10]). Taking into account the OR and the prevalences of exposure, the highest PAF was estimated for traffic exposure (7.4%), followed by physical exertion (6.2%), alcohol (5.0%), coffee (5.0%), a difference of 30 μg/m3 in PM10 (4.8%), negative emotions (3.9%), anger (3.1%), heavy meal (2.7%), positive emotions (2.4%), sexual activity (2.2%), cocaine use (0.9%), marijuana smoking (0.8%) and respiratory infections (0.6%). Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of myocardial infarction, it is of similar magnitude (PAF 5-7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance. The research on air pollution and health at Hasselt University is supported by a grant from the Flemish Scientific Fund (FWO, Krediet aan navorsers/G.0873.11), tUL-impulse financing, and bijzonder onderzoeksfonds (BOF) and at the Katholieke Universiteit Leuven by the sustainable development programme of BELSPO (Belgian Science Policy).

Including impacts of particulate emissions on marine ecosystems in life cycle assessment: the case of offshore oil and gas production.

PubMed

Veltman, Karin; Huijbregts, Mark A J; Rye, Henrik; Hertwich, Edgar G

2011-10-01

Life cycle assessment is increasingly used to assess the environmental performance of fossil energy systems. Two of the dominant emissions of offshore oil and gas production to the marine environment are the discharge of produced water and drilling waste. Although environmental impacts of produced water are predominantly due to chemical stressors, a major concern regarding drilling waste discharge is the potential physical impact due to particles. At present, impact indicators for particulate emissions are not yet available in life cycle assessment. Here, we develop characterization factors for 2 distinct impacts of particulate emissions: an increased turbidity zone in the water column and physical burial of benthic communities. The characterization factor for turbidity is developed analogous to characterization factors for toxic impacts, and ranges from 1.4 PAF (potentially affected fraction) · m(3) /d/kg(p) (kilogram particulate) to 7.0 x 10³ [corrected] for drilling mud particles discharged from the rig. The characterization factor for burial describes the volume of sediment that is impacted by particle deposition on the seafloor and equals 2.0 × 10(-1) PAF · m(3) /d/kg(p) for cutting particles. This characterization factor is quantified on the basis of initial deposition layer characteristics, such as height and surface area, the initial benthic response, and the recovery rate. We assessed the relevance of including particulate emissions in an impact assessment of offshore oil and gas production. Accordingly, the total impact on the water column and on the sediment was quantified based on emission data of produced water and drilling waste for all oil and gas fields on the Norwegian continental shelf in 2008. Our results show that cutting particles contribute substantially to the total impact of offshore oil and gas production on marine sediments, with a relative contribution of 55% and 31% on the regional and global scale, respectively. In contrast, the contribution of particulate emissions to the total impact on the marine water column is of minor importance. We conclude that particles are an important stressor in marine ecosystems, particularly for marine sediment, and particulate emissions should therefore be included in a (life cycle) impact assessment of offshore oil and gas production. Copyright © 2011 SETAC.

Family psychosocial characteristics influencing criminal behaviour and mortality--possible mediating factors: a longitudinal study of male and female subjects in the Stockholm Birth Cohort.

PubMed

af Klinteberg, Britt; Almquist, Ylva; Beijer, Ulla; Rydelius, Per-Anders

2011-10-02

Family psychosocial characteristics in childhood have been associated with children's development into criminal behaviour and mortality. This study explored these possible relationships and examined alcohol and/or drug use and mental problems as possible mediating factors, highlighting gender-specific patterns. Data from Swedish subjects born in 1953 (n = 14,294) from the Stockholm Birth Cohort study were examined. Several indicators of adverse family factors and individual problems were included in the present study. The information was derived from various data sources, covering different periods. Gender-specific associations with incidence of criminality (1966-1980) and mortality (1981-2009) were analysed using logistic regression. Furthermore, the population attributable fraction (PAF) was calculated for all variables in the fully adjusted models which were positively related to the outcome. Overall incidence of criminality and mortality was (m/f 32.3/6.6) and (m/f 6.1/3.5), respectively. The results showed that all aspects of family psychosocial and individual problems studied were associated with criminality for both genders. Among males, individual problems seemed to partly mediate these relations, but the associations remained statistically significant. Interestingly, the PAF analysis revealed a reduction in criminality of 17.5% when individual problems with alcohol and/or drug use were considered. Among females, a significant impact of alcohol and/or drug use on the association between family psychosocial characteristics and subsequent criminality was obtained. Inclusion of father's occupational class only somewhat reduced the estimates for the genders. Concerning male mortality, father's alcohol abuse was significantly related to an increased risk. When individual criminality was accounted for, the association was substantially reduced but remained statistically significant. Among females, when adjusting for family psychosocial factors, only the association between parents' mental problems and females' mortality was significant. None of the individual problem variables managed to explain this association. Family psychosocial characteristics were associated with both subsequent criminal behaviour and mortality. These connections were partly explained by individual risk factors, especially by alcohol and/or drug use. The practical implications of the findings point to the importance of addressing the individual's alcohol and/or drug use in reducing criminal behaviour, which would also lower the mortality rates.

Family psychosocial characteristics influencing criminal behaviour and mortality - possible mediating factors: a longitudinal study of male and female subjects in the Stockholm Birth Cohort

PubMed Central

2011-01-01

Background Family psychosocial characteristics in childhood have been associated with children's development into criminal behaviour and mortality. This study explored these possible relationships and examined alcohol and/or drug use and mental problems as possible mediating factors, highlighting gender-specific patterns. Methods Data from Swedish subjects born in 1953 (n = 14,294) from the Stockholm Birth Cohort study were examined. Several indicators of adverse family factors and individual problems were included in the present study. The information was derived from various data sources, covering different periods. Gender-specific associations with incidence of criminality (1966-1980) and mortality (1981-2009) were analysed using logistic regression. Furthermore, the population attributable fraction (PAF) was calculated for all variables in the fully adjusted models which were positively related to the outcome. Results Overall incidence of criminality and mortality was (m/f 32.3/6.6) and (m/f 6.1/3.5), respectively. The results showed that all aspects of family psychosocial and individual problems studied were associated with criminality for both genders. Among males, individual problems seemed to partly mediate these relations, but the associations remained statistically significant. Interestingly, the PAF analysis revealed a reduction in criminality of 17.5% when individual problems with alcohol and/or drug use were considered. Among females, a significant impact of alcohol and/or drug use on the association between family psychosocial characteristics and subsequent criminality was obtained. Inclusion of father's occupational class only somewhat reduced the estimates for the genders. Concerning male mortality, father's alcohol abuse was significantly related to an increased risk. When individual criminality was accounted for, the association was substantially reduced but remained statistically significant. Among females, when adjusting for family psychosocial factors, only the association between parents' mental problems and females' mortality was significant. None of the individual problem variables managed to explain this association. Conclusions Family psychosocial characteristics were associated with both subsequent criminal behaviour and mortality. These connections were partly explained by individual risk factors, especially by alcohol and/or drug use. The practical implications of the findings point to the importance of addressing the individual's alcohol and/or drug use in reducing criminal behaviour, which would also lower the mortality rates. PMID:21962152

An In Silico Model of Endotoxic Shock Mediators (Briefing Charts)

DTIC Science & Technology

2012-03-12

complex probably because receptor activates multiple signaling pathways choline P O acetyl...calcium mobilization phospholipase C phospholipase D phospholipase A2 eicosanoids inositol metabolism protein kinase C COOH NH2 PAF

Safety and Efficacy of Cryoballoon Ablation for Paroxysmal Atrial Fibrillation in Japan　- Results From the Japanese Prospective Post-Market Surveillance Study.

PubMed

Okumura, Ken; Matsumoto, Kazuo; Kobayashi, Yoshinori; Nogami, Akihiko; Hokanson, Robert B; Kueffer, Fred

2016-07-25

Outcomes of cryoballoon ablation for paroxysmal atrial fibrillation (PAF) have been reported in the Western countries but not in Japan. The CRYO-Japan PMS study was a single-arm, observational, multicenter, prospective study of the 2nd-generation cryoballoon Arctic Front Advance(TM). We evaluated device- and procedure-related complications and clinical outcomes at 6 months. The 616 patients (male, 72%; mean age, 63±11 years) were enrolled from 33 Japanese hospitals. Of all patients, 610 had PAF, and procedural data were analyzed in 607. A subset of 328 patients was followed for 6 months for the primary efficacy analysis. AF recurrence outside the 3-month blanking period or repeat ablation was considered treatment failure. Pulmonary vein isolation was achieved in 606/607 patients (99.8%); 1 patient (0.3%) had a repeat ablation during the blanking period. Freedom from AF at 6 months was 88.4% (95% CI: 84.1-91.6%). Device- and/or procedure-related adverse events included phrenic nerve injury unresolved at hospital discharge in 9/616 patients (1.5%), which resolved within 6 months in 7, pericardial effusion in 5/616 (0.8%), and tamponade in 4/616 (0.6%). One non-device-related death from pneumonia was reported 6 days post-procedure. Cryoballoon ablation is safe and effective for Japanese PAF patients, with 88.4% AF freedom at 6 months post-ablation. (Circ J 2016; 80: 1744-1749).

Identification of exopolysaccharides produced by fluorescent pseudomonads associated with commercial mushroom (Agaricus bisporus) production.

PubMed

Fett, W F; Wells, J M; Cescutti, P; Wijey, C

1995-02-01

The acidic exopolysaccharides (EPSs) from 63 strains of mushroom production-associated fluorescent pseudomonads which were mucoid on Pseudomonas agar F medium (PAF) were isolated, partially purified, and characterized. The strains were originally isolated from discolored lesion which developed postharvest on mushroom (Agaricus bisporus) caps or from commercial lots of mushroom casing medium. An acidic galactoglucan, previously named marginalan, was produced by mucoid strains of the saprophyte Pseudomonas putida and the majority of mucoid strains of saprophytic P. fluorescens (biovars III and V) isolated from casing medium. One biovar II strain (J1) of P. fluorescens produced alginate, a copolymer of mannuronic and guluronic acids, and one strain (H13) produced an apparently unique EPS containing neutral and amino sugars. Of 10 strains of the pathogen "P. gingeri," the causal agent of mushroom ginger blotch, 8 gave mucoid growth on PAF. The "P. gingeri" EPS also was unique in containing both neutral sugar and glucuronic acid. Mucoid, weakly virulent strains of "P. reactans" produced either alginate or marginalan. All 10 strains of the pathogen P. tolaasii, the causal agent of brown blotch of mushrooms were nonnmucoid on PAF. Production of EPS by these 10 strains plus the 2 nonmucoid strains of "P. gingeri" also was negative on several additional solid media as well as in two broth media tested. The results support our previous studies indicating that fluorescent pseudomonads are a rich source of novel EPSs.

Effects of cardiorespiratory fitness and weight status on knowledge of physical activity and fitness, attitude toward physical education, and physical activity.

PubMed

Chen, Senlin; Gu, Xiangli

2018-02-20

The purpose of this study was to examine the effects of cardiorespiratory fitness and weight status on knowledge of physical activity and fitness (PAF knowledge), attitude toward physical education (PE), and physical activity. A total of 343 middle school students participated in the study (Age: M/SD = 12.76/.94, ranging from 11 to 14 years old). PE Metrics™ was used to measure PAF knowledge, and Attitude toward Physical Education Questionnaire and Youth Activity Profile were used to measure attitude, physical activity and sedentary behavior. Fitness and weight status were assessed using FitnessGram and converted to in Healthy Fitness Zone (HFZ) or Not in HFZ. Two-way multivariate analyses of covariance (MANCOVA; gender and grade as covariates) showed a significant group effect for cardiorespiratory fitness (Λ Pilla  = .07, F 4,255  = 5.03, p = .001, [Formula: see text] = .07) but not for weight status (p = .57). PAF knowledge (F 1,258  = 9.49, p < .01, [Formula: see text]= .04), attitude (F 1,258  = 4.45, p < .05, [Formula: see text]= .02) and sedentary behavior (F 1,258  = 6.89, p < .01, [Formula: see text]= .03) all favored the HFZ group. The findings reinforce the importance of promoting cardiorespiratory fitness in middle school PE as students acquire attitude, knowledge, and behaviors needed for active-living.

Identification of exopolysaccharides produced by fluorescent pseudomonads associated with commercial mushroom (Agaricus bisporus) production.

PubMed Central

Fett, W F; Wells, J M; Cescutti, P; Wijey, C

1995-01-01

The acidic exopolysaccharides (EPSs) from 63 strains of mushroom production-associated fluorescent pseudomonads which were mucoid on Pseudomonas agar F medium (PAF) were isolated, partially purified, and characterized. The strains were originally isolated from discolored lesion which developed postharvest on mushroom (Agaricus bisporus) caps or from commercial lots of mushroom casing medium. An acidic galactoglucan, previously named marginalan, was produced by mucoid strains of the saprophyte Pseudomonas putida and the majority of mucoid strains of saprophytic P. fluorescens (biovars III and V) isolated from casing medium. One biovar II strain (J1) of P. fluorescens produced alginate, a copolymer of mannuronic and guluronic acids, and one strain (H13) produced an apparently unique EPS containing neutral and amino sugars. Of 10 strains of the pathogen "P. gingeri," the causal agent of mushroom ginger blotch, 8 gave mucoid growth on PAF. The "P. gingeri" EPS also was unique in containing both neutral sugar and glucuronic acid. Mucoid, weakly virulent strains of "P. reactans" produced either alginate or marginalan. All 10 strains of the pathogen P. tolaasii, the causal agent of brown blotch of mushrooms were nonnmucoid on PAF. Production of EPS by these 10 strains plus the 2 nonmucoid strains of "P. gingeri" also was negative on several additional solid media as well as in two broth media tested. The results support our previous studies indicating that fluorescent pseudomonads are a rich source of novel EPSs. PMID:7574589

[Regulatory mechanisms in focal cerebral ischemia. New possibilities in neuroprotective therapy].

PubMed

Nagy, Zoltán; Simon, László; Bori, Zoltán

2002-03-20

Permanent or temporary disruption of cerebral blood flow rapidly depletes brain regions of their limited energy reserves (glycogen, glucose, oxygen, ATP) leading to an energy crisis. Tissue damage occurs due to the energy crisis. The central part of the damage, the ischaemic "core" region is surrounded by zones of the shell-like penumbra. Necrotic, as well as apoptotic cell death could be identified in the penumbra. Going away from the ischaemic core different neurochemical processes are occurring by space and time. "Immediate early response" genes (c-fos, fos-B, c-Jun, krox 20, 24) are activated, heatshock proteins (hsp 70, 72, HSF, HSE, HIF), cytokines (TNF-alpha, IL-1 beta), inflammatory factors (COX), adhesion and glial factors (ICAM-1, ELAM-1, P-selectin), vasoactive factors (IL-6, -10, PAF), reactive oxigen radicals and connected factors (O2, OH, NO, NOS, SOD) are produced within minutes and hours. Cell deaths, necrosis and apoptosis due to the activation of calpains, caspases and nucleases occur in days. In parallel, growth factors and plasticity proteins (BDNF, NGF, TGF-beta, VEGF, PDGF, GAP-43) are activated as a basis of functional rehabilitation.

[Giving up the tobacco habit through the application of the Smoker's Aid Program in the Chantrea Health Centre].

PubMed

Nuin, M A; Fuertes, C; Ancizu, P; Espelosín, G; Royo, C; Sarasa, I

1997-01-01

This is a prospective descriptive study of intervention without aleatory assignation, carried out in the Chantrea Health Centre. Its aim is to determine the characteristics of the smokers who are taking part in two interventions by the Smokers' Aid Program (Programa de Ayuda al Fumador-PAF), and to evaluate the factors that influence the latter's success. The characteristics of 100 smokers were analyzed. They were offered one of the two PAF interventions: Minimal Intervention 1 (MN1): they are given a support brochure in the first consultations, contacted by telephone after one month and called to consultation after 6 months to measure CO. Minimal Intervention 2 (MN2): the smoker makes 5 consultations of support in giving up smoking (+ or - nicotine patches) with the doctor, nurse or social worker indiscriminately. The factors that were influential in abandoning the habit with 65 subjects were evaluated. 60% of the subjects were male with an average age of 41 (DE 29). 29% showed a pathology related to tobacco, with no relation found between this and the success of the interventions. Those who chose MN2 (38%) had started tobacco consumption at an earlier age and were more dependent on nicotine. Of the 65 smokers who completed the program, 37% continued not to smoke after 6 months. Those who managed to give up smoking were of a greater average age, had spent more years smoking and belonged above all to the MN1 intervention. Notable successes are achieved if the actions are carried out by the First Aid Team. We find no significant differences between the characteristics of those who give up smoking and those who do not. Not even a serious pathology, related to tobacco, is predictive of success. The smoker's dependence on nicotine must be taken into account in the intervention.

Acute Lower Respiratory Infection in Childhood and Household Fuel Use in Bhaktapur, Nepal

PubMed Central

Bates, Michael N.; Chandyo, Ram K.; Valentiner-Branth, Palle; Pokhrel, Amod K.; Mathisen, Maria; Basnet, Sudha; Shrestha, Prakash S.; Strand, Tor A.

2013-01-01

Background: Globally, solid fuels are used by about 3 billion people for cooking. These fuels have been associated with many health effects, including acute lower respiratory infection (ALRI) in young children. Nepal has a high prevalence of use of biomass for cooking and heating. Objective: This case–control study was conducted among a population in the Bhaktapur municipality, Nepal, to investigate the relationship of cookfuel type to ALRI in young children. Methods: Cases with ALRI and age-matched controls were enrolled from an open cohort of children 2–35 months old, under active monthly surveillance for ALRI. A questionnaire was used to obtain information on family characteristics, including household cooking and heating appliances and fuels. The main analysis was carried out using conditional logistic regression. Population-attributable fractions (PAF) for stove types were calculated. Results: A total of 917 children (452 cases and 465 controls) were recruited into the study. Relative to use of electricity for cooking, ALRI was increased in association with any use of biomass stoves [odds ratio (OR) = 1.93; 95% CI: 1.24, 2.98], kerosene stoves (OR = 1.87; 95% CI: 1.24, 2.83), and gas stoves (OR = 1.62; 95% CI: 1.05, 2.50). Use of wood, kerosene, or coal heating was also associated with ALRI (OR = 1.45; 95% CI: 0.97, 2.14), compared with no heating or electricity or gas heating. PAFs for ALRI were 18.0% (95% CI: 8.1, 26.9%) and 18.7% (95% CI: 8.4%–27.8%), for biomass and kerosene stoves, respectively. Conclusions: The study supports previous reports indicating that use of biomass as a household fuel is a risk factor for ALRI, and provides new evidence that use of kerosene for cooking may also be a risk factor for ALRI in young children. PMID:23512278

Lung inflammatory response syndrome after cardiac-operations and treatment of lornoxicam

PubMed Central

Tsakiridis, Kosmas; Mpakas, Andreas; Kesisis, George; Arikas, Stamatis; Argyriou, Michael; Siminelakis, Stavros; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Tsiouda, Theodora; Sarika, Eirini; Katamoutou, Ioanna; Zarogoulidis, Konstantinos

2014-01-01

The majority of patients survive after extracorporeal circulation without any clinically apparent deleterious effects. However, disturbances exist in various degrees sometimes, which indicate the harmful effects of cardiopulmonary bypass (CPB) in the body. Several factors during extracorporeal circulation either mechanical dependent (exposure of blood to non-biological area) or mechanical independent (surgical wounds, ischemia and reperfusion, alteration in body temperature, release of endotoxins) have been shown to trigger the inflammatory reaction of the body. The complement activation, the release of cytokines, the leukocyte activation and accumulation as well as the production of several “mediators” such as oxygen free radicals, metabolites of arachidonic acid, platelet activating factors (PAF), nitric acid, and endothelin. The investigation continues today on the three metabolites of lornoxicam (the hydroxylated metabolite and two other metabolites of unknown chemical composition) to search for potential new pharmacological properties and activities. PMID:24672703

Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montrucchio, G.; Alloatti, G.; Mariano, F.

1990-07-01

This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the firstmore » minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion.« less

Child Abuse Experiences and Perceived Need for Care and Mental Health Service Use among Members of the Canadian Armed Forces

PubMed Central

Turner, Sarah; Taillieu, Tamara; Cheung, Kristene; Zamorski, Mark; Boulos, David; Sareen, Jitender

2017-01-01

Objective: Child abuse is associated with poor mental health outcomes in adulthood. However, little is known about how a history of child abuse may be related to perceived need for care (PNC) and mental health service use (MHSU) among Canadian military personnel. The objectives of this study were to determine 1) the relationship between child abuse history and PNC and 2) the relationship between child abuse history and MHSU in the Canadian military. Method: Data were drawn from the 2013 Canadian Forces Mental Health Survey (n = 6692 Regular Force personnel between the ages of 18 and 60 years). Logistic regression was used to examine the relationships between individual child abuse types and PNC and MHSU while adjusting for sociodemographic variables, the presence of mental disorders, deployment-related variables, and other types of child abuse. Population attributable fractions (PAFs) were calculated to estimate the proportion of PNC and MHSU that may be attributable to child abuse. Results: Each individual child abuse type was associated with increased odds of PNC and MHSU after adjusting for all covariates (adjusted odds ratio ranging from 1.26 to 1.80). PAFs showed that if any child abuse did not occur, PNC and MHSU among Regular Force personnel may be reduced by approximately 14.3% and 11.3%, respectively. Conclusions: This study highlights that preenlistment factors, such as a history of child abuse, have an independent association with PNC and MHSU and hence need to be considered when assessing the mental health service needs of the Canadian Regular Force personnel. PMID:28562093

Child Abuse Experiences and Perceived Need for Care and Mental Health Service Use among Members of the Canadian Armed Forces.

PubMed

Turner, Sarah; Taillieu, Tamara; Cheung, Kristene; Zamorski, Mark; Boulos, David; Sareen, Jitender; Afifi, Tracie O

2017-06-01

Child abuse is associated with poor mental health outcomes in adulthood. However, little is known about how a history of child abuse may be related to perceived need for care (PNC) and mental health service use (MHSU) among Canadian military personnel. The objectives of this study were to determine 1) the relationship between child abuse history and PNC and 2) the relationship between child abuse history and MHSU in the Canadian military. Data were drawn from the 2013 Canadian Forces Mental Health Survey ( n = 6692 Regular Force personnel between the ages of 18 and 60 years). Logistic regression was used to examine the relationships between individual child abuse types and PNC and MHSU while adjusting for sociodemographic variables, the presence of mental disorders, deployment-related variables, and other types of child abuse. Population attributable fractions (PAFs) were calculated to estimate the proportion of PNC and MHSU that may be attributable to child abuse. Each individual child abuse type was associated with increased odds of PNC and MHSU after adjusting for all covariates (adjusted odds ratio ranging from 1.26 to 1.80). PAFs showed that if any child abuse did not occur, PNC and MHSU among Regular Force personnel may be reduced by approximately 14.3% and 11.3%, respectively. This study highlights that preenlistment factors, such as a history of child abuse, have an independent association with PNC and MHSU and hence need to be considered when assessing the mental health service needs of the Canadian Regular Force personnel.

Gastrointestinal Endogenous Protein-Derived Bioactive Peptides: An in Vitro Study of Their Gut Modulatory Potential

PubMed Central

Dave, Lakshmi A.; Hayes, Maria; Mora, Leticia; Montoya, Carlos A.; Moughan, Paul J.; Rutherfurd, Shane M.

2016-01-01

A recently proposed paradigm suggests that, like their dietary counterparts, digestion of gastrointestinal endogenous proteins (GEP) may also produce bioactive peptides. With an aim to test this hypothesis, in vitro digests of four GEP namely; trypsin (TRYP), lysozyme (LYS), mucin (MUC), serum albumin (SA) and a dietary protein chicken albumin (CA) were screened for their angiotensin-I converting (ACE-I), renin, platelet-activating factor-acetylhydrolase (PAF-AH) and dipeptidyl peptidase-IV inhibitory (DPP-IV) and antioxidant potential following simulated in vitro gastrointestinal digestion. Further, the resultant small intestinal digests were enriched to obtain peptides between 3–10 kDa in size. All in vitro digests of the four GEP were found to inhibit ACE-I compared to the positive control captopril when assayed at a concentration of 1 mg/mL, while the LYS < 3-kDa permeate fraction inhibited renin by 40% (±1.79%). The LYS < 10-kDa fraction inhibited PAF-AH by 39% (±4.34%), and the SA < 3-kDa fraction inhibited DPP-IV by 45% (±1.24%). The MUC < 3-kDa fraction had an ABTS-inhibition antioxidant activity of 150 (±24.79) µM trolox equivalent and the LYS < 10-kDa fraction inhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) by 54% (±1.62%). Moreover, over 190 peptide-sequences were identified from the bioactive GEP fractions. The findings of the present study indicate that GEP are a significant source of bioactive peptides which may influence gut function. PMID:27043546

Analysis of Bearing Errors from Acoustic Arrays

DTIC Science & Technology

2002-04-25

BPp F ; ?v<Bq+/ mQ= -0_3pP* 6 . 0 zDg:2 l-¡ppA?-0/0/3p ;<= pA?_3]�?-0_3/ H | v<Bv,-0p?AF3u3+_ > F3 � > -0ppC,-¡pA?_3],`aBDpx...O bQZ : | JZ �TG | ZAUXw G w n ZiK�Z | OPb | v<B��{-@Bq�pq4 F3 *’-0]’-@F9],p_3]’C��hF3+Q��],C,-0],u9p`aF9]�?_3-0]<BDC�-0]�?v,-0p+Bq* F3 +?X_8...B?v<F9pAB F3 �P?v,B�_ ; ?v, F3 +px_3],C pv<F ; /0C�]< F3 ? = B`aF9],pA?A+ ;

Pilot Feasibility Study of an Oncology Financial Navigation Program.

PubMed

Shankaran, Veena; Leahy, Tony; Steelquist, Jordan; Watabayashi, Kate; Linden, Hannah; Ramsey, Scott; Schwartz, Naomi; Kreizenbeck, Karma; Nelson, Judy; Balch, Alan; Singleton, Erin; Gallagher, Kathleen; Overstreet, Karen

2018-02-01

Few studies have reported on interventions to alleviate financial toxicity in patients with cancer. We developed a financial navigation program in collaboration with our partners, Consumer Education and Training Services (CENTS) and Patient Advocate Foundation (PAF), to improve patient knowledge about treatment costs, provide financial counseling, and to help manage out-of-pocket expenses. We conducted a pilot study to assess the feasibility and impact of this program. Patients with cancer received a financial education course followed by monthly contact with a CENTS financial counselor and a PAF case manager for 6 months. We measured program adherence, self-reported financial burden and anxiety, program satisfaction, and type of assistance provided. Thirty-four patients (median age, 60.5 years) were consented (85% white and 50% commercially insured). Debt, income declines, and loans were reported by 55%, 55%, and 30% of patients, respectively. CENTS counselors assisted most often with budgeting, retirement planning, and medical bill questions. PAF case managers assisted with applications for appropriate insurance coverage, cost of living issues (eg, housing, transportation), and disability applications. High financial burden and anxiety about costs (4 or 5 on a Likert scale) were reported at baseline by 37% and 47% of patients, respectively. Anxiety about costs decreased over time in 33% of patients, whereas self-reported financial burden did not substantially change. Implementing an oncology financial navigation program is feasible, provides concrete assistance in navigating the cost of care, and mitigates anxiety about costs in a subset of patients. Future work will focus on measuring the program's impact on financial and clinical outcomes.

Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

PubMed

Grassi, S; Frondaroli, A; Pessia, M; Pettorossi, V E

2001-08-08

In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

Burden of disease attributed to ambient air pollution in Thailand: A GIS-based approach.

PubMed

Pinichka, Chayut; Makka, Nuttapat; Sukkumnoed, Decharut; Chariyalertsak, Suwat; Inchai, Puchong; Bundhamcharoen, Kanitta

2017-01-01

Growing urbanisation and population requiring enhanced electricity generation as well as the increasing numbers of fossil fuel in Thailand pose important challenges to air quality management which impacts on the health of the population. Mortality attributed to ambient air pollution is one of the sustainable development goals (SDGs). We estimated the spatial pattern of mortality burden attributable to selected ambient air pollution in 2009 based on the empirical evidence in Thailand. We estimated the burden of disease attributable to ambient air pollution based on the comparative risk assessment (CRA) framework developed by the World Health Organization (WHO) and the Global Burden of Disease study (GBD). We integrated geographical information systems (GIS)-based exposure assessments into spatial interpolation models to estimate ambient air pollutant concentrations, the population distribution of exposure and the concentration-response (CR) relationship to quantify ambient air pollution exposure and associated mortality. We obtained air quality data from the Pollution Control Department (PCD) of Thailand surface air pollution monitoring network sources and estimated the CR relationship between relative risk (RR) and concentration of air pollutants from the epidemiological literature. We estimated 650-38,410 ambient air pollution-related fatalities and 160-5,982 fatalities that could have been avoided with a 20 reduction in ambient air pollutant concentrations. The summation of population-attributable fraction (PAF) of the disease burden for all-causes mortality in adults due to NO2 and PM2.5 were the highest among all air pollutants at 10% and 7.5%, respectively. The PAF summation of PM2.5 for lung cancer and cardiovascular disease were 16.8% and 14.6% respectively and the PAF summations of mortality attributable to PM10 was 3.4% for all-causes mortality, 1.7% for respiratory and 3.8% for cardiovascular mortality, while the PAF summation of mortality attributable to NO2 was 7.8% for respiratory mortality in Thailand. Mortality due to ambient air pollution in Thailand varies across the country. Geographical distribution estimates can identify high exposure areas for planners and policy-makers. Our results suggest that the benefits of a 20% reduction in ambient air pollution concentration could prevent up to 25% of avoidable fatalities each year in all-causes, respiratory and cardiovascular categories. Furthermore, our findings can provide guidelines for future epidemiological investigations and policy decisions to achieve the SDGs.

Women’s and men’s reports of past-year prevalence of intimate partner violence and rape and women’s risk factors for intimate partner violence: A multicountry cross-sectional study in Asia and the Pacific

PubMed Central

Fulu, Emma; Tabassam Naved, Ruchira; Chirwa, Esnat; Dunkle, Kristin; Haardörfer, Regine; Garcia-Moreno, Claudia

2017-01-01

Background Understanding the past-year prevalence of male-perpetrated intimate partner violence (IPV) and risk factors is essential for building evidence-based prevention and monitoring progress to Sustainable Development Goal (SDG) 5.2, but so far, population-based research on this remains very limited. The objective of this study is to compare the population prevalence rates of past-year male-perpetrated IPV and nonpartner rape from women’s and men’s reports across 4 countries in Asia and the Pacific. A further objective is to describe the risk factors associated with women’s experience of past-year physical or sexual IPV from women’s reports and factors driving women’s past-year experience of partner violence. Methods and findings This paper presents findings from the United Nations Multi-country Study on Men and Violence in Asia and the Pacific. In the course of this study, in population-based cross-sectional surveys, 5,206 men and 3,106 women aged 18–49 years were interviewed from 4 countries: Cambodia, China, Papua New Guinea (PNG), and Sri Lanka. To measure risk factors, we use logistic regression and structural equation modelling to show pathways and mediators. The analysis was not based on a written plan, and following a reviewer’s comments, some material was moved to supplementary files and the regression was performed without variable elimination. Men reported more lifetime perpetration of IPV (physical or sexual IPV range 32.5%–80%) than women did experience (physical or sexual IPV range 27.5%–67.4%), but women’s reports of past-year experience (physical or sexual IPV range 8.2%–32.1%) were not very clearly different from men’s (physical or sexual IPV range 10.1%–34.0%). Women reported much more emotional/economic abuse (past-year ranges 1.4%–5.7% for men and 4.1%–27.7% for women). Reports of nonpartner rape were similar for men (range 0.8%–1.9% in the past year) and women (range 0.4%–2.3% in past year), except in Bougainville, where they were higher for men (11.7% versus 5.7%). The risk factor modelling shows 4 groups of variables to be important in experience of past-year sexual and/or physical IPV: (1) poverty, (2) all childhood trauma, (3) quarrelling and women’s limited control in relationships, and (4) partner factors (substance abuse, unemployment, and infidelity). The population attributable fraction (PAF) was largest for quarrelling often, but the second greatest PAF was for the group related to exposure to violence in childhood. The relationship control variable group had the third highest PAF, followed by other partner factors. Currently married women were also more at risk. In the structural model, a resilience pathway showed less poverty, higher education, and more gender-equitable ideas were connected and conveyed protection from IPV. These are all amenable risk factors. This research was cross-sectional, so we cannot be sure of the temporal sequence of exposure, but the outcome being a past-year measure to some extent mitigates this problem. Conclusions Past-year IPV indicators based on women’s reported experience that were developed to track SDG 5 are probably reasonably reliable but will not always give the same prevalence as may be reported by men. Report validity requires further research. Interviews with men to track past-year nonpartner rape perpetration are feasible and important. The findings suggest a range of factors are associated with past-year physical and/or sexual IPV exposure; of particular interest is the resilience pathway suggested by the structural model, which is highly amenable to intervention and explains why combining economic empowerment of women and gender empowerment/relationship skills training has been successful. This study provides additional rationale for scaling up violence prevention interventions that combine economic and gender empowerment/relationship skills building of women, as well as the value of investing in girls’ education with a view to long-term violence reduction. PMID:28873087

Women's and men's reports of past-year prevalence of intimate partner violence and rape and women's risk factors for intimate partner violence: A multicountry cross-sectional study in Asia and the Pacific.

PubMed

Jewkes, Rachel; Fulu, Emma; Tabassam Naved, Ruchira; Chirwa, Esnat; Dunkle, Kristin; Haardörfer, Regine; Garcia-Moreno, Claudia

2017-09-01

Understanding the past-year prevalence of male-perpetrated intimate partner violence (IPV) and risk factors is essential for building evidence-based prevention and monitoring progress to Sustainable Development Goal (SDG) 5.2, but so far, population-based research on this remains very limited. The objective of this study is to compare the population prevalence rates of past-year male-perpetrated IPV and nonpartner rape from women's and men's reports across 4 countries in Asia and the Pacific. A further objective is to describe the risk factors associated with women's experience of past-year physical or sexual IPV from women's reports and factors driving women's past-year experience of partner violence. This paper presents findings from the United Nations Multi-country Study on Men and Violence in Asia and the Pacific. In the course of this study, in population-based cross-sectional surveys, 5,206 men and 3,106 women aged 18-49 years were interviewed from 4 countries: Cambodia, China, Papua New Guinea (PNG), and Sri Lanka. To measure risk factors, we use logistic regression and structural equation modelling to show pathways and mediators. The analysis was not based on a written plan, and following a reviewer's comments, some material was moved to supplementary files and the regression was performed without variable elimination. Men reported more lifetime perpetration of IPV (physical or sexual IPV range 32.5%-80%) than women did experience (physical or sexual IPV range 27.5%-67.4%), but women's reports of past-year experience (physical or sexual IPV range 8.2%-32.1%) were not very clearly different from men's (physical or sexual IPV range 10.1%-34.0%). Women reported much more emotional/economic abuse (past-year ranges 1.4%-5.7% for men and 4.1%-27.7% for women). Reports of nonpartner rape were similar for men (range 0.8%-1.9% in the past year) and women (range 0.4%-2.3% in past year), except in Bougainville, where they were higher for men (11.7% versus 5.7%). The risk factor modelling shows 4 groups of variables to be important in experience of past-year sexual and/or physical IPV: (1) poverty, (2) all childhood trauma, (3) quarrelling and women's limited control in relationships, and (4) partner factors (substance abuse, unemployment, and infidelity). The population attributable fraction (PAF) was largest for quarrelling often, but the second greatest PAF was for the group related to exposure to violence in childhood. The relationship control variable group had the third highest PAF, followed by other partner factors. Currently married women were also more at risk. In the structural model, a resilience pathway showed less poverty, higher education, and more gender-equitable ideas were connected and conveyed protection from IPV. These are all amenable risk factors. This research was cross-sectional, so we cannot be sure of the temporal sequence of exposure, but the outcome being a past-year measure to some extent mitigates this problem. Past-year IPV indicators based on women's reported experience that were developed to track SDG 5 are probably reasonably reliable but will not always give the same prevalence as may be reported by men. Report validity requires further research. Interviews with men to track past-year nonpartner rape perpetration are feasible and important. The findings suggest a range of factors are associated with past-year physical and/or sexual IPV exposure; of particular interest is the resilience pathway suggested by the structural model, which is highly amenable to intervention and explains why combining economic empowerment of women and gender empowerment/relationship skills training has been successful. This study provides additional rationale for scaling up violence prevention interventions that combine economic and gender empowerment/relationship skills building of women, as well as the value of investing in girls' education with a view to long-term violence reduction.

Agonist-evoked changes in cytosolic pH and calcium concentration in human platelets: studies in physiological bicarbonate.

PubMed

Sage, S O; Jobson, T M; Rink, T J

1990-01-01

1. Cytosolic pH (pHi) and calcium concentration ([Ca2+]i) have been investigated in the presence and absence of physiological HCO3- in human platelets co-loaded with the fluorescent indicators BCECF and Fura-2. Basal pHi and changes evoked by butyrate, thrombin, platelet activating factor (PAF), ADP and phorbol ester were investigated, as were the effects of removing external Na+. 2. In the presence of physiological HCO3- and CO2, basal pHi was 7.02 +/- 0.04 compared with 7.15 +/- 0.05 in the absence of HCO3-. Estimated cytosolic buffering power was reduced from 35.6 +/- 3.0 to 14.5 +/- 0.4 mM/pH unit by the omission of HCO3-. 3. Thrombin evoked an immediate acidification of 0.03 +/- 0.01 pH units in the presence of HCO3- and 0.07 +/- 0.01 pH units in its absence. The acidifications were followed by a slow alkalinization. The final pHi was 0.10 +/- 0.01 units above basal in the presence of HCO3- and 0.08 +/- 0.02 units above basal in the absence of HCO3-. The initial acidification was significantly greater in the absence of HCO3-. The subsequent increase in pHi was similar in the presence and absence of this ion, but the calculated loss of proton equivalents was greater in the presence of HCO3-. 4. Replacement of extracellular Na+ with N-methyl-D-glucamine resulted in a fall in basal pHi and abolished recovery from thrombin-evoked acidification in both the presence and absence of HCO3-. 5. In the presence of HCO3-, PAF and ADP evoked an intracellular acidification similar to that caused by thrombin. However, with PAF and ADP, the subsequent recovery in pHi was slow and did not rise above basal levels. Phorbol dibutyrate, an activator of protein kinase C, evoked a similar elevation in pHi of 0.04 +/- 0.01 units over 3 min in the presence and absence of HCO3-. 6. Stopped-flow fluorimetric measurements were made of both BCECF and Fura-2 fluorescence in the presence of HCO3-. In the presence and absence of external Ca2+, thrombin-evoked rises in [Ca2+]i peaked before any cytoplasmic alkalinization occurred. ADP evoked rapid elevations in [Ca2+]i, but caused no alkalinization.(ABSTRACT TRUNCATED AT 400 WORDS)

Prevention of atrial fibrillation by inter-atrial septum pacing guided by electrophysiological testing, in patients with delayed interatrial conduction.

PubMed

Manolis, A G; Katsivas, A G; Vassilopoulos, C; Koutsogeorgis, D; Louvros, N E

2002-04-01

Interatrial septum (IAS) pacing seems efficient in synchronizing atrial depolarization in patients (pts) with delayed inter-atrial conduction, but its clinical role in preventing atrial tachyarrhythmias is still debated. This study was conducted in order to evaluate the clinical efficacy of IAS pacing guided by pace mapping of the IAS, as an alternative treatment modality in pts with drug refractory paroxysmal atrial fibrillation (PAF). We evaluated 29 pts (13 male, 16 female, 60 +/- 11 years), with drug refractory PAF, normal sinus node function and prolonged inter-atrial conduction time (P wave 142 +/- 10 ms). Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle and distal coronary sinus (CS) were recorded. The IAS was paced from multiple sites. The site of IAS where the timing between HRA and distal CS was <20 ms was considered the most suitable for synchronizing the atria. This site was found to be superior to the CS os. near the fossa ovalis in all pts. An active fixation atrial lead was positioned at this site and a standard lead was placed in the right ventricle. During IAS pacing, the P wave duration decreased significantly to 107 +/- 15 ms (P<0.001). At implant, the atrial sensing was 2.3 +/- 0.7 mV, the atrial pacing threshold was 0.95 +/- 0.15 V (0.5 ms) and the impedance was 760 +/- 80 Ohm. We evaluated the pts during four periods of 3 months duration each. The first period (control) was before pacemaker implantation, while the pts were under antiarrhythmic treatment. During the subsequent two periods, we evaluated the clinical efficacy of IAS pacing to prevent PAF recurrences, in AAT (75 bpm) and AAIR (75-140 bpm) mode, with random selection of the order and after discontinuation of antiarrhythmic treatment. During the fourth period, the same AAIR mode was assessed, but antiarrhythmic drugs were also administered. We compared the arrhythmia free interval among the four periods. The proportion of atrial paced beats in AAIR pacing mode plus antiarrhythmics was significantly higher compared with the drug-free period in AAIR mode (57 +/- 9% and 49 +/- 9% respectively, P=0017) and with AAT pacing mode (44 +/- 10%,(, P<0.001). In AAT mode, the arrhythmia free interval was 24.2 +/- 5.1 days, while it was 26.2 +/- 5.7 days in AAIR mode. These intervals did not differ significantly from the pre-implantation period (24.1 +/- 6.3 days). The arrhythmia free interval in AAIR pacing in combination with antiarrhythmic drug therapy was 38.7 +/- 8.1 days and this was significantly longer than the previous periods (P<0.05). Atrial septal pacing in combination with antiarrhythmic drug therapy reduced the incidence of PAF in pts with prolonged inter-atrial conduction times. Pace mapping of the IAS is an attractive technique to assess the shortest atrial activation time between HRA and distal CS. Whether placement of the atrial lead based on the shortest HRA--distal CS time is the best place in the IAS to prevent PAF still remains to be proven.

Genuine functions of P-glycoprotein (ABCB1).

PubMed

Mizutani, Takaharu; Masuda, Masatoshi; Nakai, Emi; Furumiya, Kenji; Togawa, Hiroshi; Nakamura, Yutaka; Kawai, Yuko; Nakahira, Keiko; Shinkai, Shigeko; Takahashi, Kazuhiko

2008-02-01

P-glycoprotein (P-gp, ABCB1, MDR1) was recognized as a drug-exporting protein from cancer cells three decade ago. Apart from the multidrug transporter side effects of P-gp, normal physiological functions of P-gp have been reported. P-gp could be responsible for translocating platelet-activating factor (PAF) across the plasma membrane and PAF inhibited drug transport mediated by P-gp in cancer cells. P-gp regulated the translocation of sphingomyelin (SM) and GlcCer, and short chain C(6)-NBD-GlcCer was found in the apical medium of P-gp cells exclusively and not in the basolateral membrane. SM plays an important role in the esterification of cholesterol. High expression of P-gp prevents stem-cell differentiation, leading to the proliferation and amplification of this cell repertoire, and functional P-gp plays a fundamental role in regulating programmed cell death, apoptosis. The transporter function of P-gp is therefore necessary to protect cells from death. P-gp can translocate both C(6)-NBD-PC and C(6)-NBD-PE across the apical membrane. This PC translocation was also confirmed with [(3)H]choline radioactivity. Progesterone is not transported by P-gp, but blocks P-gp-mediated efflux of other drugs and P-gp can mediate the transport of a variety of steroids. Cells transfected with human P-gp esterified more cholesterol. P-gp might also be involved in the transport of cytokines, particularly IL-1beta, IL-2, IL-4 and IFNgamma, out of activated normal lymphocytes into the surrounding medium. P-gp expression is also associated with a volume-activated chloride channel, thus P-gp is bifunctional with both transport and channel regulators. We also present information about P-gp polymorphism and new structural concepts, "gate" and "twist", of the P-gp structure.

Rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolomics approach to study the effects of jieduquyuziyin prescription on systemic lupus erythematosus.

PubMed

Ding, Xinghong; Hu, Jinbo; Wen, Chengping; Ding, Zhishan; Yao, Li; Fan, Yongsheng

2014-01-01

Jieduquyuziyin prescription (JP), a traditional Chinese medicine (TCM) prescription, has been widely used for the clinical treatment of systemic lupus erythematosus (SLE). However, the complex chemical constituents of JP and the multifactorial pathogenesis of SLE make research on the therapeutic mechanism of JP in SLE challenging. In this paper, a serum metabolomics approach based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF/MS) was employed to acquire the metabolic characteristics of serum samples obtained from mice in the SLE model group, JP-treated group, prednisone acetate (PA)-treated group and control group. The orthogonal partial least squares (OPLS) was applied to recognize metabolic patterns, and an obvious separation of groups was obtained. Thirteen metabolites, namely, phosphatidylethanolamine (PE 20:3), hepoxilin B3, lyso- phosphatidylethanolamine (lyso-PE 22:6), 12S-hydroxypentaenoic acid (12S-HEPE), traumatic acid, serotonin, platelet-activating factor (PAF), phosphatidylcholine (PC 20:5),eicosapentaenoic acid (EPA), 12(S)-hydroxyei- cosatetraenoic acid (12S-HETE), 14-hydroxy docosahexaenoic acid (14-HDOHE), lyso-phosphatidylcholine (lyso-PC 20:4), and indole acetaldehyde, were identified and characterized as differential metabolites involved in the pathogenesis of SLE. After treatment with JP, the relative content of 12(S)-HETE, PAF, 12(S)-HEPE, EPA, PE (20:3), Lyso-PE(22:6), and 14-HDOHE were effectively regulated, which suggested that the therapeutic effects of JP on SLE may involve regulating disturbances to the metabolism of unsaturated fatty acid, tryptophan and phospholipid. This research also demonstrated that metabolomics is a powerful tool for researching complex disease mechanisms and evaluating the mechanism of action of TCM.

Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, Daniel K.; Fujioka, Kazutoshi; Issa, Roger S.

2008-04-01

Serine hydrolase KIAA1363 is an acetyl monoalkylglycerol ether (AcMAGE) hydrolase involved in tumor cell invasiveness. It is also an organophosphate (OP) insecticide-detoxifying enzyme. The key to understanding these dual properties was the use of KIAA1363 +/+ (wildtype) and -/- (gene deficient) mice to define the role of this enzyme in brain and other tissues and its effectiveness in vivo in reducing OP toxicity. KIAA1363 was the primary AcMAGE hydrolase in brain, lung, heart and kidney and was highly sensitive to inactivation by chlorpyrifos oxon (CPO) (IC{sub 50} 2 nM) [the bioactivated metabolite of the major insecticide chlorpyrifos (CPF)]. Although theremore » was no difference in hydrolysis product monoalkylglycerol ether (MAGE) levels in +/+ and -/- mouse brains in vivo, isopropyl dodecylfluorophosphonate (30 mg/kg) and CPF (100 mg/kg) resulted in 23-51% decrease in brain MAGE levels consistent with inhibition of AcMAGE hydrolase activity. On incubating +/+ and -/- brain membranes with AcMAGE and cytidine-5'-diphosphocholine, the absence of KIAA1363 activity dramatically increased de novo formation of platelet-activating factor (PAF) and lyso-PAF, signifying that metabolically-stabilized AcMAGE can be converted to this bioactive lipid in brain. On considering detoxification, KIAA1363 -/- mice were significantly more sensitive than +/+ mice to ip-administered CPF (100 mg/kg) and parathion (10 mg/kg) with increased tremoring and mortality that correlated for CPF with greater brain acetylcholinesterase inhibition. Docking AcMAGE and CPO in a KIAA1363 active site model showed similar positioning of their acetyl and trichloropyridinyl moieties, respectively. This study establishes the relevance of KIAA1363 in ether lipid metabolism and OP detoxification.« less

Diagnostic Yield of Extended Cardiac Patch Monitoring in Patients with Stroke or TIA.

PubMed

Tung, Christie E; Su, Derek; Turakhia, Mintu P; Lansberg, Maarten G

2014-01-01

It is important to evaluate patients with transient ischemic attack (TIA) or stroke for atrial fibrillation (AF) because the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. This study describes the diagnostic yield of a patch-based, single-use, and water-resistant 14-day continuous cardiac rhythm monitor (ZIO Patch) in patients with stroke or TIA. We obtained data from the manufacturer and servicer of the ZIO Patch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented. One thousand one hundred seventy-one monitoring reports were analyzed. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 5.0% of all reports. The mean duration before the first episode of paroxysmal AF (PAF) was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 h. The mean PAF burden was 12.7% of the total monitoring duration. Excellent quality of the recordings and very good patient compliance coupled with a substantial proportion of AF detection beyond the first 48 h of monitoring suggest that the cardiac patch is superior to conventional 48-h Holter monitors for AF detection in patients with stroke or TIA.

Assessing the Ecotoxicologic Hazards of a Pandemic Influenza Medical Response

PubMed Central

Colizza, Vittoria; Schmitt, Heike; Andrews, Johanna; Balcan, Duygu; Huang, Wei E.; Keller, Virginie D.J.; Vespignani, Alessandro; Williams, Richard J.

2011-01-01

Background: The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers. Objectives: We assessed the ecotoxicologic risks of a pandemic influenza medical response. Methods: To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers. Results: Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0–14% and 5–32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0–14% and 0–30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range). Conclusions: The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity. PMID:21367688

Assessing the ecotoxicologic hazards of a pandemic influenza medical response.

PubMed

Singer, Andrew C; Colizza, Vittoria; Schmitt, Heike; Andrews, Johanna; Balcan, Duygu; Huang, Wei E; Keller, Virginie D J; Vespignani, Alessandro; Williams, Richard J

2011-08-01

The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers. We assessed the ecotoxicologic risks of a pandemic influenza medical response. To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers. Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0-14% and 5-32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0-14% and 0-30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range). The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity.

Contribution of overweight and obesity to adverse pregnancy outcomes among immigrant and non-immigrant women in Berlin, Germany.

PubMed

Reiss, Katharina; Breckenkamp, Jürgen; Borde, Theda; Brenne, Silke; David, Matthias; Razum, Oliver

2015-10-01

Maternal excessive weight and smoking are associated with an increased risk of pregnancy complications and adverse pregnancy outcomes. In Germany, immigrant women have a higher prevalence of pre-pregnancy overweight/obesity compared with autochthonous women. We compared the contribution of pre-pregnancy overweight/obesity to adverse pregnancy outcomes among immigrant and autochthonous women in Berlin/Germany. Data from 2586 immigrant women (from Turkey, Lebanon, other countries of origin) and 2676 autochthonous women delivering in three maternity hospitals of Berlin within 12 months (2011/2012) was used. Cox regression models were applied to estimate the association between overweight/obesity and smoking with the outcomes large-for-gestational-age (LGA), small-for-gestational-age (SGA), preterm birth (PTB) and extreme preterm-birth (E-PTB). Population attributive fractions (PAF) were calculated to quantify the proportion of the outcomes attributable to overweight/obesity and smoking, respectively. Prevalence of overweight and obesity was 33.4% among autochthonous and 53.6% among Turkish women. Prevalence risk ratios of excessive weight were highest for LGA infants among immigrant and autochthonous women. The PAFs were -11.8% (SGA), +16.3% (LGA), +3.6% (PTB) and +16.5% (E-PTB) for the total study population. Overweight/obesity is strongly associated with an increased risk of delivering an LGA infant among both immigrant and autochthonous women. Compared with autochthonous women, the contribution of excessive weight to LGA is even higher among immigrant women, in whom PAFs of overweight/obesity even exceed those of smoking for some outcomes. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Effects of yoga in patients with paroxysmal atrial fibrillation - a randomized controlled study.

PubMed

Wahlstrom, Maria; Rydell Karlsson, Monica; Medin, Jörgen; Frykman, Viveka

2017-01-01

Patients with atrial fibrillation often have an impaired quality of life (QoL). Practising yoga may decrease stress and have positive effects on mental and physical health. The aim of this study was to investigate whether yoga can improve QoL and decrease blood pressure and heart rate in patients with paroxysmal atrial fibrillation (PAF). In this pilot study, 80 patients diagnosed with PAF were randomized to standard treatment (control group, n=40) or standard treatment in combination with yoga (yoga group, n=40) during a 12-week period. QoL, blood pressure and heart rate were evaluated at baseline and at the end of the study (12 (+2) weeks). EuroQoL-5D (EQ-5D) Visual Analogue Scale (VAS) and the two dimensions in Short-Form Health Survey (SF-36) were used to evaluate QoL. At baseline there was a significant difference in QoL between the groups in EQ-5D VAS- scale ( p=0.02) and SF-36 mental health score ( p<0.001) in which the control group had higher scores. At the end of the study, the yoga group averaged higher SF-36 mental health scores. There was a significant difference between the two groups ( p=0.016), but no differences in EQ-5D VAS- scale and physiological health score was seen between the two groups. At the end of the study, the yoga group had significantly lower heart rate ( p=0.024) and systolic ( p=0.033) and diastolic blood pressure ( p<0.001) compared to the control group. Yoga with light movements and deep breathing may lead to improved QoL, lower blood pressure and lower heart rate in patients with PAF compared to a control group. Yoga could be a complementary treatment method to standard therapy.

Remote magnetic navigation with irrigated tip catheter for ablation of paroxysmal atrial fibrillation.

PubMed

Miyazaki, Shinsuke; Shah, Ashok J; Xhaët, Olivier; Derval, Nicolas; Matsuo, Seiichiro; Wright, Matthew; Nault, Isabelle; Forclaz, Andrei; Jadidi, Amir S; Knecht, Sébastien; Rivard, Lena; Liu, Xingpeng; Linton, Nick; Sacher, Frédéric; Hocini, Mélèze; Jaïs, Pierre; Haïssaguerre, Michel

2010-12-01

The remote magnetic navigation system (MNS) has been used with a nonirrigated magnetic catheter for atrial fibrillation (AF) ablation. The objective of this study was to evaluate the feasibility and efficiency of the newly available irrigated tip magnetic catheter for index pulmonary vein isolation (PVI) in patients with paroxysmal AF (PAF). Between January 2008 and June 2009, 30 consecutive patients with drug-resistant PAF underwent circular mapping catheter-guided PVI with MNS (MNS group). The outcomes were compared retrospectively with those of a conventional hand-controlled ablation technique during the same period in 44 consecutive patients (manual group). All 4 pulmonary veins were successfully isolated in both groups except in 4 patients in the MNS group. Radiofrequency and procedure duration were higher in the MNS group (60 ± 27 versus 43 ± 16 minutes; P = 0.0019) than in the manual group (246 ± 50 versus 153 ± 51 minutes; P < 0.0001). In the patients who underwent only PVI, total fluoroscopic time also was longer in the MNS group than in the manual group (58 ± 24 versus 40 ± 14 minutes; P = 0.0002). At 12-month follow-up after a single procedure, 69.0% of the patients in MNS group and 61.8% of patients in manual group were free of atrial tachyarrhythmia without antiarrhythmic drugs. There was no significant difference in the atrial tachyarrhythmia-free survival between the 2 groups (P = 0.961). Cardiac tamponade occurred in 1 patient in the manual group. In patients with PAF, MNS-guided PVI with the newly available irrigated tip magnetic catheter backed up with manual ablation whenever required is feasible. However, it requires longer ablation, fluoroscopy, and procedural times than the conventional approach in the early experience stage.

Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP(+) induced neurotoxicity.

PubMed

Maghsoudi, Amirhossein; Fakharzadeh, Saideh; Hafizi, Maryam; Abbasi, Maryam; Kohram, Fatemeh; Sardab, Shima; Tahzibi, Abbas; Kalanaky, Somayeh; Nazaran, Mohammad Hassan

2015-03-01

Parkinson's disease (PD) is the world's second most common dementia, which the drugs available for its treatment have not had effects beyond slowing the disease process. Recently nanotechnology has induced the chance for designing and manufacturing new medicines for neurodegenerative disease. It is demonstrated that by tuning the size of a nanoparticle, the physiological effect of the nanoparticle can be controlled. Using novel nanochelating technology, three nano complexes: Pas (150 nm), Paf (100 nm) and Pac (40 nm) were designed and in the present study their neuroprotective effects were evaluated in PC12 cells treated with 1-methyl-4-phenyl-pyridine ion (MPP (+)). PC12 cells were pre-treated with the Pas, Paf or Pac nano complexes, then they were subjected to 10 μM MPP (+). Subsequently, cell viability, intracellular free Calcium and reactive oxygen species (ROS) levels, mitochondrial membrane potential, catalase (CAT) and superoxide dismutase (SOD) activity, Glutathione (GSH) and malondialdehyde (MDA) levels and Caspase 3 expression were evaluated. All three nano complexes, especially Pac, were able to increase cell viability, SOD and CAT activity, decreased Caspase 3 expression and prevented the generation of ROS and the loss of mitochondrial membrane potential caused by MPP(+). Pre-treatment with Pac and Paf nano complexes lead to a decrease of intracellular free Calcium, but Pas nano complex could not decrease it. Only Pac nano complex decreased MDA levels and other nano complexes could not change this parameter compared to MPP(+) treated cells. Hence according to the results, all nanochelating based nano complexes induced neuroprotective effects in an experimental model of PD, but the smallest nano complex, Pac, showed the best results.

Results of preventive radioiodine therapy in euthyroid patients with history of hyperthyroidism prior to administration of amiodarone with permanent atrial fibrillation--a preliminary study.

PubMed

Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Małgorzata; Woliński, Kosma; Płazińska, Maria Teresa; Miechowicz, Izabela; Kwiecińska, Barbara; Czepczyński, Rafał; Królicki, Leszek; Ruchała, Marek

2014-01-01

Radioiodine (RAI) therapy is a standard procedure in the treatment of hyperthyroidism. However, the use of RAI in euthyroid patients requiring chronic administration of amiodarone (AM) where other antiarrhythmic drugs may lack efficacy is still controversial. The aim of this study was to assess the safety and efficacy of an AM therapy prior to treatment with radioiodine therapy in euthyroid patients with permanent atrial fibrillation (PAF), who had been treated for hyperthyroidism in the past. This was a retrospective observational study. Patients were assessed at baseline and two, six, eight, and 12 months after RAI therapy. 17 euthyroid patients with PAF were qualified to the RAI (female/male 3/14; age range 65 to 87, median 71). The patients required chronic administration of AM as a prophylaxis against sudden death. Each patient received an ablative dose of 800 MBq (22 mCi) of 131I. At baseline and during follow-up, no side effects of the therapy and no signs of drug intolerance were observed. Subclinical hyperthyroidism occurred in two (11.8%) cases after two months of RAI and five weeks of AM administration. In this situation, RAI therapy was repeated. Three patients (17.6%) after six months, and another two (11.8%) after eight months, required an additional dose of 131I due to amiodarone-induced thyrotoxicosis (AIT). Twelve patients (70.6%) returned to spontaneous sinus rhythm within two months. Fourteen patients (82.4%) had sinus rhythm during follow-up after six and 12 months of treatment. Preventive RAI in euthyroid (but previously hyperthyroid) patients with PAF before administration of AM may be the method of choice. This is particularly important for patients who will require permanent AM administration as a life-saving drug.

Impact of occupational carcinogens on lung cancer risk in a general population

PubMed Central

De Matteis, Sara; Consonni, Dario; Lubin, Jay H; Tucker, Margaret; Peters, Susan; Vermeulen, Roel CH; Kromhout, Hans; Bertazzi, Pier Alberto; Caporaso, Neil E; Pesatori, Angela C; Wacholder, Sholom; Landi, Maria Teresa

2012-01-01

Background Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. Methods We applied a new job–exposure matrix (JEM) to translate lifetime work histories, collected by personal interview and coded into standard job titles, into never, low and high exposure levels for six known/suspected occupational lung carcinogens in the Environment and Genetics in Lung cancer Etiology (EAGLE) population-based case–control study, conducted in Lombardy region, Italy, in 2002–05. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in men (1537 cases and 1617 controls), by logistic regression adjusted for potential confounders, including smoking and co-exposure to JEM carcinogens. The population attributable fraction (PAF) was estimated as impact measure. Results Men showed an increased lung cancer risk even at low exposure to asbestos (OR: 1.76; 95% CI: 1.42–2.18), crystalline silica (OR: 1.31; 95% CI: 1.00–1.71) and nickel–chromium (OR: 1.18; 95% CI: 0.90–1.53); risk increased with exposure level. For polycyclic aromatic hydrocarbons, an increased risk (OR: 1.64; 95% CI: 0.99–2.70) was found only for high exposures. The PAFs for any exposure to asbestos, silica and nickel–chromium were 18.1, 5.7 and 7.0%, respectively, equivalent to an overall PAF of 22.5% (95% CI: 14.1–30.0). This corresponds to about 1016 (95% CI: 637–1355) male lung cancer cases/year in Lombardy. Conclusions These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even at low exposures, in a general population. PMID:22467291

Impact of occupational carcinogens on lung cancer risk in a general population.

PubMed

De Matteis, Sara; Consonni, Dario; Lubin, Jay H; Tucker, Margaret; Peters, Susan; Vermeulen, Roel Ch; Kromhout, Hans; Bertazzi, Pier Alberto; Caporaso, Neil E; Pesatori, Angela C; Wacholder, Sholom; Landi, Maria Teresa

2012-06-01

Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. We applied a new job-exposure matrix (JEM) to translate lifetime work histories, collected by personal interview and coded into standard job titles, into never, low and high exposure levels for six known/suspected occupational lung carcinogens in the Environment and Genetics in Lung cancer Etiology (EAGLE) population-based case-control study, conducted in Lombardy region, Italy, in 2002-05. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in men (1537 cases and 1617 controls), by logistic regression adjusted for potential confounders, including smoking and co-exposure to JEM carcinogens. The population attributable fraction (PAF) was estimated as impact measure. Men showed an increased lung cancer risk even at low exposure to asbestos (OR: 1.76; 95% CI: 1.42-2.18), crystalline silica (OR: 1.31; 95% CI: 1.00-1.71) and nickel-chromium (OR: 1.18; 95% CI: 0.90-1.53); risk increased with exposure level. For polycyclic aromatic hydrocarbons, an increased risk (OR: 1.64; 95% CI: 0.99-2.70) was found only for high exposures. The PAFs for any exposure to asbestos, silica and nickel-chromium were 18.1, 5.7 and 7.0%, respectively, equivalent to an overall PAF of 22.5% (95% CI: 14.1-30.0). This corresponds to about 1016 (95% CI: 637-1355) male lung cancer cases/year in Lombardy. These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even at low exposures, in a general population.

Does the STAF score help detect paroxysmal atrial fibrillation in acute stroke patients?

PubMed

Horstmann, S; Rizos, T; Güntner, J; Hug, A; Jenetzky, E; Krumsdorf, U; Veltkamp, R

2013-01-01

Detecting paroxysmal atrial fibrillation (pAF) soon after acute cerebral ischaemia has a major impact on secondary stroke prevention. Recently, the STAF score, a composite of clinical and instrumental findings, was introduced to identify stroke patients at risk of pAF. We aimed to validate this score in an independent study population. Consecutive patients admitted to our stroke unit with acute ischaemic stroke were prospectively enrolled. The diagnostic work-up included neuroimaging, neuroultrasound, baseline 12-channel electrocardiogram (ECG), 24-h Holter ECG, continuous ECG monitoring, and echocardiography. Presence of AF was documented according to the medical history of each patient and after review of 12-lead ECG, 24-h Holter ECG, or continuous ECG monitoring performed during the stay on the ward. Additionally, a telephone follow-up visit was conducted for each patient after 3 months to inquire about newly diagnosed AF. Items for each patient-age, baseline NIHSS, left atrial dilatation, and stroke etiology according to the TOAST criteria - were assessed to calculate the STAF score. Overall, 584 patients were enrolled in our analysis. AF was documented in 183 (31.3%) patients. In multivariable analysis, age, NIHSS, left atrial dilatation, and absence of vascular etiology were independent predictors for AF. The logistic AF-prediction model of the STAF score revealed fair classification accuracy in receiver operating characteristic curve analysis with an area under the curve of 0.84. STAF scores of ≥5 had a sensitivity of 79% and a specificity of 74% for predicting AF. The value of the STAF score for predicting the risk of pAF in stroke patients is limited. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Overweight and obesity on the island of Ireland: an estimation of costs

PubMed Central

Dee, Anne; Callinan, Aoife; Doherty, Edel; O'Neill, Ciaran; McVeigh, Treasa; Sweeney, Mary Rose; Staines, Anthony; Kearns, Karen; Fitzgerald, Sarah; Sharp, Linda; Kee, Frank; Hughes, John; Balanda, Kevin; Perry, Ivan J

2015-01-01

Objectives The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches. Methods Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality. Results The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease. Conclusions The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs. PMID:25776042

Preventing large birth size in women with preexisting diabetes mellitus: The benefit of appropriate gestational weight gain.

PubMed

Kim, Shin Y; Sharma, Andrea J; Sappenfield, William; Salihu, Hamisu M

2016-10-01

To estimate the percentage of infants with large birth size attributable to excess gestational weight gain (GWG), independent of prepregnancy body mass index, among mothers with preexisting diabetes mellitus (PDM). We analyzed 2004-2008 Florida linked birth certificate and maternal hospital discharge data of live, term (37-41weeks) singleton deliveries (N=641,857). We calculated prevalence of large-for-gestational age (LGA) (birth weight-for-gestational age≥90th percentile) and macrosomia (birth weight>4500g) by GWG categories (inadequate, appropriate, or excess). We used multivariable logistic regression to estimate the relative risk (RR) of large birth size associated with excess compared to appropriate GWG among mothers with PDM. We then estimated the population attributable fraction (PAF) of large birth size due to excess GWG among mothers with PDM (n=4427). Regardless of diabetes status, half of mothers (51.2%) gained weight in excess of recommendations. Large birth size was higher in infants of mothers with PDM than in infants of mothers without diabetes (28.8% versus 9.4% for LGA, 5.8% versus 0.9% for macrosomia). Among women with PDM, the adjusted RR of having an LGA infant was 1.7 (95% CI 1.5, 1.9) for women with excess GWG compared to those with appropriate gain; the PAF was 27.7% (95% CI 22.0, 33.3). For macrosomia, the adjusted RR associated with excess GWG was 2.1 (95% CI 1.5, 2.9) and the PAF was 38.6% (95% CI 24.9, 52.4). Preventing excess GWG may avert over one-third of macrosomic term infants of mothers with PDM. Effective strategies to prevent excess GWG are needed. Published by Elsevier Inc.

Micropore engineering of carbonized porous aromatic framework (PAF-1) for supercapacitors application.

PubMed

Li, Yanqiang; Roy, Soumyajit; Ben, Teng; Xu, Shixian; Qiu, Shilun

2014-07-07

Micropore engineering of porous carbons on the effect of capacitance was explored using a carbonized porous aromatic framework (PAF-1). The porous carbons obtained through different carbonization methods show different pore structures enabling us to do this. The capacitance was measured both in aqueous electrolyte and different organic electrolytes. The porous carbons prepared by KOH activation show both high microporous volume, which is beneficial for charge storage, and mesoporous volume, which is devoted to fast ion diffusion in the pores; properties which are highly desirable. It shows a capacitance as high as 280 F g(-1) and 203 F g(-1) at a current density of 1 A g(-1) in 6.0 M KOH and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMImTFSI), respectively. We also demonstrate the effect of diffusion and that of geometric packing of the electrolyte ions in the pores, where a commensurate match of the electrolyte ions with the pores of carbonized materials control and influence significantly the capacitance of these materials.

The Fraction of Cancer Attributable to Ways of Life, Infections, Occupation, and Environmental Agents in Brazil in 2020

PubMed Central

Azevedo e Silva, Gulnar; de Moura, Lenildo; Curado, Maria Paula; Gomes, Fabio da Silva; Otero, Ubirani; de Rezende, Leandro Fórnias Machado; Daumas, Regina Paiva; Guimarães, Raphael Mendonça; Meira, Karina Cardoso; Leite, Iuri da Costa; Valente, Joaquim Gonçalves; Moreira, Ronaldo Ismério; Koifman, Rosalina; Malta, Deborah Carvalho; Mello, Marcia Sarpa de Campos; Guedes, Thiago Wagnos Guimarães; Boffetta, Paolo

2016-01-01

Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country. PMID:26863517

17 CFR 229.1103 - (Item 1103) Transaction summary and risk factors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... summary and risk factors. 229.1103 Section 229.1103 Commodity and Securities Exchanges SECURITIES AND... (Regulation AB) § 229.1103 (Item 1103) Transaction summary and risk factors. (a) Prospectus summary. In... be assigned. (b) Risk factors. In providing the information required by Item 503(c) of Regulation S-K...

17 CFR 229.1103 - (Item 1103) Transaction summary and risk factors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... summary and risk factors. 229.1103 Section 229.1103 Commodity and Securities Exchanges SECURITIES AND... (Regulation AB) § 229.1103 (Item 1103) Transaction summary and risk factors. (a) Prospectus summary. In... be assigned. (b) Risk factors. In providing the information required by Item 503(c) of Regulation S-K...

The dark side of the ring: role of the DNA sliding surface of PCNA.

PubMed

De March, Matteo; De Biasio, Alfredo

2017-12-01

The proliferating cell nuclear antigen (PCNA) sliding clamp lies at the heart of the accurate duplication of eukaryotic genomes. While the outer surface of the PCNA ring interacts with polymerases and other factors, the role of the inner wall facing the DNA is elusive. Recent evidence shows that conserved basic residues in the PCNA central channel create a specific surface that recognizes the DNA backbone and enables the clamp to slide by rotationally tracking the DNA helix. The sliding surface can be modulated (i) through lysine acetylation, which triggers PCNA degradation during nucleotide excision repair (NER) and stimulates repair by homologous recombination (HR) or (ii) through binding of the protein factor p15 PAF , which turns off DNA lesion bypass. Thus, the inner surface of PCNA is unexpectedly highly regulated to control resistance to DNA damage. From a structural viewpoint, we reflect on these findings that open a new perspective on PCNA function and offer opportunities to develop tools to manipulate the DNA damage response in cancer treatment.

Burden of disease attributed to ambient air pollution in Thailand: A GIS-based approach

PubMed Central

Pinichka, Chayut; Makka, Nuttapat; Sukkumnoed, Decharut; Chariyalertsak, Suwat; Inchai, Puchong

2017-01-01

Background Growing urbanisation and population requiring enhanced electricity generation as well as the increasing numbers of fossil fuel in Thailand pose important challenges to air quality management which impacts on the health of the population. Mortality attributed to ambient air pollution is one of the sustainable development goals (SDGs). We estimated the spatial pattern of mortality burden attributable to selected ambient air pollution in 2009 based on the empirical evidence in Thailand. Methods We estimated the burden of disease attributable to ambient air pollution based on the comparative risk assessment (CRA) framework developed by the World Health Organization (WHO) and the Global Burden of Disease study (GBD). We integrated geographical information systems (GIS)-based exposure assessments into spatial interpolation models to estimate ambient air pollutant concentrations, the population distribution of exposure and the concentration-response (CR) relationship to quantify ambient air pollution exposure and associated mortality. We obtained air quality data from the Pollution Control Department (PCD) of Thailand surface air pollution monitoring network sources and estimated the CR relationship between relative risk (RR) and concentration of air pollutants from the epidemiological literature. Results We estimated 650–38,410 ambient air pollution-related fatalities and 160–5,982 fatalities that could have been avoided with a 20 reduction in ambient air pollutant concentrations. The summation of population-attributable fraction (PAF) of the disease burden for all-causes mortality in adults due to NO2 and PM2.5 were the highest among all air pollutants at 10% and 7.5%, respectively. The PAF summation of PM2.5 for lung cancer and cardiovascular disease were 16.8% and 14.6% respectively and the PAF summations of mortality attributable to PM10 was 3.4% for all-causes mortality, 1.7% for respiratory and 3.8% for cardiovascular mortality, while the PAF summation of mortality attributable to NO2 was 7.8% for respiratory mortality in Thailand. Conclusion Mortality due to ambient air pollution in Thailand varies across the country. Geographical distribution estimates can identify high exposure areas for planners and policy-makers. Our results suggest that the benefits of a 20% reduction in ambient air pollution concentration could prevent up to 25% of avoidable fatalities each year in all-causes, respiratory and cardiovascular categories. Furthermore, our findings can provide guidelines for future epidemiological investigations and policy decisions to achieve the SDGs. PMID:29267319

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

PubMed

Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

2009-05-13

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

PubMed Central

Leung, Fiona Wan Lun; Lam, Hugh Simon; Tam, Yuk Him; To, Ka Fai; Cheung, Hon Ming; Leung, Kam Tong; Poon, Terence Chuen Wai; Lee, Kim Hung; Li, Karen; Fok, Tai Fai

2012-01-01

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients. PMID:22606320

Department of Defense Chemical, Biological, Radiological, and Nuclear Defense Program. FY2003-2005 Performance Plan

DTIC Science & Technology

2004-05-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to...baselined. Long Range Biometric Target ID System Explore technologies for a long range biometric target identification system. 3.5.1.6

Quantitative genetic-interaction mapping in mammalian cells

PubMed Central

Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

2013-01-01

Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ~11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape. PMID:23407553

The Sound of Feedback in Higher Education

ERIC Educational Resources Information Center

Savin-Baden, Maggi

2010-01-01

Whilst there is considerable literature on feedback for students and on the use of audio feedback, literature in the area of podcasting assignment feedback (PAF) remains sparse. Partly, this may be due to a lack of clarity about what counts as feedback, the way in which feedback is located pedagogically and the relationship between feedback…

Laboratory Simulations of Martian and Venusian Aeolian Processes

NASA Technical Reports Server (NTRS)

Greeley, Ronald

1999-01-01

The objective of this work was to conduct research in the Planetary Aeolian Facility (PAF) at NASA-Ames Research Center as a laboratory for the planetary science community and to carry-out experiments on the physics and geology of particles moved by winds, and for the development of instruments and spacecraft components for planetary missions.

Massage Therapy in Children with Asthma: A Systematic Review and Meta-Analysis.

PubMed

Wu, Ji; Yang, Xi-Wen; Zhang, Ming

2017-01-01

To systematically evaluate the efficacy of massage, a traditional treatment method of traditional Chinese medicine on children with asthma. Literatures from 5 databases using the date ranging from 1 January, 1990, to 13 December, 2016, were reviewed, which were all randomized controlled trials evaluating the efficacy on children with asthma and effect on lung function mainly by massage therapy. 14 researches with 1299 patients were included in the meta-analysis. Compared with control group, a better efficacy was found in treatment group, which focused on massage therapy. Compared with control group, there was remarkable increase on FEV1 as well as PEF in treatment group. All studies have shown that massage therapy has a significantly positive effect on children with asthma, improves the pulmonary function parameters of large airway, reduces the plasma concentrations of PAF and prostaglandin, and increases the levels of PAF-AH and DP1; therefore, it greatly improves pulmonary function. However, the limited research designs of included studies lead to high risk of bias. More randomized controlled trials with better methodological quality are needed to further confirm the effectiveness of massage.

Influence of temperature and molecular structure on ionic liquid solvation layers.

PubMed

Wakeham, Deborah; Hayes, Robert; Warr, Gregory G; Atkin, Rob

2009-04-30

Atomic force microscopy (AFM) force profiling is used to investigate the structure of adsorbed and solvation layers formed on a mica surface by various room temperature ionic liquids (ILs) ethylammonium nitrate (EAN), ethanolammonium nitrate (EtAN), ethylammonium formate (EAF), propylammonium formate (PAF), ethylmethylammonium formate (EMAF), and dimethylethylammonium formate (DMEAF). At least seven layers are observed for EAN at 14 degrees C (melting point 13 degrees C), decreasing as the temperature is increased to 30 degrees C due to thermal energy disrupting solvophobic forces that lead to segregation of cation alkyl tails from the charged ammonium and nitrate moieties. The number and properties of the solvation layers can also be controlled by introducing an alcohol moiety to the cation's alkyl tail (EtAN), or by replacing the nitrate anion with formate (EAF and PAF), even leading to the detection of distinct cation and anion sublayers. Substitution of primary by secondary or tertiary ammonium cations reduces the number of solvation layers formed, and also weakens the cation layer adsorbed onto mica. The observed solvation and adsorbed layer structures are discussed in terms of the intermolecular cohesive forces within the ILs.

A poly(acrylonitrile)-functionalized porous aromatic framework synthesized by atom-transfer radical polymerization for the extraction of uranium from seawater

DOE PAGES

Yue, Yanfeng; Zhang, Chenxi; Tang, Qing; ...

2015-10-30

In order to ensure a sustainable reserve of fuel for nuclear power generation, tremendous research efforts have been devoted to developing advanced sorbent materials for extracting uranium from seawater. In this work, a porous aromatic framework (PAF) was surface-functionalized with poly(acrylonitrile) through atom-transfer radical polymerization (ATRP). Batches of this adsorbent were conditioned with potassium hydroxide (KOH) at room temperature or 80 °C prior to contact with a uranium-spiked seawater simulant, with minimal differences in uptake observed as a function of conditioning temperature. A maximum capacity of 4.81 g-U/kg-ads was obtained following 42 days contact with uranium-spiked filtered environmental seawater, whichmore » demonstrates a comparable adsorption rate. A kinetic investigation revealed extremely rapid uranyl uptake, with more than 80% saturation reached within 14 days. Furthermore, relying on the semiordered structure of the PAF adsorbent, density functional theory (DFT) calculations reveal cooperative interactions between multiple adsorbent groups yield a strong driving force for uranium binding.« less

Mediators of mast cells in bullous pemphigoid and dermatitis herpetiformis.

PubMed

Zebrowska, Agnieszka; Wagrowska-Danilewicz, Malgorzata; Danilewicz, Marian; Stasikowska-Kanicka, Olga; Kulczycka-Siennicka, Lilianna; Wozniacka, Anna; Waszczykowska, Elzbieta

2014-01-01

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

Mediators of Mast Cells in Bullous Pemphigoid and Dermatitis Herpetiformis

PubMed Central

Stasikowska-Kanicka, Olga; Kulczycka-Siennicka, Lilianna; Wozniacka, Anna; Waszczykowska, Elzbieta

2014-01-01

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP. PMID:25400334

Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study.

PubMed

Tong, Tammy Y N; Wareham, Nicholas J; Khaw, Kay-Tee; Imamura, Fumiaki; Forouhi, Nita G

2016-09-29

Despite convincing evidence in the Mediterranean region, the cardiovascular benefit of the Mediterranean diet is not well established in non-Mediterranean countries and the optimal criteria for defining adherence are unclear. The population attributable fraction (PAF) of adherence to this diet is also unknown. In the UK-based EPIC-Norfolk prospective cohort, we evaluated habitual diets assessed at baseline (1993-1997) and during follow-up (1998-2000) using food-frequency questionnaires (n = 23,902). We estimated a Mediterranean diet score (MDS) using cut-points projected from the Mediterranean dietary pyramid, and also three other pre-existing MDSs. Using multivariable-adjusted Cox regression with repeated measures of MDS and covariates, we examined prospective associations between each MDS with incident cardiovascular diseases (CVD) by 2009 and mortality by 2013, and estimated PAF for each outcome attributable to low MDS. We observed 7606 incident CVD events (2818/100,000 person-years) and 1714 CVD deaths (448/100,000). The MDS based on the Mediterranean dietary pyramid was significantly associated with lower incidence of the cardiovascular outcomes, with hazard ratios (95 % confidence intervals) of 0.95 (0.92-0.97) per one standard deviation for incident CVD and 0.91 (0.87-0.96) for CVD mortality. Associations were similar for composite incident ischaemic heart disease and all-cause mortality. Other pre-existing MDSs showed similar, but more modest associations. PAF due to low dietary pyramid based MDS (<95th percentile) was 3.9 % (1.3-6.5 %) for total incident CVD and 12.5 % (4.5-20.6 %) for CVD mortality. Greater adherence to the Mediterranean diet was associated with lower CVD incidence and mortality in the UK. This diet has an important population health impact for the prevention of CVD.

Diseases Burden of Chronic Obstructive Pulmonary Disease (COPD) Attributable to Ground-Level Ozone in Thailand: Estimates Based on Surface Monitoring Measurements Data.

PubMed

Pinichka, Chayut; Bundhamcharoen, Kanitta; Shibuya, Kenji

2015-05-14

Ambient ozone (O3) pollution has increased globally since preindustrial times. At present, O3 is one of the major air pollution concerns in Thailand, and is associated with health impacts such as chronic obstructive pulmonary disease (COPD). The objective of our study is to estimate the burden of disease attributed to O3 in 2009 in Thailand based on empirical evidence. We estimated disability-adjusted life years (DALYs) attributable to O3 using the comparative risk assessment framework in the Global Burden of Diseases (GBD) study. We quantified the population attributable fraction (PAF), integrated from Geographic Information Systems (GIS)-based spatial interpolation, the population distribution of exposure, and the exposure-response coefficient to spatially characterize exposure to ambient O3 pollution on a national scale. Exposure distribution was derived from GIS-based spatial interpolation O3 exposure model using Pollution Control Department Thailand (PCD) surface air pollution monitor network sources. Relative risk (RR) and population attributable fraction (PAF) were determined using health impact function estimates for O3. PAF (%) of COPD attributable to O3 were determined by region: at approximately, Northern=2.1, Northeastern=7.1, Central=9.6, Eastern=1.75, Western=1.47 and Southern=1.74. The total COPD burden attributable to O3 for Thailand in 2009 was 61,577 DALYs. Approximately 0.6% of the total DALYs in Thailand is male: 48,480 DALYs; and female: 13,097 DALYs. This study provides the first empirical evidence on the health burden (DALYs) attributable to O3 pollution in Thailand. Varying across regions, the disease burden attributable to O3 was 0.6% of the total national burden in 2009. Better empirical data on local specific sites, e.g. urban and rural areas, alternative exposure assessment, e.g. land use regression (LUR), and a local concentration-response coefficient are required for future studies in Thailand.

Overweight and obesity on the island of Ireland: an estimation of costs.

PubMed

Dee, Anne; Callinan, Aoife; Doherty, Edel; O'Neill, Ciaran; McVeigh, Treasa; Sweeney, Mary Rose; Staines, Anthony; Kearns, Karen; Fitzgerald, Sarah; Sharp, Linda; Kee, Frank; Hughes, John; Balanda, Kevin; Perry, Ivan J

2015-03-16

The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches. Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality. The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease. The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The economic burden of not meeting food recommendations in Canada: The cost of doing nothing.

PubMed

Lieffers, Jessica R L; Ekwaru, John Paul; Ohinmaa, Arto; Veugelers, Paul J

2018-01-01

Few studies have estimated the economic burden of chronic diseases (e.g., type 2 diabetes, cardiovascular diseases, cancers) attributable to unhealthy eating. In this study, we estimated the economic burden of chronic disease attributable to not meeting Canadian food recommendations. We first obtained chronic disease risk estimates for intakes of both protective (1. vegetables; 2. fruit; 3. whole grains; 4. milk; 5. nuts and seeds) and harmful (6. processed meat; 7. red meat; 8. sugar-sweetened beverages) foods from the Global Burden of Disease Study, and food intakes from the 2004 Canadian Community Health Survey 24-hour dietary recalls (n = 33,932 respondents). We then calculated population attributable fractions (PAFs) for all relevant food-chronic disease combinations by age and sex groups. These PAFs were then mathematically combined for each disease for each age and sex group. We then estimated attributable costs by multiplying these combined PAFs with estimated 2014 annual direct health care (hospital, drug, physician) and indirect (human capital approach) costs for each disease. We found that not meeting recommendations for the eight foods was responsible for CAD$13.8 billion/year (direct health care: CAD$5.1 billion, indirect: CAD$8.7 billion). Nuts and seeds and whole grains were the top cost contributors rather than vegetables and fruit. Our findings suggest that unhealthy eating constitutes a tremendous economic burden to Canada that is similar in magnitude to the burden of smoking and larger than that of physical inactivity which were estimated using similar approaches. A status quo in promotion of healthy eating will allow this burden to continue. Interventions to reduce the health and economic burden of unhealthy eating in Canada may be more effective if they are broad in focus and include promotion of nuts and seeds and whole grains along with vegetables and fruit rather than have a narrow focus such as primarily on vegetables and fruit.

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

PubMed

DeVille, J Brian; Svinarich, J Thomas; Dan, Dan; Wickliffe, Andrew; Kantipudi, Charan; Lim, Hae W; Plummer, Lisa; Baker, James; Kowalski, Marcin; Baydoun, Hassan; Jenkins, Mark; Chang-Sing, Peter

2014-06-01

Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

PubMed

Mathias, C J; Senard, J M; Braune, S; Watson, L; Aragishi, A; Keeling, J E; Taylor, M D

2001-08-01

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Population Activities Fund Agency (PAFA): the journey so far.

PubMed

1993-01-01

Mechanisms are needed funding Nigerian Federal efforts to implement the National Policy on Population for Development, which was approved by the Armed Forces Ruling Council in February, 1988. Subprojects of the Population Activities Fund Agency (PAFA) which were approves are: the integration of family planning (FP) into maternal and child health (MCH) the promotion of Fp through health education, tertiary centers for reproductive health, public enlightenment on population, population/family life education in primary schools, monitoring of National Population Project impact, and integration of population into planning and budgeting. The last obstacle to implementation of PAFA's activities is the signing into law the decree establishing PAFA as a parastatal. The passage is required for continued operations. The national Population for Development policy is unique in providing for quantitative targets, which has attracted the needed financial support of agencies such as the World Bank. As part of the National Population Policy, the National Population Program (NPP) is developing an effective strategy for securing funding and evaluation of subprojects that are designed and implemented b Collaborating Agencies (CAs), both private and public. NPP aims 1) to provide funds for qualified CAs through the Population Activities Fund (PAF) and Agency (PAFA); 2) to monitor PAFA, which manages PAf with the Department of Population Activities, and 3) to stimulate analysis of sociocultural constraints to fertility reduction and international comparisons, and to design innovative interventions through the Population Research Fund (PRF). PAFA funds implementing agencies at all government and nongovernment levels with approaches to population information and services. The goal of PAFA is to realize NPP objectives. The motto is "Towards an improved quality of life for every Nigerian." The mandate is to provide funding for the PAF and NPP, to monitor CAs, to provide assistance to CAs preparing Phase II subprojects, and to supervise and guide CAs on funding, procurement, and implementation.

Composite cements benefit from light-curing.

PubMed

Lührs, Anne-Katrin; De Munck, Jan; Geurtsen, Werner; Van Meerbeek, Bart

2014-03-01

To investigate the effect of curing of composite cements and a new ceramic silanization pre-treatment on the micro-tensile bond strength (μTBS). Feldspathic ceramic blocks were luted onto dentin using either Optibond XTR/Nexus 3 (XTR/NX3; Kerr), the silane-incorporated 'universal' adhesive Scotchbond Universal/RelyX Ultimate (SBU/RXU; 3M ESPE), or ED Primer II/Panavia F2.0 (ED/PAF; Kuraray Noritake). Besides 'composite cement', experimental variables were 'curing mode' ('AA': complete auto-cure at 21°C; 'AA*': complete auto-cure at 37°C; 'LA': light-curing of adhesive and auto-cure of cement; 'LL': complete light-curing) and 'ceramic surface pre-treatment' ('HF/S/HB': hydrofluoric acid ('HF': IPS Ceramic Etching Gel, Ivoclar-Vivadent), silanization ('S': Monobond Plus, Ivoclar-Vivadent) and application of an adhesive resin ('HB': Heliobond, Ivoclar-Vivadent); 'HF/SBU': 'HF' and application of the 'universal' adhesive Scotchbond Universal ('SBU'; 3M ESPE, only for SBU/RXU)). After water storage (7 days at 37°C), ceramic-dentin sticks were subjected to μTBS testing. Regarding the 'composite cement', the significantly lowest μTBSs were measured for ED/PAF. Regarding 'curing mode', the significantly highest μTBS was recorded when at least the adhesive was light-cured ('LA' and 'LL'). Complete auto-cure ('AA') revealed the significantly lowest μTBS. The higher auto-curing temperature ('AA*') increased the μTBS only for ED/PAF. Regarding 'ceramic surface pre-treatment', only for 'LA' the μTBS was significantly higher for 'HF/S/HB' than for 'HF/SBU'. Complete auto-cure led to inferior μTBS than when either the adhesive (on dentin) or both adhesive and composite cement were light-cured. The use of a silane-incorporated adhesive did not decrease luting effectiveness when also the composite cement was light-cured. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Use of a repetitive DNA probe to type clinical and environmental isolates of Aspergillus flavus from a cluster of cutaneous infections in a neonatal intensive care unit.

PubMed

James, M J; Lasker, B A; McNeil, M M; Shelton, M; Warnock, D W; Reiss, E

2000-10-01

Aspergillus flavus is second to A. fumigatus as a cause of invasive aspergillosis, but no standard method exists for molecular typing of strains from human sources. A repetitive DNA sequence cloned from A. flavus and subcloned into a pUC19 vector, pAF28, was used to type 18 isolates from diverse clinical, environmental, and geographic sources. The restriction fragment length polymorphisms generated with EcoRI- or PstI-digested genomic DNA and probed with digoxigenin-labeled pAF28 revealed complete concordance between patterns. Eighteen distinct fingerprints were observed. The probe was used to investigate two cases of cutaneous A. flavus infection in low-birth-weight infants in a neonatal intensive care unit (NICU). Both infants were transported by the same ambulance and crew to the NICU on the same day. A. flavus strains of the same genotype were isolated from both infants, from a roll of tape used to fasten their umbilical catheters, from a canvas bag used to store the tape in the ambulance, and from the tape tray in the ambulance isolette. These cases highlight the need to consider exposures in critically ill neonates that might occur during their transport to the NICU and for stringent infection control practices. The hybridization profiles of strains from a second cluster of invasive A. flavus infections in two pediatric hematology-oncology patients revealed a genotype common to strains from a definite case patient and a health care worker. A probable case patient was infected with a strain with a genotype different from that of the strain from the definite case patient but highly related to that of an environmental isolate. The high degree of discrimination and reproducibility obtained with the pAF28 probe underscores its utility for typing clinical and environmental isolates of A. flavus.

Use of a Repetitive DNA Probe To Type Clinical and Environmental Isolates of Aspergillus flavus from a Cluster of Cutaneous Infections in a Neonatal Intensive Care Unit

PubMed Central

James, Michael J.; Lasker, Brent A.; McNeil, Michael M.; Shelton, Mark; Warnock, David W.; Reiss, Errol

2000-01-01

Aspergillus flavus is second to A. fumigatus as a cause of invasive aspergillosis, but no standard method exists for molecular typing of strains from human sources. A repetitive DNA sequence cloned from A. flavus and subcloned into a pUC19 vector, pAF28, was used to type 18 isolates from diverse clinical, environmental, and geographic sources. The restriction fragment length polymorphisms generated with EcoRI- or PstI-digested genomic DNA and probed with digoxigenin-labeled pAF28 revealed complete concordance between patterns. Eighteen distinct fingerprints were observed. The probe was used to investigate two cases of cutaneous A. flavus infection in low-birth-weight infants in a neonatal intensive care unit (NICU). Both infants were transported by the same ambulance and crew to the NICU on the same day. A. flavus strains of the same genotype were isolated from both infants, from a roll of tape used to fasten their umbilical catheters, from a canvas bag used to store the tape in the ambulance, and from the tape tray in the ambulance isolette. These cases highlight the need to consider exposures in critically ill neonates that might occur during their transport to the NICU and for stringent infection control practices. The hybridization profiles of strains from a second cluster of invasive A. flavus infections in two pediatric hematology-oncology patients revealed a genotype common to strains from a definite case patient and a health care worker. A probable case patient was infected with a strain with a genotype different from that of the strain from the definite case patient but highly related to that of an environmental isolate. The high degree of discrimination and reproducibility obtained with the pAF28 probe underscores its utility for typing clinical and environmental isolates of A. flavus. PMID:11015372

[Anticoagulant therapy in patients with permanent atrial fibrillation - evidence based medicine and clinical practice].

PubMed

Bozić, Ivona; Capkun, Vesna; Bozić, Dorotea; Karabuva, Svjetlana; Caljkusić, Kresimir; Trgo, Gorana; Carević, Vedran; Fabijanić, Damir

2013-01-01

Objective of study was to assess the concordance of the tromboprophylactic treatment in patients with permanent atrial fibrillation (pAF) with guidelines of the European Society of Cardiology. Prospective cross-sectional study consecutivelly included 674 patients (400 S59%C male) discharged from cardiology department with the diagnosis pAF. The thromboembolic risk (TE) has been established according to CHA2DS2-VASc score, whereas the bleeding risk has been assessed according to HAS-BLED score. 578 (86%) belonged to the group of high, 57 (8%) to the group of moderate, and 39 (6%) patients to the group of low TE risk. 601 (89%) patients received thromboprophylaxis: 310 (46%) warfarin, 258 (38%) acetylsalicylic acid, and 33 (5%) patients clopidogrel. Warfarin has been prescribed to 47% of patients with high, 49% of patients with moderate and to 26% of patients with low TE risk (P=0.03). Acetylsalicylic acid (ASA) has equally been prescribed to patients of all TE risk groups: low, moderate and high (39% vs. 39% vs.38%/o; P=0.998). ASA (P<0.001) and warfarin (P=0.007) have been used more frequently in the group of patients with high bleeding risk, in which the same incidence of warfarin and ASA administration has been registered (53% vs. 47%; P=0.416). Age > or =75 has been an independent predictor of non-administration (OR 1.7; 95% CI 1.2-2.4; P=0.003), whereas the history of stroke was for warfarin administration (OR 0.47; 95% CI 0.29-0.76; P-0.002). In prescribing thromboprophylaxis to patients with pAF, cardiologists do not observe the recommended clinical guidelines. Despite nonexistence of contraindications, a significant number of patients with high TE risk has not been administered warfarin. At the same time, warfarin has been administered to the patients with low TE risk, exposing them unnecessarily to the undesired effect of anticoagulant treatment.

Long-term follow-up of patients with paroxysmal atrial fibrillation and severe left atrial scarring: comparison between pulmonary vein antrum isolation only or pulmonary vein isolation combined with either scar homogenization or trigger ablation.

PubMed

Mohanty, Sanghamitra; Mohanty, Prasant; Di Biase, Luigi; Trivedi, Chintan; Morris, Eli Hamilton; Gianni, Carola; Santangeli, Pasquale; Bai, Rong; Sanchez, Javier E; Hranitzky, Patrick; Gallinghouse, G Joseph; Al-Ahmad, Amin; Horton, Rodney P; Hongo, Richard; Beheiry, Salwa; Elayi, Claude S; Lakkireddy, Dhanunjaya; Madhu Reddy, Yaruva; Viles Gonzalez, Juan F; Burkhardt, J David; Natale, Andrea

2017-11-01

Left atrial (LA) scarring, a consequence of cardiac fibrosis is a powerful predictor of procedure-outcome in atrial fibrillation (AF) patients undergoing catheter ablation. We sought to compare the long-term outcome in patients with paroxysmal AF (PAF) and severe LA scarring identified by 3D mapping, undergoing pulmonary vein isolation (PVAI) only or PVAI and the entire scar areas (scar homogenization) or PVAI+ ablation of the non-PV triggers. Totally, 177 consecutive patients with PAF and severe LA scarring were included. Patients underwent PVAI only (n = 45, Group 1), PVAI+ scar homogenization (n = 66, Group 2) or PVAI+ ablation of non-PV triggers (n = 66, Group 3) based on operator's choice. Baseline characteristics were similar across the groups. After first procedure, all patients were followed-up for a minimum of 2 years. The success rate at the end of the follow-up was 18% (8 pts), 21% (14 pts), and 61% (40 pts) in Groups 1, 2, and 3, respectively. Cumulative probability of AF-free survival was significantly higher in Group 3 (overall log-rank P <0.01, pairwise comparison 1 vs. 3 and 2 vs. 3 P < 0.01). During repeat procedures, non-PV triggers were ablated in all. After average 1.5 procedures, the success rates were 28 (62%), 41 (62%), and 56 (85%) in Groups 1, 2, and 3, respectively (log-rank P< 0.001). In patients with PAF and severe LA scarring, PVAI+ ablation of non-PV triggers is associated with significantly better long-term outcome than PVAI alone or PVAI+ scar homogenization. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Abnormalities of the QT interval in primary disorders of autonomic failure.

PubMed

Choy, A M; Lang, C C; Roden, D M; Robertson, D; Wood, A J; Robertson, R M; Biaggioni, I

1998-10-01

Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Patterning ecological risk of pesticide contamination at the river basin scale.

PubMed

Faggiano, Leslie; de Zwart, Dick; García-Berthou, Emili; Lek, Sovan; Gevrey, Muriel

2010-05-01

Ecological risk assessment was conducted to determine the risk posed by pesticide mixtures to the Adour-Garonne river basin (south-western France). The objectives of this study were to assess the general state of this basin with regard to pesticide contamination using a risk assessment procedure and to detect patterns in toxic mixture assemblages through a self-organizing map (SOM) methodology in order to identify the locations at risk. Exposure assessment, risk assessment with species sensitivity distribution, and mixture toxicity rules were used to compute six relative risk predictors for different toxic modes of action: the multi-substance potentially affected fraction of species depending on the toxic mode of action of compounds found in the mixture (msPAF CA(TMoA) values). Those predictors computed for the 131 sampling sites assessed in this study were then patterned through the SOM learning process. Four clusters of sampling sites exhibiting similar toxic assemblages were identified. In the first cluster, which comprised 83% of the sampling sites, the risk caused by pesticide mixture toward aquatic species was weak (mean msPAF value for those sites<0.0036%), while in another cluster the risk was significant (mean msPAF<1.09%). GIS mapping allowed an interesting spatial pattern of the distribution of sampling sites for each cluster to be highlighted with a significant and highly localized risk in the French department called "Lot et Garonne". The combined use of the SOM methodology, mixture toxicity modelling and a clear geo-referenced representation of results not only revealed the general state of the Adour-Garonne basin with regard to contamination by pesticides but also enabled to analyze the spatial pattern of toxic mixture assemblage in order to prioritize the locations at risk and to detect the group of compounds causing the greatest risk at the basin scale. Copyright 2010 Elsevier B.V. All rights reserved.

Learning Style Scales: a valid and reliable questionnaire.

PubMed

Abdollahimohammad, Abdolghani; Ja'afar, Rogayah

2014-01-01

Learning-style instruments assist students in developing their own learning strategies and outcomes, in eliminating learning barriers, and in acknowledging peer diversity. Only a few psychometrically validated learning-style instruments are available. This study aimed to develop a valid and reliable learning-style instrument for nursing students. A cross-sectional survey study was conducted in two nursing schools in two countries. A purposive sample of 156 undergraduate nursing students participated in the study. Face and content validity was obtained from an expert panel. The LSS construct was established using principal axis factoring (PAF) with oblimin rotation, a scree plot test, and parallel analysis (PA). The reliability of LSS was tested using Cronbach's α, corrected item-total correlation, and test-retest. Factor analysis revealed five components, confirmed by PA and a relatively clear curve on the scree plot. Component strength and interpretability were also confirmed. The factors were labeled as perceptive, solitary, analytic, competitive, and imaginative learning styles. Cronbach's α was >0.70 for all subscales in both study populations. The corrected item-total correlations were >0.30 for the items in each component. The LSS is a valid and reliable inventory for evaluating learning style preferences in nursing students in various multicultural environments.

Influence of Eye Movements, Auditory Perception, and Phonemic Awareness in the Reading Process

ERIC Educational Resources Information Center

Megino-Elvira, Laura; Martín-Lobo, Pilar; Vergara-Moragues, Esperanza

2016-01-01

The authors' aim was to analyze the relationship of eye movements, auditory perception, and phonemic awareness with the reading process. The instruments used were the King-Devick Test (saccade eye movements), the PAF test (auditory perception), the PFC (phonemic awareness), the PROLEC-R (lexical process), the Canals reading speed test, and the…

Screening for anti-inflammatory activity of 12 Arnica (Asteraceae) species assessed by inhibition of NF-kappaB and release of human neutrophil elastase.

PubMed

Ekenäs, Catarina; Zebrowska, Anna; Schuler, Barbara; Vrede, Tobias; Andreasen, Katarina; Backlund, Anders; Merfort, Irmgard; Bohlin, Lars

2008-12-01

Several species in the genus Arnica have been used in traditional medicine to treat inflammatory-related disorders. Extracts of twelve Arnica species and two species closely related to arnica ( Layia hieracioides and Madia sativa) were investigated for inhibition of human neutrophil elastase release and inhibition of transcription factor NF-kappaB. Statistical analyses reveal significant differences in inhibitory capacities between extracts. Sesquiterpene lactones of the helenanolide type, of which some are known inhibitors of human neutrophil elastase release and NF-kappaB, are present in large amounts in the very active extracts of A. montana and A. chamissonis. Furthermore, A. longifolia, which has previously not been investigated, shows a high activity similar to that of A. montana and A. chamissonis in both bioassays. Sesquiterpene lactones of the xanthalongin type are present in large amounts in A. longifolia and other active extracts and would be interesting to evaluate further. COX-2:cyclooxygenase 2 EMSA:electrophoretic mobility shift assay fMLP: N-formyl-methionyl-leucyl-phenylalanine HaCaT:human keratinocyte HNE:human neutrophil elastase IkappaB:inhibitory subunit of kappaB iNOS:inducible nitric oxide synthase NF-kappaB:nuclear factor kappaB PAF:platelet activating factor STL:sesquiterpene lactone TNF-alpha:tumor necrosis factor alpha.

Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter.

PubMed

Yuan, Xuejun; Zhao, Jian; Zentgraf, Hanswalter; Hoffmann-Rohrer, Urs; Grummt, Ingrid

2002-11-01

In mammals, growth-dependent regulation of rRNA synthesis is brought about by the transcription initiation factor TIF-IA. TIF-IA is associated with a fraction of the TBP-containing factor TIF-IB/SL1 and the initiation-competent form of RNA polymerase I (Pol I). We investigated the mechanisms that down-regulate cellular pre-rRNA synthesis and demonstrate that nutrient starvation, density arrest and protein synthesis inhibitors inactivate TIF-IA and impair the association of TIF-IA with Pol I. Moreover, we used a panel of TIF-IA deletion mutants to map the domains that mediate the interaction of TIF-IA with Pol I and TIF-IB/SL1. We found that amino acids 512-609 interact with two subunits of Pol I, RPA43 and PAF67, whereas a short, conserved motif (LARAK, amino acids 411-415) is required for the association of TIF-IA with TAF(I)95 and TAF(I)68. The results uncover an interphase for essential protein-protein interactions that facilitate Pol I preinitiation complex formation.

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52) – a novel type of 5-lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo

PubMed Central

Greiner, C; Hörnig, C; Rossi, A; Pergola, C; Zettl, H; Schubert-Zsilavecz, M; Steinhilber, D; Sautebin, L; Werz, O

2011-01-01

BACKGROUND AND PURPOSE 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS HZ52, 1.5 mg·kg−1 i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB4 levels and protected mice (10 mg·kg−1, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca2+. CONCLUSIONS AND IMPLICATIONS HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers. PMID:21506958

Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005-2011.

PubMed

Esteghamati, Alireza; Etemad, Koorosh; Koohpayehzadeh, Jalil; Abbasi, Mehrshad; Meysamie, Alipasha; Noshad, Sina; Asgari, Fereshteh; Mousavizadeh, Mostafa; Rafei, Ali; Khajeh, Elias; Neishaboury, Mohamadreza; Sheikhbahaei, Sara; Nakhjavani, Manouchehr

2014-02-01

To estimate the prevalence and trends of diabetes mellitus (DM) and impaired fasting glucose (IFG), 2005-2011, and to determine the contribution of obesity to DM prevalence. Data from Surveillance of Risk Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011 were gathered. DM was defined as presence of self-reported previous diagnosis or a fasting plasma glucose (FPG)≥7 mmol/L. IFG was diagnosed with FPG levels between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005-2011 were determined by extrapolating survey results to Iran's adult population. Population attributable fraction (PAF) of obesity was also calculated. In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41-16.78) and 11.37% (95%CI: 9.86-12.89) among 25-70 years, respectively. DM was more common in older age (p < 0.0001), in women (p = 0.0216), and in urban-dwellers (p = 0.0001). In 2005-2011, trend analysis revealed a 35.1% increase in DM prevalence (OR: 1.04, 95%CI: 1.01-1.07, p = 0.011); albeit, IFG prevalence remained relatively unchanged (OR: 0.98, 95%CI: 0.95-1.00, p = 0.167). In this period, DM awareness improved; undiagnosed DM prevalence decreased from 45.7% to 24.7% (p < 0.001). PAF analysis demonstrated that 33.78%, 10.25%, and 30.56% of the prevalent DM can be attributed to overweight (BMI≥25kg/m(2)), general obesity (BMI≥30 kg/m(2)), and central obesity (waist circumference≥90 cm), respectively. Additionally, the DM increase rate in 2005-2011, was 20 times higher in morbidly obese compared with lean individuals. More than four million Iranian adults have DM which has increased by 35% over the past seven years, owing in large part, to expanding obesity epidemic. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.

PubMed

Grimminger, F; Mayser, P; Papavassilis, C; Thomas, M; Schlotzer, E; Heuer, K U; Führer, D; Hinsch, K D; Walmrath, D; Schill, W B

1993-08-01

Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.

A psychometric evaluation of the Chinese version of the nursing home survey on patient safety culture.

PubMed

Lin, Shu-Yuan; Tseng, Wei Ting; Hsu, Miao-Ju; Chiang, Hui-Ying; Tseng, Hui-Chen

2017-12-01

To test the psychometric properties of the Chinese version of the Nursing Home Survey on Patient Safety Culture scale among staff in long-term care facilities. The Nursing Home Survey on Patient Safety Culture scale is a standard tool for safety culture assessment in nursing homes. Extending its application to different types of long-term care facilities and varied ethnic populations is worth pursuing. A national random survey. A total of 306 managers and staff completed the Chinese version of the Nursing Home Survey on Patient Safety Culture scale among 30 long-term care facilities in Taiwan. Content validity and construct validity were tested by content validity index (CVI) and principal axis factor analysis (PAF) with Promax rotation. Concurrent validity was tested through correlations between the scale and two overall rating items. Reliability was computed by intraclass correlation coefficient and Cronbach's α coefficients. Statistical analyses such as descriptive, Pearson's and Spearman's rho correlations and PAF were completed. Scale-level and item-level CVIs (0.91-0.98) of the Chinese version of the Nursing Home Survey on Patient Safety Culture scale were satisfactory. Four-factor construct and merged item composition differed from the Nursing Home Survey on Patient Safety Culture scale, and it accounted for 53% of variance. Concurrent validity was evident by existing positive correlations between the scale and two overall ratings of resident safety. Cronbach's α coefficients of the subscales and the Chinese version of the Nursing Home Survey on Patient Safety Culture scale ranged from .76-.94. The Chinese version of the Nursing Home Survey on Patient Safety Culture scale identified essential dimensions to reflect the important features of a patient safety culture in long-term care facilities. The researchers introduced the Chinese version of the Nursing Home Survey on Patient Safety Culture for safety culture assessment in long-term care facilities, but further testing of the reliability of the scale in a large Chinese sample and in different long-term care facilities was recommended. The Chinese version of the Nursing Home Survey on Patient Safety Culture scale was developed to increase the users' intention towards safety culture assessment. It can identify areas for improvement, understand safety culture changes over time and evaluate the effectiveness of interventions. © 2017 John Wiley & Sons Ltd.

Theoretical Foundations of Software Technology.

DTIC Science & Technology

1983-02-14

major research interests are software testing, aritificial intelligence , pattern recogu- tion, and computer graphics. Dr. Chandranekaran is currently...produce PASCAL language code for the problems. Because of its relationship to many issues in Artificial Intelligence , we also investigated problems of...analysis to concurmt-prmcess software re- are not " intelligent " enough to discover these by themselves, ouirl more complex control flow models. The PAF

Size and cell number of the utricle in kinetotically swimming fish: a parabolic aircraft flight study

NASA Astrophysics Data System (ADS)

Bäuerle, A.; Anken, R. H.; Hilbig, R.; Baumhauer, N.; Rahmann, H.

2004-01-01

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behavior during PAFs (especially so-called spinning movements and looping responses) and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalization of gravity in teleosteans) of fish swimming kinetotically at microgravity in comparison with animals from the same batch who swam normally. On the histological level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100 μm 2), however, was reduced in kinetotic animals ( p < 0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in malformed sensory epithelia.

Enzymatic hydrolysis of pretreated Alfa fibers (Stipa tenacissima) using β-d-glucosidase and xylanase of Talaromyces thermophilus from solid-state fermentation.

PubMed

Mallek-Fakhfakh, Hanen; Fakhfakh, Jawhar; Walha, Kamel; Hassairi, Hajer; Gargouri, Ali; Belghith, Hafedh

2017-10-01

This work aims at realizing an optimal hydrolysis of pretreated Alfa fibers (Stipa tenacissima) through the use of enzymes produced from Talaromyces thermophilus AX4, namely β-d-glucosidase and xylanase, by a solid state fermentation process of an agro-industrial waste (wheat bran supplemented with lactose). The carbon source was firstly selected and the optimal values of three other parameters were determined: substrate loading (10g), moisture content (85%) and production time (10days); which led to an optimized enzymatic juice. The outcome was then supplemented with cellulases of T. reesei and used to optimize the enzymatic saccharification of alkali-pretreated Alfa fibers (PAF). The maximum saccharification yield of 83.23% was achieved under optimized conditions (substrate concentration 3.7% (w/v), time 144h and enzyme loading of 0.8 FPU, 15U CMCase, 60U β-d-glucosidase and 125U xylanase).The structural modification of PAF due to enzymatic saccharification was supported by the changes of morphologic and chemical composition observed through macroscopic representation, FTIR and X-Ray analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum.

PubMed

Perales, J; Amorim, C Z; Rocha, S L; Domont, G B; Moussatché, H

1992-11-01

The pharmacological modulation of mice paw oedema produced by Bothrops jararaca venom (BJV) has been studied. Intraplantar injection of BJV (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. BJV heated at 100 degrees C for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. The BJV oedema was not inhibited by the anti-histamine meclizine, the inhibitor of histamine and serotonin, cyproheptadine, PAF-acether antagonist WEB 2170 or by the anti-leukotrienes C4/D4, LY 171883. Dexamethasone, aspirin, indomethacin, and the dual cyclooxygenase and lipoxygenase inhibitor BW 755C inhibited BJV-induced oedema indicating that arachidonic acid metabolism products via the cyclooxygenase pathway participate in its genesis and/or maintenance. The antibothropic fraction (ABF) (25-200 micrograms/paw) isolated from Didelphis marsupialis serum neutralized the oedema induced by the venom with and without heating, the hemorrhage induced by BJV and partially blocked the oedema induced by bradykinin and by cellulose sulphate. The oedema produced by histamine, serotonin, PAF-acether or leukotriene C4 was not inhibited.

[Estimation on the mortality and disease burden attributed to selected risk factors in Shandong province].

PubMed

Xu, Ai-qiang; Sun, Jian-dong; Lu, Zi-long; Ma, Ji-xiang; Fu, Zhen-tao; Guo, Xiao-lei

2008-10-01

To determine the major health related risk factors and provide evidence for policy-making, using health burden analysis on selected factors among general population from Shandong province. Based on data derived from the Third Death of Cause Sampling Survey in Shandong, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) were calculated according to the GBD methodology. Deaths and DALYs attributed to the selected risk factors were than estimated together with the PAF data from GBD 2001 study. The indirect method was employed to estimate the YLDs. 51.09% of the total deaths and 31.83% of the total DALYs from the Shandong population were resulted from the 19 selected risk factors. High blood pressure, smoking, low fruit and vegetable intake, alcohol consumption, indoor smoke from solid fuels, high cholesterol, urban air pollution, physical inactivity, overweight and obesity and unsafe injections in health care settings were identified as the top 10 risk factors for mortality which together caused 50.21% of the total deaths. Alcohol use, smoking, high blood pressure, low fruit and vegetable intake, indoor smoke from solid fuels, overweight and obesity, high cholesterol, physical inactivity, urban air pollution and iron-deficiency anemia were proved as the top 10 risk factors related to disease burden and were responsible for 29.04% of the total DALYs. Alcohol use, smoking and high blood pressure were determined as the major risk factors which influencing the health of residents in Shandong. The mortality and burden of disease could be reduced significantly if these major factors were effectively under control.

A Review of Multi-Threat Medical Countermeasures Against Chemical Warfare and Terrorism

DTIC Science & Technology

2004-11-01

the frequently lethal cell populations can be induced or recruited by different condi- ARDS.ś," ARDS is also associated with pulmonary toxicity of...and PAF receptor antagonist actions of benzodiazepines 19 compounds reduced SM histopathology greater than might synergistically protect against nerve...drugs, consisting of five capsaicin analogs, a flammatory pathways are also strongly implicated in NMDA single cyclooxygenase inhibitor, indomethacin

Department of Defense Chemical and Biological Defense Program. FY2004-2006 Performance Plan

DTIC Science & Technology

2005-03-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to identify...Range Biometric Target ID System Explore technologies for a long range biometric target identification system. Air Containment Monitoring System...Continue development of systems for contained air monitoring for chemical agents.Long Range Biometric Air Containment Monitoring System Continued

Population attributable fraction of incident HIV infections associated with alcohol consumption in fishing communities around Lake Victoria, Uganda

PubMed Central

Kiwanuka, Noah; Ssetaala, Ali; Ssekandi, Ismail; Nalutaaya, Annet; Kitandwe, Paul Kato; Ssempiira, Julius; Bagaya, Bernard Ssentalo; Balyegisawa, Apolo; Kaleebu, Pontiano; Hahn, Judith; Lindan, Christina; Sewankambo, Nelson Kaulukusi

2017-01-01

Background Although the association between alcohol consumption and HIV risk is well documented, few studies have examined the magnitude of new HIV infections that could be prevented by controlling alcohol use. We report the population attributable fraction (PAF) of incident HIV infections due to alcohol consumption among the HIV high-risk population of fishing communities along Lake Victoria, Uganda. Methods In a community-based cohort study, 1607 HIV sero-negative participants aged 18–49 years were enrolled from eight fishing communities along Lake Victoria, Uganda. At follow up 12 months later, 1288 (80.1%) were seen and interviewed. At baseline and follow-up visits, participants completed interviewer-administered questionnaires on alcohol consumption, demographics, and sexual risk behavior, and were tested for HIV infection. HIV incidence and adjusted incident rate ratios (adjusted IRRs) were estimated using Poisson regression models; the crude and adjusted PAFs of incident HIV infections associated with alcohol consumption were calculated using the Greenland and Drescher method for cohort studies. Results Among the 1288 participants seen at follow up, 53.5% reported drinking alcohol of whom 24.4% drank occasionally (2 days a week or less) and 29.1% drank regularly (3–7 days a week). Forty eight incident HIV infections occurred giving an incidence rate of 3.39/100 person years at-risk (pyar) (95% CI, 2.55–4.49). Compared to non-drinkers, the adjusted IRR of HIV was 3.09 (1.13–8.46) among occasional drinkers and 5.34 (2.04–13.97) among regular drinkers. The overall adjusted PAF of incident HIV infections due alcohol was 64.1 (95% CI; 23.5–83.1); ranging from 52.3 (11.9–74.2) among Muslims to 71.2 (32.6–87.7) for participants who reported ≥ 2 sexual partners in the past 12 months. Conclusion In fishing communities along Lake Victoria, Uganda, 64% of new HIV infections can be attributed to drinking alcohol. Interventions to reduce alcohol consumption should be integrated in HIV/AIDS prevention activities for populations in whom both HIV and alcohol consumption are highly prevalent. PMID:28207844

Abnormalities of the QT interval in primary disorders of autonomic failure

NASA Technical Reports Server (NTRS)

Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

1998-01-01

BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

PubMed Central

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro

2018-01-01

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms. PMID:29748512

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

PubMed

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro

2018-05-10

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O -glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut ( Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Intracellular calcium rise is not a necessary step for the stimulated actin polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yassin, R.

1986-03-01

Stimulation of rabbit peritoneal neutrophils by many chemotactic (formyl Methionyl-Leucyl-Phenylalanine (fMLP), Leukotriene B/sub 4/ (LTB/sub 4/)) and non-chemotactic (phorbol 12-myristate, 13-acetate (PMA), platelet activating factor (PAF), and the calcium ionophore A23187) factors produces rapid and dose dependent increases in the amount of actin associated with the cytoskeleton. The stimulated increase in cytoskeletal actin does not appear to require a rise in the intracellular concentration of free calcium. The increase in cytoskeletal actin produced by A23187 is transient and does not depend on the presence of calcium in the suspending medium. In the presence of extracellular calcium, the effect of themore » ionophore is biphasic with respect to concentration. The increases in actin association with cytoskeletal produced by fMLP, LTB/sub 4/, and A23187 but not by PMA, are inhibited by hyperosmolarity and pertussis toxin pretreatment. On the other hand, the addition of hyperosmolarity or pertussis toxin has small effect on the rise in the intracellular calcium produced by A23187. The results presented here suggest that an increase in the intracellular concentration of free calcium is not necessary for the stimulated increases in cytoskeletal actin.« less

Relation of Salivary PAF Periodontal Disease in Periodontal Maintenance and Refractory Periodontitis Patients

DTIC Science & Technology

1991-05-01

Knox, 1974). Studies have demonstrated the presence of streptococci and lactobacilli throughout the oral cavity , as well as in developing dental... oral cavity , it is apparent that these compounds have the potential to play a role in the initiation and progression of inflammatory oral disease...junctional epithelium and into the gingival sulcus and oral cavity . The perivascular connective tissue matrix becomes altered most likely by

Extraction of Lanthanide and Actinide Ions from Aqueous Mixtures Using a Carboxylic Acid-Functionalized Porous Aromatic Framework

DOE PAGES

Demir, Selvan; Brune, Nicholas K.; Van Humbeck, Jeffrey F.; ...

2016-04-08

Porous aromatic frameworks (PAFs) incorporating a high concentration of acid functional groups possess characteristics that are promising for use in separating lanthanide and actinide metal ions, as required in the treatment of radioactive waste. These materials have been shown to be indefinitely stable to concentrated acids and bases, potentially allowing for multiple adsorption/stripping cycles. Additionally, the PAFs combine exceptional features from MOFs and inorganic/ activated carbons giving rise to tunable pore surfaces and maximum chemical stability. Herein, we present a study of the adsorption of selected metal ions, Sr 2+, Fe 3+, Nd 3+, and Am 3+, from aqueous solutionsmore » employing a carbon-based porous aromatic framework, BPP-7 (Berkeley Porous Polymer-7). This material displays high metal loading capacities together with excellent adsorption selectivity for neodymium over strontium based on Langmuir adsorption isotherms and ideal adsorbed solution theory (IAST) calculations. Based in part upon X-ray absorption spectroscopy studies, the stronger adsorption of neodymium is attributed to multiple metal ion and binding site interactions resulting from the densely functionalized and highly interpenetrated structure of BPP-7. Finally, recyclability and combustibility experiments demonstrate that multiple adsorption/stripping cycles can be completed with minimal degradation of the polymer adsorption capacity.« less

Predicting the aquatic risk of realistic pesticide mixtures to species assemblages in Portuguese river basins.

PubMed

Silva, Emília; Daam, Michiel A; Cerejeira, Maria José

2015-05-01

Although pesticide regulatory tools are mainly based on individual substances, aquatic ecosystems are usually exposed to multiple pesticides from their use on the variety of crops within the catchment of a river. This study estimated the impact of measured pesticide mixtures in surface waters from 2002 and 2008 within three important Portuguese river basins ('Mondego', 'Sado' and 'Tejo') on primary producers, arthropods and fish by toxic pressure calculation. Species sensitivity distributions (SSDs), in combination with mixture toxicity models, were applied. Considering the differences in the responses of the taxonomic groups as well as in the pesticide exposures that these organisms experience, variable acute multi-substance potentially affected fractions (msPAFs) were obtained. The median msPAF for primary producers and arthropods in surface waters of all river basins exceeded 5%, the cut-off value used in the prospective SSD approach for deriving individual environmental quality standards. A ranking procedure identified various photosystem II inhibiting herbicides, with oxadiazon having the relatively largest toxic effects on primary producers, while the organophosphorus insecticides, chlorfenvinphos and chlorpyrifos, and the organochloride endosulfan had the largest effects on arthropods and fish, respectively. These results ensure compliance with European legislation with regard to ecological risk assessment and management of pesticides in surface waters. Copyright © 2015. Published by Elsevier B.V.

Continuous citric acid production in repeated-fed batch fermentation by Aspergillus niger immobilized on a new porous foam.

PubMed

Yu, Bin; Zhang, Xin; Sun, Wenjun; Xi, Xun; Zhao, Nan; Huang, Zichun; Ying, Zhuojun; Liu, Li; Liu, Dong; Niu, Huanqing; Wu, Jinglan; Zhuang, Wei; Zhu, Chenjie; Chen, Yong; Ying, Hanjie

2018-06-20

The efficiency of current methods for industrial production of citric acid is limited. To achieve continuous citric acid production with enhanced yield and reduced cost, immobilized fermentation was employed in an Aspergillus niger 831 repeated fed-batch fermentation system. We developed a new type of material (PAF201), which was used as a carrier for the novel adsorption immobilization system. Hydrophobicity, pore size and concentration of carriers were researched in A. niger immobilization. The efficiency of the A. niger immobilization process was analyzed by scanning electron microscopy. Then eight-cycle repeated fed-batch cultures for citric acid production were carried out over 600 h, which showed stable production with maximum citric acid concentrations and productivity levels of 162.7 g/L and 2.26 g L -1  h -1 , respectively. Compared with some other literatures about citric acid yield, PAF201 immobilization system is 11.3% higher than previous results. These results indicated that use of the new adsorption immobilization system could greatly improve citric acid productivity in repeated fed-batch fermentation. Moreover, these results could provide a guideline for A.niger or other filamentous fungi immobilization in industry. Copyright © 2018 Elsevier B.V. All rights reserved.

Secondary Stroke Prevention: Improving Diagnosis and Management with Newer Technologies.

PubMed

Imam, Yahia Z; D'Souza, Atlantic; Malik, Rayaz A; Shuaib, Ashfaq

2016-12-01

Treatment of hypertension, diabetes, high cholesterol, smoking cessation, and healthy lifestyle have all contributed to the decline in the incidence of vascular disease over the last several decades. Patients who suffer an acute stroke are at a high risk for recurrence. Introduction of newer technologies and their wider use allows for better identification of patients in whom the risk of recurrence following an acute stroke may be very high. Traditionally, the major focus for diagnosis and management has focused on patient history, examination, imaging for carotid stenosis/occlusion, and detection of AF and paroxysmal AF (PAF) with 24-48 h cardiac monitoring. This review focuses on the usefulness of three newer investigative tools that are becoming widely available and lead to better prevention. Continuous ambulatory blood pressure measurements for 24 h or longer and 3D Doppler measures of the carotid arteries provide key useful information on the state of vascular health and enhance our ability to monitor the response to preventive therapies. Furthermore, the detection of PAF can be significantly improved with prolonged cardiac monitoring for 3 weeks or longer, enabling the initiation of appropriate prevention therapy. This review will focus on the potential impact and importance of these emerging technologies on the prevention of recurrent stroke in high-risk patients.

Educational inequalities in mortality of patients with atrial fibrillation in Norway.

PubMed

Akerkar, Rupali; Ebbing, Marta; Sulo, Gerhard; Ariansen, Inger; Igland, Jannicke; Tell, Grethe S; Egeland, Grace M

2017-04-01

We explored the educational gradient in mortality in atrial fibrillation (AF) patients. We prospectively followed patients hospitalized with AF as primary discharge diagnosis in the Cardiovascular Disease in Norway 2008-2012 project. The average length of follow-up was 2.4 years. Mortality by educational level was assessed by Cox proportional hazard models. Population attributable fractions (PAF) were calculated. Analyses stratified by age (≤75 and >75 years of age), and adjusted for age, gender, medical intervention, and Charlson Comorbidity Index. Of 42,138 AF patients, 16% died by end of 2012. Among younger patients, those with low education (≤10 years) had a HR of 2.3 (95% confidence interval 2.0, 2.6) for all-cause mortality relative to those with any college or university education. Similar results were observed for cardiovascular mortality. Disparities in mortality were greater among younger than older patients. A PAF of 35.9% (95% confidence interval 27.9, 43.1) was observed for an educational level of high school/vocational school or less versus higher education in younger patients. Increasing educational level associated with better prognosis suggesting underlying education-related behavioral and medical determinants of mortality. A considerable proportion of mortality within 5 years following hospital discharge could be prevented.

Health care and lost productivity costs of overweight and obesity in New Zealand.

PubMed

Lal, Anita; Moodie, Marj; Ashton, Toni; Siahpush, Mohammad; Swinburn, Boyd

2012-12-01

To estimate the costs of health care and lost productivity attributable to overweight and obesity in New Zealand (NZ) in 2006. A prevalence-based approach to costing was used in which costs were calculated for all cases of disease in the year 2006. Population attributable fractions (PAFs) were calculated based on the relative risks obtained from large cohort studies and the prevalence of overweight and obesity. For each disease, the PAF was multiplied by the total health care cost. The costs of lost productivity associated with premature mortality were estimated using both the Human Capital approach (HCA) and Friction Cost approach (FCA). Health care costs attributable to overweight and obesity were estimated to be NZ$686m or 4.5% of New Zealand's total health care expenditure in 2006. The costs of lost productivity using the FCA were estimated to be NZ$98m and NZ$225m using the HCA. The combined costs of health care and lost productivity using the FCA were $784m and $911m using the HCA. The cost burden of overweight and obesity in NZ is considerable. Policies and interventions are urgently needed to reduce the prevalence of obesity thereby decreasing these substantial costs. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

Extraction of Lanthanide and Actinide Ions from Aqueous Mixtures Using a Carboxylic Acid-Functionalized Porous Aromatic Framework

PubMed Central

2016-01-01

Porous aromatic frameworks (PAFs) incorporating a high concentration of acid functional groups possess characteristics that are promising for use in separating lanthanide and actinide metal ions, as required in the treatment of radioactive waste. These materials have been shown to be indefinitely stable to concentrated acids and bases, potentially allowing for multiple adsorption/stripping cycles. Additionally, the PAFs combine exceptional features from MOFs and inorganic/activated carbons giving rise to tunable pore surfaces and maximum chemical stability. Herein, we present a study of the adsorption of selected metal ions, Sr2+, Fe3+, Nd3+, and Am3+, from aqueous solutions employing a carbon-based porous aromatic framework, BPP-7 (Berkeley Porous Polymer-7). This material displays high metal loading capacities together with excellent adsorption selectivity for neodymium over strontium based on Langmuir adsorption isotherms and ideal adsorbed solution theory (IAST) calculations. Based in part upon X-ray absorption spectroscopy studies, the stronger adsorption of neodymium is attributed to multiple metal ion and binding site interactions resulting from the densely functionalized and highly interpenetrated structure of BPP-7. Recyclability and combustibility experiments demonstrate that multiple adsorption/stripping cycles can be completed with minimal degradation of the polymer adsorption capacity. PMID:27163056

Proximal attrition facets: morphometric, demographic, and aging characteristics.

PubMed

Sarig, Rachel; Hershkovitz, Israel; Shvalb, Nir; Sella-Tunis, Tatiana; May, Hila; Vardimon, Alexander D

2014-08-01

Although interproximal attrition is considered to be limited in modern populations, it has important clinical implications. However, in contrast to occlusal attrition, proximal attrition receives limited scientific attention. The main purpose of the current study was to fill this void. Seven-hundred and sixty-five teeth were collected from 255 skulls of subjects 18-75 yr of age. For each individual, three mandibular teeth (the first and second premolars and the first molar) were examined for proximal attrition facets (PAFs). The results provide detailed information on the size, shape, and location of the facets according to age cohort, gender, and ethnicity. The validity of the method used to measure the facets was also examined. The major findings were as follows: PAFs are usually located on the upper half of the crown proximal aspect; in each tooth, the mesial facet is more lingually positioned and the distal facet is more buccally positioned; the majority of the facets are subrectangular in shape; the size of the facets tends to increase in an anteroposterior direction (from premolars to molars); and facet size and location are age- and sex-dependent and ethnicity-independent. It is our recommendation that dentists bear in mind that interproximal attrition is a dynamic, long-term process and needs to be considered in many clinical scenarios. © 2014 Eur J Oral Sci.

Effect of physical inactivity on major noncommunicable diseases and life expectancy in Brazil.

PubMed

de Rezende, Leandro Fornias Machado; Rabacow, Fabiana Maluf; Viscondi, Juliana Yukari Kodaira; Luiz, Olinda do Carmo; Matsudo, Victor Keihan Rodrigues; Lee, I-Min

2015-03-01

In Brazil, one-fifth of the population reports not doing any physical activity. This study aimed to assess the impact of physical inactivity on major noncommunicable diseases (NCDs), all-cause mortality and life expectancy in Brazil, by region and sociodemographic profile. We estimated the population attributable fraction (PAF) for physical inactivity associated with coronary heart disease, type 2 diabetes, breast cancer, colon cancer, and all-cause mortality. To calculate the PAF, we used the physical inactivity prevalence from the 2008 Brazilian Household Survey and relative risk data in the literature. In Brazil, physical inactivity is attributable to 3% to 5% of all major NCDs and 5.31% of all-cause mortality, ranging from 5.82% in the southeastern region to 2.83% in the southern region. Eliminating physical inactivity would increase the life expectancy by an average of 0.31 years. This reduction would affect mainly individuals with ≥ 15 years of schooling, male, Asian, elderly, residing in an urban area and earning ≥ 2 times the national minimum wage. In Brazil, physical inactivity has a major impact on NCDs and mortality, principally in the southeastern and central-west regions. Public policies and interventions promoting physical activity will significantly improve the health of the population.

Impacts of pesticide mixtures in European rivers as predicted by the Species Sensitivity Distribution (SSD) models and SPEAR bioindication

NASA Astrophysics Data System (ADS)

Jesenska, Sona; Liess, Mathias; Schäfer, Ralf; Beketov, Mikhail; Blaha, Ludek

2013-04-01

Species sensitivity distribution (SSD) is statistical method broadly used in the ecotoxicological risk assessment of chemicals. Originally it has been used for prospective risk assessment of single substances but nowadays it is becoming more important also in the retrospective risk assessment of mixtures, including the catchment scale. In the present work, SSD predictions (impacts of mixtures consisting of 25 pesticides; data from several catchments in Germany, France and Finland) were compared with SPEAR-pesticides, which a bioindicator index based on biological traits responsive to the effects of pesticides and post-contamination recovery. The results showed statistically significant correlations (Pearson's R, p<0.01) between SSD (predicted msPAF values) and values of SPEAR-pesticides (based on field biomonitoring observations). Comparisons of the thresholds established for the SSD and SPEAR approaches (SPEAR-pesticides=45%, i.e. LOEC level, and msPAF = 0.05 for SSD, i.e. HC5) showed that use of chronic toxicity data significantly improved the agreement between the two methods but the SPEAR-pesticides index was still more sensitive. Taken together, the validation study shows good potential of SSD models in predicting the real impacts of micropollutant mixtures on natural communities of aquatic biota.

Cancers in Australia in 2010 attributable to the consumption of alcohol.

PubMed

Pandeya, Nirmala; Wilson, Louise F; Webb, Penelope M; Neale, Rachel E; Bain, Christopher J; Whiteman, David C

2015-10-01

To estimate the proportion and numbers of cancers occurring in Australia in 2010 that are attributable to alcohol consumption. We estimated the population attributable fraction (PAF) of cancers causally associated with alcohol consumption using standard formulae incorporating prevalence of alcohol consumption and relative risks associated with consumption and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that might have occurred under the hypothetical scenario that an intervention reduced alcohol consumption, so that no-one drank >2 drinks/day. An estimated 3,208 cancers (2.8% of all cancers) occurring in Australian adults in 2010 could be attributed to alcohol consumption. The greatest numbers were for cancers of the colon (868) and female breast cancer (830). The highest PAFs were for squamous cell carcinomas of the oral cavity/pharynx (31%) and oesophagus (25%). The incidence of alcohol-associated cancer types could have been reduced by 1,442 cases (4.3%)--from 33,537 to 32,083--if no Australian adult consumed >2 drinks/day. More than 3,000 cancers were attributable to alcohol consumption and thus were potentially preventable. Strategies that limit alcohol consumption to guideline levels could prevent a large number of cancers in Australian adults. © 2015 The Authors.

In vitro effects of polychlorinated biphenyls on human platelets.

PubMed Central

Raulf, M; König, W

1991-01-01

Incubation of human platelets with polychlorinated biphenyls (PCB) induced and modulated cellular responses to a different degree. 3,3',4,4'-tetrachlorobiphenyl (TCB) was a more potent inducer of platelet aggregation, serotonin release and 12-HETE generation compared to the other PCB [2,2',3,3'-TCB,3,3'-dichlorobiphenyl (DCB),2,2',4,5,5'-pentachlorobiphenyl (PCB)]. 3,3',4,4'-TCB showed synergistic effects, in combination with other PCB, such as an enhanced formation of 12-HETE, when 3,3'-DCB and 2,2',3,3'-TCB were applied simultaneously. The combined incubation of platelets with PCB and sodium fluoride (NaF), an activator of G-proteins, resulted in synergistic 12-HETE generation compared to stimulation with NaF or PCB alone. Furthermore, when platelets were incubated with the PCB the enzymatic steps controlling the metabolism of the platelet-activating factor (PAF) were modulated. A direct relationship between the extent of platelet activation and the chloro-substitution pattern of PCB exists. PMID:1901832

Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription

PubMed Central

Wozniak, Glenn G.

2014-01-01

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression. PMID:25085417

'Low-acid' sulfide oxidation using nitrate-enriched groundwater

NASA Astrophysics Data System (ADS)

Donn, Michael; Boxall, Naomi; Reid, Nathan; Meakin, Rebecca; Gray, David; Kaksonen, Anna; Robson, Thomas; Shiers, Denis

2016-04-01

Acid drainage (AMD/ARD) is undoubtedly one of the largest environmental, legislative and economic challenges facing the mining industry. In Australia alone, at least 60m is spent on AMD related issues annually, and the global cost is estimated to be in the order of tens of billions US. Furthermore, the challenge of safely and economically storing or treating sulfidic wastes will likely intensify because of the trend towards larger mines that process increasingly higher volumes of lower grade ores and the associated sulfidic wastes and lower profit margins. While the challenge of managing potentially acid forming (PAF) wastes will likely intensify, the industrial approaches to preventing acid production or ameliorating the effects has stagnated for decades. Conventionally, PAF waste is segregated and encapsulated in non-PAF tips to limit access to atmospheric oxygen. Two key limitations of the 'cap and cover' approach are: 1) the hazard (PAF) is not actually removed; only the pollutant linkage is severed; and, 2) these engineered structures are susceptible to physical failure in short-to-medium term, potentially re-establishing that pollutant linkage. In an effort to address these concerns, CSIRO is investigating a passive, 'low-acid' oxidation mechanism for sulfide treatment, which can potentially produce one quarter as much acidity compared with pyrite oxidation under atmospheric oxygen. This 'low-acid' mechanism relies on nitrate, rather than oxygen, as the primary electron accepter and the activity of specifically cultured chemolithoautotrophic bacteria and archaea communities. This research was prompted by the observation that, in deeply weathered terrains of Australia, shallow (oxic to sub-oxic) groundwater contacting weathering sulfides are commonly inconsistent with the geochemical conditions produced by ARD. One key characteristic of these aquifers is the natural abundance of nitrate on a regional scale, which becomes depleted around the sulfide bodies, and where pH remains neutral. The "low-acid" oxidation of sulfides with nitrate as an electron acceptor has been demonstrated at the laboratory scale. In 90-day microcosm respirometry experiments, we exposed a mixture of pulverized quartz and pyrite -rich ore to natural, high-nitrate groundwater and inoculated the microcosms with a culture of aerobic and anaerobic nitrate-dependent iron and sulfur-oxidising microorganisms, which were enriched from ore, groundwater and activated waste water. Incubations were performed under both oxic and anoxic conditions, in addition to abiotic controls. Initial results show that oxidation of the sulfides under nitrate-rich and microbially enhanced conditions does produce less acid than the same material under oxic conditions, and to some degree can match the models as long as oxygen ingress can be controlled. These results are the focus of further research into how this process can be enhanced and whether it can be applied in the field. Nitrate-driven oxidation of sulfides could potentially be used as a new approach to reduce acid generation and leaching of contaminants from waste dumps, in a passive or actively managed process designed to deplete and/or ameliorate (i.e. through surface passivation) the mineralogical hazard. Developing our understanding of biological aspects of these processes may also allow testing of longer-term "bio-caps" for various tailings and dump materials.

Global burden of human papillomavirus and related diseases.

PubMed

Forman, David; de Martel, Catherine; Lacey, Charles J; Soerjomataram, Isabelle; Lortet-Tieulent, Joannie; Bruni, Laia; Vignat, Jerome; Ferlay, Jacques; Bray, Freddie; Plummer, Martyn; Franceschi, Silvia

2012-11-20

The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Mortality and life expectancy that attributable to high blood pressure in Chinese people in 2013].

PubMed

Zeng, X Y; Liu, S W; Wang, L J; Zhang, M; Yin, P; Liu, Y N; Zhao, Z P; Wang, L M

2017-08-10

Objective: To estimate the deaths (mortality) and life expectancy that attributable to high blood pressure in people from different regions and gender, in China in 2013. Methods: Data was from the 'China Chronic Disease Risk Factor Surveillance 2013' and the 'China National Mortality Surveillance 2013'. According to the comparative risk assessment theory, population attributable fraction ( PAF ) of high blood pressure by gender, urban-rural, east-central-west regions was calculated before the estimations on deaths (mortality) and life expectancy attributable to high blood pressure was made. Results: In 2013, among the Chinese people aged 25 years old and above, the mean SBP was (129.48±20.27) mmHg. High blood pressure[SBP>(115±6) mmHg]caused 20.879 million deaths and accounted for 22.78% of the total deaths. SBP, deaths, mortality rate and standardized mortality rate that attributable to high blood pressure all appeared higher in men [(131.15±18.73) mmHg, 11.517 million, 165.56/100 000 and 106.97/100 000, respectively]than in women[(127.79±21.60) mmHg, 9.362 million, 141.99/100 000 and 68.93/100 000, respectively]. SBP, deaths, mortality rate and PAF were all seen higher in rural[(130.25±20.66) mmHg, 11.234 million, 178.58/100 000 and 23.59%, respectively]than in urban[(128.58±19.77) mmHg, 9.645 million, 132.87/100 000 and 21.54%, respectively]areas. However, levels of SBP were similar in the east, central or west regions, with attributable deaths, attributable mortality rate and PAF the highest as 7.658 million 179.93/100 000, and 26.72% respectively. In 2013, among the Chinese people aged 25 years old and above, deaths caused by cardiovascular disease and chronic kidney disease attributable to high blood pressure were 19.912 million and 0.966 million, accounting for 52.31% of the total deaths due to cardiovascular diseases and 62.11% to the total chronic kidney diseases. The top three deaths attributable to high blood pressure were ischemic heart disease (6.656 million), hemorrhagic stroke (5.331 million) and ischemic stroke (3.593 million). When the effect of high blood pressure had been eliminated, the life expectancy per capita would have increased by 2.86 years old, with higher in women than in men (3.07 and 2.64 years old, respectively), higher in central than in east and west (3.48, 2.56 and 2.58 years, respectively) areas, in rural than in urban (2.97 and 2.59 years, respectively) areas. Conclusions: In 2013, the number of deaths attributable to high blood pressure was around 20.9 million, accounting for 22.78% of the total deaths, and appeared higher in men than in women, in rural than in urban, in central than in east and west areas. The mortality burden induced by ischemic heart disease, hemorrhagic stroke and ischemic stroke was most serious since the high blood pressure brought about 2.86 years of lost in life expectancy.

Change in lifestyle behaviors and diabetes risk: evidence from a population-based cohort study with 10 year follow-up.

PubMed

Feldman, Adina L; Long, Gráinne H; Johansson, Ingegerd; Weinehall, Lars; Fhärm, Eva; Wennberg, Patrik; Norberg, Margareta; Griffin, Simon J; Rolandsson, Olov

2017-03-29

Promoting positive changes in lifestyle behavior in the whole population may be a feasible and effective approach to reducing type 2 diabetes burden, but the impact of population shifts of modifiable risk factors remains unclear. Currently most of the evidence on modifiable lifestyle behavior and type 2 diabetes risk on a population level comes from studies of between-individual differences. The objective of the study was to investigate the association and potential impact on disease burden for within-individual change in lifestyle behavior and diabetes risk. Population-based prospective cohort study of 35,680 participants aged 30-50 at baseline in 1990-2003 in Västerbotten County, Sweden (follow-up until 2013). Five self-reported modifiable lifestyle behaviors (tobacco use, physical activity, alcohol intake, dietary fiber intake and dietary fat intake) were measured at baseline and 10 year follow-up. Lifestyle behaviors were studied separately, and combined in a score. Incident diabetes was detected by oral glucose tolerance tests. Multivariate logistic regression models and population attributable fractions (PAF) were used to analyze the association between change in lifestyle behavior between baseline and 10 year follow-up, and risk of incident diabetes. Incident diabetes was detected in 1,184 (3.3%) participants at 10 year follow-up. There was a reduced diabetes risk associated with increase in dietary fiber intake, odds ratio (OR) 0.79 (95% confidence interval (CI) 0.66, 0.96) for increase of at least one unit standard deviation (3.0 g/1,000 kcal) of the baseline distribution, PAF 16.0% (95% CI 4.2, 26.4%). Increase in the lifestyle behavior score was associated with reduced diabetes risk, OR 0.92 (95% CI 0.85, 0.99) per unit increase of the score. These results support a causal link between lifestyle behavior and type 2 diabetes incidence. A small shift in lifestyle behaviors, in particular intake of dietary fiber, has the potential to reduce diabetes burden in the population and might be a suitable target for public health intervention.