[The changes of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain].

PubMed

He, Jian-hua; Xu, Li; Shen, Yu; Kong, Ming-jian; Shi, Lin-yu; Ma, Zheng-liang

2015-01-01

To investigate the changes in the levels of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain. Male SD rats weighting 180 - 220 g were randomly divided into two groups(n = 48): normal saline group (NS group), complete Freund's adjuvant group (CFA group). Rats were given injections of CFA 100 µl in left hind paw in group CFA, and an equal volume of saline was given injection in group NS. Mechanical withdraw threshold(MWT) and thermal withdraw latency(TWL) were measured at before injection(T0 and 3 h, 1 d, 3 d, 7 d, 14 d, and 21 d after injection(T1-7). Four rats were chosen from each group at T0-7 and sacrificed, and L4-5 segments of the spinal cord horn were removed for measurement of the expression of monocarboxylate transporter-2 by Western blot analysis. In CFA group, mechanical hyperalgesia and allodynia appeared on the 3 h after CFA injection, then until the day 14. The expression of monocarboxylate transporter-2 in the spinal dorsal horn of rats in CFA group was significantly higher than that in normal control group at T1-6(P <0.05). The protein level of monocarboxylate transporter-2 was apparently correlated with MWT and TWL(P <0.01 and P <0.05) in CFA group. The level of monocarboxylate transporter-2 in spinal dorsal horn is significantly increased in a rat model of chronic inflammatory pain and the change may involve in the formation and maintenance of central sensitization in spinal cord of chronic inflammatory uain.

Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

PubMed

Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

2017-02-01

The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

PubMed

Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model.

PubMed

Nagarkar, Bhagyashri; Jagtap, Suresh

2017-04-04

Aim of the present study was to evaluate anti-inflammatory activity of newly developed polyherbal formulations DF1911, DF2112 and DF2813. These newly developed formulations are modifications of Dashamoola, a well known Ayurvedic formulation, along with addition of new plants. Complete Freund's adjuvant (CFA) induced inflammation in rat was used as an experimental model. Effects of the treatment in rats were monitored by physiological and biochemical parameters, histopathology and through gene expression studies. Diclofenac sodium showed maximum percentage inhibition (56.8 ± 3.5%) of paw edema followed by Dashamoola Kwatha (19.9 ± 1.8%). Among test formulations treated groups, DF1911 at 250 mg/kg bw (48.2 ± 5.4%, p < 0.001) and DF2112 at 250 mg/kg bw (49.9 ± 3.5%, p < 0.001) showed significant and maximum increase in percentage inhibition of paw edema as compared to Dashamoola Kwatha. Hematological alterations in CFA rats were normalized after treatment with test formulations. Results of serum markers and histopathological observations also supported the activity of formulations. Increased MDA levels in liver tissue of CFA injected animals significantly (p < 0.05) decreased by Diclofenac sodium and test formulation treated groups. DF1911, DF2112 and DF2813 showed down-regulation of IL1-β (~6.4-fold, ~5.2-fold and ~7.6-fold), IL-6 (~1.1-fold, ~1.6-fold and ~1.9-fold), TNF-α (~2.0-fold, ~4.6-fold and ~3.5-fold), and iNOS (~1.2-fold, ~1.8-fold and ~1.1-fold) in inflamed paw tissue compared to negative control group, respectively. The anti-inflammatory effects of DF1911 and DF2112 in rats were significantly higher than the Dashamoola Kwatha and are comparable to Diclofenac sodium.

Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats

PubMed Central

Kim, Wangin; Park, Sangbin; Kim, Youg Ran; Shin, Wook; Lee, Yumi; Choi, Donghee; Kim, Mirae; Lee, Hyunju; Kim, Seonjong; Na, Changsu

2016-01-01

Ganghwaljetongyeum (GHJTY) has been used as a standard treatment for arthritis for approximately 15 years at the Korean Medicine Hospital of Dongshin University. GHJTY is composed of 18 medicinal herbs, of which five primary herbs were selected and named new Ganghwaljetongyeum (N-GHJTY). The purpose of the present study was to observe the effect of N-GHJTY on arthritis and to determine its mechanism of action. After confirming arthritis induction using complete Freund's adjuvant (CFA) in rats, N-GHJTY (62.5, 125, and 250 mg/kg/day) was administered once a day for 10 days. In order to determine pathological changes, edema of the paws and weight were measured before and for 10 days after N-GHJTY administration. Cytokine (TNF-α, IL-1β, and IL-6) levels and histopathological lesions in the knee joint were also examined. Edema in the paw and knee joint of N-GHJTY-treated rats was significantly decreased at 6, 8, and 10 days after administration, compared to that in the CFA-control group, while weight consistently increased. Rats in N-GHJTY-treated groups also recovered from the CFA-induced pathological changes and showed a significant decline in cytokine levels. Taken together, our results showed that N-GHJTY administration was effective in inhibiting CFA-induced arthritis via anti-inflammatory effects while promoting cartilage recovery by controlling cytokine levels. PMID:27382402

Variable transcriptional responsiveness of the P2X3 receptor gene during CFA-induced inflammatory hyperalgesia.

PubMed

Nuñez-Badinez, Paulina; Sepúlveda, Hugo; Diaz, Emilio; Greffrath, Wolfgang; Treede, Rolf-Detlef; Stehberg, Jimmy; Montecino, Martin; van Zundert, Brigitte

2018-05-01

The purinergic receptor P2X3 (P2X3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2X3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2X3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background, and/or epigenetics. In this study, we sought to get insights into the molecular mechanisms responsible for inflammatory hyperalgesia by determining P2X3-R expression in DRG neurons of juvenile male rats that received a Complete Freund's Adjuvant (CFA) bilateral paw injection. We demonstrate that all CFA-treated rats showed inflammatory hyperalgesia, however, only a fraction (14-20%) displayed increased P2X3-R mRNA levels, reproducible across both sides. Immunostaining assays did not reveal significant increases in the percentage of P2X3-positive neurons, indicating that increased P2X3-R at DRG somas is not critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin immunoprecipitation (ChIP) assays showed a correlated (R 2  = 0.671) enrichment of the transcription factor Runx1 and the epigenetic active mark histone H3 acetylation (H3Ac) at the P2X3-R gene promoter in a fraction of the CFA-treated rats. These results suggest that animal-specific increases in P2X3-R mRNA levels are likely associated with the genetic/epigenetic context of the P2X3-R locus that controls P2X3-R gene transcription by recruiting Runx1 and epigenetic co-regulators that mediate histone acetylation. © 2017 Wiley Periodicals, Inc.

Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats

PubMed Central

2013-01-01

Background Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. Results EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat’s paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. Conclusions The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats. PMID:23517865

Assessments of Immunomodulatory and Inflammatory effects against Induction of Entamoeba histolytica (HM1 IMS strain) crude extract Antigen in Complete Freund's Adjuvant Induced Rheumatoid Arthritis Female Wistar Rats.

PubMed

Bagde, Swati; Singh, Vinod

2015-01-01

Today it is well known about mechanisms of cell communication, how the cells that mediate immune response and tissue injury accumulate in tissues but the aetiology of rheumatoid arthritis (RA) is still unknown. This study was to evaluate immunomodulatory effects of crude Entamoeba histolytica (HM1 IMS strain) antigen in complete freund's adjuvant female wistar rats by studying the alterations in humoral and cell mediated immune responses and also the inflammatory effects by evaluating the changes in body weight, paw thickness, biochemical, serological, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) and histopathology activities. Animals were randomly divided into six groups (n=6). CFA was induced in arthritic, drug and AA+CFA group whereas, 0.5ml amoebic antigen was induced subplantal in AA group while 0.5ml dose of amoebic antigen was given orally to AA+CFA group for 7-28th days. Indomethacin was used as a standard drug. Effects of amoebic antigen were associated with increased paw thickness and decreased body weight when compared to healthy control showed a significant difference. Oral administration of amoebic antigen has showed increased severe symptoms of arthritis in AA+CFA on comparison to healthy control rats. Significant increase in serum level of IL-6 and α TNF were found in AA group followed by AA+CFA group whereas, decrease in concentration of IL-10 was appear in AA+CFA group on comparison to arthritic and healthy control group (P<0.05). Histopathology of AA group showed severe signs of necrotic and degenerative changes on comparison to healthy control group. Thus the results demonstrated that E. histolytica alone or in combination with CFA increased bone damage, with alterations in antioxidant level in liver and kidney tissue homogenates as well as showed immunomodulatory arthritogenic properties which may contribute and raise joint inflammation.

Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

PubMed

Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

2012-10-01

Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum.

PubMed

Petty, R E; Hunt, D W; Mathers, D M; McCormick, A Q; Barker, H; Southwood, T R; Corson, L

1994-08-01

To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII-IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII-IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis rats given ip M. butyricum and 2 arthritic animals also developed uveitis. Uveitis occurs infrequently in arthritic rats given spleen cells from CFA injected animals. The ip administration of M. butyricum constitutes a novel disease model in which the immunopathological relationships between arthritis and uveitis may be more reliably studied.

Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA-induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression.

PubMed

Yang, Lin; Yang, Lianxue; Gao, Xiulai

2010-07-01

Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA-induced thermal hyperalgesia of rats.

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Site-dependent modulating effects of conjugated fatty acids from safflower oil in a rat two-stage carcinogenesis model in female Sprague-Dawley rats.

PubMed

Kimoto, N; Hirose, M; Futakuchi, M; Iwata, T; Kasai, M; Shirai, T

2001-07-10

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats.

PubMed

Zhang, Rui-Xin; Li, Aihui; Liu, Bing; Wang, Linbo; Ren, Ke; Zhang, Haiqing; Berman, Brian M; Lao, Lixing

2008-04-01

Although it has been shown that pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) facilitate perception of noxious inputs at the spinal level, the mechanisms have not been understood. This study determined the cell type that produces IL-1beta, the co-localization of IL-1 receptor type I (IL-1RI) and Fos and NR1 in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NR1 phosphorylation and hyperalgesia in a rat model of inflammatory pain. Phosphorylation of NR1, an essential subunit of the NMDA receptor (NMDAR), is known to modulate NMDAR activity and facilitate pain. Hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08ml, 40microg Mycobacterium tuberculosis) into one hind paw of each rat. Paw withdrawal latency (PWL) was tested before CFA (-48h) for baseline and 2 and 24h after CFA to assess hyperalgesia. IL-1ra was given (i.t.) 24h before CFA to block the action of basal IL-1beta and 2h prior to each of two PWL tests to block CFA-induced IL-1beta. Spinal cords were removed for double immunostaining of IL-1beta/neuronal marker and IL-1beta/glial cell markers, IL-1RI/Fos and IL-1RI/NR1, and for Western blot to measure NR1 phosphorylation. The data showed that: (1) astrocytes produce IL-1beta, (2) IL-1RI is localized in Fos- and NR1-immunoreactive neurons within the spinal dorsal horn, and (3) IL-1ra at 0.01mg/rat significantly increased PWL (P<0.05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain.

Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

PubMed

Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

2017-07-01

The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

PubMed

Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

2017-06-03

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (p<0.05). In addition, intensity-dependent decreases in RBF during hind paw stimulation were attenuated by chronic pain at T2 (p's<0.05) and T10 (p's<0.05), but less so at T10 compared with T2 (p's<0.05). These results indicate that chronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

PubMed Central

2013-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Methods Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. Results CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. Conclusions TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway. PMID:23768044

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

PubMed

Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.

Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2009-01-01

Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappaB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50mul of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappaB on days 3 and 7, and of IL-6 on days 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.

Effects of dietary cis and trans unsaturated and saturated fatty acids on the glucose metabolites and enzymes of rats.

PubMed

Bernal, Claudio A; Rovira, Jordi; Colandré, María E; Cussó, Roser; Cadefau, Joan A

2006-05-01

The aim of the present study was to examine whether the level of dietary cis fatty acid (cFA), or the isomers (trans or cis) and/or the saturation of the fatty acids at high dietary fat levels altered the intracellular glucose metabolites and certain regulatory enzyme activities in the skeletal muscle and liver of rats. The animals were fed for 30 d on either a recommended control diet (7 % cFA, w/w) or a high-fat diet (20 % fatty acids, w/w). The high-fat diet was enriched with either cFA, trans fatty acid (tFA), a moderate proportion of saturated fatty acid (MSFA), or a high proportion of saturated fatty acid (HSFA). The most striking findings were observed in the gastrocnemius muscle with a HSFA diet. There was a significant increase in glucose-6-phosphate (306 %), glucose-1-phosphate (245 %), fructose-6-phosphate (400 %), fructose-1,6-bisphosphate (86 %), glyceraldehyde-3-phosphate (38 %), pyruvate (341 %), lactate (325 %), citrate (79 %) and the bisphosphorylated sugars as compared with the cFA diet. These changes were paralleled by an increase in muscle triacylglycerol content (49 %) and a decrease in glucose (39 %). In addition, the amount of cFA and the other types of fatty acid (i.e. tFA and MSFA) led to no great differences in glucose metabolism as compared with the respective control group. These data support the hypothesis that glucose changes induced by a HSFA diet are a multifaceted abnormality. Glucose and lactate transport and intracellular glucose metabolism could be the key biochemical defects involved in this detrimental effect on glucose metabolism.

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis

PubMed Central

Tekieh, E.; Zaringhalam, Jalal; Manaheji, H.; Maghsoudi, N.; Alani, B.; Zardooz, H.

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment. PMID:27857662

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

PubMed

Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Effect of simvastatin injections on temporomandibular joint inflammation in growing rats.

PubMed

George, Mark D; Owen, Callista M; Reinhardt, Adam L; Giannini, Peter J; Marx, David B; Reinhardt, Richard A

2013-05-01

Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Expression of Vesicular Glutamate Transporters VGLUT1 and VGLUT2 in the Rat Dental Pulp and Trigeminal Ganglion following Inflammation

PubMed Central

Hong, Jae Hyun; Kim, Yun Sook; Choi, So Young; Kim, Tae Heon; Cho, Yi Sul; Bae, Yong Chul

2014-01-01

Background There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund’s adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis. Results The density of VGLUT2− immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group. Conclusions These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation. PMID:25290694

Expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in the rat dental pulp and trigeminal ganglion following inflammation.

PubMed

Yang, Eun Sun; Jin, Myoung Uk; Hong, Jae Hyun; Kim, Yun Sook; Choi, So Young; Kim, Tae Heon; Cho, Yi Sul; Bae, Yong Chul

2014-01-01

There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund's adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis. The density of VGLUT2- immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group. These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation.

Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

PubMed

Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

2009-08-25

Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

SPINAL TRANSLOCATOR PROTEIN (TSPO) MODULATES PAIN BEHAVIOR IN RATS WITH CFA-INDUCED MONOARTHRITIS

PubMed Central

Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

2009-01-01

Translocator protein 18kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund’s Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on day 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral lamina I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Day 7 and 14. Moreover, TSPO was co-localized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain. PMID:19555675

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

PubMed

Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

2017-02-01

Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic. © 2016 European Pain Federation - EFIC®.

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

PubMed

Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Gabapentin decreases microglial cells and reverses bilateral hyperalgesia and allodynia in rats with chronic myositis.

PubMed

Rosa, A S; Freitas, M F; Rocha, I R C; Chacur, M

2017-03-15

In the present work, we investigated the antinociceptive effect of gabapentin in a chronic myositis model and its interference in spinal glial cells. Chronic myositis was induced by injection of Complete Freund Adjuvant (CFA) into the right gastrocnemius (GS) muscle of rats and tests for evaluating mechanical hyperalgesia, thermal hyperalgesia and tactile allodynia were performed. Pharmacological treatment with gabapentin was administrated intrathecally and 100μg and 200μg doses were tested. For analyzing astrocytes and microglia in the spinal cord, immunochemistry assay was performed. It was found that gabapentin 200μg reverted CFA-induced chronic muscle pain bilaterally, in all applied tests and it was able to attenuate microglial but not astrocytes activation in the dorsal horn of spinal cord. In conclusion, gabapentin was able to inhibit hyperalgesia and allodynia in chronic myositis and also to attenuate spinal microglial activation. Therefore, gabapentin could be used as treatment for targeting chronic muscle pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state.

PubMed

Refsgaard, L K; Hoffmann-Petersen, J; Sahlholt, M; Pickering, D S; Andreasen, J T

2016-03-15

The place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2 × 5 min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. The PEAP results suggest that this paradigm might be successfully applied in mice to study affective pain. CFA treatment was associated with increased anxiety-like behaviour and anhedonia; however, this appeared unrelated to the PEAP responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

PubMed

Lutz, Norbert W; Fernandez, Carla; Pellissier, Jean-François; Cozzone, Patrick J; Béraud, Evelyne

2013-01-01

Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA) and spinal-cord homogenate (SC-H), whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group). Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE) or extra-cerebral (AA) inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and/or due to the presence of systemic proinflammatory molecules. Regardless of the nature of these mechanisms, our findings may be of interest for future clinical studies, e.g. by in-vivo magnetic resonance spectroscopy.

Regulation of the Trigeminal NR1 Subunit Expression Induced by Inflammation of the Temporomandibular Joint Region in Rats

PubMed Central

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2012-01-01

Expression of the N-methyl-D-aspartate receptor (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor kappa B (NF-κB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50 μl of complete Freund’s adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on day 1, 3 and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-κB on day 3 and 7, and of IL-6 on day 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-κB inhibitor (PDTC) for six days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for six days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-κB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats. PMID:19058915

PG110, A Humanized Anti-NGF Antibody, Reverses Established Pain Hypersensitivity in Persistent Inflammatory Pain, but not Peripheral Neuropathic Pain, Rat Models.

PubMed

Djouhri, Laiche

2016-11-01

Chronic inflammatory and peripheral neuropathic pain (PNP) is a major health problem for which effective drug treatment is lacking. The pathophysiology of these debilitating conditions is incompletely understood, but nerve growth factor (NGF) is believed to play a major role. NGF-antagonism has previously been shown to prevent pain hypersensitivity in rodent models of acute inflammatory pain and PNP, but most of those animal studies did not address the more clinically relevant issue of whether NGF-antagonism provides relief of established chronic pain behavior. Therefore, the aim of this study was to investigate whether blocking NGF actions with a humanized anti-NGF monoclonal antibody (PG110) would reverse/attenuate established pain hypersensitivity in rat models of chronic/persistent inflammatory pain and PNP. The complete Freund's adjuvant (CFA) rat model of persistent inflammatory pain, and the L5 spinal nerve axotomy (SNA) model of PNP, were used in the present study. The effect of a single intravenous injection (10, 30, and 300 µg/kg) of an anti-NGF antibody PG110 on heat and mechanical hypersensitivity was assessed 5 and 7 days after CFA and SNA, respectively. Compared to vehicle treated group, PG110 dose dependently attenuated established heat and mechanical hypersensitivity induced by CFA, but not that induced by SNA. The anti-allodynic and anti-hyperalgesic effects of PG110 in the CFA model were similar to those of the positive control naproxen (30 mg/kg, i.v.). These findings suggest that therapies that target NGF or its receptors may be effective for treatment of persistent/chronic inflammatory pain, but probably not PNP. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats.

PubMed

Koch, Diana A; Silva, Rodrigo B M; de Souza, Alessandra H; Leite, Carlos E; Nicoletti, Natália F; Campos, Maria M; Laufer, Stefan; Morrone, Fernanda B

2014-03-01

Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. Male Wistar rats (180-200 g) were used for the complete Freund's adjuvant (CFA)-induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

PubMed

Imbe, Hiroki; Kimura, Akihisa

2017-09-01

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight bearing evaluation in inflammatory, neuropathic and cancer chronic pain in freely moving rats.

PubMed

Tétreault, Pascal; Dansereau, Marc-André; Doré-Savard, Louis; Beaudet, Nicolas; Sarret, Philippe

2011-09-01

Preclinical pain assessment remains a key step for the development of new and potent painkillers. Significant progress in pain evaluation has been achieved with the development of non-reflexive tools. Seeking efficient and clinically relevant devices for pain-related quality of life assessment, we evaluated a new Dynamic Weight Bearing (DWB) device based on pressure captors in three different preclinical chronic pain models. Inflammatory (CFA), neuropathic (CCI) and bone cancer pain (femoral tumor) models were evaluated in Sprague Dawley rats for mechanical allodynia using dynamic von Frey for pain-related behaviors and DWB for discomfort. We observed similar impairment patterns in all of the models for both von Frey (allodynia) and DWB (weight balance) during the complete observation period, starting at day 3 in CCI- and CFA-affected limbs and at day 14 in bone cancer-afflicted rats, indicating that the DWB could be a useful tool for supporting pain assessment. Interestingly, we demonstrated that the main compensation, when animals experienced pain, was seen in the forepaws, ranging from 46% to 69% of increased load compared to normal. Other pain-related coping behaviors were also measured, such as the time spent on each paw and the contact surface. Our results revealed that CFA, CCI and cancerous rats decreased the use of their ipsilateral hind paws by 30% and showed a 50% reduction in paw surface pressed against the floor. In conclusion, this new device improves methods for preclinical evaluation of discomfort and quality of life proxies and could be helpful in screening putative analgesics. Copyright © 2011 Elsevier Inc. All rights reserved.

Morphological changes in hind limb muscles elicited by adjuvant-induced arthritis of the rat knee.

PubMed

Ozawa, J; Kurose, T; Kawamata, S; Yamaoka, K

2010-02-01

We investigated qualitative and quantitative changes in rat hind limb muscles caused by complete Freund's adjuvant (CFA)-induced knee joint pain. One week after CFA injection, muscle atrophy was induced only on the CFA-injected side. Wet weight of the rectus femoris (RF) and soleus (SOL) muscles were significantly decreased by 20% and 19%, respectively. The reduction in cross-sectional areas by CFA was similar for fast and slow muscle fibers in the RF (10% vs 15%, respectively) and SOL muscles (16% vs 16%, respectively). At the light microscopic level, pathological changes were not found in the RF muscles on both sides, although the infiltration of mononuclear cells and muscle regeneration were found in the SOL muscles on CFA-injected and contralateral control sides. On the other hand, electron microscopy revealed degenerative changes in the RF and SOL muscles on the CFA-injected side. Interestingly, sarcomere hypercontraction, indicating overexercise, was observed to a limited extent in the SOL muscles on the control side. In conclusions, knee joint pain can trigger the rapid development of muscle atrophy with degenerative changes not only in thigh but also calf muscles. This indicates that early interventions to inhibit joint pain or inflammation may prevent muscle atrophy.

Demosaicking algorithm for the Kodak-RGBW color filter array

NASA Astrophysics Data System (ADS)

Rafinazari, M.; Dubois, E.

2015-01-01

Digital cameras capture images through different Color Filter Arrays and then reconstruct the full color image. Each CFA pixel only captures one primary color component; the other primary components will be estimated using information from neighboring pixels. During the demosaicking algorithm, the two unknown color components will be estimated at each pixel location. Most of the demosaicking algorithms use the RGB Bayer CFA pattern with Red, Green and Blue filters. The least-Squares Luma-Chroma demultiplexing method is a state of the art demosaicking method for the Bayer CFA. In this paper we develop a new demosaicking algorithm using the Kodak-RGBW CFA. This particular CFA reduces noise and improves the quality of the reconstructed images by adding white pixels. We have applied non-adaptive and adaptive demosaicking method using the Kodak-RGBW CFA on the standard Kodak image dataset and the results have been compared with previous work.

Anti-arthritic Effects of Total Flavonoids from Juniperus sabina on Complete Freund's Adjuvant Induced Arthritis in Rats

PubMed Central

Zhao, Jun; Liu, Tao; Xu, Fang; You, Shuping; Xu, Fang; Li, Chenyang; Gu, Zhengyi

2016-01-01

Context: Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of many ailments including rheumatoid arthritis (RA). Aims: To confirm the therapeutic effect of total flavonoids from J. sabina (JSTF) on RA-induced by Complete Freund's Adjuvant (CFA) in rats. Settings and Design: Wistar rats (200 ± 20 g) were immunized by intradermal injection of 0.1 mL of CFA into the right hind metatarsal footpad. JSTF was administered orally at the dose of 125,250 and 500 mg/kg on 14 days after the induction of adjuvant arthritis. Tripterygium glycoside (20 mg/kg) was used as a positive control. Paw swelling, arthritic score, body weight loss, serum cytokines, inflammatory mediators, and histological change were measured. Results: We found that JSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic score (P < 0.05). The overproduction of tumor necrosis factor alpha and interleukin 1beta were remarkably suppressed in the serum of JSTF (125,500 mg/kg) treated rats (P < 0.05). Histopathological studies also showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animals. Six flavonoids were isolated and from JSTF by various chromatographic methods and identified as follows: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L-rhamnoside, and rutin. Conclusions: These results suggest the potential therapeutically effect of JSTF as an anti-arthritis agent toward CFA-induced arthritis in rats, and verified therapeutic applications of J. sabina on RA in folk medicine. SUMMARY Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of rheumatoid arthritisJSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic scoreHistopathological studies showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animalsSix flavonoids were isolated and from JSTF including: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L- rhamnoside, and rutin. Abbreviations used: JSTF: Total flavonoids from Juniperus sabina; CFA: Complete Freund's Adjuvant; TG: Tripterygium glycoside; TNF-α: Tumor necrosis factor alpha; IL-1β: Interleukin 1beta; IL-6: Interleukin 6; H and E: Hematoxylin and eosin. PMID:27601846

A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

PubMed

Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

2016-01-01

Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

In vitro effects of coal fly ashes: hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells

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

van Maanen, J.M.; Borm, P.J.; Knaapen, A

1999-12-15

The authors measured iron release, acellular generation of hydroxyl radicals, and oxidative DNA damage and cytotoxicity in rat lung epithelial (RLE) cells by different coal fly ashes (CFA) that contain both quartz and iron. Seven samples of CFA with different particle size and quartz content (up to 14.1%) were tested along with silica (alpha-quartz), ground coal, and coal mine dust (respirable) as positive control particles, and fine TiO{sub 2} (anatase) as a negative control. Five test samples were pulverized fuel ashes (PFA), two samples were coal gasification (SCG) ashes (quartz content {lt} 0.1%), and one sample was a ground coal.more » No marked differences between SCG and PFA fly ashes were observed, and toxicity did not correlate with physicochemical characteristics or effect parameters. Stable surface radicals were only detected in the reference particles silica and coal mine dust, but not in CFA. On the other hand, hydroxyl radical generation by all fly ashes was observed in the presence of hydrogen peroxide. Also a relationship between acellular hydroxyl radical generation and oxidative DNA damage in RLE cells by CFA was observed. The respirable ashes (MAT023, 38, and 41) showed an extensive level of hydroxyl radical generation in comparison to nonrespirable fly ashes and respirable references. This was related to the iron mobilization from these particles. Themechanisms by which CFA and the positive references (silica, coal mine dust) affect rat lung epithelial cells seem to be different, and the data suggest that quartz in CFA does not act the same as quartz in silica or coal mine dust. However, the results indicate an important role for size and iron release in generation and subsequent effects of reactive oxygen species caused by CFA.« less

Correlation of nitric oxide levels in the cerebellum and spinal cord of experimental autoimmune encephalomyelitis rats with clinical symptoms.

PubMed

Ljubisavljevic, Srdjan; Stojanovic, Ivana; Pavlovic, Dusica; Milojkovic, Maja; Vojinovic, Slobodan; Sokolovic, Dusan; Stevanovic, Ivana

2012-01-01

Experimental autoimmune encephalomyelitis (EAE) is a well-established cell-mediated autoimmune inflammatory disease of the CNS, which has been used as a model of the human demyelinating disease. EAE is characterized by infiltration of the CNS by lymphocytes and mononuclear cells, microglial and astrocytic hypertrophy, and demyelination which cumulatively contribute to clinical expression of the disease. EAE was induced in female Sprague-Dawley rats, 3 months old (300 g ± 20 g), by immunization with myelin basic protein (MBP) in combination with Complete Freund's adjuvant (CFA). The animals were divided into 7 groups: control, EAE, CFA, EAE + aminoguanidine (AG), AG, EAE + N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the level of nitric oxide (NO(·)) production was determined by measuring nitrite and nitrate concentrations in 10% homogenate of cerebellum and spinal cord. Obtained results showed that the level of NO(·) was significantly increased in all examined tissues of the EAE rats compared to the control and CFA groups. Also, AG and NAC treatment decreased the level of NO(·) in all tissues compared to the EAE group. The level of NO(·) is increased significantly in the spinal cord compared to the cerebellum. The clinical course of the EAE was significantly decreased in the EAE groups treated with AG and NAC during the development of the disease compared to EAE group and its correlates with the NO(·) level in cerebellum and spinal cord. The findings of our work suggest that NO(·) and its derivatives play an important role in multiple sclerosis (MS). It may be the best target for new therapies in human demyelinating disease and recommend the new therapeutic approaches based on a decreased level of NO(·) during the course of MS.

Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund's adjuvant-induced arthritic rats: involvement of cellular inflammatory mediators and other biomarkers.

PubMed

Gohil, Priyanshee; Patel, Vimal; Deshpande, Shrikalp; Chorawala, Mehul; Shah, Gaurang

2018-02-01

Alteration of microbiota is related with rheumatoid arthritis (RA) and administration of certain probiotics showed an improvement in RA. The present study was designed to find out the anti-arthritic activity of cell wall content of Lactobacillus plantarum in complete Freund's adjuvant (CFA)-induced arthritis in rats. Freund's adjuvant was injected into the left footpad in female rats on day 0 and dexamethasone (1 mg kg -1 , s.c.) & cell wall content of L. plantarum (10 5 , 10 7 , and 10 9  cfu/animal, s.c.) treatment were given from day 7 to 21. The change in body weight, paw volume and arthritic index, joint stiffness, gait test, mobility test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, serum rheumatoid factor (RF), and serum TNF-α was measured on day 21. Cell wall content of L. plantarum treated animals showed improvement in all the parameters as compared to that in CFA-treated animals and exert anti-arthritic activity.

Measuring persistent temporomandibular joint nociception in rats and two mice strains.

PubMed

Kramer, Phillip R; Kerins, Carolyn A; Schneiderman, Emet; Bellinger, Larry L

2010-04-19

Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestrained and untrained male and female Sprague-Dawley rats for up to two days. In this study, we first found that injection of complete Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal duration for 19 days and also decreased meal frequency for 42 days. Interestingly, the meal duration varied significantly from day to day within the 19 day period. TMJ interleukin-1 beta (IL-1 beta) and calcitonin gene-related peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected animals and the level of these markers was attenuated as the meal duration decreased with time. Control animals injected with saline into the TMJ or CFA into the knee did not show a significant lengthening in meal duration but did show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ CFA injections showed a significantly lengthened meal duration on four of the seven days measured using end-of-the meal definition of 5 or 10 min. No other meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1 beta. Seven days post-injection, both IL-6 and IL-1 beta were significantly elevated. No change in CGRP was detected. In this study C57Bl/6 mice also received TMJ CFA injections, but they did not show a lengthening in any meal pattern or significant increases in IL-1 beta, IL-6 or CGRP. Our data show, for the first time, that meal duration can be used to measure CFA-induced nociception in the TMJ over the course of several weeks in unrestrained rats and for up to seven days in the DBA/1LacJ mouse strain. In addition, C57Bl/6 mice are resistant to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice. (c) 2010 Elsevier Inc. All rights reserved.

In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

PubMed

Mahdi, Harith Jameel; Khan, Nurzalina Abdul Karim; Asmawi, Mohd Zaini Bin; Mahmud, Roziahanim; A/L Murugaiyah, Vikneswaran

2018-03-01

The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

AMPAkines have novel analgesic properties in rat models of persistent neuropathic and inflammatory pain.

PubMed

Le, Alexander M; Lee, Michelle; Su, Chen; Zou, Anthony; Wang, Jing

2014-11-01

Novel analgesics that do not suppress the respiratory drive are urgently needed. Glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors plays important roles in central pain circuits. AMPAkines augment AMPA receptor function and have been shown to stimulate the respiratory drive to oppose opioid-induced hypoventilation. However, their role in chronic pain states remains unknown. The authors studied AMPAkines (CX546 and CX516) in rat spared nerve injury (SNI) model of neuropathic pain and Complete Freund's Adjuvant (CFA) model of inflammatory pain. They measured the effect of AMPAkines on mechanical and cold allodynia. They also evaluated their effect on depressive symptoms of pain using the forced swim test, as time of immobility on this test has been used as a measure for behavioral despair, a feature of depression. The authors found that CX546, compared with dimethyl sulfoxide (DMSO) control, reduced both mechanical and sensory allodynia in SNI (DMSO group, n = 9; CX546 group, n = 11) and CFA models (both DMSO and CX546 groups, n = 9). They found that CX546, compared with control, also reduced depressive symptoms of pain by decreasing immobility on the forced swim test in both SNI (both DMSO and CX546 groups, n = 8) and CFA models (both DMSO and CX546 groups, n = 10). Finally, they found that CX516, compared with control, also reduced mechanical and cold allodynia in the SNI model (both DMSO and CX516 groups, n = 10). AMPAkines alleviate pain hypersensitivity as well as depression-like behavior associated with long-lasting nerve injury and inflammatory insult.

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72).

PubMed

Lukács, M; Warfvinge, K; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

2017-12-01

Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C 1 -C 2 regions of the spinal cord. We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C 1 -C 2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

New models of experimental parotitis and parotid gland distension in rats.

PubMed

Okada-Ogawa, Akiko; Shinoda, Masamichi; Honda, Kuniya; Iwata, Koichi

2012-01-01

A significant reduction of the escape threshold to mechanical stimulation of the lateral facial skin was observed bilaterally at days 2 and 3 after unilateral complete Freund's adjuvant (CFA) administration into parotid gland. A slight reduction of mechanical escape threshold was also observed in rats with saline administration. The parotid gland inflammation was verified and quantified by measuring the tissue Evans' blue dye extravasation. The Evans' blue concentration in the parotid gland tissues was significantly greater in the CFA-injected rats than that of the saline-injected rats at 72 h after treatment. On day 10 after CFA administration into the parotid gland, the Evans' blue concentration was recovered to the control level. The administration of capsaicin into the parotid gland did not alter neuronal activities in the transition zone between the trigeminal spinal subnucleus interpolaris and caudalis (Vi/Vc). In contrast, capsaicin administration induced significant increases in the receptive field size and mechanical and cold responses of neurons located in superficial laminae of the C1/C2. The subgroup of C1/C2 neurons responded to mechanical distension of the parotid gland, whereas no Vi/Vc neurons responded to parotid distension.

[Effect of preamputation pain on the behavioral changes and spinal astrocytic activation in amputated rats].

PubMed

Chen, Xiaoxia; Zuo, Yunxia; Lian, Yangyang; Song, Li; Xiao, Hong

2012-03-01

To determine the effect of preamputation pain on the behavioral response and astrocytic activation in the spinal cord of amputated rats, and to assess the association between preamputation pain and chronic amputation-related pain. A total of 84 adult male SD rats were randomly distributed into an NA group (n=42) and a PA group (n=42). The NA group was intraplantarly injected with saline 100 μL, while the PA group was intraplantarly injected with complete Freund's adjuvant (CFA) 100 μL in both cases at 7 d before the amputation. Thermal withdrawal latency (TWL) was measured before the injection and at 1, 3, 5, and 7 d after the injection. All rats were amputated on the 7th day. The TWL, diet and water intake were measured on 1, 3, 5, 7, 10, 14, 17, 21, and 28 d after the amputation. Expression of glial fibrillary acidic protein (GFAP) in the L4-6 of spinal cord was measured by immunohistochemistry before the saline/ CFA injection, 7 d after the injection and 1, 3, 5, 7, 10 d after the amputation.. The TWL significantly decreased on 1, 3, 5, and 7 d after the intraplantar administration of CFA compared with the basic value in the PA group (P<0.05), while there was no difference between 1, 3, 5, and 7 d after the intraplantar administration of saline and the basic value in the NA group (P>0.05). In addtions to the basic value, the TWL of the PA group was shorter than that of the NA group at the above-mentioned time-points (P<0.05). Compared with the preoperative level, the diet and water intake decreased significantly after the amputation in both groups, but recovered to the preoperative levels, by 3 d after the amputation in the NA group, and by 5 d after the amputation in the PA group. Compared with the TWL of the residual limb on the day of amputation, the TWL of the residual limb increased significantly 3 d after the amputation and remained elevated until 28 d after the amputation in the NA group (P<0.05), while there was no difference between each time point after the amputation and the day of the amputation in the PA group. Compared with the basic value, there was an obviously high expression of GFAP in the NA group beginning on the day of amputation and in the PA group 7 d after the CFA injection (P<0.05). After the amputation, the expression of GFAP was significantly higher in the PA group (P<0.05). Preamputation pain delays the recovery and activates the spinal astrocytes which may turn the acute postoperative pain into a chronic one.

ACUTE PULMONARY AND SYSTEMIC EFFECTS OF INHALED COAL FLY ASH IN RATS: COMPARISON TO AMBIENT ENVIRONMENTAL PARTICLES

EPA Science Inventory

Although primary particle emissions of ash from coal-fired power plants are well controlled, coal fly ash (CFA) can still remain a significant fraction of the overall particle exposure for some plant workers and highly impacted communities. The effect of CFA on pulmonary and syst...

Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

PubMed

Arora, R; Kuhad, A; Kaur, I P; Chopra, K

2015-08-01

Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance. © 2014 European Pain Federation - EFIC®

KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

PubMed

Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

2016-12-01

Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.

The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats.

PubMed

Zhang, Hong-Hai; Zhang, Xiao-Qin; Xue, Qing-Sheng; Yan-Luo; Huang, Jin-Lu; Zhang, Su; Shao, Hai-Jun; Lu, Han; Wang, Wen-Yuan; Yu, Bu-Wei

2014-01-01

Cyclin-dependent kinase 5 (Cdk5) has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) via the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway in the dorsal horn of the spinal cord in rats. Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine. Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF/TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF/TrkB signaling cascade may present a potential target for anti-inflammatory pain.

Evaluation of a hyperspectral image database for demosaicking purposes

NASA Astrophysics Data System (ADS)

Larabi, Mohamed-Chaker; Süsstrunk, Sabine

2011-01-01

We present a study on the the applicability of hyperspectral images to evaluate color filter array (CFA) design and the performance of demosaicking algorithms. The aim is to simulate a typical digital still camera processing pipe-line and to compare two different scenarios: evaluate the performance of demosaicking algorithms applied to raw camera RGB values before color rendering to sRGB, and evaluate the performance of demosaicking algorithms applied on the final sRGB color rendered image. The second scenario is the most frequently used one in literature because CFA design and algorithms are usually tested on a set of existing images that are already rendered, such as the Kodak Photo CD set containing the well-known lighthouse image. We simulate the camera processing pipe-line with measured spectral sensitivity functions of a real camera. Modeling a Bayer CFA, we select three linear demosaicking techniques in order to perform the tests. The evaluation is done using CMSE, CPSNR, s-CIELAB and MSSIM metrics to compare demosaicking results. We find that the performance, and especially the difference between demosaicking algorithms, is indeed significant depending if the mosaicking/demosaicking is applied to camera raw values as opposed to already rendered sRGB images. We argue that evaluating the former gives a better indication how a CFA/demosaicking combination will work in practice, and that it is in the interest of the community to create a hyperspectral image dataset dedicated to that effect.

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex.

PubMed

Touvykine, Boris; Mansoori, Babak K; Jean-Charles, Loyda; Deffeyes, Joan; Quessy, Stephan; Dancause, Numa

2016-03-01

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)--the putative premotor area in rats--in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions. © The Author(s) 2015.

Endogenous Prolactin Generated During Peripheral Inflammation Contributes to Thermal Hyperalgesia

PubMed Central

Scotland, Phoebe E.; Patil, Mayur; Belugin, Sergei; Henry, Michael A.; Goffin, Vincent; Hargreaves, Kenneth M.; Akopian, Armen N.

2011-01-01

Prolactin (PRL) is a hormone and a neuromodulator. PRL sensitizes TRPV1 responses in sensory neurons, but it is not clear whether peripheral inflammation results in the release of endogenous PRL, or whether endogenous PRL is capable of acting as an inflammatory mediator in a sex-dependent manner. To address these questions, we examined inflammation-induced release of endogenous PRL, and its regulation of thermal hyperalgesia in female and male rats. PRL is expressed in several types of peripheral neuronal and non-neuronal cells, including TRPV1-positive nerve fibers, preadipocytes and activated macrophages/monocytes localized in the vicinity of nerves. Evaluation of PRL levels in hindpaws and plasma indicated that complete Freund’s adjuvant (CFA) stimulates release of peripheral, but not systemic PRL within 6–48h in both ovariectomized females with estradiol replacement (OVX-E) and male rats. The time course of release varies in OVX-E and male rats. We next employed the prolactin receptor (PRL-R) antagonist, Δ1-9-G129R-hPRL to assess the role of locally-produced PRL in nociception. Applied at a ratio of 1:1 (PRL:Δ1-9-G129R-hPRL; 40nM each), this antagonist was able to nearly (≈80%) reverse PRL-induced sensitization of capsaicin responses in rat sensory neurons. CFA-induced inflammatory thermal hyperalgesia in OVX-E rat hindpaws was significantly reduced in a dose-dependent manner by the PRL-R antagonist at the 6h, but not the 24h time point. In contrast, PRL contributed to inflammatory thermal hyperalgesia in male rats at 24h, but not 6h. In summary, these findings indicate that inflammation leads to accumulation of endogenous PRL in female and male rats. Further, PRL acts as an inflammatory mediator at different time points for female and male rats. PMID:21777304

Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia.

PubMed

Scotland, Phoebe E; Patil, Mayur; Belugin, Sergei; Henry, Michael A; Goffin, Vincent; Hargreaves, Kenneth M; Akopian, Armen N

2011-09-01

Prolactin (PRL) is a hormone and a neuromodulator. It sensitizes TRPV1 (transient receptor potential cation channel subfamily V member 1) responses in sensory neurons, but it is not clear whether peripheral inflammation results in the release of endogenous PRL, or whether endogenous PRL is capable of acting as an inflammatory mediator in a sex-dependent manner. To address these questions, we examined inflammation-induced release of endogenous PRL, and its regulation of thermal hyperalgesia in female and male rats. PRL is expressed in several types of peripheral neuronal and non-neuronal cells, including TRPV1-positive nerve fibers, preadipocytes and activated macrophages/monocytes localized in the vicinity of nerves. Evaluation of PRL levels in hindpaws and plasma indicated that complete Freund's adjuvant (CFA) stimulates release of peripheral, but not systemic, PRL within 6-48 h in both ovariectomized females with estradiol replacement (OVX-E) and intact male rats. The time course of release varies in OVX-E and intact male rats. We next employed the prolactin receptor (PRL-R) antagonist Δ1-9-G129R-hPRL to assess the role of locally produced PRL in nociception. Applied at a ratio of 1 : 1 (PRL:Δ1-9-G129R-hPRL; 40 nm each), this antagonist was able to nearly (≈ 80%) reverse PRL-induced sensitization of capsaicin responses in rat sensory neurons. CFA-induced inflammatory thermal hyperalgesia in OVX-E rat hindpaws was significantly reduced in a dose-dependent manner by the PRL-R antagonist at 6 h but not at 24 h. In contrast, PRL contributed to inflammatory thermal hyperalgesia in intact male rats at 24, but not at 6 h. These findings indicate that inflammation leads to accumulation of endogenous PRL in female and male rats. Furthermore, PRL acts as an inflammatory mediator at different time points for female and intact male rats. © 2011 UT Health Science Center San Antonio. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

[Expression of hemokinin-1 in rat spinal cord after peripheral inflammation].

PubMed

Ando, Yuko

2009-06-01

Hemokinin-1 (HK-1) is a novel peptide described as a member of the tachykinin family. Substance P (SP), a representative member of the tachykinin family, has been well characterized and is thought to play a part in inflammation and pain. While several studies indicate that HK-1 is involved in inflammation and pain, the biological functions of HK-1 are not fully understood. In the present study we investigated the expression of HK-1 mRNA (TAC4) and SP mRNA (TAC1) in the dorsal spinal cord of rat after inducing peripheral inflammation by administering complete Freund's adjuvant (CFA) into the hind paw, using real-time RT-PCR. In the behavioral studies, the thresholds of withdrawal response of the hind paw to thermal stimulation significantly decreased on the ipsilateral side, but not on the contralateral side, 6 hours after CFA injection and thermal hyperalgesia persisted until 4 days after CFA injection. The level of HK-1 mRNA expression significantly increased on the bilateral sides of the dorsal spinal cord 6 hours after CFA injection and returned to the base level 1 day after injection. On the other hand, the level of SP mRNA expression did not change in the spinal cord 6 hours and 1 day after CFA injection. These results indicate that HK-1 may contribute to inflammatory pain, in the early phase, in a different manner from SP.

Focusing of light through turbid media by curve fitting optimization

NASA Astrophysics Data System (ADS)

Gong, Changmei; Wu, Tengfei; Liu, Jietao; Li, Huijuan; Shao, Xiaopeng; Zhang, Jianqi

2016-12-01

The construction of wavefront phase plays a critical role in focusing light through turbid media. We introduce the curve fitting algorithm (CFA) into the feedback control procedure for wavefront optimization. Unlike the existing continuous sequential algorithm (CSA), the CFA locates the optimal phase by fitting a curve to the measured signals. Simulation results show that, similar to the genetic algorithm (GA), the proposed CFA technique is far less susceptible to the experimental noise than the CSA. Furthermore, only three measurements of feedback signals are enough for CFA to fit the optimal phase while obtaining a higher focal intensity than the CSA and the GA, dramatically shortening the optimization time by a factor of 3 compared with the CSA and the GA. The proposed CFA approach can be applied to enhance the focus intensity and boost the focusing speed in the fields of biological imaging, particle trapping, laser therapy, and so on, and might help to focus light through dynamic turbid media.

Antihypernociceptive and antioxidant effects of Petersianthus macrocarpus stem bark extracts in rats with complete Freund's adjuvant-induced persistent inflammatory pain.

PubMed

Bomba, Francis Desire Tatsinkou; Wandji, Bibiane Aimée; Fofié, Christian Kuete; Kamanyi, Albert; Nguelefack, Télesphore Benoit

2017-03-14

Background Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is a plant used in Cameroonian folk medicine to cure ailments such as inflammation and pain. Previous work showed that aqueous (AEPM) and methanol (MEPM) extracts from the stem bark of P. macrocarpus possess acute analgesic activities. The present study evaluates whether the same extracts could inhibit persistent hyperalgesia induced by complete Freund's adjuvant (CFA) in rats. Methods Inflammatory pain was induced by intraplantar injection of CFA into the left hind paw of Wistar rats. AEPM and MEPM were administered either acutely or chronically by the oral route at the doses of 100 and 200 mg/kg/day. The mechanical hyperalgesia was tested using an analgesimeter, while the locomotion activity at the end of experiment was evaluated with an open-field device. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were assayed in the brain and spinal cord of rats subjected to 14 days chronic treatment. Results AEPM and MEPM at both doses significantly (p<0.001) inhibited the acute and chronic mechanical hyperalgesia induced by CFA. Although not significant, both extracts increased the mobility of CFA-injected animals. AEPM significantly (p<0.01) reduced the level of nitrate at 100 mg/kg, MDA at 200 mg/kg and significantly (p<0.05) increased the SOD in the spinal cord. MEPM significantly increased the SOD content and reduced the MDA concentration in the brain but had no effect on the nitrate. Conclusions AEPM and MEPM exhibit acute and chronic antihyperalgesic activities. In addition, both extracts possess antioxidant properties that might strengthen their chronic antihyperalgesic effects.

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin.

PubMed

Liu, Yan-Li; Lin, Hai-Ming; Zou, Rong; Wu, Jun-Chao; Han, Rong; Raymond, Laurence N; Reid, Paul F; Qin, Zheng-Hong

2009-02-01

Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis.

PubMed

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-05-19

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis

PubMed Central

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-01-01

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund’s adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain. PMID:25988362

Parameter-specific analgesic effects of electroacupuncture mediated by degree of regulation TRPV1 and P2X3 in inflammatory pain in rats.

PubMed

Fang, J Q; Du, J Y; Fang, J F; Xiao, T; Le, X Q; Pan, N F; Yu, J; Liu, B Y

2018-05-01

Observing the parameter-specific anti-hyperalgesic effects of EA with different stimulation times and frequencies on painful hyperalgesia mediated by the level of TRPV1 and P2X3 expression in DRG after CFA injection. The model was induced by the injection of CFA in each rat's right hind paw. EA treatment was applied to the bilateral ST36 and BL60. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested with Von Frey filaments and the radiant heat source of the test instrument, respectively. TRPV1 and P2X3 expressions were measured by immunofluorescence and western blot. αβ-meATP and capsaicine combined with EA were further utilized to investigate the change in PWL. Different stimulation times (20, 30, 45 min) combined with different frequencies (2 Hz, 100 Hz, 2/100 Hz) of EA have analgesic effects on the PWT and PWL; however, the level of the hypoalgesic efficacy of EA was primarily associated with EA frequency. The analgesic effect of EA was better at 100 Hz than at 2 Hz. The level of regulation of 100 Hz EA on TRPV1 and P2X3 in DRG was greater than that of 2 Hz. Furthermore, both TRPV1 agonist and P2X3 agonist may impair the level of EA analgesia. EA has a parameter-specific effect on chronic inflammatory pain relief, which primarily depend on the stimulation frequency and not on the stimulation time at a certain stimulation time. The parameter-specific analgesic effect of EA is at least partially related to mediation of the protein level of TRPV1 and P2X3 expression in DRG of CFA rats. Copyright © 2018 Elsevier Inc. All rights reserved.

TRPV1 channel-mediated bilateral allodynia induced by unilateral masseter muscle inflammation in rats.

PubMed

Simonic-Kocijan, Suncana; Zhao, Xuehong; Liu, Wen; Wu, Yuwei; Uhac, Ivone; Wang, KeWei

2013-12-30

Pain in masticatory muscles is among the most prominent symptoms of temperomandibular disorders (TMDs) that have diverse and complex etiology. A common complaint of TMD is that unilateral pain of craniofacial muscle can cause a widespread of bilateral pain sensation, although the underlying mechanism remains unknown. To investigate whether unilateral inflammation of masseter muscle can cause a bilateral allodynia, we generated masseter muscle inflammation induced by unilateral injection of complete Freund's adjuvant (CFA) in rats, and measured the bilateral head withdrawal threshold at different time points using a von Frey anesthesiometer. After behavioral assessment, both right and left trigeminal ganglia (TRG) were dissected and examined for histopathology and transient receptor potential vanilloid 1 (TRPV1) mRNA expression using quantitative real-time PCR analysis. A significant increase in TRPV1 mRNA expression occurred in TRG ipsilateral to CFA injected masseter muscle, whereas no significant alteration in TRPV1 occurred in the contralateral TRG. Interestingly, central injection of TRPV1 antagonist 5-iodoresiniferatoxin into the hippocampus significantly attenuated the head withdrawal response of both CFA injected and non-CFA injected contralateral masseter muscle. Our findings show that unilateral inflammation of masseter muscle is capable of inducing bilateral allodynia in rats. Upregulation of TRPV1 at the TRG level is due to nociception caused by inflammation, whereas contralateral nocifensive behavior in masticatory muscle nociception is likely mediated by central TRPV1, pointing to the involvement of altered information processing in higher centers.

Amelioratory effect of flavonoids rich Pergularia daemia extract against CFA induced arthritic rats.

PubMed

Ananth, Devanesan Arul; Rameshkumar, Angappan; Jeyadevi, Ramachandran; Aseervatham, G Smilin Bell; Sripriya, Jaganathan; Bose, Prabaharan Chandra; Sivasudha, Thilagar

2016-05-01

Pergularia daemia Forsk. (Asclepiadaceae) is a traditionally reported medicinal herb used to treat joint pain and arthritis. However, there are no scientific reports about anti-arthritic activity of P. daemia methanolic extract on rats as animal model. This study identifies bioactive compounds present in the P. daemia methanolic extract and evaluates its anti-arthritic potential in CFA induced arthritic rats. Phytoconstituents of P. daemia extract were examined using LC-ESI/MS method. Anti-arthritic activity of P. daemia extract was determined by various biochemical experiments (RF, ESR and CRP), ultrasonography and histological analysis. LC-ESI/MS analysis resulted in the identification of major flavonoids compounds such as formononetin, qurecetin, chrysoeriol, taxifolin and naringenin. Serum biomarker analysis, after the treatment with PDME (500mg/kg b.w.) revealed that the hemoglobin (11.84±0.42g/dL) and RBC (8.38±0.67million/mm(3)) levels were significantly increased whereas WBC (8.91±0.38thousands/mm(3)), RF (17.94±0.45IU/mL), ESR (7.91±0.12mm/h) and CRP (22.56±0.26mg/L) levels were decreased when compared with the CFA induced arthritic control group. Histology results revealed that treatment with PDME has resulted in significant prevention against bony destruction by decreasing soft tissue swelling and narrowing of joint spaces (250 and 500mg/kg b.w.). Anti-arthritic effect of P. daemia might be due to the presence of these bioactive flavonoids. These findings lend pharmacological support to the reported folkloric use of P. daemia in the treatment and management of painful, arthritic inflammatory conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-gamma-expressing Th1-like cells and up-regulation of TGF-beta mRNA in mononuclear cells.

PubMed

Ma, C G; Zhang, G X; Xiao, B G; Wang, Z Y; Link, J; Olsson, T; Link, H

1996-02-13

Oral and nasal administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR and complete Freund's adjuvant (CFA) resulted in prevention or marked decrease of the severity of experimental autoimmune myasthenia gravis (EAMG) and suppression of AChR-specific B-cell responses and of AChR-reactive T-cell function. To examine the involvement of immunoregulatory cytokines and the underlying mechanisms involved in tolerance induction, in situ hybridization with radiolabeled cDNA oligonucleotide proves was adopted to enumerate mononuclear cells (MNC) expressing mRNA for the proinflammatory cytokine interferon-gamma (IFN-gamma), the B cell-stimulating interleukin-4 (IL-4), and the immunosuppressive transforming growth factor-beta (TGF-beta). Popliteal and inguinal lymph nodes from EAMG rats contained elevated numbers of AChR-reactive IFN-gamma, IL-4, and TGF-beta mRNA-expressing cells, compared to control rats receiving PBS orally or nasally and injected with CFA only. Oral and nasal tolerance was accompanied by decreased numbers of AChR-reactive IFN-gamma and IL-4 mRNA-expressing cells and strong up-regulation of TGF-beta mRNA-positive cells in lymphoid organs when compared to nontolerized EAMG control rats. The results suggest that IFN-gamma and IL-4 are central effector molecules in the development of EAMG and that TGF-beta plays an important role in tolerance induction to EAMG.

Free and nanoencapsulated vitamin D3 : effects on E-NTPDase and E-ADA activities in an animal model with induced arthritis.

PubMed

da Silveira, Karine Lanes; da Silveira, Leonardo Lanes; Thorstenberg, Maria Luiza Prates; Cabral, Fernanda Licker; Castilhos, Livia Gelain; Rezer, João Felipe Peres; de Andrade, Diego Fontana; Beck, Ruy Carlos Ruver; Einloft Palma, Heloísa; de Andrade, Cinthia Melazzo; Pereira, Renata da Silva; Martins, Nara Maria Beck; Bertonchel Dos Santos, Claudia de Mello; Leal, Daniela Bitencourt Rosa

2016-06-01

The effect of vitamin D3 in oral solution (VD3 ) and vitamin D3 -loaded nanocapsules (NC-VD3 ) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3 . Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3 . The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd. The effects promoted by both formulations of vitamin D3 , either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis. Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis. Copyright © 2016 John Wiley & Sons, Ltd.

Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats.

PubMed

Voon, Fui-Ling; Sulaiman, Mohd Roslan; Akhtar, Muhammad Nadeem; Idris, Mohamad Fauzi; Akira, Ahmad; Perimal, Enoch Kumar; Israf, Daud Ahmad; Ming-Tatt, Lee

2017-01-05

Boesenbergia rotunda (L.) Mansf. had been traditionally used as herbs to treat pain and rheumatism. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is a compound isolated from Boesenbergia rotunda (L.) Mansf.. Previous study had shown the potential of cardamonin in inhibiting the release of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. Thus, the possible therapeutic effect of cardamonin in the rheumatoid arthritis (RA) joints is postulated. This study was performed to investigate the anti-arthritic properties of cardamonin in rat model of induced RA, particularly on the inflammatory and pain response of RA. Rheumatoid arthritis paw inflammation was induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA) in Sprague Dawley rats. Using four doses of cardamonin (0.625, 1.25, 2.5, and 5.0mg/kg), anti-arthritic activity was evaluated through the paw edema, mechanical allodynia and thermal hyperalgesia responses. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma level of TNF-α, IL-1β, and IL-6. Histological slides were prepared from the harvested rat paws to observe the arthritic changes in the joints. Behavioral, biochemical, and histological studies showed that cardamonin demonstrated significant inhibition on RA-induced inflammatory and pain responses as well as progression of joint destruction in rats. ELISA results showed that there was significant inhibition in TNF-α, IL-1β, and IL-6 levels in plasma of the cardamonin-treated RA rats. Overall, cardamonin possesses potential anti-arthritic properties in CFA-induced RA rat model. Copyright © 2016 Elsevier B.V. All rights reserved.

Immune stimulation improves endocrine and neural fetal outcomes in a model of maternofetal thyrotoxicosis.

PubMed

Ahmed, R G; Abdel-Latif, M; Mahdi, Emad A; El-Nesr, Khalid A

2015-12-01

The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20μl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10μg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocrine function were evaluated by observing some histopathological investigations in pregnant rats and measuring some biochemical parameters in dams and their fetuses at GD 20. In hyperthyroid group, an increase in maternofetal serum thyroxine (T4), triiodothyronine (T3) and a decrease in thyrotropin (TSH) levels were noticed, while the concentrations of fetal serum growth hormone (GH) and insulin-like growth factor-1 (IGF1) levels were increased at tested GD with respect to control and CFA groups. Moreover, the activity of uterine and placental myeloperoxidase (MPO) was increased (P<0.001) in CFA and CFA-treated hyperthyroid groups in respect to control or hyperthyroid groups, respectively. The gestational thyrotoxicosis led to some histopathological lesions in uterine and placental tissues characterized by severe degeneration in trophoblast spongioblast cell layer with congestion, mild congested blood vessels in the endometrium and deficient in spiral artery remodeling. Although, the elevation in fetal serum transforming growth factor-beta (TGFβ) and cerebellar monoamines [norepineprine (NE), epinephrine (E), dopamine (DA) and 5-hydroxytryptamine (5-HT)] was observed, the reduction in fetal serum tumor necrosis factor-alpha (TNFα) and adipokines (Leptin and adiponectin) was detected. Treatment of dams with CFA showed an obviously reversing and protecting effect against hyperthyroid perturbations. Thus, the maternal CFA can be used in treatment of the fetal neuroendocrine dysfunctions. Copyright © 2015 Elsevier B.V. All rights reserved.

6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant.

PubMed

Levy, Arkene Sa; Simon, Oswald; Shelly, Janet; Gardener, Michael

2006-10-01

6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200-250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 +/- 0.2 mm to 1.0 +/- 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 +/- 0.6 mm to 0.8 +/- 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 +/- 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.

6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant

PubMed Central

Levy, Arkene SA; Simon, Oswald; Shelly, Janet; Gardener, Michael

2006-01-01

Background 6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200–250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). Results Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 ± 0.2 mm to 1.0 ± 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 ± 0.6 mm to 0.8 ± 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 ± 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. Conclusion From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats. PMID:17010215

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

PubMed Central

Johnston, Ian N.; Maier, Steven F.; Rudy, Jerry W.; Watkins, Linda R.

2017-01-01

There is evidence that pain can impact cognitive function in people. The present study evaluated whether Pavlovian fear conditioning in rats would be reduced if conditioning were followed by persistent inflammatory pain induced by a subcutaneous injection of dilute formalin or complete Freund's adjuvant (CFA) on the dorsal lumbar surface of the back. Formalin-induced pain specifically impaired contextual fear conditioning but not auditory cue conditioning (Experiment 1A). Moreover, formalin pain only impaired contextual fear conditioning if it was initiated within 1 h of conditioning and did not have a significant effect if initiated 2, 8 or 32 h after (Experiments 1A and 1B). Experiment 2 showed that formalin pain initiated after a session of context pre-exposure reduced the ability of that pre-exposure to facilitate contextual fear when the rat was limited to a brief exposure to the context during conditioning. Similar impairments in context- but not CS-fear conditioning were also observed if the rats received an immediate post-conditioning injection with CFA (Experiment 3). Finally, we confirmed that formalin and CFA injected s.c. on the back induced pain-indicative behaviours, hyperalgesia and allodynia with a similar timecourse to intraplantar injections (Experiment 4). These results suggest that persistent pain impairs learning in a hippocampus-dependent task, and may disrupt processes that encode experiences into long-term memory. PMID:21920390

Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.

PubMed

Wang, Dongmei; Ruan, Liqin; Hong, Yanguo; Chabot, Jean-Guy; Quirion, Rémi

2013-01-01

We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.

PubMed

Du, Jun-Ying; Fang, Jian-Qiao; Liang, Yi; Fang, Jun-Fan

2014-09-01

Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia. We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn. Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-Term Treatment by Vitamin B1 and Reduction of Serum Proinflammatory Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis

PubMed Central

Zaringhalam, Jalal; Akbari, Akhtar; Zali, Alireza; Manaheji, Homa; Nazemian, Vida; Shadnoush, Mahdi; Ezzatpanah, Somayeh

2016-01-01

Introduction: Immune system is involved in the etiology and pathophysiology of inflammation and vitamins are important sources of substances inducing nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines in the inflammation and pain induction, this study aimed to assess the effects of long-term administration of vitamin B1 on the proinflammatory cytokines, edema, and hyperalgesia during the acute and chronic phases of adjuvant-induced arthritis. Methods: On the first day of study, inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of rats. Vitamin B1 at doses of 100, 150, and 200 mg/kg was administrated intraperitoneally during 21 days of the study. Antinociceptive and anti-inflammatory effects of vitamin B1 were also compared to indomethacin (5 mg/kg). Inflammatory symptoms such as thermal hyperalgesia and paw edema were measured by radiant heat and plethysmometer, respectively. Serum TNF-α and IL-1β levels were checked by rat standard enzyme-linked immune sorbent assay (ELISA) specific kits. Results: The results indicated that vitamin B1(150 and 200 mg/kg) attenuated the paw edema, thermal hyperalgesia, and serum levels of TNF-α and IL-1β during both phases of CFA-induced inflammation in a dose-dependent manner. Effective dose of vitamin B1(150 mg/kg) reduced inflammatory symptoms and serum levels of TNF-α and IL-1β compare to indomethacin during the chronic phase of inflammation. Conclusion: Anti-inflammatory and antihyperalgesic effects of vitamin B1 during CFA-induced arthritis, more specifically after chronic vitamin B1 administration, suggest its therapeutic property for inflammation. PMID:27872694

Antiarthritic activity of Majoon Suranjan (a polyherbal Unani formulation) in rat

PubMed Central

Singh, Surender; Nair, Vinod; Gupta, Y.K.

2011-01-01

Background & objectives: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. Methods: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. Results: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. Interpretation & conclusions: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA. PMID:21985823

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

PubMed

Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-inflammatory effects of vitamin E on adjuvant-induced arthritis in rats.

PubMed

Rossato, Mateus Fortes; Hoffmeister, Carin; Tonello, Raquel; de Oliveira Ferreira, Ana Paula; Ferreira, Juliano

2015-04-01

Vitamin E (vit-E) is a lipophilic antioxidant, and its anti-inflammatory activity is still not full characterized. Thus, our goal was to investigate the anti-inflammatory effect of repeated vit-E treatment in the arthritis induced by the intraplantar injection of complete Freund's adjuvant (CFA). We observed an increase in arthritis scores, interleukin-1β and H2O2 levels, neutrophil and macrophage infiltration, thermal hyperalgesia, mechanical allodynia, and loss of function induced by intraplantar CFA injection. These effects were unaltered after 1 day, partially reversed after 3 days, and inhibited after 9 days after vit-E treatment. Furthermore, the concentration of vit-E was reduced and that of tumor necrosis factor-alpha was increased in the CFA-injected paw. Both effects were reversed from 1 to 9 days after vit-E treatment. However, vit-E treatment did not alter CFA-induced edema at any time. Thus, vit-E treatment produced an anti-inflammatory effect of slow onset in CFA, which demonstrates a disease-modifying drug profile.

Evaluation of disease modifying activity of Coriandrum sativum in experimental models

PubMed Central

Nair, Vinod; Singh, Surender; Gupta, Y.K.

2012-01-01

Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. Methods: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF-α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA. PMID:22446868

Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

PubMed Central

Ruan, Xiaosai; Sack, David A.; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development. PMID:25803825

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

PubMed

Ruan, Xiaosai; Sack, David A; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.

The water extract of Veratrilla baillonii could attenuate the subacute toxicity induced by Aconitum brachypodum.

PubMed

Yu, You; Yi, Xue-Jia; Mei, Zhi-Yi; Li, Jun; Huang, Xian-Ju; Yang, Guang-Zhong; Ma, Li-Qun; Gao, Yue

2016-12-01

Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China. To further address the mechanism of the detoxication of Veratrilla baillonii, the effect of water decoction of Veratrilla baillonii (WVBF) on subacute toxicology of SD rats induced by Aconitum brachypodum (CFA), a genus Aconitum, was determined and studied in the present work. The clinical behavior and number of survivors for different dosage of WVBF (25, 50, 100mg/kg) on CFA (4mg/kg) induced rats were observed until day 28. Histological changes and haematological parameters were evaluated. Moreover, Na + -K + -ATPase pathway in heart as well as key enzymes in liver were determined to further discuss the mechanism. The results showed that the exposure of CFA led to some subacute toxicity to rats, especially male ones, accompanied with abnormality of serum biochemical index in rats' serum. The toxicological target organs of CFA may be the heart, liver, kidney and brain. It is demonstrated that WVBF could attenuate the toxicity induced by Aconitum brachypodum via promoting the metabolic enzymes CYP3A1 and CYP3A2 in liver, downregulating the expression of Sodium/Calcium exchanger 1 (NCX1) and SCN5A sodium channal mRNA, and inducing Na + /K + -ATPase activity in heart. This study provides insights into detoxifying measures of Aconitum plants. Aconitum brachypodum may lead to subacute toxicity of rats after long term of administration, and the toxicity could be attenuated by Veratrilla baillonii via promoting the metabolic enzymes in liver, downregulating the expression of NCX1 and SCN5A mRNA, and inducing Na + /K + -ATPase activity in heart. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effects of gonadal hormones on the peripheral cannabinoid receptor 1 (CB1R) system under a myositis condition in rats.

PubMed

Niu, Katelyn Y; Zhang, Youping; Ro, Jin Y

2012-11-01

In this study, we assessed the effects of peripherally administered cannabinoids in an orofacial myositis model, and the role of sex hormones in cannabinoid receptor (CBR) expression in trigeminal ganglia (TG). Peripherally administered arachidonylcyclopropylamide (ACPA), a specific CB1R agonist, significantly attenuated complete Freund's adjuvant (CFA)-induced mechanical hypersensitivity in the masseter muscle in male rats. The ACPA effect was blocked by a local administration of AM251, a specific CB1R antagonist, but not by AM630, a specific CB2R antagonist. In female rats, a 30-fold higher dose of ACPA was required to produce a moderate reduction in mechanical hypersensitivity. CFA injected in masseter muscle significantly upregulated CB1R mRNA expression in TG in male, but not in female, rats. There was a close correlation between the CB1R mRNA levels in TG and the antihyperalgesic effect of ACPA. Interleukin (IL)-1β and IL-6, which are elevated in the muscle tissue following CFA treatment, induced a significant upregulation of CB1R mRNA expression in TG from male rats. The upregulation of CB1R was prevented in TG cultures from orchidectomized male rats, which was restored by the application of testosterone. The cytokines did not alter the CB1R mRNA level in TG from intact as well as ovariectomized female rats. Neither estradiol supplement nor estrogen receptor blockade had any effects on CB1R expression. These data indicate that testosterone, but not estradiol, is required for the regulation of CB1Rs in TG under inflammatory conditions, which provide explanations for the sex differences in the antihyperalgesic effects of peripherally administered cannabinoids. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia.

PubMed

Ding, Ruoting; Jiang, Hui; Sun, Baihui; Wu, Xiaoliang; Li, Wei; Zhu, Siyuan; Liao, Congrui; Zhong, Zhaoming; Chen, Jianting

2016-12-01

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund's adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund׳s adjuvant induced arthritis in rats.

PubMed

Lin, Bing; Zhao, Yong; Han, Ping; Yue, Wei; Ma, Xue-Qin; Rahman, Khalid; Zheng, Cheng-Jian; Qin, Lu-Ping; Han, Ting

2014-08-08

Xanthium strumarium L. fruit (Xanthiu fruit) has been traditionally used as a medicinal herb in China for the treatment of many ailments including rheumatoid arthritis. However, the anti-arthritic activity of Xanthium strumarium fruit has still not been demonstrated. In the present study, we confirmed that the extract of Xanthium strumarium (EXS) prevents rheumatoid arthritis induced by Complete Freund׳s Adjuvant (CFA) in rats. Male Wistar rats (160±10 g) were immunized by intradermal injection of 0.1 mL of CFA into the left hind metatarsal footpad. EXS was administered orally at a dose of 300 and 75 mg/kg once a day after the induction of adjuvant arthritis. Methotrexate (3 mg/kg, twice a week) was used as a positive control. Paw swelling, arthritic score, body weight loss, spleen index, thymus index, serum cytokines, inflammatory mediators and histological change were measured. The chemical profile of EXS was analyzed by HPLC-DAD. We found that the EXS significantly suppressed paw swelling and arthritic score, increased body weight loss and decreased the thymus index. The overproduction of TNF-α and IL-1β were remarkably suppressed in the serum of all EXS-treated rats, and in contrast IL-10 was markedly increased. The level of COX-2 and 5-LOX was also decreased with EXS treatment. Ten phenolic acid derivatives were identified from 14 detected peaks by HPLC-DAD with the reference substances and verified by LC-MS. These results suggest the potential effect of EXS as an anti-arthritis agent towards CFA-induced arthritis in rats. Xanthium strumarium has the potential to be regarded as a candidate for use in general therapeutics and as an immune-modulatory medicine in rheumatoid arthritis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Therapeutic effect of umbelliferon-α-D-glucopyranosyl-(2(I)→1(II))-α-D-glucopyranoside on adjuvant-induced arthritic rats.

PubMed

Kumar, Vikas; Anwar, Firoz; Verma, Amita; Mujeeb, Mohd

2015-06-01

The aim and objective of the present investigation was to evaluate the antiarthritic and antioxidant effect of umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside (UFD) in chemically induced arthritic rats. The different doses of the UFD were tested against the turpentine oil (TO), formaldehyde induced acute arthritis and complete fruend's adjuvant (CFA) induced chronic arthritis in Wistar rats. Arthritic assessment and body weight was measured at regular interval till 28 days. On day 28, all the groups animals were anaesthetized, blood were collected from the puncturing the ratro orbital and estimated the hematological parameters. The animals were sacrificed; synovial tissue was extracted and estimated the malonaldehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The different doses of the UFD showed the protective effect against turpentine oil, formaldehyde induced acute arthritis and CFA induced chronic arthritis at dose dependent manner. Acute model of arthritis such as TOand formaldehyde induced inflammation due to releasing of the inflammatory mediators; significantly inhibited by the UFD at dose dependent manner. CFA induced arthritic rats treated with the different doses of the UFD showed the inhibitory effect on the delayed increase in joint diameter as seen in arthritic control group rats. UFD significantly improved the arthritic index, body weight and confirmed the antiarthritic effect. UFD showed the effect on the hematological parameter such as improved the level of the RBC, Hb and decline the level of the EBC, ESR and confirmed the immune suppressive effect. UFD significantly improved the level of the endogenous antioxidant and confirmed the antioxidant effect. This present investigation suggests that the UFD has prominent antiarthritic impact which can be endorsed to its antiarthritic and antioxidant effects.

Selective adsorption mechanisms of antilipidemic and non-steroidal anti-inflammatory drug residues on functionalized silica-based porous materials in a mixed solute.

PubMed

Suriyanon, Nakorn; Permrungruang, Jutima; Kaosaiphun, Jidanan; Wongrueng, Aunnop; Ngamcharussrivichai, Chawalit; Punyapalakul, Patiparn

2015-10-01

The selective adsorption mechanisms of naproxen (NAP), acetaminophen (ACT), and clofibric acid (CFA) on silica-based porous materials were examined by single and mixed-batch adsorption. Effects of the types and densities of surface functional groups on adsorption capacities were determined, including the role of hydrophobic and hydrophilic dissolved organic matters (DOMs). Hexagonal mesoporous silica (HMS), superparamagnetic HMS (HMS-SP) and SBA-15 were functionalized and applied as adsorbents. Compared with powdered activated carbon (PAC), amine-functionalized HMS had a better adsorption capacity for CFA, but PAC possessed a higher adsorption capacity for the other pharmaceuticals than HMS and its two derivatives. In contrast to PAC, the adsorption capacity of the mesoporous silicas varied with the solution pH, being highest at pH 5. Electrostatic interactions and hydrogen bonding were found to be the main mechanisms. Increase in grafted amine group density on silica surfaces can enhance the CFA adsorption capacity. Further, hydrophilic DOM can decrease CFA adsorption capacities on amino-grafted adsorbents by adsorption site competition, while hydrophobic DOM can interfere with CFA adsorption by the interaction between hydrophobic DOM and CFA. Finally, in a competitive adsorption study, the adsorption capacity of hydrophilic adsorbents for acidic pharmaceuticals varied with their pKa values. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats: involvement of the cyclooxygenase activity in the spinal cord.

PubMed

Mi, Wen-Li; Mao-Ying, Qi-Liang; Liu, Qiong; Wang, Xiao-Wei; Wang, Yan-Qing; Wu, Gen-Cheng

2008-09-30

Electroacupuncture (EA) can effectively control the exaggerated pain in humans with inflammatory disease and animals with experimental inflammatory pain. However, there have been few investigations on the effect of co-administration of EA and analgesics and the underlying synergistic mechanism. Using behavioral test, RT-PCR analysis, enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA), the present study demonstrated that (1) Unilateral intra-articular injection of complete Freund's adjuvant (CFA) produced a constant hyperalgesia and an up-regulation of the prostaglandin E(2) (PGE(2)) level as well as the tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in the spinal cord; (2) Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), at a dose of 2, 10, and 20 mg/kg (twice daily, p.o.), presented a dose-dependent anti-hyperalgesic effect; (3) Repeated EA stimulation of ipsilateral 'Huan-Tiao' (GB30) and 'Yang-Ling-Quan' (GB34) acupoints significantly suppressed CFA-induced hyperalgesia, and markedly inhibited the CFA-induced increase of the level of PGE(2) as well as IL-1beta, IL-6, and TNF-alpha in the spinal cord; (4) EA combined with low dose of celecoxib (2 mg/kg, twice daily, p.o.) greatly enhanced the anti-hyperalgesic effects of EA, with a synergistic reversing effect on CFA-induced up-regulation of spinal PGE(2), but not on the IL-1beta, IL-6, or TNF-alpha. These data indicated that repeated EA combined with low dose of celecoxib produced synergistic anti-hyperalgesic effect in the CFA-induced monoarthritic rats, which could be made possible by regulating the activity of spinal COX, hence the spinal PGE(2) level. Thus, this combination may provide an effective strategy for pain management.

Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase ﴾HO﴿-1/related factor 2 pathway.

PubMed

Fan, Rong; Pan, Tong; Zhu, An-Li; Zhang, Mei-Hong

2017-10-01

Naringenin, a bioflavonoid present in various species of citrus fruit, tomatoes and grapes, has been shown to have various pharmacological effects. We evaluated the anti-arthritic potential of naringenin in formaldehyde-induced inflammation and complete Freund's adjuvant (CFA)-induced arthritis. For both evaluations, rats were divided into groups of six. Different doses of naringenin (5, 10 and 20mg/kg) were used in the models. Body weight and the arthritic index were assessed. Biochemical and antioxidant parameters were determined. Naringenin dose-dependently reduced joint inflammation, decreasing the joint diameter and inflammatory cell infiltration. Naringenin-treated rats showed an improvement in the synovium redox status (down-regulation of malondialdehyde and glutathione and up-regulation of Catalase (CAT) and superoxide dismutase levels). Naringenin significantly reduced the level of the inflammatory marker TNF-α. Naringenin increased Nrf-2/HO-1 and reduced NF-κB mRNA levels in CFA-treated animal joints. Additionally, naringenin treatment decreased the expression of extracellular matrix degrading enzymes, such as matrix metalloproteinase (MMP-3 and MMP-9), in CFA-induced arthritic rats. We conclude that naringenin exerts anti-arthritic effects by downregulating NF-κB and activating the Nrf-2/HO-1 pathway. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The role of P2X3 receptors in bilateral masseter muscle allodynia in rats

PubMed Central

Tariba Knežević, Petra; Vukman, Robert; Antonić, Robert; Kovač, Zoran; Uhač, Ivone; Simonić-Kocijan, Sunčana

2016-01-01

Aim To determine the relationship between bilateral allodynia induced by masseter muscle inflammation and P2X3 receptor expression changes in trigeminal ganglia (TRG) and the influence of intramasseteric P2X3 antagonist administration on bilateral masseter allodynia. Methods To induce bilateral allodynia, rats received a unilateral injection of complete Freund’s adjuvant (CFA) into the masseter muscle. Bilateral head withdrawal threshold (HWT) was measured 4 days later. Behavioral measurements were followed by bilateral masseter muscle and TRG dissection. Masseter tissue was evaluated histopathologically and TRG tissue was analyzed for P2X3 receptor mRNA expression by using quantitative real-time polymerase chain reaction (PCR) analysis. To assess the P2X3 receptor involvement in nocifensive behavior, two doses (6 and 60 μg/50 μL) of selective P2X3 antagonist A-317491 were administrated into the inflamed masseter muscle 4 days after the CFA injection. Bilateral HWT was measured at 15-, 30-, 60-, and 120-minute time points after A-317491 administration. Results HWT was bilaterally reduced after the CFA injection (P < 0.001). Intramasseteric inflammation was confirmed ipsilaterally to the CFA injection. Quantitative real-time PCR analysis demonstrated enhanced P2X3 expression in TRG ipsilaterally to CFA administration (P < 0.01). In comparison with controls, the dose of 6 μg of A-317491 significantly increased bilateral HWT at 15-, 30-, and 60-minute time points after the A-317491 administration (P < 0.001), whereas the dose of 60 μg of A-317491 was efficient at all time points ipsilaterally (P = 0.004) and at 15-, 30-, and 60-minute time points contralaterally (P < 0.001). Conclusion Unilateral masseter inflammation can induce bilateral allodynia in rats. The study provided evidence that P2X3 receptors can functionally influence masseter muscle allodynia and suggested that P2X3 receptors expressed in TRG neurons are involved in masseter inflammatory pain conditions. PMID:28051277

Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

PubMed Central

Luan, Shuo; Wan, Qing; Luo, Haijie; Li, Xiao; Ke, Songjian; Lin, Caina; Wu, Yuanyuan; Wu, Shaoling; Ma, Chao

2015-01-01

Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use. PMID:25607736

Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

PubMed

Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman

2017-02-01

Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The possible mechanisms might be that BoNT/A prevents the release of nociceptive nerve peptides at the injection site and then suppresses the expression of inflammatory cytokines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute procedural outcomes of orbital atherectomy for the treatment of common femoral artery disease: Sub-analysis of the CONFIRM Registries.

PubMed

Lee, Michael S; Heikali, Daniel; Mustapha, Jihad; Adams, George; Mahmud, Ehtisham

2017-08-01

This analysis compared the angiographic outcomes of patients treated with orbital atherectomy for calcified common femoral artery (CFA) and superficial femoral artery (SFA) disease. The ideal revascularization strategy for CFA disease is unknown. Endarterectomy has been considered the standard of care for CFA disease for over 50 years. Endovascular intervention is becoming more commonly used to revascularize the CFA given the advances in technology and the less invasive nature of the procedure. Patient demographics, lesion characteristics, and procedure data for all CONFIRM patients with at least one CFA lesion location ( n=147 patients; n=200 lesions) were compared to patients with at least one SFA lesion location ( n=1508 patients; n=2367 lesions). The primary endpoint was angiographic complication, defined as the composite of dissection, perforation, slow flow, closure, spasm, embolism, or thrombosis. The CFA group had more patients with Rutherford class 4 and shorter lesion length. The CFA group had a higher final residual stenosis, shorter total run time, and shorter total inflation time. The primary endpoint was lower in the CFA group compared with the SFA group (17% vs 24%, p=0.02), driven by a lower dissection rate (10% vs 15%, p=0.04). Plaque modification of the CFA with orbital atherectomy was safe and compared favorably with SFA disease. The need for bail-out stenting was low. A randomized trial is needed to determine the ideal treatment strategy for calcified CFA disease.

Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) in Rodents: possible mechanism of actions.

PubMed

Ishola, Ismail O; Olayemi, Sunday O; Oreagba, Ibrahim A; Ifeanyi, Chikaodili I; Popoola, Temidayo O

2015-12-20

The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for the treatment of various ailments including arthritis. The present study sought to investigate the antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA). HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar injection of formalin 1%v/v in saline to evaluate antinociceptive effect. Moreover, its possible mechanism of antinociceptive action was investigated through pretreatment of mice with antagonists of receptors implicated in nociception. Anti¬inflammatory effect of the extract was investigated using the carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the duration of paw licking/biting during both in the early (42.12%) and late (75.79%) phases of formalin-induced nociception. However, the antinociceptive effect elicited by HeCA was reverse by pretreatment of mice with naloxone, prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA). HeCA produced dose-dependent and time course decrease in carrageenan-induced paw oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced arthritis evidenced in the significant decrease in arthritic index comparatively similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress were attenuated by subchronic treatment with HeCA. Findings from this study shows that C. anisata possesses antinociceptive activity through possible interaction with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic pathways as well as anti-arthritic property which could be attributed to its ability to prevent the release of inflammatory mediators and oxidative stress.

Text mining factor analysis (TFA) in green tea patent data

NASA Astrophysics Data System (ADS)

Rahmawati, Sela; Suprijadi, Jadi; Zulhanif

2017-03-01

Factor analysis has become one of the most widely used multivariate statistical procedures in applied research endeavors across a multitude of domains. There are two main types of analyses based on factor analysis: Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). Both EFA and CFA aim to observed relationships among a group of indicators with a latent variable, but they differ fundamentally, a priori and restrictions made to the factor model. This method will be applied to patent data technology sector green tea to determine the development technology of green tea in the world. Patent analysis is useful in identifying the future technological trends in a specific field of technology. Database patent are obtained from agency European Patent Organization (EPO). In this paper, CFA model will be applied to the nominal data, which obtain from the presence absence matrix. While doing processing, analysis CFA for nominal data analysis was based on Tetrachoric matrix. Meanwhile, EFA model will be applied on a title from sector technology dominant. Title will be pre-processing first using text mining analysis.

Dose response study of conjugated fatty acid derived from safflower oil on mammary and colon carcinogenesis pretreated with 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Sprague-Dawley rats.

PubMed

Cheng, Jing Lei; Futakuchi, Mitsuru; Ogawa, Kumiko; Iwata, Toshio; Kasai, Masaaki; Tokudome, Shinkan; Hirose, Masao; Shirai, Tomoyuki

2003-07-10

To clarify the chemopreventive effects of conjugated fatty acid derived from safflower oil (CFA-S), rich in conjugated linoleic acid (CLA), on mammary and colon carcinogenesis, 6 week old female Sprague-Dawley (SD) rats received diet containing 0.01, 0.05, 0.1, 1, or 2% CFA-S subsequent to five times subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) at a dose of 40 mg/kg b.w. and a single 50 mg/kg b.w. intragastric application of 7,12-dimethylbenz[a]anthracene (DMBA) during the first 11 days. The experiment was terminated at week 36. Numbers of mammary tumors, colon aberrant crypt foci (ACF), and proliferative indices of mammary tumors, and colon epithelium were analyzed. The 1% dose was found to be optimal for suppression of carcinogenesis in both target organs, a good correlation being noted with between data for cell proliferation. These results suggest that a diet containing appropriate levels of CFA-S may be useful for prevention of mammary and colon cancer.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

PubMed

Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Estimation of color filter array data from JPEG images for improved demosaicking

NASA Astrophysics Data System (ADS)

Feng, Wei; Reeves, Stanley J.

2006-02-01

On-camera demosaicking algorithms are necessarily simple and therefore do not yield the best possible images. However, off-camera demosaicking algorithms face the additional challenge that the data has been compressed and therefore corrupted by quantization noise. We propose a method to estimate the original color filter array (CFA) data from JPEG-compressed images so that more sophisticated (and better) demosaicking schemes can be applied to get higher-quality images. The JPEG image formation process, including simple demosaicking, color space transformation, chrominance channel decimation and DCT, is modeled as a series of matrix operations followed by quantization on the CFA data, which is estimated by least squares. An iterative method is used to conserve memory and speed computation. Our experiments show that the mean square error (MSE) with respect to the original CFA data is reduced significantly using our algorithm, compared to that of unprocessed JPEG and deblocked JPEG data.

Photobiomodulation therapy by NIR laser in persistent pain: an analytical study in the rat.

PubMed

Micheli, Laura; Di Cesare Mannelli, Lorenzo; Lucarini, Elena; Cialdai, Francesca; Vignali, Leonardo; Ghelardini, Carla; Monici, Monica

2017-11-01

Over the past three decades, physicians have used laser sources for the management of different pain conditions obtaining controversial results that call for further investigations. In order to evaluate the pain relieving possibilities of photobiomodulation therapy (PBMT), we tested two near infrared (NIR) laser systems, with different power, against various kinds of persistent hyperalgesia animal models. In rats, articular pain was reproduced by the intra-articular injection of sodium monoiodoacetate (MIA) and complete Freund's adjuvant (CFA), while compressive neuropathy was modelled by the chronic constriction injury of the sciatic nerve (CCI). In MIA and CFA models, (NIR) laser (MLS-Mphi, ASA S.r.l., Vicenza, Italy) application was started 14 days after injury and was performed once a day for a total of 13 applications. In MIA-treated animals, the anti-hyperalgesic effect of laser began 5 min after treatment and vanished after 60 min. The subsequent applications evoked similar effects. In CFA-treated rats, laser efficacy started 5 min after treatment and disappeared after 180 min. In rats that underwent CCI, two treatment protocols with similar fluence but different power output were tested using a new experimental device called Multiwave Locked System laser (MLS-HPP). Treatments began 7 days after injury and were performed during 3 weeks for a total of 10 applications. Both protocols reduced mechanical hyperalgesia and hindlimb weight bearing alterations until 60 min after treatment with a higher efficacy recorded for the animals treated using the higher power output. In conclusion, this study supports laser therapy as a potential treatment for immediate relief of chronic articular or neuropathic pain.

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.

PubMed

Larsen, Malte Selch; Keizer, Ron; Munro, Gordon; Mørk, Arne; Holm, René; Savic, Rada; Kreilgaard, Mads

2016-05-01

Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia. A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous). The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m  = 44.1 mg/kg, V max  = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma  = 16.7 μg/mL, EC 50, brain  = 3.3 μg/mL). The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

Paederia foetida Linn. inhibits adjuvant induced arthritis by suppression of PGE(2) and COX-2 expression via nuclear factor-κB.

PubMed

Kumar, Vikas; Al-Abbasi, F A; Ahmed, Danish; Verma, Amita; Mujeeb, Mohd; Anwar, Firoz

2015-05-01

The current investigation was undertaken to determine the anti-inflammatory and antioxidant effects of Paederia foetida Linn. (PF) along with its mechanism of action when implemented in tissue protection. HPTLC was used in the identification of the compound quercetin, while in vitro analysis confirmed the significance of the antioxidant and anti-inflammatory action of PF. We initially demonstrated the in vivo anti-inflammatory effect of PF, evaluating it against a variety of phlogistic agents as well as turpentine oil, prostaglandin and arachidonic acid. Groups of rats, fasted overnight, were treated as follows: Group I: normal control (vehicle), Group II: PF (100 mg kg(-1)), Group III: arthritic control (CFA only, 0.05 ml), Group IV, V, VI: CFA (0.05 ml) + PF (25, 50 and 100 mg kg(-1)) and Group VII: CFA (0.05 ml) + indomethacin (10 mg per kg b.w.). PF significantly protected against paw edema, arthritic index and body weight alteration induced by Complete Fruend's Adjuvant (CFA). Other observations, like histological and macroscopic changes, were observed in CFA induced inflammation in knee joints. Subcutaneous administration of CFA was accompanied by proinflammatory cytokine status, as appraised by the amplification of interleukin-2 (IL-2), interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α); oxidative stress status was estimated by the enhancement of the level of lipid peroxidation (LPO) and the depletion of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). Pre-treatment with PF significantly (P < 0.001) protected against CFA induced oxidative stress and proinflammatory cytokines. More prominently, CFA administration augmented tissue and plasma superoxide (O2) and hydrogen peroxide (H2O2) levels, while the PF pre-treatment significantly (P < 0.001) reversed all CFA induced intracellular interruption. Following CFA induced arthritis, PF was tested for its free radical scavenging activity against the DPPH and ABTS radicals and its inhibitory proficiency against COX-1 and COX-2 in vitro. Considering the above, the current research confirmed momentous protection against CFA induced arthritis, which could be attributed to its anti-inflammatory and pro-oxidant nature.

The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia

PubMed Central

Fan, Hui; Gong, Nian; Li, Teng-Fei; Ma, Ai-Niu; Wu, Xiao-Yan; Wang, Ming-Wei; Wang, Yong-Xiang

2015-01-01

BACKGROUND AND PURPOSE Two peptide agonists of the glucagon-like peptide-1 (GLP-1) receptor, exenatide and GLP-1 itself, exert anti-hypersensitive effects in neuropathic, cancer and diabetic pain. In this study, we have assessed the anti-allodynic and anti-hyperalgesic effects of the non-peptide agonist WB4-24 in inflammatory nociception and the possible involvement of microglial β-endorphin and pro-inflammatory cytokines. EXPERIMENTAL APPROACH We used rat models of inflammatory nociception induced by formalin, carrageenan or complete Freund's adjuvant (CFA), to test mechanical allodynia and thermal hyperalgesia. Expression of β-endorphin and pro-inflammatory cytokines was measured using real-time quantitative PCR and fluorescent immunoassays. KEY RESULTS WB4-24 displaced the specific binding of exendin (9–39) in microglia. Single intrathecal injection of WB4-24 (0.3, 1, 3, 10, 30 and 100 μg) exerted dose-dependent, specific, anti-hypersensitive effects in acute and chronic inflammatory nociception induced by formalin, carrageenan and CFA, with a maximal inhibition of 60–80%. Spinal WB4-24 was not effective in altering nociceptive pain. Subcutaneous injection of WB4-24 was also antinociceptive in CFA-treated rats. WB4-24 evoked β-endorphin release but did not inhibit expression of pro-inflammatory cytokines in either the spinal cord of CFA-treated rats or cultured microglia stimulated by LPS. WB4-24 anti-allodynia was prevented by a microglial inhibitor, β-endorphin antiserum and a μ-opioid receptor antagonist. CONCLUSIONS AND IMPLICATIONS Our results suggest that WB4-24 inhibits inflammatory nociception by releasing analgesic β-endorphin rather than inhibiting the expression of proalgesic pro-inflammatory cytokines in spinal microglia, and that the spinal GLP-1 receptor is a potential target molecule for the treatment of pain hypersensitivity including inflammatory nociception. PMID:25176008

A New, More Powerful Approach to Multitrait-Multimethod Analyses: An Application of Second-Order Confirmatory Factor Analysis.

ERIC Educational Resources Information Center

Marsh, Herbert W.; Hocevar, Dennis

The advantages of applying confirmatory factor analysis (CFA) to multitrait-multimethod (MTMM) data are widely recognized. However, because CFA as traditionally applied to MTMM data incorporates single indicators of each scale (i.e., each trait/method combination), important weaknesses are the failure to: (1) correct appropriately for measurement…

Changes in the disposition of substance P in the rostral ventromedial medulla after inflammatory injury in the rat.

PubMed

Maduka, U P; Hamity, M V; Walder, R Y; White, S R; Li, Y; Hammond, D L

2016-03-11

This study examined whether peripheral inflammatory injury increases the levels or changes the disposition of substance P (SubP) in the rostral ventromedial medulla (RVM), which serves as a central relay in bulbospinal pathways of pain modulation. Enzyme immunoassay and reverse transcriptase quantitative polymerase chain reaction were used to measure SubP protein and transcript, respectively, in tissue homogenates prepared from the RVM and the periaqueductal gray (PAG) and cuneiform nuclei of rats that had received an intraplantar injection of saline or complete Freund's adjuvant (CFA). Matrix-Assisted Laser Desorption/Ionization Time of Flight analysis confirmed that the RVM does not contain hemokinin-1 (HK-1), which can confound measurements of SubP because it is recognized equally well by commercial antibodies for SubP. Levels of SubP protein in the RVM were unchanged four hours, four days and two weeks after injection of CFA. Tac1 transcripts were similarly unchanged in the RVM four days or two weeks after CFA. In contrast, the density of SubP immunoreactive processes in the RVM increased 2-fold within four hours and 2.7-fold four days after CFA injection; it was unchanged at two weeks. SubP-immunoreactive processes in the RVM include axon terminals of neurons located in the PAG and cuneiform nucleus. SubP content in homogenates of the PAG and cuneiform nucleus was significantly increased four days after CFA, but not at four hours or two weeks. Tac1 transcripts in homogenates of these nuclei were unchanged four days and two weeks after CFA. These findings suggest that there is an increased mobilization of SubP within processes in the RVM shortly after injury accompanied by an increased synthesis of SubP in neurons that project to the RVM. These findings are consonant with the hypothesis that an increase in SubP release in the RVM contributes to the hyperalgesia that develops after peripheral inflammatory injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation.

PubMed

Iwamoto, Tatsushige; Takasugi, Yoshihiro; Higashino, Hideaki; Ito, Hiroyuki; Koga, Yoshihisa; Nakao, Shinichi

2011-02-01

Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition. In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60 min after drug injection, the effective dose required to produce 50% response (ED(50)) of each drug was derived. Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED(50s) of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED(50s) of 1.006 pmol in intact rats and 0.310 pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats. These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats.

Quantifying the Strength of General Factors in Psychopathology: A Comparison of CFA with Maximum Likelihood Estimation, BSEM, and ESEM/EFA Bifactor Approaches.

PubMed

Murray, Aja Louise; Booth, Tom; Eisner, Manuel; Obsuth, Ingrid; Ribeaud, Denis

2018-05-22

Whether or not importance should be placed on an all-encompassing general factor of psychopathology (or p factor) in classifying, researching, diagnosing, and treating psychiatric disorders depends (among other issues) on the extent to which comorbidity is symptom-general rather than staying largely within the confines of narrower transdiagnostic factors such as internalizing and externalizing. In this study, we compared three methods of estimating p factor strength. We compared omega hierarchical and explained common variance calculated from confirmatory factor analysis (CFA) bifactor models with maximum likelihood (ML) estimation, from exploratory structural equation modeling/exploratory factor analysis models with a bifactor rotation, and from Bayesian structural equation modeling (BSEM) bifactor models. Our simulation results suggested that BSEM with small variance priors on secondary loadings might be the preferred option. However, CFA with ML also performed well provided secondary loadings were modeled. We provide two empirical examples of applying the three methodologies using a normative sample of youth (z-proso, n = 1,286) and a university counseling sample (n = 359).

Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

PubMed Central

Taylor, Bradley K.; Fu, Weisi; Kuphal, Karen E.; Stiller, Carl-Olav; Winter, Michelle K.; Chen, Wenling; Corder, Gregory F.; Urban, Janice H.; McCarson, Kenneth E.; Marvizon, Juan Carlos

2014-01-01

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu31, Pro34]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu31, Pro34]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu31, Pro34]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [35S]GTPγS binding simulated by [Leu31, Pro34]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception. PMID:24184981

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.

PubMed

Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf; Edvinsson, Lars

2015-01-01

Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.

NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9

PubMed Central

2012-01-01

Background Sustained neuroinflammation strongly contributes to the pathogenesis of pain. The clinical challenge of chronic pain relief led to the identification of molecules such as cytokines, chemokines and more recently matrix metalloproteinases (MMPs) as putative therapeutic targets. Evidence points to a founder member of the matricial CCN family, NOV/CCN3, as a modulator of these inflammatory mediators. We thus investigated the possible involvement of NOV in a preclinical model of persistent inflammatory pain. Methods We used the complete Freund's adjuvant (CFA)-induced model of persistent inflammatory pain and cultured primary sensory neurons for in vitro experiments. The mRNA expression of NOV and pro-inflammatory factors were measured with real-time quantitative PCR, CCL2 protein expression was assessed using ELISA, MMP-2 and -9 activities using zymography. The effect of drugs on tactile allodynia was evaluated by the von Frey test. Results NOV was expressed in neurons of both dorsal root ganglia (DRG) and dorsal horn of the spinal cord (DHSC). After intraplantar CFA injection, NOV levels were transiently and persistently down-regulated in the DRG and DHSC, respectively, occurring at the maintenance phase of pain (15 days). NOV-reduced expression was restored after treatment of CFA rats with dexamethasone. In vitro, results based on cultured DRG neurons showed that siRNA-mediated inhibition of NOV enhanced IL-1β- and TNF-α-induced MMP-2, MMP-9 and CCL2 expression whereas NOV addition inhibited TNF-α-induced MMP-9 expression through β1 integrin engagement. In vivo, the intrathecal delivery of MMP-9 inhibitor attenuated mechanical allodynia of CFA rats. Importantly, intrathecal administration of NOV siRNA specifically led to an up-regulation of MMP-9 in the DRG and MMP-2 in the DHSC concomitant with increased mechanical allodynia. Finally, NOV intrathecal treatment specifically abolished the induction of MMP-9 in the DRG and, MMP-9 and MMP-2 in the DHSC of CFA rats. This inhibitory effect on MMP is associated with reduced mechanical allodynia. Conclusions This study identifies NOV as a new actor against inflammatory pain through regulation of MMPs thus uncovering NOV as an attractive candidate for therapeutic improvement in pain relief. PMID:22353423

Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced arthritis.

PubMed

Koo, Sung Tae; Lee, Chang-Hyung; Shin, Yong Il; Ko, Hyun Yoon; Lee, Da Gyo; Jeong, Han-Sol

2014-01-01

We previously published an article about the pressure effect using a rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA) by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time has been suggested up to now. The purpose of our study was to acquire the optimal time for hyperbaric therapy in the RA rat model. Controlled animal study. Following injection of complete Freund's adjuvant (CFA) into one side of the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. The reduction of WBF was high at 2 days after injection and then it was spontaneously increased up to 14 days in all 3 groups. There were significant differences of WBF between 5 hours and control during the third through twelfth days, between 3 hours and control during the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours during the third through seventh days (P < 0.05). The MMP-9/MMP-2 ratio increased at 14 days after the CFA injection in all groups compared to the initial findings, however, the 3 hour group showed a smaller MMP-9/MMP-2 ratio than the control group. Although enough samples were used for the study to support our hypothesis, more samples will be needed to raise the validity and reliability. The effect of hyperbaric treatment appears to be dependent upon the elevated therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects were similar in all pressure groups. Further study will be needed to acquire the optimal pressure-treatment parameter relationship in various conditions for clinical application.

Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo.

PubMed

Zhang, Wei Kevin; Tao, Shan-Shan; Li, Ting-Ting; Li, Yu-Sang; Li, Xiao-Jun; Tang, He-Bin; Cong, Ren-Huai; Ma, Fang-Li; Wan, Chu-Jun

2016-01-01

Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever.

Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

PubMed

Kaithwas, Gaurav; Majumdar, Dipak K

2010-06-01

The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.

Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

PubMed

Cunha, Francisco Valmor Macedo; Gomes, Bruno de Sousa; Neto, Benedito de Sousa; Ferreira, Alana Rodrigues; de Sousa, Damião Pergentino; de Carvalho e Martins, Maria do Carmo; Oliveira, Francisco de Assis

2016-01-01

Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1β concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.

Phytoextraction of rhenium by lucerne (Medicago sativa) and erect milkvetch (Astragalus adsurgens) from alkaline soils amended with coal fly ash.

PubMed

He, Honghua; Dong, Zhigang; Pang, Jiayin; Wu, Gao-Lin; Zheng, Jiyong; Zhang, Xingchang

2018-07-15

Coal fly ash (CFA) is an industrial waste generated in huge amounts worldwide, and the management of CFA has become an environmental concern. Recovery of valuable metals from CFA is one of the beneficial reuse options of CFA. Rhenium (Re) is one of the rarest metals in the Earth's crust and one of the most expensive metals of strategic significance in the world market. A CFA at the Jungar Thermal Power Plant, Inner Mongolia, China, contains more Re than two alkaline soils in the surrounding region. Pot experiments were undertaken to grow lucerne (Medicago sativa) and erect milkvetch (Astragalus adsurgens) in a loessial soil and an aeolian sandy soil amended with different rates (5%, 10%, 20%, and 40%) of CFA. The results show that plant growth was considerably enhanced and Re concentration in plants was significantly increased when CFA was applied to the alkaline soils at rates of ≤20%; while in some cases plant growth was also markedly enhanced by the 40% CFA treatment, which increased plant Re concentration the most of all treatments. Both lucerne and erect milkvetch showed potential for phytoextracting Re from CFA-amended alkaline soils. Using CFA for soil amendment not only offers a potential solution for the waste disposal problem of CFA, but the phytoextraction of Re by both lucerne and erect milkvetch may also bring an economic profit in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.

PubMed

de Souza, Alessandra Hubner; Castro, Célio J; Rigo, Flavia Karine; de Oliveira, Sara Marchesan; Gomez, Renato Santiago; Diniz, Danuza Montijo; Borges, Marcia Helena; Cordeiro, Marta Nascimento; Silva, Marco Aurélio Romano; Ferreira, Juliano; Gomez, Marcus Vinicius

2013-01-01

Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

PubMed

Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

2009-11-01

Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

PubMed

Hatch, R J; Jennings, E A; Ivanusic, J J

2013-08-01

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

Effect of Mas-related gene (Mrg) receptors on hyperalgesia in rats with CFA-induced inflammation via direct and indirect mechanisms.

PubMed

Jiang, Jianping; Wang, Dongmei; Zhou, Xiaolong; Huo, Yuping; Chen, Tingjun; Hu, Fenjuan; Quirion, Rémi; Hong, Yanguo

2013-11-01

Mas oncogene-related gene (Mrg) receptors are exclusively distributed in small-sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms. A selective MrgC receptor agonist, bovine adrenal medulla peptide 8-22 (BAM8-22) or melanocyte-stimulating hormone (MSH) or the μ-opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT-PCR. CFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8-22 or MSH, given i.t., generated instant short and delayed long-lasting attenuations of CFA-induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up-regulation of neuronal NOS (nNOS), CGRP and c-Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8-22 of delayed anti-hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8-22 also increased mRNA for MORs and pro-opiomelanocortin, along with β-endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co-localized in DRG neurons. Activation of MrgC receptors suppressed up-regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up-regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain. © 2013 The British Pharmacological Society.

Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.

PubMed

Alvarado-Vazquez, P A; Morado-Urbina, C E; Castañeda-Corral, G; Acosta-Gonzalez, R I; Kitaura, H; Kimura, K; Takano-Yamamoto, T; Jiménez-Andrade, J M

2015-01-01

Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 μg/5 μL per joint), isotype control (rat IgG 10 μg/5 μL per joint) or PBS (5 μl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Inclusion of Cocoa as a Dietary Supplement Represses Expression of Inflammatory Proteins in Spinal Trigeminal Nucleus in Response to Chronic Trigeminal Nerve Stimulation

PubMed Central

Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.

2013-01-01

Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex

PubMed Central

Touvykine, Boris; Mansoori, Babak K.; Jean-Charles, Loyda; Deffeyes, Joan; Quessy, Stephan; Dancause, Numa

2015-01-01

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)—the putative premotor area in rats—in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions. PMID:25967757

Functional up-regulation of Nav1.8 sodium channel in Aβ afferent fibers subjected to chronic peripheral inflammation

PubMed Central

2014-01-01

Background Functional alterations in the properties of Aβ afferent fibers may account for the increased pain sensitivity observed under peripheral chronic inflammation. Among the voltage-gated sodium channels involved in the pathophysiology of pain, Nav1.8 has been shown to participate in the peripheral sensitization of nociceptors. However, to date, there is no evidence for a role of Nav1.8 in controlling Aβ-fiber excitability following persistent inflammation. Methods Distribution and expression of Nav1.8 in dorsal root ganglia and sciatic nerves were qualitatively or quantitatively assessed by immunohistochemical staining and by real time-polymerase chain reaction at different time points following complete Freund’s adjuvant (CFA) administration. Using a whole-cell patch-clamp configuration, we further determined both total INa and TTX-R Nav1.8 currents in large-soma dorsal root ganglia (DRG) neurons isolated from sham or CFA-treated rats. Finally, we analyzed the effects of ambroxol, a Nav1.8-preferring blocker on the electrophysiological properties of Nav1.8 currents and on the mechanical sensitivity and inflammation of the hind paw in CFA-treated rats. Results Our findings revealed that Nav1.8 is up-regulated in NF200-positive large sensory neurons and is subsequently anterogradely transported from the DRG cell bodies along the axons toward the periphery after CFA-induced inflammation. We also demonstrated that both total INa and Nav1.8 peak current densities are enhanced in inflamed large myelinated Aβ-fiber neurons. Persistent inflammation leading to nociception also induced time-dependent changes in Aβ-fiber neuron excitability by shifting the voltage-dependent activation of Nav1.8 in the hyperpolarizing direction, thus decreasing the current threshold for triggering action potentials. Finally, we found that ambroxol significantly reduces the potentiation of Nav1.8 currents in Aβ-fiber neurons observed following intraplantar CFA injection and concomitantly blocks CFA-induced mechanical allodynia, suggesting that Nav1.8 regulation in Aβ-fibers contributes to inflammatory pain. Conclusions Collectively, these findings support a key role for Nav1.8 in controlling the excitability of Aβ-fibers and its potential contribution to the development of mechanical allodynia under persistent inflammation. PMID:24606981

Knockdown of synaptic scaffolding protein Homer 1b/c attenuates secondary hyperalgesia induced by complete Freund's adjuvant in rats.

PubMed

Yao, Yong-Xing; Jiang, Zhen; Zhao, Zhi-Qi

2011-12-01

Previous studies have demonstrated that Homer 1b/c, a postsynaptic molecular scaffolding protein that binds and clusters metabotropic glutamate receptors at neuronal synapses, has an important role in the metabotropic glutamate receptor signaling process. In the current study, we investigated the possible involvement of Homer 1b/c in secondary hyperalgesia induced by complete Freund's adjuvant (CFA). Chronic inflammation was induced by injecting CFA into the left hind ankle of Wistar rats. Homer 1b/c antisense or missense oligonucleotides were intrathecally administrated (antisense, 10 μg/10 μL, 5 μg/10 μL, or 2.5 μg/10 μL, once a day; missense, 10 μg/10 μL) from 5 to 8 days after the onset of inflammation. The withdrawal threshold and withdrawal latency to mechanical or thermal stimuli were determined before and after the intrathecal administration. The expression and distribution of Homer 1b/c were examined in the spinal cord using immunological techniques. Mechanical allodynia and thermal hyperalgesia were induced within 24 hours and maintained for >2 weeks after the CFA injection. The expression of Homer 1b/c reached the highest level 7 days after inflammation and returned to baseline at day 28. Intrathecal administration of Homer 1b/c antisense oligonucleotides markedly reduced the expression of Homer 1b/c protein in the spinal cord. Additionally, administration of Homer 1b/c antisense oligonucleotides attenuated secondary mechanical hypersensitization on days 2 to 5 and reduced thermal hypersensitization on days 3 to 4. There were no effects of missense oligonucleotides on hypersensitization and the expression of Homer 1b/c. In the naïve rats, Homer 1b/c antisense oligonucleotides did not affect the mechanical and thermal responses or locomotor activity. These novel results demonstrate that Homer 1b/c in the spinal cord contributes to the maintenance of secondary hyperalgesia induced by CFA and suggest that Homer 1b/c may be a novel target for pain therapy.

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation.

PubMed

Chen, Wenjin; Guo, Shengdong; Wang, Shenggang

2016-10-22

BACKGROUND The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. MATERIAL AND METHODS Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4-L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR). In addition, luciferase reporter assay was performed to explore whether RAB23 was a target of miR-16, and qRT-PCR and Western blotting were used to confirm the regulation between RAB23 and miR-16. RESULTS The level of miR-16 was significantly decreased in the CFA-induced inflammatory pain. Intrathecal injection of miR-16 alleviates pain response and raised pain threshold. The level of RAB23 was significantly increased in the pain model, and intrathecal injection of RAB23 aggravated pain response. Luciferase reporter assay confirmed that RAB23 was a direct target of miR-16, and RAB23 was negatively regulated by miR-16. In addition, we found that simultaneous administration of SB203580 and miR-16 further alleviates pain response compared to only administration of miR-16. CONCLUSIONS Our findings suggest that miR-16 relieves chronic inflammatory pain by targeting RAB23 and inhibiting p38 MAPK activation.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.

PubMed

Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Killingsworth, Murray; Nomura, Masaru; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2010-12-15

Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin. Copyright © 2010 Elsevier B.V. All rights reserved.

Exploratory structural equation modeling of personality data.

PubMed

Booth, Tom; Hughes, David J

2014-06-01

The current article compares the use of exploratory structural equation modeling (ESEM) as an alternative to confirmatory factor analytic (CFA) models in personality research. We compare model fit, factor distinctiveness, and criterion associations of factors derived from ESEM and CFA models. In Sample 1 (n = 336) participants completed the NEO-FFI, the Trait Emotional Intelligence Questionnaire-Short Form, and the Creative Domains Questionnaire. In Sample 2 (n = 425) participants completed the Big Five Inventory and the depression and anxiety scales of the General Health Questionnaire. ESEM models provided better fit than CFA models, but ESEM solutions did not uniformly meet cutoff criteria for model fit. Factor scores derived from ESEM and CFA models correlated highly (.91 to .99), suggesting the additional factor loadings within the ESEM model add little in defining latent factor content. Lastly, criterion associations of each personality factor in CFA and ESEM models were near identical in both inventories. We provide an example of how ESEM and CFA might be used together in improving personality assessment. © The Author(s) 2014.

Dual orexin receptor antagonist 12 inhibits expression of proteins in neurons and glia implicated in peripheral and central sensitization.

PubMed

Cady, R J; Denson, J E; Sullivan, L Q; Durham, P L

2014-06-06

Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an inflammatory model of trigeminal activation, the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins that promote peripheral and central sensitization and changes in nocifensive responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin receptor 1 (OX₁R) and receptor 2 (OX₂R) were detected in trigeminal ganglia and spinal trigeminal nucleus (STN). OX₁R immunoreactivity was localized primarily in neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection. However, levels of each of these proteins in rats receiving daily oral DORA-12 were inhibited to near basal levels. Similarly, administration of DORA-12 on days 3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5 post injection. While injection of CFA mediated a nocifensive response to mechanical stimulation of the orofacial region at 2h and 3 and 5 days post injection, treatment with DORA-12 suppressed the nocifensive response on day 5. Somewhat surprisingly, nocifensive responses were again observed on day 10 post CFA stimulation in the absence of daily DORA-12 administration. Our results provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal sensory neurons by inhibiting expression of proteins associated with sensitization of peripheral and central neurons and nociception. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test.

PubMed

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-11-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. Copyright © 2015. Published by Elsevier Inc.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test

PubMed Central

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-01-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. New methods We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Results Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. Conclusion The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. PMID:26143745

TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by subsequent formalin injection of the masseter or hindpaw of rats.

PubMed

Oh, Sang-Hoon; Imbe, Hiroki; Iwai-Liao, Yasutomo

2006-08-01

The study was designed to examine the effect of persistent temporomandibular joint (TMJ) inflammation on neuronal activation in the descending pain modulatory system in response to noxious stimulus. Formalin was injected into the left masseter muscle or hindpaw of rats 10 days after injection of the left TMJ with saline or complete Freund's adjuvant (CFA). The results showed that 10-day persistent TMJ inflammation (induced by CFA) alone did not induce a significant increase in Fos-like immunoreactive (Fos-LI) neurons in the rostral ventromedial medulla (RVM) or locus coeruleus (LC), but that formalin injection of the masseter muscle or hindpaw induced a significant increase in Fos-LI neurons in the RVM and LC of rats with and without TMJ inflammation (P < 0.05). However, persistent TMJ inflammation significantly increased Fos-LI neurons in the nucleus raphe magnus (NRM) induced by subsequent formalin injection of the masseter muscle and hindpaw (70.2% increase and 53.8% increase, respectively, over the control TMJ-saline-injected rats; P < 0.05). The results suggest that persistent TMJ inflammation increases neuronal activity, in particularly in the NRM, by the plastic change of the descending pain modulatory system after ipsilateral application of a noxious stimulus to either orofacial area or a spatially remote body area.

Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.

PubMed

Kasimanickam, Vanmathy R; Kasimanickam, Ramanathan K; Dernell, William S

2014-01-01

Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA) signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM) and CYP26B1- inhibitor (1 µM) compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR-146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23 (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present contribution serves as a useful resource for further elucidation of the regulatory role of individual miRNA in RA synchronized canine spermatogenesis.

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

PubMed Central

Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

2017-01-01

Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

Biofilm formation and binding specificities of CFA/I, CFA/II and CS2 adhesions of enterotoxigenic Escherichia coli and Cfae-R181A mutant.

PubMed

Liaqat, Iram; Sakellaris, Harry

2012-07-01

Enterotoxigenic Escherichia coli (ETEC) strains are leading causes of childhood diarrhea in developing countries. Adhesion is the first step in pathogenesis of ETEC infections and ETEC pili designated colonization factor antigens (CFAs) are believed to be important in the biofim formation, colonization and host cell adhesions. As a first step, we have determined the biofilm capability of ETEC expressing various types of pili (CFA/I, CfaE-R181A mutant/CfaE tip mutant, CFA/II and CS2). Further, enzyme-linked immunosorbent assay (ELISA) assay were developed to compare the binding specificity of CFA/I, CFA/II (CS1 - CS3) and CS2 of ETEC, using extracted pili and piliated bacteria. CFA/II strain (E24377a) as well as extracted pili exhibited significantly higher binding both in biofilm and ELISA assays compared to non piliated wild type E24377a, CFA/I and CS2 strains. This indicates that co-expression of two or more CS2 in same strain is more efficient in increasing adherence. Significant decrease in binding specificity of DH5αF'lacI (q)/∆cotD (CS2) strain and MC4100/pEU2124 (CfaE-R181A) mutant strain indicated the important contribution of tip proteins in adherence assays. However, CS2 tip mutant strain (DH5αF'lacI (q)/pEU5881) showed that this specific residue may not be important as adhesions in these strains. In summary, our data suggest that pili, their minor subunits are important for biofilm formation and adherence mechanisms. Overall, the functional reactivity of strains co expressing various antigens, particularly minor subunit antigen observed in this study suggest that fewer antibodies may be required to elicit immunity to ETEC expressing a wider array of related pili.

Development and evaluation of flow through assay for detection of antibodies against porcine cysticercosis.

PubMed

Sreedevi, C; Hafeez, Md; Subramanyam, K V; Anand Kumar, P; Chengalva Rayulu, V

2011-04-01

A flow through assay (FTA) was developed on cellulose acetate membrane for the serodiagnosis of porcine cysticercosis using cyst fluid (CFA) and whole cyst antigens (WCA) of Taenia solium metacestode. The assay consisted of antigen of T. solium metacestode coated onto membrane, mounted on a flow-through test device to provide assay capture matrix. The optimum concentration of coating antigen was 250 ng. The protein A colloidal gold conjugate served as antigen-antibody detecting reagent. A total of 225 serum samples were tested using two antigens. Results were better with CFA (96.0% sensitivity; 96.0% specificity) compared to WCA (92.0% sensitivity; 96.0% specificity). The test was also compared with enzyme-linked immunosorbent assay. The ELISA showed 96 per cent sensitivity with both the antigens whereas; the specificity was 96 and 92 per cent with CFA and WCA respectively. The sensitivity and specificity of flow through assay agrees closely with those of the ELISA. The cross-reaction was observed in one out of eight hydatidosis positive pigs (12.5%) with CFA by both the assays. The highest diagnostic accuracy (96%) was obtained with CFA-FTA and CFA-ELISA. For its high sensitivity and sporadic cross-reactions, CFA-FTA appears to be suitable for practical use at field level without instrumentation.

The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant

PubMed Central

Yu, Lu; Yang, Fei; Luo, Hao; Liu, Feng-Yu; Han, Ji-Sheng; Xing, Guo-Gang; Wan, You

2008-01-01

Background The present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected until day 28 following injection. Results Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4) was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive) neurons and in small non-peptidergic (IB4 positive) neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive) neurons from day 1 to day 28. Conclusion TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia. PMID:19055783

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function.

PubMed

Kandasamy, Ram; Calsbeek, Jonas J; Morgan, Michael M

2017-01-15

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund's Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED 50 dose of morphine (3.2mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. PMID:27746208

Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation.

PubMed

Gu, Yanping; Li, Guangwen; Chen, Yong; Huang, Li-Yen Mae

2016-07-01

Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)-dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses. On the other hand, the role of PKCα in receptor sensitization was seldom considered. Here, we studied the participation of PKCα in Epac signaling in P2X3R-mediated hyperalgesia. The expression of both Epac1 and Epac2 and the level of cAMP in DRGs are greatly enhanced after complete Freund adjuvant (CFA)-induced inflammation. The expression of phosphorylated PKCα is also upregulated. Complete Freund adjuvant (CFA)-induced P2X3R-mediated hyperalgesia is not only blocked by Epac antagonists but also by the classical PKC isoform inhibitors, Go6976, and PKCα-siRNA. These CFA effects are mimicked by the application of the Epac agonist, 8-(4-chlorophenylthio)-2 -O-methyl-cAMP (CPT), in control rats, further confirming the involvement of Epacs. Because the application of Go6976 prior to CPT still reduces CPT-induced hyperalgesia, PKCα is downstream of Epacs to mediate the enhancement of P2X3R responses in DRGs. The pattern of translocation of PKCα inside DRG neurons in response to CPT or CFA stimulation is distinct from that of PKCε. Thus, in contrast to prevalent view, PKCα also plays an essential role in producing complex inflammation-induced receptor-mediated hyperalgesia.

What to do When Scalar Invariance Fails: The Extended Alignment Method for Multi-Group Factor Analysis Comparison of Latent Means Across Many Groups.

PubMed

Marsh, Herbert W; Guo, Jiesi; Parker, Philip D; Nagengast, Benjamin; Asparouhov, Tihomir; Muthén, Bengt; Dicke, Theresa

2017-01-12

Scalar invariance is an unachievable ideal that in practice can only be approximated; often using potentially questionable approaches such as partial invariance based on a stepwise selection of parameter estimates with large modification indices. Study 1 demonstrates an extension of the power and flexibility of the alignment approach for comparing latent factor means in large-scale studies (30 OECD countries, 8 factors, 44 items, N = 249,840), for which scalar invariance is typically not supported in the traditional confirmatory factor analysis approach to measurement invariance (CFA-MI). Importantly, we introduce an alignment-within-CFA (AwC) approach, transforming alignment from a largely exploratory tool into a confirmatory tool, and enabling analyses that previously have not been possible with alignment (testing the invariance of uniquenesses and factor variances/covariances; multiple-group MIMIC models; contrasts on latent means) and structural equation models more generally. Specifically, it also allowed a comparison of gender differences in a 30-country MIMIC AwC (i.e., a SEM with gender as a covariate) and a 60-group AwC CFA (i.e., 30 countries × 2 genders) analysis. Study 2, a simulation study following up issues raised in Study 1, showed that latent means were more accurately estimated with alignment than with the scalar CFA-MI, and particularly with partial invariance scalar models based on the heavily criticized stepwise selection strategy. In summary, alignment augmented by AwC provides applied researchers from diverse disciplines considerable flexibility to address substantively important issues when the traditional CFA-MI scalar model does not fit the data. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Toxicity of coal fly ash (CFA) and toxicological response of switchgrass in mycorrhiza-mediated CFA-soil admixtures.

PubMed

Awoyemi, Olushola M; Dzantor, E Kudjo

2017-10-01

Increasing support for the use of Coal fly ash (CFA) in agriculture has necessitated a better understanding of the effects of the CFA in various cropping schemes. Experiments were conducted to assess mutagenic response of a mutant strain of Salmonella enterica serovar Typhimurium (TA100) to varying concentrations of CFA-water extracts, determine oxidative stress in switchgrass (Panicum virgatum L.) at varying levels of CFA-soil admixtures, and evaluate mycorrhiza-mediated modulation of oxidative stress responses of CFA-grown switchgrass. The TA100 exposed to 0%, 5%, 10%, 15%, 20% and 25% (w/v) CFA-water extracts elicited significant (p < 0.05) mutagenic responses at 20% and 25% extract levels but not below the 15% level. In greenhouse pot experiment, CFA-soil admixtures at 7.5% and 15% (w/w) significantly (p < 0.05) decreased the activities of superoxide dismutase (SOD) by 19.1% and 28.3% respectively, compared to control soil (0% w/w CFA/soil). Under the same conditions, activities of glutathione peroxidase (GPx) decreased by 75.9% and 66.9%. In contrast to the antioxidant enzyme activities, levels of malondialdehyde (MDA) an indicator of lipid peroxidation increased significantly (p < 0.05) by 30.49% and 38.38%. Inoculation of 7.5% and 15% CFA-soil admixtures with arbuscular mycorrhizal fungi (AMF), Rhizophaga clarus enhanced the activities of both SOD and GPx in the switchgrass, while it significantly (p < 0.05) reduced the levels of MDA. The study demonstrated that incorporation of CFA (at concentrations considered to be non-mutagenic against TA100) as soil amendment produced concentration-dependent oxidative stress responses in switchgrass; however, inoculation of the CFA-soil admixtures with AMF significantly modulated the oxidative stress responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Why item parcels are (almost) never appropriate: two wrongs do not make a right--camouflaging misspecification with item parcels in CFA models.

PubMed

Marsh, Herbert W; Lüdtke, Oliver; Nagengast, Benjamin; Morin, Alexandre J S; Von Davier, Matthias

2013-09-01

The present investigation has a dual focus: to evaluate problematic practice in the use of item parcels and to suggest exploratory structural equation models (ESEMs) as a viable alternative to the traditional independent clusters confirmatory factor analysis (ICM-CFA) model (with no cross-loadings, subsidiary factors, or correlated uniquenesses). Typically, it is ill-advised to (a) use item parcels when ICM-CFA models do not fit the data, and (b) retain ICM-CFA models when items cross-load on multiple factors. However, the combined use of (a) and (b) is widespread and often provides such misleadingly good fit indexes that applied researchers might believe that misspecification problems are resolved--that 2 wrongs really do make a right. Taking a pragmatist perspective, in 4 studies we demonstrate with responses to the Rosenberg Self-Esteem Inventory (Rosenberg, 1965), Big Five personality factors, and simulated data that even small cross-loadings seriously distort relations among ICM-CFA constructs or even decisions on the number of factors; although obvious in item-level analyses, this is camouflaged by the use of parcels. ESEMs provide a viable alternative to ICM-CFAs and a test for the appropriateness of parcels. The use of parcels with an ICM-CFA model is most justifiable when the fit of both ICM-CFA and ESEM models is acceptable and equally good, and when substantively important interpretations are similar. However, if the ESEM model fits the data better than the ICM-CFA model, then the use of parcels with an ICM-CFA model typically is ill-advised--particularly in studies that are also interested in scale development, latent means, and measurement invariance.

Psychometric validation of the Persian Bergen Social Media Addiction Scale using classic test theory and Rasch models.

PubMed

Lin, Chung-Ying; Broström, Anders; Nilsen, Per; Griffiths, Mark D; Pakpour, Amir H

2017-12-01

Background and aims The Bergen Social Media Addiction Scale (BSMAS), a six-item self-report scale that is a brief and effective psychometric instrument for assessing at-risk social media addiction on the Internet. However, its psychometric properties in Persian have never been examined and no studies have applied Rasch analysis for the psychometric testing. This study aimed to verify the construct validity of the Persian BSMAS using confirmatory factor analysis (CFA) and Rasch models among 2,676 Iranian adolescents. Methods In addition to construct validity, measurement invariance in CFA and differential item functioning (DIF) in Rasch analysis across gender were tested for in the Persian BSMAS. Results Both CFA [comparative fit index (CFI) = 0.993; Tucker-Lewis index (TLI) = 0.989; root mean square error of approximation (RMSEA) = 0.057; standardized root mean square residual (SRMR) = 0.039] and Rasch (infit MnSq = 0.88-1.28; outfit MnSq = 0.86-1.22) confirmed the unidimensionality of the BSMAS. Moreover, measurement invariance was supported in multigroup CFA including metric invariance (ΔCFI = -0.001; ΔSRMR = 0.003; ΔRMSEA = -0.005) and scalar invariance (ΔCFI = -0.002; ΔSRMR = 0.005; ΔRMSEA = 0.001) across gender. No item displayed DIF (DIF contrast = -0.48 to 0.24) in Rasch across gender. Conclusions Given the Persian BSMAS was unidimensional, it is concluded that the instrument can be used to assess how an adolescent is addicted to social media on the Internet. Moreover, users of the instrument may comfortably compare the sum scores of the BSMAS across gender.

Ranolazine attenuation of CFA-induced mechanical hyperalgesia.

PubMed

Casey, Gregory P; Roberts, Jomar S; Paul, Dennis; Diamond, Ivan; Gould, Harry J

2010-01-01

To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain. Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration. Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia. Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1beta on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat's paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. IL-6 and IL-1beta play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2-5th DPOs), while IL-1beta, activity is more significant in a later stage (5-8th DPOs).

Neuronal expression of the ubiquitin ligase Nedd4-2 in rat dorsal root ganglia: modulation in the spared nerve injury model of neuropathic pain.

PubMed

Cachemaille, M; Laedermann, C J; Pertin, M; Abriel, H; Gosselin, R-D; Decosterd, I

2012-12-27

Neuronal hyperexcitability following peripheral nerve lesions may stem from altered activity of voltage-gated sodium channels (VGSCs), which gives rise to allodynia or hyperalgesia. In vitro, the ubiquitin ligase Nedd4-2 is a negative regulator of VGSC α-subunits (Na(v)), in particular Na(v)1.7, a key actor in nociceptor excitability. We therefore studied Nedd4-2 in rat nociceptors, its co-expression with Na(v)1.7 and Na(v)1.8, and its regulation in pathology. Adult rats were submitted to the spared nerve injury (SNI) model of neuropathic pain or injected with complete Freund's adjuvant (CFA), a model of inflammatory pain. L4 dorsal root ganglia (DRG) were analyzed in sham-operated animals, seven days after SNI and 48 h after CFA with immunofluorescence and Western blot. We observed Nedd4-2 expression in almost 50% of DRG neurons, mostly small and medium-sized. A preponderant localization is found in the non-peptidergic sub-population. Additionally, 55.7 ± 2.7% and 55.0 ± 3.6% of Nedd4-2-positive cells are co-labeled with Na(v)1.7 and Na(v)1.8 respectively. SNI significantly decreases the proportion of Nedd4-2-positive neurons from 45.9 ± 1.9% to 33.5 ± 0.7% (p<0.01) and the total Nedd4-2 protein to 44% ± 0.13% of its basal level (p<0.01, n=4 animals in each group, mean ± SEM). In contrast, no change in Nedd4-2 was found after peripheral inflammation induced by CFA. These results indicate that Nedd4-2 is present in nociceptive neurons, is downregulated after peripheral nerve injury, and might therefore contribute to the dysregulation of Na(v)s involved in the hyperexcitability associated with peripheral nerve injuries. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

The fluence effects of low-level laser therapy on inflammation, fibroblast-like synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.

PubMed

Hsieh, Yueh-Ling; Cheng, Yu-Jung; Huang, Fang-Chuen; Yang, Chen-Chia

2014-12-01

The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA.

The effects of pressure on arthritic knees in a rat model of CFA-induced arthritis.

PubMed

Koo, Sung Tae; Lee, Chang-Hyung; Choi, Hyeunseok; Shin, Yong Il; Ha, Ki Tae; Ye, Hanna; Shim, Hyun Bo

2013-01-01

Pain is influenced by weather changes under certain circumstances, and inflammatory pain in animal models is ameliorated by pressure, but the underlying mechanism of atmospheric pressure has not been clearly elucidated. To examine the effect of pressure on pain in an arthritic animal model. Controlled animal study. Laboratory animal study. Following an injection of complete Freund's adjuvant (CFA) into one side of a knee joint, 32 rats were assigned randomly to 2 groups and either placed under 1 or 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 5 hours. The pain levels were assessed daily for up to 2 weeks post-injection to determine the changes in weight bearing (WB) of the affected limbs. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. After arthritis induction, the rats in the 1 ATA group showed reduced WB of the affected limbs (< 10% of normal limbs). This reduction in WB peaked at 2 days after the injection and then decreased spontaneously. Nevertheless, the pain behavior lasted for more than 2 weeks. In the 2.5 ATA group, the WB was significantly better during the experiment.  The MMP-9/MMP-2 ratio increased at 7 and 14 days after the CFA injection in the 1 ATA group. However, repetitive exposure to 2.5 ATA significantly reduced this ratio in the 2.5 ATA group. Although a sufficient number of samples were used to support the hypothesis that high atmospheric pressure improves a painful condition in this study, an additional larger-scale study will be needed to confirm these findings. Exposure to elevated pressures appears to relieve arthritic pain for extended periods by reducing the inflammatory process and should be considered as a possible alternative pain-reducing therapy.

The Fluence Effects of Low-Level Laser Therapy on Inflammation, Fibroblast-Like Synoviocytes, and Synovial Apoptosis in Rats with Adjuvant-Induced Arthritis

PubMed Central

Hsieh, Yueh-Ling; Cheng, Yu-Jung; Huang, Fang-Chuen

2014-01-01

Abstract Objective: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. Background data: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. Methods: Monoarthritis was induced in adult male Sprague–Dawley rats (250–300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Results: LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. Conclusions: LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA. PMID:25394331

Bem Sex Role Inventory Validation in the International Mobility in Aging Study.

PubMed

Ahmed, Tamer; Vafaei, Afshin; Belanger, Emmanuelle; Phillips, Susan P; Zunzunegui, Maria-Victoria

2016-09-01

This study investigated the measurement structure of the Bem Sex Role Inventory (BSRI) with different factor analysis methods. Most previous studies on validity applied exploratory factor analysis (EFA) to examine the BSRI. We aimed to assess the psychometric properties and construct validity of the 12-item short-form BSRI in a sample administered to 1,995 older adults from wave 1 of the International Mobility in Aging Study (IMIAS). We used Cronbach's alpha to assess internal consistency reliability and confirmatory factor analysis (CFA) to assess psychometric properties. EFA revealed a three-factor model, further confirmed by CFA and compared with the original two-factor structure model. Results revealed that a two-factor solution (instrumentality-expressiveness) has satisfactory construct validity and superior fit to data compared to the three-factor solution. The two-factor solution confirms expected gender differences in older adults. The 12-item BSRI provides a brief, psychometrically sound, and reliable instrument in international samples of older adults.

Complete Freund's adjuvant induces experimental autoimmune myocarditis by enhancing IL-6 production during initiation of the immune response.

PubMed

Fontes, Jillian A; Barin, Jobert G; Talor, Monica V; Stickel, Natalie; Schaub, Julie; Rose, Noel R; Čiháková, Daniela

2017-06-01

Complete Freund's Adjuvant (CFA) emulsified with an antigen is a widely used method to induce autoimmune disease in animal models, yet the contribution of CFA to the immune response is not well understood. We compared the effectiveness of CFA with Incomplete Freund's Adjuvant (IFA) or TiterMax Gold Adjuvant (TMax) in experimental autoimmune myocarditis (EAM) in male mice. EAM was induced in A/J, BALB/c, and IL6KO BALB/c male mice by injection of the myocarditogenic peptide in CFA, IFA, or TMax on days 0 and 7. EAM severity was analyzed by histology on day 21. In addition, specific flow cytometry outcomes were evaluated on day 21. Only mice immunized with CFA and myocarditogenic peptide on both days 0 and 7 developed substantial myocarditis as measured by histology. We observed a significantly increased level of IL6 in the spleen 3 days after CFA immunization. In the spleen and heart on day 21, there was an expansion of myeloid cells in CFA-immunized mice, as compared to IFA or TMax-immunized animals. Recombinant IL-6 at the time of IFA immunization partially restored susceptibility of the mice to EAM. We also treated EAM-resistant IL-6 knockout mice with recombinant IL-6 around the time of the first immunization, on days -1 to 2, completely restoring disease susceptibility, showing that the requirement for IL-6 coincides with primary immunization. Examining APC populations in the lymph node draining the immunization site evidenced the contribution of IL-6 to the CFA-dependence of EAM was through controlling local dendritic cell (DC) trafficking. CFA used with myocarditogenic peptide twice is required to induce EAM in both A/J and Balb/c mice. Although IFA and TiterMax induce antibody responses, only CFA preferentially induced autoantigen-specific responses. CFA expands monocytes in the heart and in the spleen. IL-6 signaling is required during short window around primary immunization to induce EAM. In addition, IL-6 deficient mice resistance to EAM could be reversed by injecting IL-6 around first immunization. IL-6 expands dendritic cell and monocytic populations and ultimately leads to a robust T-cell driven immune response in CFA immunized mice. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Denoising Algorithm for CFA Image Sensors Considering Inter-Channel Correlation.

PubMed

Lee, Min Seok; Park, Sang Wook; Kang, Moon Gi

2017-05-28

In this paper, a spatio-spectral-temporal filter considering an inter-channel correlation is proposed for the denoising of a color filter array (CFA) sequence acquired by CCD/CMOS image sensors. Owing to the alternating under-sampled grid of the CFA pattern, the inter-channel correlation must be considered in the direct denoising process. The proposed filter is applied in the spatial, spectral, and temporal domain, considering the spatio-tempo-spectral correlation. First, nonlocal means (NLM) spatial filtering with patch-based difference (PBD) refinement is performed by considering both the intra-channel correlation and inter-channel correlation to overcome the spatial resolution degradation occurring with the alternating under-sampled pattern. Second, a motion-compensated temporal filter that employs inter-channel correlated motion estimation and compensation is proposed to remove the noise in the temporal domain. Then, a motion adaptive detection value controls the ratio of the spatial filter and the temporal filter. The denoised CFA sequence can thus be obtained without motion artifacts. Experimental results for both simulated and real CFA sequences are presented with visual and numerical comparisons to several state-of-the-art denoising methods combined with a demosaicing method. Experimental results confirmed that the proposed frameworks outperformed the other techniques in terms of the objective criteria and subjective visual perception in CFA sequences.

Gait analysis and weight bearing in pre-clinical joint pain research.

PubMed

Ängeby Möller, Kristina; Svärd, Heta; Suominen, Anni; Immonen, Jarmo; Holappa, Johanna; Stenfors, Carina

2018-04-15

There is a need for better joint pain treatment, but development of new medication has not been successful. Pre-clinical models with readouts that better reflect the clinical situation are needed. In patients with joint pain, pain at rest and pain at walking are two major complaints. We describe a new way of calculating results from gait analysis using the CatWalk™ setup. Rats with monoarthritis induced by injection of Complete Freund's Adjuvant (CFA) intra-articularly into the ankle joint of one hind limb were used to assess gait and dynamic weight bearing. The results show that dynamic weight bearing was markedly reduced for the injected paw. Gait parameters such as amount of normal step sequences, walking speed and duration of step placement were also affected. Treatment with naproxen (an NSAID commonly used for inflammatory pain) attenuated the CFA-induced effects. Pregabalin, which is used for neuropathic pain, had no effect. Reduced dynamic weight bearing during locomotion, assessed and calculated in the way we present here, showed a dose-dependent and lasting normalization after naproxen treatment. In contrast, static weight bearing while standing (Incapacitance tester) showed a significant effect for a limited time only. Mechanical sensitivity (von Frey Optihairs) was completely normalized by naproxen, and the window for testing pharmacological effect disappeared. Objective and reproducible effects, with an endpoint showing face validity compared to pain while walking in patients with joint pain, are achieved by a new way of calculating dynamic weight bearing in monoarthritic rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

PubMed

Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

2018-02-01

Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Involvement of NFκB in the antirheumatic potential of Chenopodium album L., aerial parts extracts.

PubMed

Arora, Sumit K; Itankar, Prakash R; Verma, Prashant R; Bharne, Ashish P; Kokare, Dadasaheb M

2014-08-08

Chenopodium album L. (C. album) is commonly known as Bathua in Hindi (Family: Chenopodiaceae). Traditionally, the plant is used as a laxative, diuretic, sedative and the infusion of the plant is used for the treatment of rheumatism. However, no scientific validation is available on the antirheumatic potential of the plant. In the present investigation, role of NF kappa B (NFκB) in the antiarthritic potential of extracts of aerial parts of Chenopodium album was explored and evaluated. The defatted aerial parts of Chenopodium album were successively extracted with ethylacetate, acetone, methanol and 50% methanol to study their antioxidant capacity followed by antiarthritic potential using Complete Freund׳s adjuvant (CFA) induced arthritis model in rats. The polyphenol, flavonoid and flavanone contents of different extracts were quantified and correlated with their antioxidant capacity, antiarthritic activity and NFκB inhibition potential. The experimental data indicated that the acetone extract of Chenopodium album (ACCA) has shown significant reduction in rat paw edema (80.13%) at dose level of 200 mg/kg per oral in 21 days of this study. On 22nd day, hematological and biochemical parameters were estimated and it was observed that the altered hematological parameters (Hb, RBC, WBC and ESR), biochemical parameters (Serum creatinine, total proteins and acute phase proteins) and loss in body weight in the arthritic rats were significantly brought back to near normal level by the ACCA extract. ACCA extract significantly decreased the NFκB expression in paraventricular nucleus of hypothalamus and this effect is comparable with standard indomethacine in CFA treated rats. The polyphenolic and flavonoid content of different extracts were in the range of 14.56±0.21-42.00±0.2 mg (gallic acid equivalent/g extract) and 2.20±0.003-7.33±0.5 mg (rutin equivalent/g extract) respectively. The antiarthritic activity possessed by ACCA extract can be correlated directly to its antioxidant potential, high flavonoidal content achieved by successive extraction and its capacity to inhibit the NFκB protein, as proven by immunohistochemistry study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Alkali-activated complex binders from class C fly ash and Ca-containing admixtures.

PubMed

Guo, Xiaolu; Shi, Huisheng; Chen, Liming; Dick, Warren A

2010-01-15

Processes that maximize utilization of industrial solid wastes are greatly needed. Sodium hydroxide and sodium silicate solution were used to create alkali-activated complex binders (AACBs) from class C fly ash (CFA) and other Ca-containing admixtures including Portland cement (PC), flue gas desulfurization gypsum (FGDG), and water treatment residual (WTR). Specimens made only from CFA (CFA100), or the same fly ash mixed with 40 wt% PC (CFA60-PC40), with 10 wt% FGDG (CFA90-FGDG10), or with 10 wt% WTR (CFA90-WTR10) had better mechanical performance compared to binders using other mix ratios. The maximum compressive strength of specimens reached 80.0 MPa. Geopolymeric gel, sodium polysilicate zeolite, and hydrated products coexist when AACB reactions occur. Ca from CFA, PC, and WTR precipitated as Ca(OH)(2), bonded in geopolymers to obtain charge balance, or reacted with dissolved silicate and aluminate species to form calcium silicate hydrate (C-S-H) gel. However, Ca from FGDG probably reacted with dissolved silicate and aluminate species to form ettringite. Utilization of CFA and Ca-containing admixtures in AACB is feasible. These binders may be widely utilized in various applications such as in building materials and for solidification/stabilization of other wastes, thus making the wastes more environmentally benign.

Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

PubMed

McCarson, Kenneth E

2015-09-01

Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). Copyright © 2015 John Wiley & Sons, Inc.

Annexin 1 exerts anti-nociceptive effects after peripheral inflammatory pain through formyl-peptide-receptor-like 1 in rat dorsal root ganglion.

PubMed

Pei, L; Zhang, J; Zhao, F; Su, T; Wei, H; Tian, J; Li, M; Shi, J

2011-12-01

Annexin 1 (ANXA1) has analgesic effects in inflammatory pain. We aimed to investigate the anti-nociceptive role of ANXA1, at the dorsal root ganglion (DRG) level, through an interaction with formyl-peptide-receptor-like 1 (FPR2/ALX). Inflammatory pain was evoked by injecting complete Freund's adjuvant (CFA, 50 μl) into the hindpaw of male Sprague-Dawley rats. The distribution of ANXA1 and FPR2/ALX in L4/5 DRGs was evaluated by immunofluorescence. The expression of ANXA1 was measured by western blot. The involvement of FPR2/ALX in the anti-nociception of ANXA1 was investigated by thermal (irradiant heat) and mechanical (von Frey filament) pain tests with intrathecal (i.t.) ANXA1-derived peptide (Anxa1(2-26)), FPR2/ALX agonist 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), and antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe (Boc1). ANXA1 and FPR2/ALX localized in the satellite glial cells and neurones in L4/5 DRGs. CFA treatment (n=20) increased ANXA1 expression in L4/5 DRGs within 7 days (P<0.01). I.T. Anxa1(2-26) (20 and 100 µg µl(-1)) and BML-111 (10 and 100 nmol) reduced CFA-induced thermal and mechanical nociception within 48 h (n=40) (P<0.05). However, i.t. Boc1 10 µg intensified inflammatory pain (P<0.05) and reversed the anti-nociceptive effect of Anxa1(2-26) (n=25) (P<0.05). Moreover, ANXA1 expression increased in L4/5 DRGs after i.t. Anxa1(2-26) (20 µg µl(-1)) (P<0.05) and BML-111 (10 nmol) (P<0.01) but decreased after i.t. Boc1 (10 and 100 µg) alone (P<0.01) or Boc1 (10 µg) co-injection with Anxa1(2-26) (20 µg µl(-1)) (P<0.05). Endogenous ANXA1 expression at the DRG level is involved in CFA-induced inflammatory pain, and i.t. ANXA1 20 µg µl(-1) produces its anti-nociceptive effect through FPR2/ALX.

Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

PubMed

Bi, Rui Yun; Ding, Yun; Gan, Ye Hua

2016-03-01

To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

Role of overexpressed CFA/I fimbriae in bacterial swimming

NASA Astrophysics Data System (ADS)

Cao, Ling; Suo, Zhiyong; Lim, Timothy; Jun, SangMu; Deliorman, Muhammedin; Riccardi, Carol; Kellerman, Laura; Avci, Recep; Yang, Xinghong

2012-06-01

Enterotoxigenic Escherichia coli CFA/I is a protective antigen and has been overexpressed in bacterial vectors, such as Salmonella Typhimurium H683, to generate vaccines. Effects that overexpressed CFA/I may engender on the bacterial host remain largely unexplored. To investigate, we constructed a high CFA/I expression strain, H683-pC2, and compared it to a low CFA/I expression strain, H683-pC, and to a non-CFA/I expression strain, H683-pY. The results showed that H683-pC2 was less able to migrate into semisolid agar (0.35%) than either H683-pC or H683-pY. Bacteria that migrated showed motility halo sizes of H683-pC2 < H683-pC < H683-pY. In the liquid culture media, H683-pC2 cells precipitated to the bottom of the tube, while those of H683-pY did not. In situ imaging revealed that H683-pC2 bacilli tended to auto-agglutinate within the semisolid agar, while H683-pY bacilli did not. When the cfaBE fimbrial fiber encoding genes were deleted from pC2, the new plasmid, pC2(-), significantly recovered bacterial swimming capability. Our study highlights the negative impact of overexpressed CFA/I fimbriae on bacterial swimming motility.

Role of overexpressed CFA/I fimbriae in bacterial swimming.

PubMed

Cao, Ling; Suo, Zhiyong; Lim, Timothy; Jun, Sangmu; Deliorman, Muhammedin; Riccardi, Carol; Kellerman, Laura; Avci, Recep; Yang, Xinghong

2012-06-01

Enterotoxigenic Escherichia coli CFA/I is a protective antigen and has been overexpressed in bacterial vectors, such as Salmonella Typhimurium H683, to generate vaccines. Effects that overexpressed CFA/I may engender on the bacterial host remain largely unexplored. To investigate, we constructed a high CFA/I expression strain, H683-pC2, and compared it to a low CFA/I expression strain, H683-pC, and to a non-CFA/I expression strain, H683-pY. The results showed that H683-pC2 was less able to migrate into semisolid agar (0.35%) than either H683-pC or H683-pY. Bacteria that migrated showed motility halo sizes of H683-pC2 < H683-pC < H683-pY. In the liquid culture media, H683-pC2 cells precipitated to the bottom of the tube, while those of H683-pY did not. In situ imaging revealed that H683-pC2 bacilli tended to auto-agglutinate within the semisolid agar, while H683-pY bacilli did not. When the cfaBE fimbrial fiber encoding genes were deleted from pC2, the new plasmid, pC2(-), significantly recovered bacterial swimming capability. Our study highlights the negative impact of overexpressed CFA/I fimbriae on bacterial swimming motility.

Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

PubMed

Dong, Yingchun; Li, Pengfei; Ni, Yanhong; Zhao, Junjie; Liu, Zhiqiang

2014-01-01

Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs) and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs) following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

Does ultrasound-guided lidocaine injection improve local anaesthesia before femoral artery catheterization?

PubMed

Spiliopoulos, S; Katsanos, K; Diamantopoulos, A; Karnabatidis, D; Siablis, D

2011-05-01

To present the results of a prospective, randomized, single-centre study investigating local anaesthesia before percutaneous common femoral artery (CFA) puncture and catheterization with the use of ultrasound-guided injection of lidocaine versus standard infiltration by manual palpation. Patients scheduled to undergo diagnostic or therapeutic transfemoral catheter-based procedures gave informed consent and were randomized in two groups. In the first arm local anaesthesia with lidocaine hydrochloride 1% was performed under ultrasound guidance (group U/S), while in the second arm the standard method of manual artery palpation was applied (group M). In both groups, subsequent CFA catheterization was achieved under ultrasound guidance. The primary study endpoint was peri-procedural pain level evaluated with a visual-analogue scale (VAS score 0-10). Between January 2009 and 2010, 200 patients (161 men, mean age 63±12 years) were equally assigned to each group without any significant differences in baseline demographics. Patients in group U/S experienced significantly less pain during CFA catheterization in comparison with group M with a difference of three points in mean VAS score reported (1.6±1.6 versus 4.6±1.9, p<0.0001). In addition, significantly less volume of lidocaine was used in group U/S compared to group M (16±2.7 versus 19±0.8ml, p<0.001).Total vascular access time was similar in both groups (4.4±1.3 versus 4.5±1.3min). Overall complications included two small groin haematomas in each group. Ultrasound-guided local anaesthesia of the CFA prior to percutaneous transcatheter procedures is safe and achieves superior levels of analgesia with minimal patient pain and discomfort compared to the standard method of manual palpation. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Evaluation of microRNA stability in feces from healthy dogs.

PubMed

Cirera, Susanna; Willumsen, Line M; Johansen, Thea T; Nielsen, Lise N

2018-03-01

Gastrointestinal cancer accounts for approximately 8% of all canine malignancies. Early detection of cancer may have a tremendous impact on both treatment options and prognosis. MicroRNAs (miRNAs), a class of noncoding RNAs that can be found stably expressed in body fluids and feces, have been suggested as valuable human cancer biomarkers. The purpose of the study was to investigate the feasibility of detecting miRNAs in canine feces and to determine the miRNA stability in fecal samples stored at different temperatures for different duration. The levels of 4 Canine familiaris (cfa) miRNAs (cfa-miR-16, cfa-miR-20a, cfa-miR-21, and cfa-miR-92a) were investigated by quantitative real-time PCR(qPCR) in fecal samples from 10 healthy dogs. Fecal samples were collected at 3 different time points and samples from the first time point were stored at different temperatures and for a different duration. A statistically significant difference was found in miRNA levels from samples stored at room temperature compared with samples stored at -20°C for cfa-miR-16 and cfa-miR-21. No significant difference was found in the level of the investigated miRNAs over time. Overall, miRNAs are present in dog feces at measurable levels. Some miRNAs seem to be subject to a higher degree of degradation in samples stored at room temperature for 24 hours compared with samples frozen after collection at -20°C. The investigated miRNAs were stably expressed over time. This study provides the basis for further research on miRNA expression profiles as biomarkers for gastrointestinal cancer in dogs. © 2018 American Society for Veterinary Clinical Pathology.

Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

PubMed

Bassi, N; Luisetto, R; Del Prete, D; Ghirardello, A; Ceol, M; Rizzo, S; Iaccarino, L; Gatto, M; Valente, M L; Punzi, L; Doria, A

2012-02-01

Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

MEFA (multiepitope fusion antigen)-Novel Technology for Structural Vaccinology, Proof from Computational and Empirical Immunogenicity Characterization of an Enterotoxigenic Escherichia coli (ETEC) Adhesin MEFA

PubMed Central

Duan, Qiangde; Lee, Kuo Hao; Nandre, Rahul M; Garcia, Carolina; Chen, Jianhan; Zhang, Weiping

2017-01-01

Vaccine development often encounters the challenge of virulence heterogeneity. Enterotoxigenic Escherichia coli (ETEC) bacteria producing immunologically heterogeneous virulence factors are a leading cause of children’s diarrhea and travelers’ diarrhea. Currently, we do not have licensed vaccines against ETEC bacteria. While conventional methods continue to make progress but encounter challenge, new computational and structure-based approaches are explored to accelerate ETEC vaccine development. In this study, we applied a structural vaccinology concept to construct a structure-based multiepitope fusion antigen (MEFA) to carry representing epitopes of the seven most important ETEC adhesins [CFA/I, CFA/II (CS1–CS3), CFA/IV (CS4–CS6)], simulated antigenic structure of the CFA/I/II/IV MEFA with computational atomistic modeling and simulation, characterized immunogenicity in mouse immunization, and examined the potential of structure-informed vaccine design for ETEC vaccine development. A tag-less recombinant MEFA protein (CFA/I/II/IV MEFA) was effectively expressed and extracted. Molecular dynamics simulations indicated that this MEFA immunogen maintained a stable secondary structure and presented epitopes on the protein surface. Empirical data showed that mice immunized with the tagless CFA/I/II/IV MEFA developed strong antigen-specific antibody responses, and mouse serum antibodies significantly inhibited in vitro adherence of bacteria expressing these seven adhesins. These results revealed congruence of antigen immunogenicity between computational simulation and empirical mouse immunization and indicated this tag-less CFA/I/II/IV MEFA potentially an antigen for a broadly protective ETEC vaccine, suggesting a potential application of MEFA-based structural vaccinology for vaccine design against ETEC and likely other pathogens. PMID:28944092

Mineralogical, Microstructural and Thermal Characterization of Coal Fly Ash Produced from Kazakhstani Power Plants

NASA Astrophysics Data System (ADS)

Tauanov, Z.; Abylgazina, L.; Spitas, C.; Itskos, G.; Inglezakis, V.

2017-09-01

Coal fly ash (CFA) is a waste by-product of coal combustion. Kazakhstan has vast coal deposits and is major consumer of coal and hence produces huge amounts of CFA annually. The government aims to recycle and effectively utilize this waste by-product. Thus, a detailed study of the physical and chemical properties of material is required as the data available in literature is either outdated or not applicable for recently produced CFA samples. The full mineralogical, microstructural and thermal characterization of three types of coal fly ash (CFA) produced in two large Kazakhstani power plants is reported in this work. The properties of CFAs were compared between samples as well as with published values.

Static and dynamic properties of Co2FeAl thin films: Effect of MgO and Ta as capping layers

NASA Astrophysics Data System (ADS)

Husain, Sajid; Barwal, Vineet; Kumar, Ankit; Behera, Nilamani; Akansel, Serkan; Goyat, Ekta; Svedlindh, Peter; Chaudhary, Sujeet

2017-05-01

The influence of MgO and Ta capping layers on the static and dynamic magnetic properties of Co2FeAl (CFA) Heusler alloy thin films has been investigated. It is observed that the CFA film deposited with MgO capping layer is preeminent compared to the uncapped or Ta capped CFA film. In particular, the magnetic inhomogeneity contribution to the ferromagnetic resonance line broadening and damping constant are found to be minimal for the MgO capped CFA thin film i.e., 0.12±0.01 Oe and 0.0074±0.00014, respectively. The saturation magnetization was found to be 960±25emu/cc.

Anti-nociceptive effect of dexmedetomidine in a rat model of monoarthritis via suppression of the TLR4/NF-κB p65 pathway

PubMed Central

Ji, Dong; Zhou, Yalan; Li, Shuangshuang; Li, Dai; Chen, Hui; Xiong, Yuanchang; Zhang, Yuqiu; Xu, Hua

2017-01-01

As a therapeutic target for neuropathic pain, the anti-nociceptive effects of α 2-adrenoceptors (α2AR) have attracted attention. Dexmedetomidine (DEX), a potent and highly selective α2AR agonist, has exhibited significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. The present study investigated the effect of DEX on Toll-like receptor (TLR)4 and nuclear factor (NF)-κB p65 expression, as well as the production of pro-inflammatory cytokines. The rat monoarthritis (MA) model was induced by intra-articular injection of complete Freund's adjuvant (CFA) at the ankle joint. After induction of MA, the rats were intrathecally treated with normal saline or DEX (2.5 µg) for 3 consecutive days. The concentration of interleukin-1β and −6 as well as tumor necrosis factor-α was examined by ELISA. The expression levels of TLR4 and NF-κB p65 were determined by western blot analysis and immunohistochemistry. The results indicated that the pro-inflammatory cytokines TLR4 and NF-κB p65 were significantly upregulated in MA rats. DEX treatment markedly reduced mechanical and thermal hyperalgesia, suppressed MA-induced elevation of the pro-inflammatory cytokines and inhibited the TLR4/NF-κB p65 pathway, while these effects were blocked by pre-treatment with the selective α2AR antagonist BRL44408 (15 µg) at 30 min prior to CFA injection. These results suggested that DEX has an anti-nociceptive effect via suppressing the TLR4/NF-κB p65 pathway. PMID:29201195

Evaluation of Hydration Free Energy by Level-Set Variational Implicit-Solvent Model with Coulomb-Field Approximation.

PubMed

Guo, Zuojun; Li, Bo; Dzubiella, Joachim; Cheng, Li-Tien; McCammon, J Andrew; Che, Jianwei

2013-03-12

In this article, we systematically apply a novel implicit-solvent model, the variational implicit-solvent model (VISM) together with the Coulomb-Field Approximation (CFA), to calculate the hydration free energy of a large set of small organic molecules. Because these molecules have been studied in detail by molecular dynamics simulations and other implicit-solvent models, they provide a good benchmark for evaluating the performance of VISM-CFA. With all-atom Amber force field parameters, VISM-CFA is able to reproduce well not only the experimental and MD simulated total hydration free energy but also the polar and nonpolar contributions individually. The correlation between VISM-CFA and experiments is R 2 = 0.763 for the total hydration free energy, with a root-mean-square deviation (RMSD) of 1.83 kcal/mol, and the correlation to results from TIP3P explicit water MD simulations is R 2 = 0.839 with a RMSD = 1.36 kcal/mol. In addition, we demonstrate that VISM captures dewetting phenomena in the p53/MDM2 complex and hydrophobic characteristics in the system. This work demonstrates that the level-set VISM-CFA can be used to study the energetic behavior of realistic molecular systems with complicated geometries in solvation, protein-ligand binding, protein-protein association, and protein folding processes.

Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models.

PubMed

Kumar, K; Rai, A K

2012-10-01

Curcumin, the active ingredient of the spice turmeric, has a long history as an herbal remedy for a variety of diseases. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol, and formulation PA2. They were characterized by scanning electron microscopy, revealing vesicular structures, and assessed for stability and effect on in vitro skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of formulation PA2 and PB1 were compared with a standard market product containing indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud's adjuvant (CFA) induced arthritis in rats. Further histopathological and radiographic evaluation was performed. The investigated curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin products.

Testing the psychometric properties of the Environmental Attitudes Inventory on undergraduate students in the Arab context: A test-retest approach.

PubMed

AlMenhali, Entesar Ali; Khalid, Khalizani; Iyanna, Shilpa

2018-01-01

The Environmental Attitudes Inventory (EAI) was developed to evaluate the multidimensional nature of environmental attitudes; however, it is based on a dataset from outside the Arab context. This study reinvestigated the construct validity of the EAI with a new dataset and confirmed the feasibility of applying it in the Arab context. One hundred and forty-eight subjects in Study 1 and 130 in Study 2 provided valid responses. An exploratory factor analysis (EFA) was used to extract a new factor structure in Study 1, and confirmatory factor analysis (CFA) was performed in Study 2. Both studies generated a seven-factor model, and the model fit was discussed for both the studies. Study 2 exhibited satisfactory model fit indices compared to Study 1. Factor loading values of a few items in Study 1 affected the reliability values and average variance extracted values, which demonstrated low discriminant validity. Based on the results of the EFA and CFA, this study showed sufficient model fit and suggested the feasibility of applying the EAI in the Arab context with a good construct validity and internal consistency.

Testing the psychometric properties of the Environmental Attitudes Inventory on undergraduate students in the Arab context: A test-retest approach

PubMed Central

2018-01-01

The Environmental Attitudes Inventory (EAI) was developed to evaluate the multidimensional nature of environmental attitudes; however, it is based on a dataset from outside the Arab context. This study reinvestigated the construct validity of the EAI with a new dataset and confirmed the feasibility of applying it in the Arab context. One hundred and forty-eight subjects in Study 1 and 130 in Study 2 provided valid responses. An exploratory factor analysis (EFA) was used to extract a new factor structure in Study 1, and confirmatory factor analysis (CFA) was performed in Study 2. Both studies generated a seven-factor model, and the model fit was discussed for both the studies. Study 2 exhibited satisfactory model fit indices compared to Study 1. Factor loading values of a few items in Study 1 affected the reliability values and average variance extracted values, which demonstrated low discriminant validity. Based on the results of the EFA and CFA, this study showed sufficient model fit and suggested the feasibility of applying the EAI in the Arab context with a good construct validity and internal consistency. PMID:29758021

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

PubMed

Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

2016-01-01

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Rapid assessment of the geographical distribution of lymphatic filariasis in Uganda, by screening of schoolchildren for circulating filarial antigens.

PubMed

Onapa, A W; Simonsen, P E; Baehr, I; Pedersen, E M

2005-03-01

To permit improvements in the targeting of control activities, the geographical distribution of lymphatic filariasis in Uganda was assessed by using a rapid immunochromatographic card test to check school-aged children for Wuchereria bancrofti-specific circulating filarial antigens (CFA). Survey sites were selected to represent the various ecological and topographical diversities in the country. Overall, 17,533 children from 76 sites were examined. CFA-positive cases were detected at 31 of the sites, with prevalences ranging from 0.4% to 30.7%. There appeared to be strikingly more lymphatic filariasis in the north of the country than in the south. The main focus was north of the Victoria Nile, where 27 (66%) of 41 sites had CFA-positive cases, often at high prevalences. Only four (11.4%) of the 35 sites south of the Victoria Nile had CFA-positive cases, and all four were along the western rift valley and had relatively low CFA prevalences. Geostatistical interpolation was used to create a map showing the geographical distribution of CFA prevalences in Uganda (by ordinary kriging), and to assess the population exposed to W. bancrofti transmission. Estimates based on population data from 2002 indicated that approximately 8.7 million people (35.3% of the national population) lived in areas where > 1% of the school-aged children were CFA-positive. CFA prevalences generally decreased with increasing altitude, and no CFA-positive cases were found at sites that were > 1300 m above sea level. Although it gives an under-estimate of the overall community prevalence (a fact that should be taken into account when interpreting the present results and comparing them with the results of other surveys), the screening of schoolchildren for CFA was found to be a simple and useful approach for mapping the geographical distribution of lymphatic filariasis.

CFA-4 - a fluorinated metal-organic framework with exchangeable interchannel cations.

PubMed

Fritzsche, J; Grzywa, M; Denysenko, D; Bon, V; Senkovska, I; Kaskel, S; Volkmer, D

2017-05-23

The syntheses and crystal structures of the fluorinated linker 1,4-bis(3,5-bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene (H 2 -tfpb; 1) and the novel metal-organic framework family M[CFA-4] (Coordination Framework Augsburg University-4), M[Cu 5 (tfpb) 3 ] (M = Cu(i), K, Cs, Ca(0.5)), are described. The ligand 1 is fully characterized by single crystal X-ray diffraction, photoluminescence-, NMR-, IR spectroscopy, and mass spectrometry. The copper(i)-containing MOF crystallizes in the hexagonal crystal system within the chiral space group P6 3 22 (no. 182) and the unit cell parameters are as follows: a = 23.630(5) Å, c = 41.390(5) Å, V = 20 015(6) Å 3 . M[CFA-4] features a porous 3-D structure constructed from pentanuclear copper(i) secondary building units {Cu(pz) 6 } - (pz = pyrazolate). Cu(I)[CFA-4] is fully characterized by synchrotron single crystal X-ray diffraction, thermogravimetric analysis, variable temperature powder X-ray diffraction, IR spectroscopy, photoluminescence and gas sorption measurements. Moreover, thermal stability and gas sorption properties of K[CFA-4] and Cu(I)[CFA-4] are compared.

Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

PubMed

Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

2014-02-14

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, p<0.05; L PIC, 274.2±37.3, p<0.05). These findings suggest a neuroplastic change in the IC after FS, which may be involved in the enhancement of CFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Applying Exploratory Structural Equation Modeling to Examine the Student-Teacher Relationship Scale in a Representative Greek Sample.

PubMed

Tsigilis, Nikolaos; Gregoriadis, Athanasios; Grammatikopoulos, Vasilis; Zachopoulou, Evridiki

2018-01-01

Teacher-child relationships in early childhood are a fundamental prerequisite for children's social, emotional, and academic development. The Student-Teacher Relationship Scale (STRS) is one of the most widely accepted and used instruments that evaluate the quality of teacher-child relationships. STRS is a 28-item questionnaire that assess three relational dimensions, Closeness, Conflict, and Dependency. The relevant literature has shown a pattern regarding the difficulty to support the STRS factor structure with CFA, while it is well-documented with EFA. Recently, a new statistical technique was proposed to combine the best of the CFA and EFA namely, the Exploratory Structural Equation Modeling (ESEM). The purpose of this study was (a) to examine the factor structure of the STRS in a Greek national sample. Toward this end, the ESEM framework was applied in order to overcome the limitations of EFA and CFA, (b) to confirm previous findings about the cultural influence in teacher-child relationship patterns, and (c) to examine the invariance of STRS across gender and age. Early educators from a representative Greek sample size of 535 child care and kindergarten centers completed the STRS for 4,158 children. CFA as well as ESEM procedures were implemented. Results showed that ESEM provided better fit to the data than CFA in both groups, supporting the argument that CFA is an overly restrictive approach in comparison to ESEM for the study of STRS. All primary loadings were statistically significant and were associated with their respective latent factors. Contrary to the existing literature conducted in USA and northern Europe, the association between Closeness and Dependency yielded a positive correlation. This finding is in line with previous studies conducted in Greece and confirm the existence of cultural differences in teacher-child relationships. In addition, findings supported the configural, metric, scalar, and variance/covariance equivalence of the STRS between males and females and between preschoolers (3-5 years) and early primary years (5-7 years). Latent factor means comparisons showed that females seem to have a warmer and more dependent relationship with their teachers and are less conflictual in comparison to males.

Applying Exploratory Structural Equation Modeling to Examine the Student-Teacher Relationship Scale in a Representative Greek Sample

PubMed Central

Tsigilis, Nikolaos; Gregoriadis, Athanasios; Grammatikopoulos, Vasilis; Zachopoulou, Evridiki

2018-01-01

Teacher-child relationships in early childhood are a fundamental prerequisite for children's social, emotional, and academic development. The Student-Teacher Relationship Scale (STRS) is one of the most widely accepted and used instruments that evaluate the quality of teacher-child relationships. STRS is a 28-item questionnaire that assess three relational dimensions, Closeness, Conflict, and Dependency. The relevant literature has shown a pattern regarding the difficulty to support the STRS factor structure with CFA, while it is well-documented with EFA. Recently, a new statistical technique was proposed to combine the best of the CFA and EFA namely, the Exploratory Structural Equation Modeling (ESEM). The purpose of this study was (a) to examine the factor structure of the STRS in a Greek national sample. Toward this end, the ESEM framework was applied in order to overcome the limitations of EFA and CFA, (b) to confirm previous findings about the cultural influence in teacher-child relationship patterns, and (c) to examine the invariance of STRS across gender and age. Early educators from a representative Greek sample size of 535 child care and kindergarten centers completed the STRS for 4,158 children. CFA as well as ESEM procedures were implemented. Results showed that ESEM provided better fit to the data than CFA in both groups, supporting the argument that CFA is an overly restrictive approach in comparison to ESEM for the study of STRS. All primary loadings were statistically significant and were associated with their respective latent factors. Contrary to the existing literature conducted in USA and northern Europe, the association between Closeness and Dependency yielded a positive correlation. This finding is in line with previous studies conducted in Greece and confirm the existence of cultural differences in teacher-child relationships. In addition, findings supported the configural, metric, scalar, and variance/covariance equivalence of the STRS between males and females and between preschoolers (3–5 years) and early primary years (5–7 years). Latent factor means comparisons showed that females seem to have a warmer and more dependent relationship with their teachers and are less conflictual in comparison to males. PMID:29867688

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats

PubMed Central

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A.; Hernández-Reyes, Ana Gabriela

2015-01-01

Abstract One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PubMed

Klerkx, Wenche M; Geldof, Albert A; Heintz, A Peter; van Diest, Paul J; Visser, Fredy; Mali, Willem P; Veldhuis, Wouter B

2011-05-01

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. Copyright © 2011 Wiley-Liss, Inc.

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

PubMed

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

2015-08-01

One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

PubMed

Byrd, Wyatt; Boedeker, Edgar C

2013-03-15

Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham mice as the immunized mice induced insufficient intestinal anti-LT antibody to neutralize the activity of the enterotoxin. These results show that our ETEC vaccine induced serum and mucosal antibody responses to CFA/I and LT after mucosal administration which then acted to protect the immunized mice against lung and intestinal colonization, as well as, intestinal fluid accumulation. Copyright © 2012 Elsevier B.V. All rights reserved.

Percutaneous common femoral artery interventions using angioplasty, atherectomy, and stenting.

PubMed

Mehta, Manish; Zhou, Yi; Paty, Philip S K; Teymouri, Medhi; Jafree, Kamran; Bakhtawar, Humayun; Hnath, Jeffrey; Feustel, Paul

2016-08-01

This study evaluated the feasibility, safety, and effectiveness of endovascular interventions for common femoral artery (CFA) occlusive disease. Using a prospectively maintained multicenter database, we analyzed outcomes in 167 consecutive patients who underwent percutaneous CFA interventions for Rutherford class 3 to class 6 (R3-R6) disease. The standardized treatment approach included primary percutaneous transluminal angioplasty (PTA) only, atherectomy + PTA, and provisional stenting. Outcomes included technical failure rate, recurrence, complications, and major or minor amputation rate. Data were analyzed using multivariate regression analysis. During a 7-year period, 167 patients with R3 (n = 91 [54.5%]) and R4 to R6 (n = 76 [45.5%]) disease underwent CFA interventions that included PTA only (n = 114 [68.2%]), atherectomy ± PTA (n = 38 [22.8%]), and provisional stenting (n = 15 [9.0%]) for failed atherectomy ± PTA. Procedure-related complications included pseudoaneurysm (n = 1 [0.6%]), thrombosis (n = 1 [0.6%]), distal embolization (n = 1 [0.6%]), and death (R6, n = 1 [0.06%]). CFA restenosis was observed in 34 (20.4%) patents; these underwent further percutaneous (n = 18 [10.8%]) or surgical (n = 17 [10.2%]) revascularization that included CFA endarterectomy ± femoral distal bypass. Major or minor amputations were observed in none of the R3 patients and in only three (3.9%) and five (6.5%) of the R4 to R6 patients, respectively. Compared with the atherectomy + PTA group, patients in the PTA-only group had a significantly lower patency. Furthermore, during long-term mean follow-up of 42.5 months, the CFA provisional stent group had a 100% primary patency, which was significantly better than the primary patency in the CFA nonstent groups combined (77.0%; P = .0424). Data from this study to date would suggest that percutaneous CFA interventions in select patients are relatively safe and effective. In the long term, CFA stenting has significantly better primary patency than CFA atherectomy and PTA combined. CFA atherectomy + PTA has significantly better primary patency than CFA PTA-only at midterm, especially in patients with claudication. Future randomized controlled trials are warranted. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation.

PubMed

Lemons, L L; Wiley, R G

2012-08-02

The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. Lumbar intrathecal injection of (NPY) is antinociceptive, reducing hyper-reflexia to thermal and mechanical stimulation, particularly after nerve injury and inflammation. We have also shown that intrathecal injection of the targeted cytotoxin, Neuropeptide Y-sap (NPY-sap), is also antinociceptive, reducing nocifensive reflex responses to noxious heat and formalin. In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia. Published by Elsevier Ltd.

A digital ISO expansion technique for digital cameras

NASA Astrophysics Data System (ADS)

Yoo, Youngjin; Lee, Kangeui; Choe, Wonhee; Park, SungChan; Lee, Seong-Deok; Kim, Chang-Yong

2010-01-01

Market's demands of digital cameras for higher sensitivity capability under low-light conditions are remarkably increasing nowadays. The digital camera market is now a tough race for providing higher ISO capability. In this paper, we explore an approach for increasing maximum ISO capability of digital cameras without changing any structure of an image sensor or CFA. Our method is directly applied to the raw Bayer pattern CFA image to avoid non-linearity characteristics and noise amplification which are usually deteriorated after ISP (Image Signal Processor) of digital cameras. The proposed method fuses multiple short exposed images which are noisy, but less blurred. Our approach is designed to avoid the ghost artifact caused by hand-shaking and object motion. In order to achieve a desired ISO image quality, both low frequency chromatic noise and fine-grain noise that usually appear in high ISO images are removed and then we modify the different layers which are created by a two-scale non-linear decomposition of an image. Once our approach is performed on an input Bayer pattern CFA image, the resultant Bayer image is further processed by ISP to obtain a fully processed RGB image. The performance of our proposed approach is evaluated by comparing SNR (Signal to Noise Ratio), MTF50 (Modulation Transfer Function), color error ~E*ab and visual quality with reference images whose exposure times are properly extended into a variety of target sensitivity.

Anti-rheumatoid arthritis effects of traditional Chinese herb couple in adjuvant-induced arthritis in rats.

PubMed

Pan, Ting; Cheng, Tao-Fang; Jia, Yu-Ran; Li, Ping; Li, Fei

2017-06-09

Clematis chinensis Osbeck / Notopterygium incisum Ting ex H, T-Chang (CN) is a traditional Chinese herb couple with prominent efficacy. The herb couple has been commonly used for clinical treatment of arthralgia syndrome ("Bi Zheng" in Chinese) for centuries in China, including rheumatic arthritis, osteoarthritis and gout in modern medicine. To evaluate the anti-arthritic effect of CN herb couple in a rat model of rheumatoid arthritis (RA). Rats were divided randomly into six groups with eight each. Adjuvant-induced arthritis (AIA) model was established by intradermal injection of complete Freund's adjuvant (CFA). Rats were treated orally with different dosages of CN (0.7g/kg, 2.1g/kg, 6.3g/kg) from day 16 till day 40. Ibuprofen (50.4mg/kg) served as a positive control. Spontaneous activity, body weight, paw swelling, and arthritis index (AI) were monitored throughout drug treatment. Then serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were determined by enzyme linked immunosorbent assay (ELISA) kits. In addition, histopathological examination and immunohistochemistry were used to assess the severity of arthritis. Three dosage of CN significantly ameliorated symptoms of RA via increasing body weight as well as reducing paw swelling (at dose of 6.3g/kg, p<0.01) in AIA rats. An extremely significant reduction of AI (p<0.001) was also observed with treatment of CN (6.3g/kg) compared with model group. In parallel, treatment of CN significantly down-regulated levels of TNF-α, IL-6, and VEGF both in serum (p<0.01) and in joint synovial compared with model rats. And histopathology revealed noticeable reduction in synovial hyperplasia, cartilage damage, and inflammatory infiltration by CN treatment, especially at dose of 6.3g/kg. To conclude, all results suggest that CN possesses evident anti-arthritic effects in AIA rats. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Multiepitope fusion antigen induces broadly protective antibodies that prevent adherence of Escherichia coli strains expressing colonization factor antigen I (CFA/I), CFA/II, and CFA/IV.

PubMed

Ruan, Xiaosai; Knudsen, David E; Wollenberg, Katie M; Sack, David A; Zhang, Weiping

2014-02-01

Diarrhea is the second leading cause of death in children younger than 5 years and continues to be a major threat to global health. Enterotoxigenic Escherichia coli (ETEC) strains are the most common bacteria causing diarrhea in developing countries. ETEC strains are able to attach to host small intestinal epithelial cells by using bacterial colonization factor antigen (CFA) adhesins. This attachment helps to initiate the diarrheal disease. Vaccines that induce antiadhesin immunity to block adherence of ETEC strains that express immunologically heterogeneous CFA adhesins are expected to protect against ETEC diarrhea. In this study, we created a CFA multiepitope fusion antigen (MEFA) carrying representative epitopes of CFA/I, CFA/II (CS1, CS2, and CS3), and CFA/IV (CS4, CS5, and CS6), examined its immunogenicity in mice, and assessed the potential of this MEFA as an antiadhesin vaccine against ETEC. Mice intraperitoneally immunized with this CFA MEFA exhibited no adverse effects and developed immune responses to CFA/I, CFA/II, and CFA/IV adhesins. Moreover, after incubation with serum of the immunized mice, ETEC or E. coli strains expressing CFA/I, CFA/II, or CFA/IV adhesins were significantly inhibited in adherence to Caco-2 cells. Our results indicated this CFA MEFA elicited antibodies that not only cross-reacted to CFA/I, CFA/II and CFA/IV adhesins but also broadly inhibited adherence of E. coli strains expressing these seven adhesins and suggested that this CFA MEFA could be a candidate to induce broad-spectrum antiadhesin protection against ETEC diarrhea. Additionally, this antigen construction approach (creating an MEFA) may be generally used in vaccine development against heterogenic pathogens.

Motivation and Engagement in Jamaica: Testing a Multidimensional Framework among Students in an Emerging Regional Context

ERIC Educational Resources Information Center

Martin, Andrew J.; Martin, Tamica G.; Evans, Paul

2018-01-01

This study explored motivation and engagement among 585 Jamaican middle and high school students. Motivation and engagement were assessed via students' responses to the Motivation and Engagement Scale. Confirmatory factor analysis (CFA) found satisfactory fit, and by most measures, multigroup CFA demonstrated comparable factor structure for males…

Antiallergic effect of milk fermented with lactic acid bacteria in a murine animal model.

PubMed

Peng, Sandy; Lin, Jin-Yuarn; Lin, Meei-Yn

2007-06-27

The objective of this study was to assess the antiallergic effect of fermented milk prepared, respectively, with Streptococcus thermophilus MC, Lactobacillus acidophilus B, Lactobacillus bulgaricus Lb, L. bulgaricus 448, and Bifidobacterium longum B6. Female BALB/c mice fed fermented milk were immunized intraperitoneally with ovalbumin (OVA)/complete Freund's adjuvant (CFA) to evaluate the immune response by observing the secretion of cytokines IL-2, IL-4, and IFN-gamma and serum antibody IgE. The results showed that supplementation with lactic acid bacteria fermented milk did not significantly change the IL-2 spontaneous and OVA-stimulated secretions of splenocytes. However, both spontaneous and OVA-stimulated secretions of splenocytes from mice fed lactic acid bacteria fermented milk showed significantly (P < 0.05) lower levels of IL-4 (Th2 cytokine) than those from OVA/CFA-immunized mice fed non-fermented milk (OVA/CFA-milk group). The spontaneous secretion of IFN-gamma (Th1 cytokine) by splenocytes from mice fed L. bulgaricus 448 or L. bulgaricus Lb fermented milk significantly increased as compared to that from the OVA/CFA-milk group. The results showed that the ratios of IFN-gamma to IL-4 of both spontaneous and OVA-stimulated secretions in splenocytes from mice fed lactic acid bacteria fermented milk increased significantly as compared to that of PBS- or OVA/CFA-milk groups. The serum levels of OVA-specific IgE in fermented milk fed groups, especially the group fed S. thermophilus MC fermented milk, were significantly lower than those in the OVA/CFA-milk group through a 6 week feeding experiment. The results showed that milk fermented with lactic acid bacteria demonstrated in vivo antiallergic effects on OVA/CFA-immunized mice via increasing the secretion ratio of IFN-gamma/IL-4 (Th1/Th2) by splenocytes and decreasing the serum level of OVA-specific IgE.

Time to aortic occlusion: It's all about access.

PubMed

Romagnoli, Anna; Teeter, William; Pasley, Jason; Hu, Peter; Hoehn, Melanie; Stein, Deborah; Scalea, Thomas; Brenner, Megan

2017-12-01

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less invasive method of proximal aortic occlusion compared with resuscitative thoracotomy with aortic cross-clamping (RTACC). This study compared time to aortic occlusion with REBOA and RTACC, both including and excluding time required for common femoral artery (CFA) cannulation. This was a retrospective, single-institution review of REBOA or RTACC performed between February 2013 and January 2016. Time of skin incision to aortic cross-clamp for RTACC, time required for CFA cannulation by percutaneous and open methods, and time from guide-wire insertion to balloon inflation at Zone 1 for REBOA, were obtained from videographic recordings. Eighteen RTACC and 21 REBOAs were performed. Median (Q1, Q3) time from skin incision to aortic cross-clamping was 317 seconds (227, 551 seconds). Median (Q1, Q3) time from start of arterial access to Zone 1 balloon occlusion was 474 seconds (431, 572 seconds) (vs. RTACC, p = 0.01). All REBOA procedures were performed with the same device. The median time to complete CFA cannulation was 247 seconds (range, 164-343 seconds), with no difference between percutaneous or open procedures (p = 0.07). The median (Q1, Q3) time to aortic occlusion in REBOA once arterial access had been established was 245 seconds (179, 295.5 seconds), which was significantly shorter than RTACC (p = 0.003). Once CFA access is achieved, time to aortic occlusion is faster with REBOA. Time to aortic occlusion is less than the time required to cannulate the CFA either by percutaneous or open approaches, emphasizing the importance of accurate and expedient CFA access. Resuscitative endovascular balloon occlusion of the aorta may represent a feasible alternative to thoracotomy for aortic occlusion. Time to aortic occlusion will likely decrease with the advent of newer REBOA technology. The rate-limiting portion of REBOA continues to be obtaining CFA access. Therapeutic, level V.

Prospective Cohort Study of Enterotoxigenic Escherichia coli Infections in Argentinean Children

PubMed Central

Viboud, Gloria I.; Jouve, Mabel J.; Binsztein, Norma; Vergara, Marta; Rivas, Marta; Quiroga, Marina; Svennerholm, Ann-Mari

1999-01-01

In a follow-up study, enterotoxigenic Escherichia coli (ETEC) infections in 145 children from two communities located in northeastern Argentina were monitored for 2 years. The occurrence of diarrhea was monitored by weekly household visits. Of 730 fecal specimens collected, 137 (19%) corresponded to diarrheal episodes. ETEC was isolated from a significantly higher proportion of symptomatic (18.3%) than asymptomatic (13.3%) children (P = 0.04541). Individuals of up to 24 months of age were found to have a higher risk of developing ETEC diarrhea than older children (odds ratio [OR], 3.872; P = 0.00021). When the toxin profiles were considered, only heat stable enterotoxin (ST)-producing ETEC was directly associated with diarrhea (P = 0.00035). Fifty-five percent of the ETEC isolated from symptomatic children and 19% of the ETEC isolated from asymptomatic children expressed one of the colonization factors (CFs) investigated, i.e., CF antigen I (CFA/I), CFA/II, CFA/III, and CFA/IV; coli surface antigens CS7 and CS17; and putative CFs PCFO159, PCFO166, and PCFO20, indicating a clear association between diarrhea and ETEC strains that carry these factors (P = 0.0000034). The most frequently identified CFs were CFA/IV (16%), CFA/I (10%), and CS17 (9%). CFs were mostly associated with ETEC strains that produce ST and both heat-labile enterotoxin and ST. Logistic regression analysis, applied to remove confounding effects, revealed that the expression of CFs was associated with illness independently of the toxin type (OR, 4.81; P = 0.0003). When each CF was considered separately, CS17 was the only factor independently associated with illness (OR, 16.6; P = 0.0151). Most CFs (the exception was CFA/IV) fell within a limited array of serotypes, while the CF-negative isolates belonged to many different O:H types. These results demonstrate that some CFs are risk factors for the development of ETEC diarrhea. PMID:10449460

Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

PubMed Central

Luiz, Wilson B.; Rodrigues, Juliana F.; Crabb, Joseph H.

2015-01-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 107 bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. PMID:26371126

[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

PubMed

Kim, Woosuk; Le, Thuc M; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T; Abt, Evan R; Capri, Joseph R; Austin, Wayne R; Van Valkenburgh, Juno S; Steele, Dalton; Gipson, Raymond M; Slavik, Roger; Cabebe, Anthony E; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S; Lee, Jason T; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F; Witte, Owen N; Donahue, Timothy R; Phelps, Michael E; Herschman, Harvey R; Herrmann, Ken; Czernin, Johannes; Radu, Caius G

2016-04-12

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

PubMed Central

Kim, Woosuk; Le, Thuc M.; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T.; Abt, Evan R.; Capri, Joseph R.; Austin, Wayne R.; Van Valkenburgh, Juno S.; Steele, Dalton; Gipson, Raymond M.; Slavik, Roger; Cabebe, Anthony E.; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S.; Lee, Jason T.; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F.; Witte, Owen N.; Donahue, Timothy R.; Phelps, Michael E.; Herschman, Harvey R.; Herrmann, Ken; Czernin, Johannes; Radu, Caius G.

2016-01-01

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds—[18F]Clofarabine; 2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-adenine ([18F]CFA) and 2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-guanine ([18F]F-AraG)—for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring. PMID:27035974

Oxidation of clofibric acid in aqueous solution using a non-thermal plasma discharge or gamma radiation

NASA Astrophysics Data System (ADS)

Madureira, Joana; Ceriani, Elisa; Pinhão, Nuno; Marotta, Ester; Melo, Rita; Cabo Verde, Sandra; Paradisi, Cristina; Margaça, Fernanda M. A.

2017-11-01

In this work, we study degradation of clofibric acid (CFA) in aqueous solution using either ionizing radiation from a $^{60}$Co source or a non-thermal plasma produced by discharges in the air above the solution. The results obtained with the two technologies are compared in terms of effectiveness of CFA degradation and its by-products. In both cases the CFA degradation follows a quasi-exponential decay in time well modelled by a kinetic scheme which considers the competition between CFA and all reaction intermediates for the reactive species generated in solution as well as the amount of the end product formed. A new degradation law is deduced to explain the results. Although the end-product CO$_2$ was detected and the CFA conversion found to be very high under the studied conditions, HPLC analysis reveals several degradation intermediates still bearing the aromatic ring with the chlorine substituent. The extent of mineralization is rather limited. The energy yield is found to be higher in the gamma radiation experiments.

Oxidation of clofibric acid in aqueous solution using a non-thermal plasma discharge or gamma radiation.

PubMed

Madureira, Joana; Ceriani, Elisa; Pinhão, Nuno; Marotta, Ester; Melo, Rita; Cabo Verde, Sandra; Paradisi, Cristina; Margaça, Fernanda M A

2017-11-01

In this work, we study degradation of clofibric acid (CFA) in aqueous solution using either ionizing radiation from a 60 Co source or a non-thermal plasma produced by discharges in the air above the solution. The results obtained with the two technologies are compared in terms of effectiveness of CFA degradation and its by-products. In both cases the CFA degradation follows a quasi-exponential decay in time well modelled by a kinetic scheme which considers the competition between CFA and all reaction intermediates for the reactive species generated in solution as well as the amount of the end product formed. A new degradation law is deduced to explain the results. Although the end-product CO 2 was detected and the CFA conversion found to be very high under the studied conditions, HPLC analysis reveals several degradation intermediates still bearing the aromatic ring with the chlorine substituent. The extent of mineralization is rather limited. The energy yield is found to be higher in the gamma radiation experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein.

PubMed

Lundgren, A; Leach, S; Tobias, J; Carlin, N; Gustafsson, B; Jertborn, M; Bourgeois, L; Walker, R; Holmgren, J; Svennerholm, A-M

2013-02-06

We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea containing killed recombinant E. coli bacteria expressing increased levels of ETEC colonization factors (CFs) and a recombinant protein (LCTBA), i.e. a hybrid between the binding subunits of E. coli heat labile toxin (LTB) and cholera toxin (CTB). We describe a randomized, comparator controlled, double-blind phase I trial in 60 adult Swedish volunteers of a prototype of this vaccine. The safety and immunogenicity of the prototype vaccine, containing LCTBA and an E. coli strain overexpressing the colonization factor CFA/I, was compared to a previously developed oral ETEC vaccine, consisting of CTB and inactivated wild type ETEC bacteria expressing CFA/I (reference vaccine). Groups of volunteers were given two oral doses of either the prototype or the reference vaccine; the prototype vaccine was administered at the same or a fourfold higher dosage than the reference vaccine. The prototype vaccine was found to be safe and equally well-tolerated as the reference vaccine at either dosage tested. The prototype vaccine induced mucosal IgA (fecal secretory IgA and intestine-derived IgA antibody secreting cell) responses to both LTB and CFA/I, as well as serum IgA and IgG antibody responses to LTB. Immunization with LCTBA resulted in about twofold higher mucosal and systemic IgA responses against LTB than a comparable dose of CTB. The higher dose of the prototype vaccine induced significantly higher fecal and systemic IgA responses to LTB and fecal IgA responses to CFA/I than the reference vaccine. These results demonstrate that CF over-expression and inclusion of the LCTBA hybrid protein in an oral inactivated ETEC vaccine does not change the safety profile when compared to a previous generation of such a vaccine and that the prototype vaccine induces significant dose dependent mucosal immune responses against CFA/I and LTB. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ideal, nonideal, and no-marker variables: The confirmatory factor analysis (CFA) marker technique works when it matters.

PubMed

Williams, Larry J; O'Boyle, Ernest H

2015-09-01

A persistent concern in the management and applied psychology literature is the effect of common method variance on observed relations among variables. Recent work (i.e., Richardson, Simmering, & Sturman, 2009) evaluated 3 analytical approaches to controlling for common method variance, including the confirmatory factor analysis (CFA) marker technique. Their findings indicated significant problems with this technique, especially with nonideal marker variables (those with theoretical relations with substantive variables). Based on their simulation results, Richardson et al. concluded that not correcting for method variance provides more accurate estimates than using the CFA marker technique. We reexamined the effects of using marker variables in a simulation study and found the degree of error in estimates of a substantive factor correlation was relatively small in most cases, and much smaller than error associated with making no correction. Further, in instances in which the error was large, the correlations between the marker and substantive scales were higher than that found in organizational research with marker variables. We conclude that in most practical settings, the CFA marker technique yields parameter estimates close to their true values, and the criticisms made by Richardson et al. are overstated. (c) 2015 APA, all rights reserved).

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

Performance characteristics and estimation of measurement uncertainty of three plating procedures for Campylobacter enumeration in chicken meat.

PubMed

Habib, I; Sampers, I; Uyttendaele, M; Berkvens, D; De Zutter, L

2008-02-01

In this work, we present an intra-laboratory study in order to estimate repeatability (r), reproducibility (R), and measurement uncertainty (U) associated with three media for Campylobacter enumeration, named, modified charcoal cefoperazone deoxycholate agar (mCCDA); Karmali agar; and CampyFood ID agar (CFA) a medium by Biomérieux SA. The study was performed at three levels: (1) pure bacterial cultures, using three Campylobacter strains; (2) artificially contaminated samples from three chicken meat matrixes (total n=30), whereby samples were spiked using two contamination levels; ca. 10(3)cfuCampylobacter/g, and ca. 10(4)cfuCampylobacter/g; and (3) pilot testing in naturally contaminated chicken meat samples (n=20). Results from pure culture experiment revealed that enumeration of Campylobacter colonies on Karmali and CFA media was more convenient in comparison with mCCDA using spread and spiral plating techniques. Based on artificially contaminated samples testing, values of repeatability (r) were comparable between the three media, and estimated as 0.15log(10)cfu/g for mCCDA, 0.14log(10)cfu/g for Karmali, and 0.18log(10)cfu/g for CFA. As well, reproducibility performance of the three plating media was comparable. General R values which can be used when testing chicken meat samples are; 0.28log(10), 0.32log(10), and 0.25log(10) for plating on mCCDA, Karmali agar, and CFA, respectively. Measurement uncertainty associated with mCCDA, Karmali agar, and CFA using spread plating, for combination of all meat matrixes, were +/-0.24log(10)cfu/g, +/-0.28log(10)cfu/g, and +/-0.22log(10)cfu/g, respectively. Higher uncertainty was associated with Karmali agar for Campylobacter enumeration in artificially inoculated minced meat (+/-0.48log(10)cfu/g). The general performance of CFA medium was comparable with mCCDA performance at the level of artificially contaminated samples. However, when tested at naturally contaminated samples, non-Campylobacter colonies gave similar deep red colour as that given by the typical Campylobacter growth on CFA. Such colonies were not easily distinguishable by naked eye. In general, the overall reproducibility, repeatability, and measurement uncertainty estimated by our study indicate that there are no major problems with the precision of the International Organization for Standardization (ISO) 10272-2:2006 protocol for Campylobacter enumeration using mCCDA medium.

Circulating filarial antigen in the hydrocele fluid from individuals living in a bancroftian filariasis area - Recife, Brazil: detected by the monoclonal antibody Og4C3-assay.

PubMed

Rocha, Abraham; Lima, Guilherme; Medeiros, Zulma; Aguiar-Santos, Ana; Alves, Sandra; Montarroyos, Ulisses; Oliveira, Paula; Béliz, Fátima; Netto, Maria José; Furtado, André

2004-02-01

The purpose of this study was to examine the circulating filarial antigen (CFA) detected by the monoclonal antibody (mAb) Og4C3-ELISA in paired samples of serum and hydrocele fluid from 104 men with hydrocele, living in an endemic area of Wuchereria bancrofti. Nocturnal blood specimens were filtered and examined for microfilariae (MF) and ultrasound was used in order to identify the presence of adult worms (the filaria dance sign - FDS) in the lymphatic vessels of the scrotal area. Four groups were selected according to their parasitological status: group I - 71 MF- and FDS-; group II - 21 MF+ and FDS+; group III - 10 MF- and FDS+ and group IV- 2 MF+ and FDS-. CFA was identified simultaneously (fluid and serum) in 11 (15.5%), 21 (100%), 3 (30%), and 1 (50%) in groups I, II, III, and IV, respectively. In despite of high CFA+ level (antigen Og4C3) units/ml, the Geometrical Mean (GM) = 2696) in the sera of these 36/104 paired samples, when compared to the hydrocele fluid, (GM = 1079), showed a very good correlation between the CFA level in the serum and CFA level in the fluid (r = 0.731). CFA level in the serum of the 23 microfilaremics (groups II and IV) was extremely high (GM = 4189) and was correlated with MF density (r = 0.442). These findings report for the first time the potential alternative use of the hydrocele fluid to investigate CFA using the mAb Og4C3-ELISA.

Binding of CFA/I Pili of Enterotoxigenic Escherichia coli to Asialo-GM1 Is Mediated by the Minor Pilin CfaE

PubMed Central

Madhavan, T. P. Vipin; Riches, James D.; Scanlon, Martin J.

2016-01-01

CFA/I pili are representatives of a large family of related pili that mediate the adherence of enterotoxigenic Escherichia coli to intestinal epithelial cells. They are assembled via the alternate chaperone-usher pathway and consist of two subunits, CfaB, which makes up the pilus shaft and a single pilus tip-associated subunit, CfaE. The current model of pilus-mediated adherence proposes that CFA/I has two distinct binding activities; the CfaE subunit is responsible for binding to receptors of unknown structure on erythrocyte and intestinal epithelial cell surfaces, while CfaB binds to various glycosphingolipids, including asialo-GM1. In this report, we present two independent lines of evidence that, contrary to the existing model, CfaB does not bind to asialo-GM1 independently of CfaE. Neither purified CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrate that binding activity toward asialo-GM1 resides in CfaE and this is essential for pilus binding to Caco-2 intestinal epithelial cells. We conclude that the binding activities of CFA/I pili for asialo-GM1, erythrocytes, and intestinal cells are inseparable, require the same amino acid residues in CfaE, and therefore depend on the same or very similar binding mechanisms. PMID:26975993

Binding of CFA/I Pili of Enterotoxigenic Escherichia coli to Asialo-GM1 Is Mediated by the Minor Pilin CfaE.

PubMed

Madhavan, T P Vipin; Riches, James D; Scanlon, Martin J; Ulett, Glen C; Sakellaris, Harry

2016-05-01

CFA/I pili are representatives of a large family of related pili that mediate the adherence of enterotoxigenic Escherichia coli to intestinal epithelial cells. They are assembled via the alternate chaperone-usher pathway and consist of two subunits, CfaB, which makes up the pilus shaft and a single pilus tip-associated subunit, CfaE. The current model of pilus-mediated adherence proposes that CFA/I has two distinct binding activities; the CfaE subunit is responsible for binding to receptors of unknown structure on erythrocyte and intestinal epithelial cell surfaces, while CfaB binds to various glycosphingolipids, including asialo-GM1. In this report, we present two independent lines of evidence that, contrary to the existing model, CfaB does not bind to asialo-GM1 independently of CfaE. Neither purified CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrate that binding activity toward asialo-GM1 resides in CfaE and this is essential for pilus binding to Caco-2 intestinal epithelial cells. We conclude that the binding activities of CFA/I pili for asialo-GM1, erythrocytes, and intestinal cells are inseparable, require the same amino acid residues in CfaE, and therefore depend on the same or very similar binding mechanisms. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Ras Signaling Inhibitors Attenuate Disease in Adjuvant-Induced Arthritis via Targeting Pathogenic Antigen-Specific Th17-Type Cells.

PubMed

Zayoud, Morad; Marcu-Malina, Victoria; Vax, Einav; Jacob-Hirsch, Jasmine; Elad-Sfadia, Galit; Barshack, Iris; Kloog, Yoel; Goldstein, Itamar

2017-01-01

The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization. In the present study, we tested the therapeutic and immunomodulatory effects of FTS and its derivative 5-fluoro-FTS (F-FTS) in the rat adjuvant-induced arthritis model (AIA). We show that AIA severity was significantly reduced by oral FTS and F-FTS treatment compared to vehicle control treatment. FTS was as effective as the mainstay anti-rheumatic drug methotrexate, and combining the two drugs significantly increased efficacy compared to each drug alone. We also discovered that FTS therapy inhibited both the CFA-driven in vivo induction of Th17 and IL-17/IFN-γ producing "double positive" as well as the upregulation of serum levels of the Th17-associated cytokines IL-17A and IL-22. By gene microarray analysis of effector CD4 + T cells from CFA-immunized rats, re-stimulated in vitro with the mycobacterium tuberculosis heat-shock protein 65 (Bhsp65), we determined that FTS abrogated the Bhsp65-induced transcription of a large list of genes (e.g., Il17a/f, Il22, Ifng, Csf2, Lta, and Il1a). The functional enrichment bioinformatics analysis showed significant overlap with predefined gene sets related to inflammation, immune system processes and autoimmunity. In conclusion, FTS and F-FTS display broad immunomodulatory effects in AIA with inhibition of the Th17-type response to a dominant arthritogenic antigen. Hence, targeting Ras signal-transduction cascade is a potential novel therapeutic approach for RA.

Micromagnetic studies of Full Huesler alloy, Co2FeAl, nanostructures

NASA Astrophysics Data System (ADS)

Yoritomo, Patricia; Mecholsky, Nicholas; Gyawali, Parshu; Sapkota, Keshab; Pegg, I. L.; Philip, John

2013-03-01

Co2FeAl (CFA) is a full Huesler alloy with interesting magnetic behavior and very high Curie temperature. We have carried out micromagnetic simulations on CFA nanopillars using a program, NMAG, with various dimensions and spacing. The micromagnetic simulations are compared with the experimental results that we have obtained. Nanopillars are produced using the liftoff technique after electron beam lithography. The CFA nanopillars are grown using electron beam deposition of Co, Fe and Al in the stoichiometric ratio and by further annealing at 850 K for one hour. We have simulated the magnetic behavior of CFA nanopillars ranging from 30 to 90 nm in diameter and with a height of about 115 nm. Preliminary results show the simulated coercivities are 700 Oe and 2400 Oe for 60 and 30 nm pillars. These are comparable to the experimental results that we have obtained. Magnetic behavior of polycrystalline nanowires of varying diameters is also simulated using NMAG. We will present the simulation and experimental results of nanopillars and polycrystalline nanowires in detail. This work has been supported by funding from NSF under CAREER Grant No. ECCS-0845501 and NSF-MRI, DMR-0922997.

Ameliorative Effect of Caffeic Acid on Capecitabine-Induced Hepatic and Renal Dysfunction: Involvement of the Antioxidant Defence System

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Adeyemo, Oluwatobi Adewumi

2017-01-01

Background: It has been postulated that during liver and kidney damage there is a decreased in the antioxidant status associated with a simultaneous increase in the reactive oxygen species and lipid peroxidation. In consonant with this, Capecitabine, an oral chemotherapy and inactive non-cytotoxic fluoropyrimidine considered for the treatment of advance colorectal cancer, has also been shown to induce oxidative stress in liver tissues. Caffeic acid, a typical hydroxycinnamic, has been claimed to be effective against oxidative stress. Therefore, this present work studied the protective effect of caffeic acid on oxidative stress-induced liver and kidney damage by the administration of capecitabine. Methods: Twenty-four male Wistar strain rats were randomly divided into four treatment groups: A. control, B. capecitabine (CPTB)-treated group (30 mg/kg b.w. CPTB), C. caffeic acid (CFA)-treated group (100 mg/kg b.w. CFA) and D. co-treated group with CFA (100 mg/kg b.w.) and CPTB (30 mg/kg b.w.). Results: Caffeic acid administration significantly ameliorated the elevated plasma biomarkers of hepatic and renal tissue damage induced by the capecitabine and improved enzymatic and non-enzymatic antioxidant levels in liver organ. Conclusions: The protective effect of caffeic acid could be attributed to its ability to boost the antioxidant defence system and reduce lipid peroxidation. PMID:29068374

Pain Relief with Wet Cupping Therapy in Rats is Mediated by Heat Shock Protein 70 and ß-Endorphin.

PubMed

Subadi, Imam; Nugraha, Boya; Laswati, Hening; Josomuljono, Harjanto

2017-07-01

Wet cupping therapy is a complementary therapy in pain management. The mechanism of this therapy, however, needs further elucidation. Cells injured by wet cupping therapy seem to stimulate the expression of heat shock protein 70 (HSP70). Its benefit in pain reduction could be mediated by the expression of ß-endorphin. This study aimed at determining the correlation between HSP70 and ß-endorphin after wet cupping therapy. Sixteen male Wistar rats were divided into control (CG; n=8) and treatment (TG; n=8) groups. The rats in both groups were injected with complete Freund's adjuvant (CFA) at the footpad. In the TG, wet cupping therapy was done at the left and right paralumbar regions 48 hours after the CFA injection. Twenty-four hours after therapy, the hot plate test was done to assess pain threshold. Thereafter, immunohistochemistry from the skin subjected to wet cupping therapy was conducted for HSP70 and ß-endorphin. The expression of HSP70 was significantly higher in the keratinocytes of the TG (20.25±3.53; P<0.001) than in the keratinocytes of the CG (10.50±2.44; P<0.001). The expression of ß-endorphin was significantly higher in the keratinocytes of the TG (22.37±3.52; P<0.001) than in the keratinocytes of the CG (5.12±1.72; P<0.001). The results also revealed a high correlation between HSP70 and ß-endorphin (β=0.864; P<0.001). Pain threshold after wet cupping therapy was significantly higher in the TG (22.81±6.34 s; P=0.003) than in the CG (11.78±3.56 s). The benefit of wet cupping therapy in terms of pain reduction in rats could be mediated by the expression of HSP70 and ß-endorphin.

Pain Relief with Wet Cupping Therapy in Rats is Mediated by Heat Shock Protein 70 and ß-Endorphin

PubMed Central

Subadi, Imam; Nugraha, Boya; Laswati, Hening; Josomuljono, Harjanto

2017-01-01

Background: Wet cupping therapy is a complementary therapy in pain management. The mechanism of this therapy, however, needs further elucidation. Cells injured by wet cupping therapy seem to stimulate the expression of heat shock protein 70 (HSP70). Its benefit in pain reduction could be mediated by the expression of ß-endorphin. This study aimed at determining the correlation between HSP70 and ß-endorphin after wet cupping therapy. Methods: Sixteen male Wistar rats were divided into control (CG; n=8) and treatment (TG; n=8) groups. The rats in both groups were injected with complete Freund’s adjuvant (CFA) at the footpad. In the TG, wet cupping therapy was done at the left and right paralumbar regions 48 hours after the CFA injection. Twenty-four hours after therapy, the hot plate test was done to assess pain threshold. Thereafter, immunohistochemistry from the skin subjected to wet cupping therapy was conducted for HSP70 and ß-endorphin. Results: The expression of HSP70 was significantly higher in the keratinocytes of the TG (20.25±3.53; P<0.001) than in the keratinocytes of the CG (10.50±2.44; P<0.001). The expression of ß-endorphin was significantly higher in the keratinocytes of the TG (22.37±3.52; P<0.001) than in the keratinocytes of the CG (5.12±1.72; P<0.001). The results also revealed a high correlation between HSP70 and ß-endorphin (β=0.864; P<0.001). Pain threshold after wet cupping therapy was significantly higher in the TG (22.81±6.34 s; P=0.003) than in the CG (11.78±3.56 s). Conclusions: The benefit of wet cupping therapy in terms of pain reduction in rats could be mediated by the expression of HSP70 and ß-endorphin. PMID:28761205

Spontaneous firing and evoked responses of spinal nociceptive neurons are attenuated by blockade of P2X3 and P2X2/3 receptors in inflamed rats.

PubMed

Xu, Jun; Chu, Katharine L; Brederson, Jill-Desiree; Jarvis, Michael F; McGaraughty, Steve

2012-08-01

P2X3 and P2X2/3 receptors are selectively expressed on primary afferent nociceptors and have been implicated in modulating nociception in different models of pathological pain, including inflammatory pain. In an effort to delineate further the role of P2X3 receptors (homomeric and heteromeric) in the modulation of nociceptive transmission after a chronic inflammation injury, A-317491, a potent and selective P2X3-P2X2/3 antagonist, was administered to CFA-inflamed rats in order to examine its effects on responses of spinal dorsal horn neurons to mechanical and thermal stimulation. Systemic injection of A-317491 (30 μmol/kg, i.v.) reduced the responses of wide-dynamic-range (WDR) and nociceptive specific (NS) neurons to both high-intensity mechanical (pinch) and heat (49°C) stimulation. A-317491 also decreased low-intensity (10 g von Frey hair) mechanically evoked activity of WDR neurons but did not alter WDR neuronal responses to cold stimulation (5°C). Spontaneous firing of WDR neurons in CFA-inflamed rats was also significantly attenuated by A-317491 injection. By using immunohistochemistry, P2X3 receptors were demonstrated to be enhanced in lamina II of the spinal dorsal horn after inflammation. In summary, blockade of P2X3 and P2X2/3 receptors dampens mechanical- and heat-related signaling, as well as nonevoked activity of key classes of spinal nociceptive neurons in inflamed animals. These data suggest that P2X3 and/or P2X2/3 receptors have a broad contribution to somatosensory/nociceptive transmission in rats with a chronic inflammatory injury and are consistent with previous behavioral data demonstrating antiallodynic and antihyperalgesic effects of receptor antagonists. Copyright © 2012 Wiley Periodicals, Inc.

Improved sensitivity high-definition interline CCD using the KODAK TRUESENSE color filter pattern

NASA Astrophysics Data System (ADS)

DiBella, James; Andreghetti, Marco; Enge, Amy; Chen, William; Stanka, Timothy; Kaser, Robert

2010-01-01

The KODAK TRUESENSE Color Filter Pattern has technology that for the first time is applied to a commercially available interline CCD. This 2/3" true-HD sensor will be described along with its performance attributes, including sensitivity improvement as compared to the Bayer CFA version of the same sensor. In addition, an overview of the system developed for demonstration and evaluation will be provided. Examples of the benefits of the new technology in specific applications including surveillance and intelligent traffic systems will be discussed.

Cross friction algometry (CFA): Comparison of pressure pain thresholds between patients with chronic non-specific low back pain and healthy subjects.

PubMed

Farasyn, Andre; Lassat, Bert

2016-04-01

Palpation is widely used to assess muscular sensitivity in clinical settings but still remains a subjective evaluation. This cross-sectional study assessed a newly developed cross-friction algometry making palpation measurable. The objective was to investigate the reliability of pressure pain thresholds obtained using Cross-Friction Algometry (CFA-PPTs) measured at the level of Erector spinae and Gluteus maximus central muscle parts, and to compare the CFA-PPTs between patients with chronic nonspecific low back pain (nCLBP) and matching healthy subjects. Patients presenting nCLBP to GP's and send into a Pain Center and healthy subjects recruited via university ad valvas & flyers distribution. 30 patients with nCLBP were measured for cross-friction algometry. Other evaluations consisted of the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI). The inter- and intra-reliability were tested and found to be sufficient. The mean CFA-PPT values of the Erector spinae at levels T8, T10, L1 & L3 and the Gluteus maximus of the nCLBP group were significantly lower (p ≤ 0.001) when compared to the CFA-PPT values of the healthy group. The greatest difference (-58%) was found at L1 Erector spinae level and at the superior part of the Gluteus maximus measuring point (-59%). Within the group of patients with nCLBP it was surprising to notice that there was no significant correlation between all the reference points measured using CFA-PPTs and the outcomes of the VAS and ODI scores. With the aid of CFA, the importance of local muscular disorder in the lumbar part of the Erector spinae and Gluteus maximus in patients with nCLBP is obviously demonstrated, but also reveals the very large inter-individual differences in muscular fibrosis sensitivity and/or pain behavior in daily life. This possibly re-opens the debate on which influences can be put forward as the most important: the central or the peripheral sensitization system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Magnetic resonance imaging-derived arterial peak flow in peripheral arterial disease: towards a standardized measurement.

PubMed

Versluis, B; Nelemans, P J; Wildberger, J E; Schurink, G-W; Leiner, T; Backes, W H

2014-08-01

To determine the best location to measure the arterial peak flow (APF) in patients with peripheral arterial disease in order to facilitate clinical standardization. Two hundred and fifty-nine patients with varying degrees of peripheral artery disease (PAD) and 48 patients without PAD were included. All patients underwent magnetic resonance phase-contrast imaging of the common femoral artery (CFA), superficial femoral artery (SFA), and popliteal artery (PA). APF values of patients with PAD were compared with patients with no PAD. The discriminative ability to identify PAD was evaluated by means of receiver-operator characteristic curves and the corresponding areas under the curve (AUC). Mean APF values in patients with PAD were reduced by 42%, 55% and 59% compared with non-PAD patients for the CFA, SFA, and PA, respectively (p < .01). The AUC's were 0.84, 0.92, and 0.93 for the CFA, SFA, and PA, respectively. The APF measured at the level of the PA shows the largest differences between patients with PAD and patients with no PAD and the best discriminative ability compared with the APF acquired in the CFA or SFA. The PA seems to be the most suitable level for standardized flow measurements in patients with PAD in order to obtain relevant functional information about the vascular status. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

PubMed

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation

PubMed Central

Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-01-01

Introduction The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. Aim This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Materials and Methods Albino rats of either sex were divided into five groups of six rats each (Group I – Control, Group II –Gel base, Group III –P. santalinus paste, Group IV –P. santalinus gel, Group V– Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund’s Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey’s test was used for comparison among groups. Results Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Conclusion Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation. PMID:28892928

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

PubMed

Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-07-01

The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III - P. santalinus paste, Group IV - P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

Maternal vaccination with a fimbrial tip adhesin and passive protection of neonatal mice against lethal human enterotoxigenic Escherichia coli challenge.

PubMed

Luiz, Wilson B; Rodrigues, Juliana F; Crabb, Joseph H; Savarino, Stephen J; Ferreira, Luis C S

2015-12-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 10(7) bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Continuous Firefly Algorithm for Optimal Tuning of Pid Controller in Avr System

NASA Astrophysics Data System (ADS)

Bendjeghaba, Omar

2014-01-01

This paper presents a tuning approach based on Continuous firefly algorithm (CFA) to obtain the proportional-integral- derivative (PID) controller parameters in Automatic Voltage Regulator system (AVR). In the tuning processes the CFA is iterated to reach the optimal or the near optimal of PID controller parameters when the main goal is to improve the AVR step response characteristics. Conducted simulations show the effectiveness and the efficiency of the proposed approach. Furthermore the proposed approach can improve the dynamic of the AVR system. Compared with particle swarm optimization (PSO), the new CFA tuning method has better control system performance in terms of time domain specifications and set-point tracking.

Adaptive Wiener filter super-resolution of color filter array images.

PubMed

Karch, Barry K; Hardie, Russell C

2013-08-12

Digital color cameras using a single detector array with a Bayer color filter array (CFA) require interpolation or demosaicing to estimate missing color information and provide full-color images. However, demosaicing does not specifically address fundamental undersampling and aliasing inherent in typical camera designs. Fast non-uniform interpolation based super-resolution (SR) is an attractive approach to reduce or eliminate aliasing and its relatively low computational load is amenable to real-time applications. The adaptive Wiener filter (AWF) SR algorithm was initially developed for grayscale imaging and has not previously been applied to color SR demosaicing. Here, we develop a novel fast SR method for CFA cameras that is based on the AWF SR algorithm and uses global channel-to-channel statistical models. We apply this new method as a stand-alone algorithm and also as an initialization image for a variational SR algorithm. This paper presents the theoretical development of the color AWF SR approach and applies it in performance comparisons to other SR techniques for both simulated and real data.

SSVEP recognition using common feature analysis in brain-computer interface.

PubMed

Zhang, Yu; Zhou, Guoxu; Jin, Jing; Wang, Xingyu; Cichocki, Andrzej

2015-04-15

Canonical correlation analysis (CCA) has been successfully applied to steady-state visual evoked potential (SSVEP) recognition for brain-computer interface (BCI) application. Although the CCA method outperforms the traditional power spectral density analysis through multi-channel detection, it requires additionally pre-constructed reference signals of sine-cosine waves. It is likely to encounter overfitting in using a short time window since the reference signals include no features from training data. We consider that a group of electroencephalogram (EEG) data trials recorded at a certain stimulus frequency on a same subject should share some common features that may bear the real SSVEP characteristics. This study therefore proposes a common feature analysis (CFA)-based method to exploit the latent common features as natural reference signals in using correlation analysis for SSVEP recognition. Good performance of the CFA method for SSVEP recognition is validated with EEG data recorded from ten healthy subjects, in contrast to CCA and a multiway extension of CCA (MCCA). Experimental results indicate that the CFA method significantly outperformed the CCA and the MCCA methods for SSVEP recognition in using a short time window (i.e., less than 1s). The superiority of the proposed CFA method suggests it is promising for the development of a real-time SSVEP-based BCI. Copyright © 2014 Elsevier B.V. All rights reserved.

Temporal patterns of variable relationships in person-oriented research: longitudinal models of configural frequency analysis.

PubMed

von Eye, Alexander; Mun, Eun Young; Bogat, G Anne

2008-03-01

This article reviews the premises of configural frequency analysis (CFA), including methods of choosing significance tests and base models, as well as protecting alpha, and discusses why CFA is a useful approach when conducting longitudinal person-oriented research. CFA operates at the manifest variable level. Longitudinal CFA seeks to identify those temporal patterns that stand out as more frequent (CFA types) or less frequent (CFA antitypes) than expected with reference to a base model. A base model that has been used frequently in CFA applications, prediction CFA, and a new base model, auto-association CFA, are discussed for analysis of cross-classifications of longitudinal data. The former base model takes the associations among predictors and among criteria into account. The latter takes the auto-associations among repeatedly observed variables into account. Application examples of each are given using data from a longitudinal study of domestic violence. It is demonstrated that CFA results are not redundant with results from log-linear modeling or multinomial regression and that, of these approaches, CFA shows particular utility when conducting person-oriented research.

The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats

PubMed Central

Abhari, Khadijeh; Shekarforoush, Seyed Shahram; Hosseinzadeh, Saeid; Nazifi, Saeid; Sajedianfard, Javad; Eskandari, Mohammad Hadi

2016-01-01

Background Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. Objective In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA), using arthritis-induced rat model. Design Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1) control: normal healthy rats fed with standard diet, 2) disease control (RA): arthritis-induced rats fed with standard diet, 3) prebiotic (PRE): RA+ 5% w/w long-chain inulin, 4) probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 109 spores/day B. coagulans, and 6) treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn), serum amyloid A (SAA), and TNF-α and alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively. Results Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001), which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat. PMID:27427194

The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats.

PubMed

Abhari, Khadijeh; Shekarforoush, Seyed Shahram; Hosseinzadeh, Saeid; Nazifi, Saeid; Sajedianfard, Javad; Eskandari, Mohammad Hadi

2016-01-01

Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA), using arthritis-induced rat model. Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1) control: normal healthy rats fed with standard diet, 2) disease control (RA): arthritis-induced rats fed with standard diet, 3) prebiotic (PRE): RA+ 5% w/w long-chain inulin, 4) probiotic (PRO): RA+ 10(9) spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 10(9) spores/day B. coagulans, and 6) treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn), serum amyloid A (SAA), and TNF-α and alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively. Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001), which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1 AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.

Gypsy moth (Lepidoptera: Lymantriidae) consumption and utilization of northern red oak and white oak foliage exposed to simulated acid rain and ozone

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

Cannon, W.N. Jr.

1993-06-01

Two-year-old seedlings of white oak, Quercus alba L., and red oak, Q. rubra L., were exposed to ozone (O[sub 3]) fumigations in four continuously stirred tank reactor chambers in the greenhouse for 8 h/d, 3 d/wk for 6 wk. Fumigation treatments were charcoal-filtered air (CFA) and CFA + 0.15 ppm O[sub 3]. Two simulated rain treatments, pH 4.2 and pH 3.0, of-1.25 cm were applied once each week in rain-simulation chambers. Gypsy moth, Lymantria dispar (L.), third instars were allowed to feed on leaf disks from treated seedlings for 24 h. Leaf area consumed, food assimilated, weight gain, and relativemore » growth rate (RGR) were examined. Overall, larvae fed white oak foliage consumed more foliage and gained more weight than those fed red oak foliage. Response to the fumigation and rain treatments was different for each oak species. On white oak foliage, larvae consumed significantly less foliage treated with CFA + pH 3.0 rain, but the lowest RGR occurred with the 0.15 ppm O[sub 3] + pH 4.2 rain treatment. The most food assimilated, greatest weight gain, and highest RGR occurred with the CFA + pH 4.2 rain control. Red oak foliage consumed was equivalent for all treatments, but foliage exposed to CFA + pH 3.0 rain resulted in more food assimilated, greater weight gain, and higher RGR for that species.« less

Serology of Paracoccidioidomycosis Due to Paracoccidioides lutzii

PubMed Central

Gegembauer, Gregory; Araujo, Leticia Mendes; Pereira, Edy Firmina; Rodrigues, Anderson Messias; Paniago, Anamaria Mello Miranda; Hahn, Rosane Christine; de Camargo, Zoilo Pires

2014-01-01

Paracoccidioides lutzii is a new agent of paracoccidioidomycosis (PCM) and has its epicenter localized to the Central-West region of Brazil. Serological diagnosis of PCM caused by P. lutzii has not been established. This study aimed to develop new antigenic preparations from P. lutzii and to apply them in serological techniques to improve the diagnosis of PCM due to P. lutzii. Paracoccidioides lutzii exoantigens, cell free antigen (CFA), and a TCA-precipitated antigen were evaluated in immunodiffusion (ID) tests using a total of 89 patient sera from the Central-West region of Brazil. Seventy-two sera were defined as reactive for P. brasiliensis using traditional antigens (AgPbB339 and gp43). Non-reactive sera for traditional antigens (n = 17) were tested with different P. lutzii preparations and P. lutzii CFA showed 100% reactivity. ELISA was found to be a very useful test to titer anti-P. lutzii antibodies using P. lutzii-CFA preparations. Sera from patients with PCM due to P. lutzii presented with higher antibody titers than PCM due to P. brasiliensis and heterologous sera. In western blot, sera from patients with PCM due to P. lutzii were able to recognize antigenic molecules from the P. lutzii-CFA antigen, but sera from patients with PCM due to P. brasiliensis could not recognize any P. lutzii molecules. Due to the facility of preparing P. lutzii CFA antigens we recommend its use in immunodiffusion tests for the diagnosis of PCM due to P. lutzii. ELISA and western blot can be used as complementary tests. PMID:25032829

Population culture and development: a case study.

PubMed

Hartman, P

1979-01-01

Communications and development in the broadest sense of the terms are examined in relation to evaluation of the work of the Communication Foundation for Asia (CFA). CFA produces, in conjunction with public and private development agencies, flip-charts, comics, a fieldworker's handbook for use in family planning education, sound cassette magazines for agricultural extension work, booklets and sound-slides on forming cooperatives, and other educational materials. CFA operates in the Philippines. A developmental radio drama produced by CFA delivered a pro-development message, one that tells people they can do something about their conditions/situations, compared to the passive, consumer-oriented commercial radio drama. The most prominent theme was achievement. The characters had complex motivations and displayed wide range of motives. Like other forms of propaganda, developmental radio drama is not welcomed by radio station owners. Not many people in the industry perceive the opportunity for increasing overall development and economic growth. All pressures from commercial radio are in consumerist directions while developmental drama encourages production.

Effect of nano-oxide layers on giant magnetoresistance in pseudo-spin-valves using Co 2FeAl electrodes

NASA Astrophysics Data System (ADS)

Zhang, D. L.; Xu, X. G.; Wu, Y.; Miao, J.; Jiang, Y.

2011-03-01

We studied the pseudo-spin-valves (PSVs) with a structure of Ta/Co 2FeAl/NOL 1/Co 2FeAl/Cu/Co 2FeAl/NOL 2/Ta, where NOL represents the nano-oxide layer. Compared with the normal Co 2FeAl (CFA) PSV with a structure of Ta/Co 2FeAl/Cu/Co 2FeAl/Ta, which shows only a current-in-plane (CIP) giant magnetoresistance (GMR) of 0.03%, the CFA PSV with NOLs shows a large CIP-GMR of 5.84%. The enhanced GMR by the NOLs inserted in the CFA PSV is due to the large specular reflection caused by [(CoO)(Fe 2O 3)(Al 2O 3)] in NOL 1 and [(Fe 2O 3)(Al 2O 3)(Ta 2O 5)] in NOL 2. Another reason is that the roughness of the interface between Ta and CFA is improved by the oxidation procedure.

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice.

PubMed

Favoino, E; Favia, E I; Digiglio, L; Racanelli, V; Shoenfeld, Y; Perosa, F

2014-01-01

The safety of four different adjuvants was assessed in lupus-prone New Zealand black/New Zealand white (BW)F1 mice. Four groups of mice were injected intraperitoneally with incomplete Freund's adjuvant (IFA), complete Freund's adjuvant (CFA), squalene (SQU) or aluminium hydroxide (ALU). An additional group received plain phosphate-buffered saline (PBS) (UNT group). Mice were primed at week 9 and boosted every other week up to week 15. Proteinuria became detectable at weeks 17 (IFA group), 24 (CFA group), 28 (SQU and ALU groups) and 32 (UNT group). Different mean values were obtained among the groups from weeks 17 to 21 [week 17: one-way analysis of variance (anova) P = 0·016; weeks 18 and 19: P = 0·048; weeks 20 and 21: P = 0·013] being higher in the IFA group than the others [Tukey's honestly significant difference (HSD) post-test P < 0·05]. No differences in anti-DNA antibody levels were observed among groups. Anti-RNP/Sm antibody developed at week 19 in only one CFA-treated mouse. Mean mouse weight at week 18 was lower in the ALU group than the IFA (Tukey's HSD post-test P = 0·04), CFA (P = 0·01) and SQU (P < 0·0001) groups, while the mean weight in the SQU group was higher than in the IFA (P = 0·009), CFA (P = 0·013) and UNT (P = 0·005) groups. The ALU group weight decreased by almost half between weeks 29 and 31, indicating some toxic effect of ALU in the late post-immunization period. Thus, SQU was the least toxic adjuvant as it did not (i) accelerate proteinuria onset compared to IFA; (ii) induce toxicity compared to ALU or (iii) elicit anti-RNP/Sm autoantibody, as occurred in the CFA group. © 2013 British Society for Immunology.

G-Channel Restoration for RWB CFA with Double-Exposed W Channel

PubMed Central

Park, Chulhee; Song, Ki Sun; Kang, Moon Gi

2017-01-01

In this paper, we propose a green (G)-channel restoration for a red–white–blue (RWB) color filter array (CFA) image sensor using the dual sampling technique. By using white (W) pixels instead of G pixels, the RWB CFA provides high-sensitivity imaging and an improved signal-to-noise ratio compared to the Bayer CFA. However, owing to this high sensitivity, the W pixel values become rapidly over-saturated before the red–blue (RB) pixel values reach the appropriate levels. Because the missing G color information included in the W channel cannot be restored with a saturated W, multiple captures with dual sampling are necessary to solve this early W-pixel saturation problem. Each W pixel has a different exposure time when compared to those of the R and B pixels, because the W pixels are double-exposed. Therefore, a RWB-to-RGB color conversion method is required in order to restore the G color information, using a double-exposed W channel. The proposed G-channel restoration algorithm restores G color information from the W channel by considering the energy difference caused by the different exposure times. Using the proposed method, the RGB full-color image can be obtained while maintaining the high-sensitivity characteristic of the W pixels. PMID:28165425

G-Channel Restoration for RWB CFA with Double-Exposed W Channel.

PubMed

Park, Chulhee; Song, Ki Sun; Kang, Moon Gi

2017-02-05

In this paper, we propose a green (G)-channel restoration for a red-white-blue (RWB) color filter array (CFA) image sensor using the dual sampling technique. By using white (W) pixels instead of G pixels, the RWB CFA provides high-sensitivity imaging and an improved signal-to-noise ratio compared to the Bayer CFA. However, owing to this high sensitivity, the W pixel values become rapidly over-saturated before the red-blue (RB) pixel values reach the appropriate levels. Because the missing G color information included in the W channel cannot be restored with a saturated W, multiple captures with dual sampling are necessary to solve this early W-pixel saturation problem. Each W pixel has a different exposure time when compared to those of the R and B pixels, because the W pixels are double-exposed. Therefore, a RWB-to-RGB color conversion method is required in order to restore the G color information, using a double-exposed W channel. The proposed G-channel restoration algorithm restores G color information from the W channel by considering the energy difference caused by the different exposure times. Using the proposed method, the RGB full-color image can be obtained while maintaining the high-sensitivity characteristic of the W pixels.

IRAS galaxies and the large-scale structure in the CfA slice

NASA Technical Reports Server (NTRS)

Babul, Arif; Postman, Marc

1990-01-01

The spatial distributions of the IRAS and the optical galaxies in the first CfA slice are compared. The IRAS galaxies are generally less clustered than optical ones, but their distribution is essentially identical to that of late-type optical galaxies. The discrepancy between the clustering properties of the IRAS and optical samples in the CfA slice region is found to be entirely due to the paucity of IRAS galaxies in the core of the Coma cluster. The spatial distributions of the IRAS and the optical galaxies, both late and early types, outside the dense core of the Coma cluster are entirely consistent with each other. This conflicts with the prediction of the linear biasing scenario.

CfaE tip mutations in enterotoxigenic Escherichia coli CFA/I fimbriae define critical human intestinal binding sites.

PubMed

Baker, K K; Levine, M M; Morison, J; Phillips, A; Barry, E M

2009-05-01

Enterotoxigenic Escherichia coli (ETEC) use colonization factors to attach to the human intestinal mucosa, followed by enterotoxin expression that induces net secretion and diarrhoeal illness. ETEC strain H10407 expresses CFA/I fimbriae, which are composed of multiple CfaB structural subunits and a CfaE tip subunit. Currently, the contribution of these individual fimbrial subunits in intestinal binding remains incompletely defined. To identify the role of CfaE in attachment in the native ETEC background, an R181A single-amino-acid substitution was introduced by recombination into the H10407 genome. The substitution of R181A eliminated haemagglutination and binding of intestinal mucosa biopsies in in vitro organ culture assays, without loss of CFA/I fimbriae expression. Wild-type in trans plasmid-expressed cfaE restored the binding phenotype. In contrast, in trans expression of cfaE containing amino acid 181 substitutions with similar amino acids, lysine, methionine and glutamine did not restore the binding phenotype, indicating that the loss of the binding phenotype was due to localized areas of epitope disruption. R181 appears to have an irreplaceable role in the formation of a receptor-binding feature on CFA/I fimbriae. The results specifically indicate that the CfaE tip protein is a required binding factor in CFA/I-mediated ETEC colonization, making it a potentially important vaccine antigen. © 2009 Blackwell Publishing Ltd.

Applying the Cultural Formulation Approach to Career Counseling with Latinas/os

ERIC Educational Resources Information Center

Flores, Lisa Y.; Ramos, Karina; Kanagui, Marlen

2010-01-01

In this article, the authors present two hypothetical cases, one of a Mexican American female college student and one of a Mexican immigrant adult male, and apply a culturally sensitive approach to career assessment and career counseling with each of these clients. Drawing from Leong, Hardin, and Gupta's cultural formulation approach (CFA) to…

Infrared Spectroscopy as a Tool to Study the Antioxidant Activity of Polyphenolic Compounds in Isolated Rat Enterocytes

PubMed Central

Barraza-Garza, Guillermo; Castillo-Michel, Hiram; de la Rosa, Laura A.; Martinez-Martinez, Alejandro; Pérez-León, Jorge A.; Cotte, Marine; Alvarez-Parrilla, Emilio

2016-01-01

The protective effect of different polyphenols, catechin (Cat), quercetin (Qc) (flavonoids), gallic acid (GA), caffeic acid (CfA), chlorogenic acid (ChA) (phenolic acids), and capsaicin (Cap), against H2O2-induced oxidative stress was evaluated in rat enterocytes using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy and Fourier Transform Infrared Microspectroscopy (FTIRM), and results were compared to standard lipid peroxidation techniques: conjugated dienes (CD) and Thiobarbituric Acid Reactive Substances (TBARS). Analysis of ATR-FTIR and FTIRM spectral data allowed the simultaneous evaluation of the effects of H2O2 and polyphenols on lipid and protein oxidation. All polyphenols showed a protective effect against H2O2-induced oxidative stress in enterocytes, when administered before or after H2O2. Cat and capsaicin showed the highest protective effect, while phenolic acids had weaker effects and Qc presented a mild prooxidative effect (IR spectral profile of biomolecules between control and H2O2-treated cells) according to FTIR analyses. These results demonstrated the viability to use infrared spectroscopy to evaluate the oxidant and antioxidant effect of molecules in cell systems assays. PMID:27213031

Identification of a human erythrocyte receptor for colonization factor antigen I pili expressed by H10407 enterotoxigenic Escherichia coli.

PubMed Central

Pieroni, P; Worobec, E A; Paranchych, W; Armstrong, G D

1988-01-01

We have identified a receptor for colonization factor antigen I (CFA/I) pili in human erythrocyte membranes. Erythrocyte binding assays, using whole organisms, suggested that the CFA/I receptor was a glycoprotein containing important sialic acid moieties. Subsequently, human erythrocyte membranes were extracted with lithium diiodosalicylate to obtain a soluble glycoprotein fraction from which to isolate receptors. The extracted material caused agglutination of the CFA/I+ but not the CFA/I- organisms at a protein concentration of 0.5 mg/ml. The CFA/I receptor was identified in iodinated extract by an affinity isolation procedure, using whole bacterial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of the washed, extract-coated H10407 CFA/I+ organisms revealed a band with an apparent molecular weight of 26,000 which was present in the original extract but was not observed on extract-coated H10407 CFA/I- bacteria. The addition of purified CFA/I pili reduced binding of the 26,000-molecular-weight receptor to CFA/I+ bacteria. The CFA/I-specific receptor species also bound to wheat germ agglutinin-agarose. This observation supported the suggestion that the CFA/I receptor identified in this report is a sialoglycoprotein. Images PMID:2895745

Off-pathway assembly of fimbria subunits is prevented by chaperone CfaA of CFA/I fimbriae from enterotoxigenic E. coli.

PubMed

Bao, Rui; Liu, Yang; Savarino, Stephen J; Xia, Di

2016-12-01

The assembly of the class 5 colonization factor antigen I (CFA/I) fimbriae of enterotoxigenic E. coli was proposed to proceed via the alternate chaperone-usher pathway. Here, we show that in the absence of the chaperone CfaA, CfaB, the major pilin subunit of CFA/I fimbriae, is able to spontaneously refold and polymerize into cyclic trimers. CfaA kinetically traps CfaB to form a metastable complex that can be stabilized by mutations. Crystal structure of the stabilized complex reveals distinctive interactions provided by CfaA to trap CfaB in an assembly competent state through donor-strand complementation (DSC) and cleft-mediated anchorage. Mutagenesis indicated that DSC controls the stability of the chaperone-subunit complex and the cleft-mediated anchorage of the subunit C-terminus additionally assist in subunit refolding. Surprisingly, over-stabilization of the chaperone-subunit complex led to delayed fimbria assembly, whereas destabilizing the complex resulted in no fimbriation. Thus, CfaA acts predominantly as a kinetic trap by stabilizing subunit to avoid its off-pathway self-polymerization that results in energetically favorable trimers and could serve as a driving force for CFA/I pilus assembly, representing an energetic landscape unique to class 5 fimbria assembly. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Molecular Microbiology published by John Wiley & Sons Ltd.

Opportunities and challenges in the use of coal fly ash for soil improvements--a review.

PubMed

Shaheen, Sabry M; Hooda, Peter S; Tsadilas, Christos D

2014-12-01

Coal fly ash (CFA), a by-product of coal combustion has been regarded as a problematic solid waste, mainly due to its potentially toxic trace elements, PTEs (e.g. Cd, Cr, Ni, Pb) and organic compounds (e.g. PCBs, PAHs) content. However, CFA is a useful source of essential plant nutrients (e.g. Ca, Mg, K, P, S, B, Fe, Cu and Zn). Uncontrolled land disposal of CFA is likely to cause undesirable changes in soil conditions, including contamination with PTEs, PAHs and PCBs. Prudent CFA land application offers considerable opportunities, particularly for nutrient supplementation, pH correction and ameliorating soil physical conditions (soil compaction, water retention and drainage). Since CFA contains little or no N and organic carbon, and CFA-borne P is not readily plant available, a mixture of CFA and manure or sewage sludge (SS) is better suited than CFA alone. Additionally, land application of such a mixture can mitigate the mobility of SS-borne PTEs, which is known to increase following cessation of SS application. Research analysis further shows that application of alkaline CFA with or without other amendments can help remediate at least marginally metal contaminated soils by immobilisation of mobile metal forms. CFA land application with SS or other source of organic carbon, N and P can help effectively reclaim/restore mining-affected lands. Given the variability in the nature and composition of CFA (pH, macro- and micro-nutrients) and that of soil (pH, texture and fertility), the choice of CFA (acidic or alkaline and its application rate) needs to consider the properties and problems of the soil. CFA can also be used as a low cost sorbent for the removal of organic and inorganic contaminants from wastewater streams; the disposal of spent CFA however can pose further challenges. Problems in CFA use as a soil amendment occur when it results in undesirable change in soil pH, imbalance in nutrient supply, boron toxicity in plants, excess supply of sulphate and PTEs. These problems, however, are usually associated with excess or inappropriate CFA applications. The levels of PAHs and PCBs in CFA are generally low; their effects on soil biota, uptake by plants and soil persistence, however, need to be assessed. In spite of this, co-application of CFA with manure or SS to land enhances its effectiveness in soil improvements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.

Changes in membrane lipid composition in ethanol- and acid-adapted Oenococcus oeni cells: characterization of the cfa gene by heterologous complementation.

PubMed

Grandvalet, Cosette; Assad-García, Juan Simón; Chu-Ky, Son; Tollot, Marie; Guzzo, Jean; Gresti, Joseph; Tourdot-Maréchal, Raphaëlle

2008-09-01

Cyclopropane fatty acid (CFA) synthesis was investigated in Oenococcus oeni. The data obtained demonstrated that acid-grown cells or cells harvested in the stationary growth phase showed changes in fatty acid composition similar to those of ethanol-grown cells. An increase of the CFA content and a decrease of the oleic acid content were observed. The biosynthesis of CFAs from unsaturated fatty acid phospholipids is catalysed by CFA synthases. Quantitative real-time-PCR experiments were performed on the cfa gene of O. oeni, which encodes a putative CFA synthase. The level of cfa transcripts increased when cells were harvested in stationary phase and when cells were grown in the presence of ethanol or at low pH, suggesting transcriptional regulation of the cfa gene under different stress conditions. In contrast to Escherichia coli, only one functional promoter was identified upstream of the cfa gene of O. oeni. The function of the cfa gene was confirmed by complementation of a cfa-deficient E. coli strain. Nevertheless, the complementation remained partial because the conversion percentage of unsaturated fatty acids into CFA of the complemented strain was much lower than that of the wild-type strain. Moreover, a prevalence of cycC19 : 0 was observed in the membrane of the complemented strain. This could be due to a specific affinity of the CFA synthase from O. oeni. In spite of this partial complementation, the complemented strain of E. coli totally recovered its viability after ethanol shock (10 %, v/v) whereas its viability was only partly recovered after an acid shock at pH 3.0.

Coal fly ash and lime addition enhances the rate and efficiency of decomposition of food waste during composting.

PubMed

Wong, Jonathan W-C; Fung, Shun On; Selvam, Ammaiyappan

2009-07-01

To evaluate the use of coal fly ash (CFA) on the decomposition efficiency of food waste, synthetic food waste was mixed with lime at 1.5% and 3% (equivalent to 0.94% and 1.88% CaCO(3), respectively), CFA at 5%, 10% and 15% with lime so as to achieve CaCO(3) equivalent of 1.88% and composted for 42 days in a thermophilic 20 l composter with two replicates each. Alkaline materials at 1.88% CaCO(3) equivalent successfully buffered the pH during the composting and enhanced the decomposition efficiency. When these buffering was achieved with CFA+lime, the composting period could be shortened to approximately 28 days compared with approximately 42 days in 3% lime. Organic decomposition in terms of CO(2) loss, carbon turnover and nitrogen transformation were significantly higher for treatments with 1.88% CaCO(3) equivalent. Nutrient transformations and compost maturity parameters indicated that addition of CFA (5-10%) with lime at 1.88% CaCO(3) equivalent enhances the decomposition efficiency and shortens the composting period by 35%.

Comparison of the performance of IFA, CFA, and ELISA assays for the serodiagnosis of acute Q fever by quality assessment.

PubMed

Herremans, Tineke; Hogema, Boris M; Nabuurs, Marrigje; Peeters, Marcel; Wegdam-Blans, Marjolijn; Schneeberger, Peter; Nijhuis, Carla; Notermans, Daan W; Galama, Joep; Horrevorts, Anton; van Loo, Inge H M; Vlaminckx, Bart; Zaaijer, Hans L; Koopmans, Marion P; Berkhout, Hanneke; Socolovschi, Cristina; Raoult, Didier; Stenos, John; Nicholson, William; Bijlmer, Henk

2013-01-01

The indirect immunofluorescence assay (IFA) is considered the reference method for diagnosing Q fever, but serology is also performed by complement fixation assay (CFA) or enzyme-linked immunosorbent assay (ELISA). However, comparability between these assays is not clear, and therefore a quality assessment was performed. A total of 25 serum samples from negative controls, Q fever patients, and a serial diluted high-positive sample were analyzed in 10 Dutch laboratories. Six laboratories performed CFA, 5 performed IFA, and 5 performed ELISAs. Three international reference laboratories from Australia, France, and the USA also participated in this study. Qualitative values between laboratories using the same methods were within close range, and all 3 methods correctly identified acute Q fever patients. The IFA, ELISA, and CFA are all suitable serodiagnostic assays to diagnose acute Q fever, but the IFA remains an important tool in the follow-up of patients and in identifying patients at risk for developing chronic Q fever. Copyright © 2013 Elsevier Inc. All rights reserved.

Improved Stability of Tuberculosis Drug Fixed-Dose Combination Using Isoniazid-Caffeic Acid and Vanillic Acid Cocrystal.

PubMed

Battini, Swapna; Mannava, M K Chaitanya; Nangia, Ashwini

2018-06-01

The classic fixed-dose combination (FDC) of 4 tuberculosis drugs, namely rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol dihydrochloride (EDH) has the twin issues of physical stability and RIF cross-reaction in the 4-FDC. The major reason for these quality issues is the interaction between RIF and INH to yield isonicotinyl hydrazone in drug tablets. Pharmaceutical cocrystals of INH with caffeic acid (CFA) (PZA + EDH + RIF + INH-CFA cocrystal) and vanillic acid (VLA) (PZA + EDH + RIF + INH-VLA cocrystal) are able to stabilize the FDC formulation compared with the reference batch (PZA + EDH + RIF + INH). Stability studies under accelerated humidity and temperature stress conditions of 40°C and 75% relative humidity showed that the physical stability of the cocrystal formulation was superior by powder X-ray diffraction and scanning electron microscopy analysis, and chemical purity was analyzed by high-performance liquid chromatography. Changes in the composition and structure were monitored on samples drawn at 7, 15, 22, and 30 days of storage. FDC-INH-CFA cocrystal batch exhibited greater stability compared with FDC-INH-VLA cocrystal and FDC reference drug batches. The superior stability of INH-CFA cocrystal is attributed to the presence of stronger hydrogen bonds and cyclic O-H⋯O synthon in the crystal structure. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

PubMed

Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

2016-05-01

Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli

PubMed Central

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli.

PubMed

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue.

Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE.

PubMed

Cowden, W B; Cullen, F A; Staykova, M A; Willenborg, D O

1998-08-01

Rat strains vary in their susceptibility to experimental autoimmune encephalomyelitis (EAE) and in many cases, factors other than MHC antigens are thought to play a role in this. We found that PVG rats, which have a very low susceptibility to EAE, were rendered highly susceptible to clinical disease when treated with N-methylarginine (NMA) an inhibitor of nitric oxide synthase (NOS). The clinical course of the ensuing disease in NMA-treated PVG rats was in most cases fulminating in nature and accompanied by some mortality. Following immunisation with myelin basic protein (MBP)-complete Freund's adjuvant (CFA), PVG rats developed higher serum levels of the surrogate markers of nitric oxide production, reactive nitrogen intermediates (RNI; nitrite and nitrate), than did their Lewis counterparts. This in vivo finding was reflected in vitro, where the levels of RNI produced in 24, 48 and 72 h IFN-gamma-stimulated spleen cell cultures for PVG rats were significantly higher than those for Lewis rats. A mechanism by which increased NO production might protect PVG rats against clinical EAE was suggested by the finding that lymph node cells, isolated from NMA-treated MBP-immunised PVG rats, proliferated in response to MBP at a rate approximately 3 x greater than those from MBP-immunised, saline treated rats. Thus, the greater number of MBP-specific T cells generated in the NOS inhibitor-treated vs. untreated rats could account for their increased susceptibility to developing clinical EAE. The findings in this study suggest that NO plays a role in protecting PVG rats against developing EAE.

Long-Term Temporal Imprecision of Information Coding in the Anterior Cingulate Cortex of Mice with Peripheral Inflammation or Nerve Injury

PubMed Central

Li, Xiang-Yao; Wang, Ning; Wang, Yong-Jie; Zuo, Zhen-Xing; Koga, Kohei; Luo, Fei

2014-01-01

Temporal properties of spike firing in the central nervous system (CNS) are critical for neuronal coding and the precision of information storage. Chronic pain has been reported to affect cognitive and emotional functions, in addition to trigger long-term plasticity in sensory synapses and behavioral sensitization. Less is known about the possible changes in temporal precision of cortical neurons in chronic pain conditions. In the present study, we investigated the temporal precision of action potential firing in the anterior cingulate cortex (ACC) by using both in vivo and in vitro electrophysiological approaches. We found that peripheral inflammation caused by complete Freund's adjuvant (CFA) increased the standard deviation (SD) of spikes latency (also called jitter) of ∼51% of recorded neurons in the ACC of adult rats in vivo. Similar increases in jitter were found in ACC neurons using in vitro brain slices from adult mice with peripheral inflammation or nerve injury. Bath application of glutamate receptor antagonists CNQX and AP5 abolished the enhancement of jitter induced by CFA injection or nerve injury, suggesting that the increased jitter depends on the glutamatergic synaptic transmission. Activation of adenylyl cyclases (ACs) by bath application of forskolin increased jitter, whereas genetic deletion of AC1 abolished the change of jitter caused by CFA inflammation. Our study provides strong evidence for long-term changes of temporal precision of information coding in cortical neurons after peripheral injuries and explains neuronal mechanism for chronic pain caused cognitive and emotional impairment. PMID:25100600

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

PubMed Central

Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Testing for measurement invariance and latent mean differences across methods: interesting incremental information from multitrait-multimethod studies

PubMed Central

Geiser, Christian; Burns, G. Leonard; Servera, Mateu

2014-01-01

Models of confirmatory factor analysis (CFA) are frequently applied to examine the convergent validity of scores obtained from multiple raters or methods in so-called multitrait-multimethod (MTMM) investigations. We show that interesting incremental information about method effects can be gained from including mean structures and tests of MI across methods in MTMM models. We present a modeling framework for testing MI in the first step of a CFA-MTMM analysis. We also discuss the relevance of MI in the context of four more complex CFA-MTMM models with method factors. We focus on three recently developed multiple-indicator CFA-MTMM models for structurally different methods [the correlated traits-correlated (methods – 1), latent difference, and latent means models; Geiser et al., 2014a; Pohl and Steyer, 2010; Pohl et al., 2008] and one model for interchangeable methods (Eid et al., 2008). We demonstrate that some of these models require or imply MI by definition for a proper interpretation of trait or method factors, whereas others do not, and explain why MI may or may not be required in each model. We show that in the model for interchangeable methods, testing for MI is critical for determining whether methods can truly be seen as interchangeable. We illustrate the theoretical issues in an empirical application to an MTMM study of attention deficit and hyperactivity disorder (ADHD) with mother, father, and teacher ratings as methods. PMID:25400603

Upregulation of β-1,4-galactosyltransferase I in rat spinal cord with experimental autoimmune encephalomyelitis.

PubMed

Zhao, Jianmei; Gao, Ying; Cheng, Chun; Yan, Meijuan; Wang, Jian

2013-03-01

Inflammatory infiltration has been recently emphasized in the demyelinating diseases of the central nervous system including multiple sclerosis. β-1,4-Galactosyltransferase I (β-1,4-GalT-I) is a major galactosyltransferase responsible for selectin-ligand biosynthesis, mediating rolling of the inflammatory lymphocytes. In the present study, Western blot showed that expression of β-1,4-GalT-I was low in normal or complete Freund's adjuvant (CFA) control rats' spinal cords, and it began to increase since early stage and peaked at E4 stage of experimental autoimmune encephalomyelitis (EAE) and restored approximately at normal level in the recovery stage. Immunohistochemisty revealed that upregulation of β-1,4-GalT-I was predominantly distributed in the white matter of spinal cord , while there was also some increased staining of β-1,4-GalT-I in the grey matter. Meanwhile, the expression of E-selectin, the substrate of β-1,4-GalT-I, was significantly increased, with a peak at E4 stage of EAE, and gradually decreased thereafter. Lectin blot showed that the protein bands with molecular weights of 65-25 kDa reacted a remarkable increase at the peak stage of EAE when compared with the normal and CFA control. Ricinus Communis Agglutinin-I (RCA-I) histochemistry revealed that RCA-Ι-positive signals were most intense in white matter of lumbosacral spinal cord at the peak stage of EAE (E4). Immunohistochemistry showed that β-1,4-GalT-I and CD62E, a marker for E-selectin stainings located in a considerable number of ED1 (+) macrophages in perivascular or in the white matter in EAE lesions, and a good co-localization of ED1 (+) cells with CD62E was observed. All these results suggest that β-1,4-GalT-I might serve as an inflammatory mediator regulating adhesion and migration of inflammatory cells in EAE, possibly through influencing the modification of galactosylated carbohydrate chains to modulate selectin-ligand biosynthesis and interaction with E-selectin.

Characterizations of coal fly ash nanoparticles and induced in vitro toxicity in cell lines

NASA Astrophysics Data System (ADS)

Sambandam, Bharathi; Palanisami, Eganathan; Abbugounder, Rajasekar; Prakhya, Balakrishnamurthy; Thiyagarajan, Devasena

2014-02-01

The present study illustrates the characterization and cytotoxicity studies of coal fly ash nanoparticles (CFA-NPs). The coal fly ash (CFA) collected from electrostatic precipitator of a coal-fired power plant and the average size of the CFA-NPs was found to be 9-50 nm. Imaging techniques showed predominantly homogenous spherical shaped nanoparticles. The X-ray diffraction analysis and energy dispersive X-ray (EDAX) analysis spectra reveal the elemental constituents of the CFA-NPs contain several toxic heavy metals. Cytotoxicity of CFA-NPs was determined by MTT assay. Cellular metabolism is inhibited in a dose dependent manner by CFA concentrations varying from 13 to 800 μg mL-1. After 48 h exposure, the Hep2, A549 and HepG2 cell lines prove more sensitive to CFA-NPs at varying levels which results in IC50 (50 % inhibitory concentration) cytotoxicity end point.

Comparison of H2S adsorption by two hydrogel composite (HBC) derived by Empty Fruit Bunch (EFB) biochar and Coal Fly Ash (CFA)

NASA Astrophysics Data System (ADS)

Meri, N. H.; Alias, A. B.; Talib, N.; Rashid, Z. A.; Ghani, W. A. W. A. K.

2018-03-01

This study are covered the adsorption performance of two adsorbent Empty Fruit Bunch Hydrogel Biochar Composite (EFB-HBC) and Coal Fly Ash Hydrogel Composite (CFA-HC) on hydrogen sulphide. The EFB biochar were produce by pyrolysed and heated from room temperature to 550˚C at 10˚C/min under the Nitrogen flow. Meanwhile, coal fly ash collected from a power plant located in Selangor, Malaysia. Both of the materials is a waste from different industries and became the precursor to our adsorbents. EFB biochar and coal fly ash has been synthesized to become hydrogel by polymerization process with acrylamide (AAm) as monomer, N,N’-methylene bisacry lamide (MBA) as cross linker and ammonium persulfate (APS) as initiator. In addition, because of the speciality of hydrogel itself, which is has high ability in storing water, the effect of H2O wetness on EFB-HBC and CFA-HC were investigate in adsorption of H2S. EFB-HBC gave a longest breakthrough time and highest adsorption capacity compared with CFA-HC in both condition (dry/wet). The result also indicated that, the increased the bed height, increased the adsorption capacity.

Epstein-Barr virus-transformed B-cells as efficient antigen presenting cells to propagate Aspergillus-specific cytotoxic T-lymphocytes.

PubMed

Ramadan, Gamal

2008-01-01

To overcome the cytotoxic T-lymphocytes (CTL) expansion limitations imposed by the lack of sufficient dendritic cells (DC) alternative sources of autologous antigen presenting cells (APC) such as Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (BLCL), which are easy to establish in vitro, have been considered and studied in the present work. Non-adherent peripheral blood mononuclear cells of three healthy donors were repeatedly primed with autologous Aspergillus fumigatus commercial culture-filtrate antigen-pulsed fast monocyte-derived DC (Aspf-CFA-DC) alone, Aspf-CFA-pulsed BLCL (Aspf-CFA-BLCL) alone or Aspf-CFA-BLCL after one, two, or three primings with Aspf-CFA-DC (1DC/BLCL, 2DC/BLCL or 3DCIBLCL; respectively). After 5th priming, lines generated by Aspf-CFA-BLCL only showed strong/weak lytic activity for EBV/Aspf; respectively. Aspf-specific lytic activity in all donors was increased by increasing the number of primings with Aspf-CFA-DC before switching to Aspf-CFA-BLCL (18.20 +/- 1.65% versus 35.67 +/- 1.02% and 40.03 +/- 1.41% in bulk cultures generated by 1DC/BLCL versus 2DC/BLCL and 3DC/BLCL, respectively). Bulk cultures generated by Aspf-CFA-BLCL after at least two primings with Aspf-CFA-DC showed approximately the same Aspf-specific lytic activity, effector cell phenotype, expansion level and percentage expression of IFN-gamma, CD69 and CD107a without any significant differences (p > 0.05) as standard bulk cultures generated by only Aspf-CFA-DC. Thus, this study explored the use of a combined DC/BLCL protocol to establish/propagate Aspf-specific CTL for adoptive immunotherapy to prevent or treat invasive pulmonary aspergillosis.

Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy.

PubMed

Tian, Bole; Hao, Jianqiang; Zhang, Yu; Tian, Lei; Yi, Huimin; O'Brien, Timothy D; Sutherland, David E R; Hering, Bernhard J; Guo, Zhiguang

2009-01-27

Immunotherapy with Complete Freund's adjuvant (CFA) is effective in ameliorating autoimmunity in diabetic nonobese diabetic (NOD) mice. We investigated whether CFA treatment up-regulates CD4+CD25+Foxp3+ regulatory T cells and increases transforming growth factor (TGF)-beta1 production in diabetic NOD mice. New-onset diabetic NOD mice were treated with CFA and exendin-4, a potent analog of glucagon-like peptide-1. Reversal of diabetes was determined by monitoring blood glucose level. Ameliorating autoimmunity through immunoregulation was assessed by adoptive transfer. Regulatory T cells in the peripheral blood, spleen, thymus, and pancreatic nodes were measured. TGF-beta1 in plasma and the insulin content in the pancreas were also measured. Immunostainings for insulin and BrdU were performed. New-onset diabetes could be reversed in 38% of NOD mice treated with CFA alone and in 86% of NOD mice treated with both CFA and exendin-4. Diabetes adoptive transfer by splenocytes from CFA-treated NOD mice was delayed. The percentage of CD4+CD25+Foxp3+ regulatory T cells in the pancreatic lymph nodes of CFA-treated NOD mice was significantly increased at 1, 5, and 15 to 17 weeks after treatment. TGF-beta1 in the plasma of CFA-treated NOD mice was also significantly increased. Combining CFA with exendin-4 treatment significantly increased the insulin content and the numbers of insulin and BrdU double-labeled beta cells in the islets. Our results demonstrated that CFA treatment ameliorates autoimmunity in diabetic NOD mice by up-regulating CD4=CD25+Foxp3+ regulatory T cells and increasing TGF-beta1 production. Exendin-4 enhanced the effect of CFA on reversing diabetes in NOD mice by stimulating beta-cell replication.

Evaluation of the measurement model and clinically important differences for menopause-specific quality of life associated with bazedoxifene/conjugated estrogens.

PubMed

Bushmakin, Andrew G; Abraham, Lucy; Pinkerton, JoAnn V; Cappelleri, Joseph C; Mirkin, Sebastian

2014-08-01

This study aims to confirm the factor structure of the Menopause-Specific Quality of Life (MENQOL) questionnaire by using confirmatory factor analysis (CFA) and to determine whether improvements in menopause-specific health-related quality of life (HRQOL) observed with bazedoxifene (BZA)/conjugated estrogens (CE) relative to placebo are clinically meaningful. Postmenopausal women with seven or more moderate to severe hot flushes per day (or ≥50 per wk) received BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, or placebo for 12 weeks. HRQOL and treatment satisfaction were evaluated using the MENQOL questionnaire and the Menopause Symptoms Treatment Satisfaction Questionnaire, respectively. The structure of the MENQOL questionnaire was evaluated using CFA. To estimate clinically important differences (CIDs) in HRQOL, we used a repeated-measures model to estimate changes in MENQOL domain and total scores using Menopause Symptoms Treatment Satisfaction Questionnaire items as anchors. The CFA model fits the MENQOL data (Bentler's comparative fit index >0.9). CID estimates ranged from 0.5 to 1.2 for the MENQOL domains and total score. Change from baseline in MENQOL vasomotor domain score for BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg compared with placebo was greater than the estimated CID, as were changes in MENQOL physical domain and total scores for BZA 20 mg/CE 0.625 mg compared with placebo. CFA confirms the factor structure of the MENQOL questionnaire. Treatment with BZA/CE provides clinically meaningful improvements in HRQOL in a population of postmenopausal women with bothersome vasomotor symptoms.

Temporal Patterns of Variable Relationships in Person-Oriented Research: Longitudinal Models of Configural Frequency Analysis

ERIC Educational Resources Information Center

von Eye, Alexander; Mun, Eun Young; Bogat, G. Anne

2008-01-01

This article reviews the premises of configural frequency analysis (CFA), including methods of choosing significance tests and base models, as well as protecting [alpha], and discusses why CFA is a useful approach when conducting longitudinal person-oriented research. CFA operates at the manifest variable level. Longitudinal CFA seeks to identify…

Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer’s Quality of Life Questionnaire C30: a confirmatory versus exploratory approach

PubMed Central

Costa, Daniel SJ; Aaronson, Neil K; Fayers, Peter M; Grimison, Peter S; Janda, Monika; Pallant, Julie F; Rowen, Donna; Velikova, Galina; Viney, Rosalie; Young, Tracey A; King, Madeleine T

2014-01-01

Background Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure. Aim To determine whether confirmatory factor analysis (CFA) is more appropriate and efficient than EFA to derive a HSCS from the European Organisation for the Research and Treatment of Cancer’s core HRQOL questionnaire, Quality of Life Questionnaire (QLQ-C30), given its well-established domain structure. Methods QLQ-C30 (Version 3) data were collected from 356 patients receiving palliative radiotherapy for recurrent/metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter informed by the established QLQ-C30 structure and views of both patients and clinicians on which are the most relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch analysis. Results CFA results generally supported the proposed QLQ-C30 structure (comparative fit index =0.99, Tucker–Lewis index =0.99, root mean square error of approximation =0.04). EFA revealed fewer factors and some items cross-loaded on multiple factors. Further assessment of dimensionality with Rasch analysis allowed better alignment of the EFA dimensions with those detected by CFA. Conclusion CFA was more appropriate and efficient than EFA in producing clinically interpretable results for the HSCS for a proposed new cancer-specific MAUI. Our findings suggest that CFA should be recommended generally when deriving a preference-based measure from a HRQOL measure that has an established domain structure. PMID:25395875

CFA-2 and CFA-3 (Coordination Framework Augsburg University-2 and -3); novel MOFs assembled from trinuclear Cu(I)/Ag(I) secondary building units and 3,3',5,5'-tetraphenyl-bipyrazolate ligands.

PubMed

Grzywa, Maciej; Geßner, Christof; Denysenko, Dmytro; Bredenkötter, Björn; Gschwind, Fabienne; Fromm, Katharina M; Nitek, Wojciech; Klemm, Elias; Volkmer, Dirk

2013-05-21

The syntheses of H2-phbpz, [Cu2(phbpz)]·2DEF·MeOH (CFA-2) and [Ag2(phbpz)] (CFA-3) (H2-phbpz = 3,3',5,5'-tetraphenyl-1H,1'H-4,4'-bipyrazole) compounds and their crystal structures are described. The Cu(I) containing metal-organic framework CFA-2 crystallizes in the tetragonal crystal system, within space group I4(1)/a (no. 88) and the following unit cell parameters: a = 30.835(14), c = 29.306(7) Å, V = 27 865(19) Å(3). CFA-2 features a flexible 3-D three-connected two-fold interpenetrated porous structure constructed of triangular Cu(I) subunits. Upon exposure to different kinds of liquids (MeOH, EtOH, DMF, DEF) CFA-2 shows pronounced breathing effects. CFA-3 crystallizes in the monoclinic crystal system, within space group P2(1)/c (no. 14) and the following unit cell parameters: a = 16.3399(3), b = 32.7506(4), c = 16.2624(3) Å, β = 107.382(2)°, V = 8305.3(2) Å(3). In contrast to the former compound, CFA-3 features a layered 2-D three-connected structure constructed from triangular Ag(i) subunits. Both compounds are characterized by elemental and thermogravimetric analyses, single crystal structure analysis and X-ray powder diffraction, FTIR- and fluorescence spectroscopy. Preliminary results on oxygen activation in CFA-2 are presented and potential improvements in terms of framework robustness and catalytic efficiency are discussed.

Comparative Model Tests of SDP and CFA Pile Groups in Non-Cohesive Soil

NASA Astrophysics Data System (ADS)

Krasiński, Adam; Kusio, Tomasz

2015-02-01

The research topic relates to the subject of deep foundations supported on continuous flight auger (CFA) piles and screw displacement piles (SDP). The authors have decided to conduct model tests of foundations supported on the group of piles mentioned above and also the tests of the same piles working as a single. The tests are ongoing in Geotechnical Laboratory of Gdaňsk University of Technology. The description of test procedure, interpretation and analysis of the preliminary testing series results are presented in the paper.

45 CFR 2106.1 - Rules for determining if an individual is the subject of a record.

Code of Federal Regulations, 2010 CFR

2010-10-01

... maintained by CFA listed in the CFA Notices of Systems of Records or it should describe the type of record in sufficient detail to reasonably identify the system of records. Notice of CFA Systems of Records will be made... sufficient identifying information to allow CFA to determine if there is a record pertaining to the...

cfa-miR-143 Promotes Apoptosis via the p53 Pathway in Canine Influenza Virus H3N2-Infected Cells.

PubMed

Zhou, Pei; Tu, Liqing; Lin, Xi; Hao, Xiangqi; Zheng, Qingxu; Zeng, Weijie; Zhang, Xin; Zheng, Yun; Wang, Lifang; Li, Shoujun

2017-11-25

MicroRNAs regulate multiple aspects of the host response to viral infection. This study verified that the expression of cfa-miR-143 was upregulated in vivo and in vitro by canine influenza virus (CIV) H3N2 infection. To understand the role of cfa-miR-143 in CIV-infected cells, the target gene of cfa-miR-143 was identified and assessed for correlations with proteins involved in the apoptosis pathway. A dual luciferase reporter assay showed that cfa-miR-143 targets insulin-like growth factor binding protein 5 (Igfbp5). Furthermore, a miRNA agomir and antagomir of cfa-miR-143 caused the downregulation and upregulation of Igfbp5, respectively, in CIV-infected madin-darby canine kidney (MDCK) cells. This study demonstrated that cfa-miR-143 stimulated p53 and caspase3 activation and induced apoptosis via the p53 pathway in CIV H3N2-infected cells. In conclusion, CIV H3N2 induced the upregulation of cfa-miR-143, which contributes to apoptosis via indirectly activating the p53-caspase3 pathway.

Annealing and thickness effects on magnetic properties of Co2FeAl alloy films

NASA Astrophysics Data System (ADS)

Wang, Ke; Xu, Zhan; Ling, Fujin; Wang, Yahong; Dong, Shuo

2018-03-01

Co2FeAl (CFA) films in a wide thickness range between 2 and 100 nm are sputtered at room temperature. Perpendicular magnetic anisotropy (PMA) is achieved in the annealed structure of Pd/CFA/MgO with CFA thickness ranging between 2.3 and 4.9 nm. PMA as high as 2 × 106 erg/cm3 is demonstrated in the structures annealed in the temperature range between 300 and 350 °C. Positive contributions to the PMA made by the interfaces of Pd/CFA and CFA/MgO are identified. For the as-deposited structure of MgO/CFA/Ta with thick CFA alloy up to 5 nm or above a high effective saturation magnetization of 983.9 ± 30.1 emu/cc is derived from the fitting and an in-plane uniaxial magnetic anisotropy of 104 erg/cm3 in magnitude is revealed by angular dependent magnetic measurements. In addition to the increase in saturation magnetization, a fourfold cubic magnetic anisotropy is found to develop with annealing, in line with the improvement of the crystalline structure confirmed by X-ray diffraction measurements. Out results provide some useful information for the design of the CFA-based magnetoelectronic devices.

Satellite DNA Sequences in Canidae and Their Chromosome Distribution in Dog and Red Fox.

PubMed

Vozdova, Miluse; Kubickova, Svatava; Cernohorska, Halina; Fröhlich, Jan; Rubes, Jiri

2016-01-01

Satellite DNA is a characteristic component of mammalian centromeric heterochromatin, and a comparative analysis of its evolutionary dynamics can be used for phylogenetic studies. We analysed satellite and satellite-like DNA sequences available in NCBI for 4 species of the family Canidae (red fox, Vulpes vulpes, VVU; domestic dog, Canis familiaris, CFA; arctic fox, Vulpes lagopus, VLA; raccoon dog, Nyctereutes procyonoides procyonoides, NPR) by comparative sequence analysis, which revealed 86-90% intraspecies and 76-79% interspecies similarity. Comparative fluorescence in situ hybridisation in the red fox and dog showed signals of the red fox satellite probe in canine and vulpine autosomal centromeres, on VVUY, B chromosomes, and in the distal parts of VVU9q and VVU10p which were shown to contain nucleolus organiser regions. The CFA satellite probe stained autosomal centromeres only in the dog. The CFA satellite-like DNA did not show any significant sequence similarity with the satellite DNA of any species analysed and was localised to the centromeres of 9 canine chromosome pairs. No significant heterochromatin block was detected on the B chromosomes of the red fox. Our results show extensive heterogeneity of satellite sequences among Canidae and prove close evolutionary relationships between the red and arctic fox. © 2017 S. Karger AG, Basel.

Identification of protein-ligand binding sites by the level-set variational implicit-solvent approach.

PubMed

Guo, Zuojun; Li, Bo; Cheng, Li-Tien; Zhou, Shenggao; McCammon, J Andrew; Che, Jianwei

2015-02-10

Protein–ligand binding is a key biological process at the molecular level. The identification and characterization of small-molecule binding sites on therapeutically relevant proteins have tremendous implications for target evaluation and rational drug design. In this work, we used the recently developed level-set variational implicit-solvent model (VISM) with the Coulomb field approximation (CFA) to locate and characterize potential protein–small-molecule binding sites. We applied our method to a data set of 515 protein–ligand complexes and found that 96.9% of the cocrystallized ligands bind to the VISM-CFA-identified pockets and that 71.8% of the identified pockets are occupied by cocrystallized ligands. For 228 tight-binding protein–ligand complexes (i.e, complexes with experimental pKd values larger than 6), 99.1% of the cocrystallized ligands are in the VISM-CFA-identified pockets. In addition, it was found that the ligand binding orientations are consistent with the hydrophilic and hydrophobic descriptions provided by VISM. Quantitative characterization of binding pockets with topological and physicochemical parameters was used to assess the “ligandability” of the pockets. The results illustrate the key interactions between ligands and receptors and can be very informative for rational drug design.

Oral Escherichia coli Colonization Factor Antigen I (CFA/I) Fimbriae Ameliorate Arthritis via IL-35, not IL-27

PubMed Central

Kochetkova, Irina; Thornburg, Theresa; Callis, Gayle; Holderness, Kathryn; Maddaloni, Massimo; Pascual, David W.

2014-01-01

A Salmonella therapeutic expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) fimbriae protects against collagen-induced arthritis (CIA) by eliciting two regulatory T cell (Treg) subsets: TGF-β-producing Foxp3−CD39+CD4+ and IL-10-producing Foxp3+CD39+CD4+ T cells. However, it is unclear if CFA/I fimbriae alone are protective, and if other regulatory cytokines are involved especially in the context for the EBI3-sharing cytokines, Treg-derived IL-35 and APC-derived IL-27, both capable of suppressing Th17 cells and regulating autoimmune diseases. Subsequent evaluation revealed that a single oral dose of purified, soluble CFA/I fimbriae protected against CIA as effectively as Salmonella-CFA/I, and found Foxp3+CD39+CD4+ T cells as the source of secreted IL-35, whereas IL-27 production by CD11c+ cells was inhibited. Inquiring into their relevance, CFA/I fimbriae-treated IL-27 receptor-deficient (WSX-1−/−) mice were equally protected against CIA as wild-type mice suggesting a limited role for IL-27. In contrast, CFA/I fimbriae-mediated protection was abated in EBI3−/− mice accompanied by the loss of TGF-β- and IL-10-producing Tregs. Adoptive transfer of B6 CD39+CD4+ T cells to EBI3−/− mice with concurrent CFA/I plus IL-35 treatment effectively stimulated Tregs suppressing proinflammatory CII-specific Th cells. Opposingly, recipients co-transferred with B6 and EBI3−/− CD39+CD4+ T cells and treated with CFA/I plus IL-35 failed in protecting mice implicating the importance for endogenous IL-35 to confer CFA/I-mediated protection. Thus, CFA/I fimbriae stimulate IL-35 required for the co-induction of TGF-β and IL-10. PMID:24337375

Symptom structure and severity: a comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia.

PubMed

Stefanovics, Elina A; Krystal, John H; Rosenheck, Robert A

2014-05-01

To describe and compare the structure and relative severity of symptoms in clinical trial patients diagnosed with Post Traumatic Stress Disorder (PTSD) or schizophrenia using the Positive and Negative Syndrome Scale (PANSS), developed originally to evaluate symptoms of schizophrenia. This secondary data analysis used baseline PANSS symptom ratings (n=267) from a six-month multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD. First, using a split-half design, Exploratory Factor Analysis (EFA) was employed to identify independent factors which were then compared to published factor structures for schizophrenia. Next, Confirmatory Factor Analysis (CFA) was applied to the second half of the sample to compare the results of the EFA and published factor structures. Finally, T-tests were used to compare the severity of factor scores between the PTSD sample and the baseline PANSS ratings from the Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) schizophrenia sample (n=1460). EFA suggested five factors similar to those identified in a summary of 29 schizophrenia studies by Wallwork (Schizophrenia Research, 137:246-250). CFA showed that the five factor Wallwork model fit the data better than the EFA, although both had relatively high goodness of fit. T-tests showed that the PTSD sample had more severe symptoms on the Depressive factor, and the schizophrenia sample on the Positive, Negative, and Disorganized factors, with no significant difference on the Excited factor. Veterans with PTSD had similar symptom structure to patients with schizophrenia on the PANSS, but were less symptomatic on psychosis-related factors and more symptomatic on depression. Dimensional symptom factors can be virtually the same across diagnoses. Published by Elsevier Inc.

Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.

PubMed

Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

2015-06-21

To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity

PubMed Central

Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

2015-01-01

AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05). CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome. PMID:26109804

Comparison of monoclonal and polyclonal ELISAs for fecal elastase in patients with cystic fibrosis and pancreatic insufficiency.

PubMed

Borowitz, Drucy; Lin, Rong; Baker, Susan S

2007-02-01

Two enzyme-linked immunosorbent assay methodologies are used to detect pancreatic insufficiency: monoclonal and polyclonal. We sought to compare these assays in patients with cystic fibrosis and to correlate these with the coefficient of fat absorption (CFA). As part of a larger study, subjects had stool elastase measured by both methods while taking exogenous enzymes. Subjects subsequently stopped enzymes and had a fecal fat balance study performed; the CFA was then calculated. One hundred twenty-four subjects participated in this substudy. The median values for the monoclonal and polyclonal assays were 0.3 and 22.75 microg/g, respectively. The correlation coefficient between the 2 tests was 0.86 (P < 0.0001). The correlation coefficients between CFA and the monoclonal and polyclonal assays were 0.24 (P = 0.006) and 0.10 (P = 0.27), respectively. If the criterion standard definition of pancreatic insufficiency was set at a CFA < 90% and the test definition of pancreatic insufficiency was set at <100 microg/g, then the monoclonal and polyclonal assay positive predictive values were 97.6% (120 of 123) and 97.4% (111 of 114), respectively. The positive predictive value of both monoclonal and polyclonal fecal elastase in patients with cystic fibrosis is extremely good; however, correlation of either test with CFA was poor. The median value for the polyclonal elastase assay is higher than for the monoclonal assay, which could potentially lead to lower sensitivity of the polyclonal assay at lower cutpoints for the monoclonal assay is used.

Evaluation of the disease modifying activity of Colchicum luteum Baker in experimental arthritis.

PubMed

Nair, Vinod; Singh, Surender; Gupta, Y K

2011-01-27

Colchicum luteum (CL) has been traditionally used in the Unani system of medicine as a chief ingredient of many polyherbal formulations for the treatment of joint pain and rheumatoid arthritis (RA). To evaluate the antiarthritic activity of CL hydroalcoholic extract (CLHE) in formaldehyde and complete Freund's adjuvant (CFA) induced arthritis. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. Joint swelling was measured on days 8, 9 and 10 in formaldehyde induced arthritis and days 3, 7, 14 and 21 in CFA induced arthritis. In order to evaluate the effect of CLHE on disease progression, serum TNF-α level and synovial expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was determined in CFA induced arthritis. CLHE produced a significant and dose dependent inhibition of joint swelling during the entire duration of the study in both, formaldehyde and CFA induced arthritis. Serum TNF-α level was also reduced significantly in a dose dependent manner in all the CLHE treated groups. The expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was also found to be less in the CLHE treated group as compared to control. We believe that the antiarthritic activity of CLHE was due to its modulatory effect on the expression of proinflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of CL in the treatment of RA and other inflammatory joint disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Interfacial Dzyaloshinskii-Moriya interaction sign in Ir/Co2FeAl systems investigated by Brillouin light scattering

NASA Astrophysics Data System (ADS)

Belmeguenai, M.; Gabor, M. S.; Roussigné, Y.; Petrisor, T.; Mos, R. B.; Stashkevich, A.; Chérif, S. M.; Tiusan, C.

2018-02-01

C o2FeAl (CFA) ultrathin films, of various thicknesses (0.9 nm ≤tCFA≤1.8 nm ), have been grown by sputtering on Si substrates, using Ir as a buffer layer. The magnetic properties of these structures have been studied by vibrating sample magnetometry (VSM), miscrostrip ferromagnetic resonance (MS-FMR), and Brillouin light scattering (BLS) in the Damon-Eshbach geometry. VSM characterizations show that films are mostly in-plane magnetized and the saturating field perpendicular to the film plane increases with decreasing CFA thickness suggesting the existence of a perpendicular interface anisotropy. The presence of a magnetic dead layer of 0.44 nm has been detected by VSM. The MS-FMR with the magnetic field applied perpendicularly to the film plane has been used to determine the gyromagnetic factor. The BLS measurements reveal a pronounced nonreciprocal spin wave propagation, due to the interfacial Dzyaloshinskii-Moriya interaction (DMI) induced by the Ir interface with CFA, which increases with decreasing CFA thickness. The DMI sign has been found to be the same (negative) as that of Pt/Co, in contrast to the ab initio calculation on Ir/Co, where it is found to be positive. The thickness dependence of the effective DMI constant shows the existence of two regimes similarly to that of the perpendicular anisotropy constant. The surface DMI constant Ds was estimated to be -0.37 pJ /m for the thickest samples, where a linear thickness dependence of the effective DMI constant has been observed.

Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization

PubMed Central

Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison

2017-01-01

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3–17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways. PMID:25511566

Defeat and entrapment: more than meets the eye? Applying network analysis to estimate dimensions of highly correlated constructs.

PubMed

Forkmann, Thomas; Teismann, Tobias; Stenzel, Jana-Sophie; Glaesmer, Heide; de Beurs, Derek

2018-01-25

Defeat and entrapment have been shown to be of central relevance to the development of different disorders. However, it remains unclear whether they represent two distinct constructs or one overall latent variable. One reason for the unclarity is that traditional factor analytic techniques have trouble estimating the right number of clusters in highly correlated data. In this study, we applied a novel approach based on network analysis that can deal with correlated data to establish whether defeat and entrapment are best thought of as one or multiple constructs. Explanatory graph analysis was used to estimate the number of dimensions within the 32 items that make up the defeat and entrapment scales in two samples: an online community sample of 480 participants, and a clinical sample of 147 inpatients admitted to a psychiatric hospital after a suicidal attempt or severe suicidal crisis. Confirmatory Factor analysis (CFA) was used to test whether the proposed structure fits the data. In both samples, bootstrapped exploratory graph analysis suggested that the defeat and entrapment items belonged to different dimensions. Within the entrapment items, two separate dimensions were detected, labelled internal and external entrapment. Defeat appeared to be multifaceted only in the online sample. When comparing the CFA outcomes of the one, two, three and four factor models, the one factor model was preferred. Defeat and entrapment can be viewed as distinct, yet, highly associated constructs. Thus, although replication is needed, results are in line with theories differentiating between these two constructs.

ACE/AACE Inspection and Analysis Handbook. Part 2. Engineering

DTIC Science & Technology

1985-06-30

Albania Lek Lebanon Pound Algeria Diner Lsotho Lott Argentina New Peso Liberia Dollar Australia Dollar Libya Diner Austria Schilling Liechtenstein...Maldives Rupee Bllize Doll ar Mali Franc Benin CFA Franc Malta Pound eruda Dollar Mauritania OgutyaBolivia Peso Mauritius Rupee Botswana Pula Mx io Peso ...Canada Dollar Netherlands Guilder Central African Eap. CFA Franc New Zealand Dollar Chad CFA Franc Niceragua Cordoba Chile Peso Niger CFA Franc China Yuan

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

PubMed Central

Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

PubMed Central

Chen, Wenling; Marvizón, Juan Carlos G.

2009-01-01

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

PubMed

Chen, W; Marvizón, J C G

2009-06-16

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models.

PubMed

Chen, Q; Muramoto, K; Masaaki, N; Ding, Y; Yang, H; Mackey, M; Li, W; Inoue, Y; Ackermann, K; Shirota, H; Matsumoto, I; Spyvee, M; Schiller, S; Sumida, T; Gusovsky, F; Lamphier, M

2010-05-01

Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E(2) (PGE(2)) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE(2) EP(4) receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. Effects of PGE(2) and a novel EP(4) receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. Stimulation of the EP(4) receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE(2) antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen- and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. PGE(2) stimulates EP(4) receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP(4) receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.

A potential vaccine for cocaine abuse prophylaxis.

PubMed

Bagasra, O; Forman, L J; Howeedy, A; Whittle, P

1992-01-01

Presently, there are estimated to be 1.5 to 2.0 million individuals infected with HIV-1 in the U.S. and about 12 million worldwide. In the U.S. over 90% of reported cases of AIDS occurred among two subgroups, homosexual males and intravenous substance abusers (IVSAs). Currently, there is no anti-cocaine addiction medication available. In order to explore vaccination as an alternative means for protection against cocaine addition, we immunized inbred male Fisher rats with either cocaine emulsification in complete Freund adjuvant (CFA) or with cocaine conjugated with keyhole limpet hemocyanin (KLH), as carrier plus CFA. Animals were initially immunized with 0.1 mg/animal of cocaine or cocaine-KLH. Animals were given a booster with the corresponding agents after 4 weeks. Ten animals/group were used. Controls received normal saline at the time of immunizations. These animals were injected, intraperitoneally, with 25 mg/kg of cocaine, and were examined for the analgesic effect of cocaine by the hot plate method. The average analgesic effect of cocaine was significantly reduced (p greater than 0.03) in animals immunized with cocaine-KLH (13.77 s) as compared to saline controls (21.6 s). Fifty percent of the animals (5/10) in the cocaine-KLH group and 33% of the animals (3/9) in the cocaine immunized group appeared completely resistant to the effect of cocaine on the central nervous system (CNS). We also have determined the levels of cocaine-specific antibodies produced by each animal by an ELISA method. Degree of protection from cocaine seems to correlate well with the amount of anti-cocaine antibodies produced by each animal (-0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

VizieR Online Data Catalog: SNe II light curves & spectra from the CfA (Hicken+, 2017)

NASA Astrophysics Data System (ADS)

Hicken, M.; Friedman, A. S.; Blondin, S.; Challis, P.; Berlind, P.; Calkins, M.; Esquerdo, G.; Matheson, T.; Modjaz, M.; Rest, A.; Kirshner, R. P.

2018-01-01

Since all of the optical photometry reported here was produced as part of the CfA3 and CfA4 processing campaigns, see Hicken+ (2009, J/ApJ/700/331) and Hicken+ (2012, J/ApJS/200/12) for greater details on the instruments, observations, photometry pipeline, calibration, and host-galaxy subtraction used to create the CfA SN II light curves. (8 data files).

Dependence of PERT endpoint on endogenous lipase activity.

PubMed

Gao, Wen-Yi; Mulberg, Andrew E

2014-11-01

To clarify and to understand the potential for misinterpretation of change in fecal fat quantitation during pancreatic enzyme replacement therapy (PERT) trials for treatment of exocrine pancreatic insufficiency. Analysis of clinical trials submitted to the U.S. Food and Drug Administration (FDA) for approval of PERT that enrolled 123 cystic fibrosis adult and pediatric patients treated with Creon, Pertzye, Ultresa, and Zenpep. The CFA% defines lipase activity as a percentage of converting substrate of "Total Daily Dietary Fat Intake." PERT trials performed to date have modified the definition to converting the "Shared Daily Fat Intake," generating "Partial CFA" for the exogenous lipase: the higher the activity of coexisting endogenous lipase, the lower the "Partial CFA" of exogenous measured. This review shows that "Partial CFA" is not CFA. Enrollment of patients with low HPLA during treatment may improve the interpretability of "Partial CFA" measured by PERT trials.

Masculinity, Femininity and Androgyny: A Methodological and Theoretical Critique.

ERIC Educational Resources Information Center

Marsh, Herbert W.; Myers, Margaret

The three primary purposes of this investigation were: (1) to apply confirmatory factor analysis (CFA) to responses from three instruments--Bem Sex Role Inventory (BSRI), Comrey Personality Scales (CPS), and Australian Sex-Role Scale (ASRS)--designed to measure masculinity (M) and femininity (F); (2) to determine the correlation between M and F on…

The development of the Problematic Online Gaming Questionnaire (POGQ).

PubMed

Demetrovics, Zsolt; Urbán, Róbert; Nagygyörgy, Katalin; Farkas, Judit; Griffiths, Mark D; Pápay, Orsolya; Kökönyei, Gyöngyi; Felvinczi, Katalin; Oláh, Attila

2012-01-01

Online gaming has become increasingly popular. However, this has led to concerns that these games might induce serious problems and/or lead to dependence for a minority of players. The aim of this study was to uncover and operationalize the components of problematic online gaming. A total of 3415 gamers (90% males; mean age 21 years), were recruited through online gaming websites. A combined method of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) was applied. Latent profile analysis was applied to identify persons at-risk. EFA revealed a six-factor structure in the background of problematic online gaming that was also confirmed by a CFA. For the assessment of the identified six dimensions--preoccupation, overuse, immersion, social isolation, interpersonal conflicts, and withdrawal--the 18-item Problematic Online Gaming Questionnaire (POGQ) proved to be exceedingly suitable. Based on the latent profile analysis, 3.4% of the gamer population was considered to be at high risk, while another 15.2% was moderately problematic. The POGQ seems to be an adequate measurement tool for the differentiated assessment of gaming related problems on six subscales.

Cross-cultural validity of Morningness-Eveningness Stability Scale improved (MESSi) in Iran, Spain and Germany.

PubMed

Rahafar, Arash; Randler, Christoph; Díaz-Morales, Juan F; Kasaeian, Ali; Heidari, Zeinab

2017-01-01

Morningness-Eveningness Stability Scale improved (MESSi) is a newly constructed measure to assess circadian types and amplitude. In this study, we applied this measure to participants from three different countries: Germany, Spain and Iran. Confirmatory factorial analysis (CFA) of MESSi displayed mediocre fit in the three countries. Comparing increasingly stringent models using multigroup confirmatory factor analyses indicated at least partial measurement invariance (metric invariance) by country for Morning Affect and Distinctness subscales. Age was positively related to Morning Affect (MA), and negatively related to Eveningness (EV) and Distinctness (DI). Men reported higher MA than women, whereas women reported higher DI than men. Regarding country effect, Iranian participants reported highest MA compared to Spaniards and Germans, whereas Germans reported higher DI compared to Iranians and Spaniards. As a conclusion, our study corroborated the validity and reliability of MESSi across three different countries with different geographical and cultural characteristics.

Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: sexual dimorphism and diergism at the spinal cord level.

PubMed

Nacka-Aleksić, Mirjana; Djikić, Jasmina; Pilipović, Ivan; Stojić-Vukanić, Zorica; Kosec, Duško; Bufan, Biljana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

2015-10-01

Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-γ+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-γ+:IL-17+IL-10+ cell ratio was shifted towards IL-17+IFN-γ+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1β and IL-6, but downregulated TGF-β mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. Copyright © 2015 Elsevier Inc. All rights reserved.

Void statistics of the CfA redshift survey

NASA Technical Reports Server (NTRS)

Vogeley, Michael S.; Geller, Margaret J.; Huchra, John P.

1991-01-01

Clustering properties of two samples from the CfA redshift survey, each containing about 2500 galaxies, are studied. A comparison of the velocity distributions via a K-S test reveals structure on scales comparable with the extent of the survey. The void probability function (VPF) is employed for these samples to examine the structure and to test for scaling relations in the galaxy distribution. The galaxy correlation function is calculated via moments of galaxy counts. The shape and amplitude of the correlation function roughly agree with previous determinations. The VPFs for distance-limited samples of the CfA survey do not match the scaling relation predicted by the hierarchical clustering models. On scales not greater than 10/h Mpc, the VPFs for these samples roughly follow the hierarchical pattern. A variant of the VPF which uses nearly all the data in magnitude-limited samples is introduced; it accounts for the variation of the sampling density with velocity in a magnitude-limited survey.

Void statistics of the CfA redshift survey

NASA Astrophysics Data System (ADS)

Vogeley, Michael S.; Geller, Margaret J.; Huchra, John P.

1991-11-01

Clustering properties of two samples from the CfA redshift survey, each containing about 2500 galaxies, are studied. A comparison of the velocity distributions via a K-S test reveals structure on scales comparable with the extent of the survey. The void probability function (VPF) is employed for these samples to examine the structure and to test for scaling relations in the galaxy distribution. The galaxy correlation function is calculated via moments of galaxy counts. The shape and amplitude of the correlation function roughly agree with previous determinations. The VPFs for distance-limited samples of the CfA survey do not match the scaling relation predicted by the hierarchical clustering models. On scales not greater than 10/h Mpc, the VPFs for these samples roughly follow the hierarchical pattern. A variant of the VPF which uses nearly all the data in magnitude-limited samples is introduced; it accounts for the variation of the sampling density with velocity in a magnitude-limited survey.

Transient Receptor Potential Vanilloid-1 (TRPV1) Is a Mediator of Lung Toxicity for Coal Fly Ash Particulate Material

PubMed Central

Deering-Rice, Cassandra E.; Johansen, Mark E.; Roberts, Jessica K.; Thomas, Karen C.; Romero, Erin G.; Lee, Jeewoo; Yost, Garold S.; Veranth, John M.

2012-01-01

Environmental particulate matter (PM) pollutants adversely affect human health, but the molecular basis is poorly understood. The ion channel transient receptor potential vanilloid-1 (TRPV1) has been implicated as a sensor for environmental PM and a mediator of adverse events in the respiratory tract. The objectives of this study were to determine whether TRPV1 can distinguish chemically and physically unique PM that represents important sources of air pollution; to elucidate the molecular basis of TRPV1 activation by PM; and to ascertain the contributions of TRPV1 to human lung cell and mouse lung tissue responses exposed to an insoluble PM agonist, coal fly ash (CFA1). The major findings of this study are that TRPV1 is activated by some, but not all of the prototype PM materials evaluated, with rank-ordered responses of CFA1 > diesel exhaust PM > crystalline silica; TRP melastatin-8 is also robustly activated by CFA1, whereas other TRP channels expressed by airway sensory neurons and lung epithelial cells that may also be activated by CFA1, including TRPs ankyrin 1 (A1), canonical 4α (C4α), M2, V2, V3, and V4, were either slightly (TRPA1) or not activated by CFA1; activation of TRPV1 by CFA1 occurs via cell surface interactions between the solid components of CFA1 and specific amino acid residues of TRPV1 that are localized in the putative pore-loop region; and activation of TRPV1 by CFA1 is not exclusive in mouse lungs but represents a pathway by which CFA1 affects the expression of selected genes in lung epithelial cells and airway tissue. PMID:22155782

[Economic evaluation of rapid diagnostic tests in malaria treatment].

PubMed

Faye, Adama; Ndiaye, Papa; Diagne-Camara, Maty; Badiane, Ousseynou; Wone, Issa; Diongue, Mayassine; Seck, Ibrahima; Dia, Anta Tal; Dia, Amadou Lamine

2010-01-01

This study aimed to evaluate the economic implications of rapid diagnostic tests (RDTs) on malaria management through the rational use of artemisinin-based combination therapy (ACT). The study was carried out in 2006 from November 10th to December 10th; it focused on patients who were seen and treated with ACT for suspicion of uncomplicated malaria in the health district of Ziguinchor, Senegal. The variables studied included age, sex, RDT results, and costs of care and RDT. The cost of care for malaria, estimated in CFA Francs, was evaluated both with and without the use of RDT. Among the 379 patients, 25,1% were aged 0-4 years, 12,7% of 5-14 years and 62,2% of at least 15 years; 51% were women. The result of the RDT was negative in 60% of cases. Without the use of diagnostic testing, the cost of care for all 379 cases was estimated at 299 957 CFA: patient contributions would cover 184 500 CFA and the State would cover the rest (115 457 CFA). With the use of RDTs, the overall cost of the RDT screening for 379 patients and the cost of treatment for the 150 positive cases amounted to 254 786 CFA, with patients bearing the cost of 205 550 CFA and the State subsidizing up to 49 236 CFA. RDT can help identify the positive cases of malaria, and avoid up to 60% of unnecessary treatments, corresponding to an estimated 27 297 cases at the district level and 584 630 cases nationally. The RDT also allow a more rational use of ACTs and a lower risk of emergence of Plasmodium resistance. The use of RDTs could result in savings of 45 171 CFA at the level of the district health centre and 111 240 136 CFA nationally.

An Illustration of the Exploratory Structural Equation Modeling (ESEM) Framework on the Passion Scale

PubMed Central

Tóth-Király, István; Bõthe, Beáta; Rigó, Adrien; Orosz, Gábor

2017-01-01

While exploratory factor analysis (EFA) provides a more realistic presentation of the data with the allowance of item cross-loadings, confirmatory factor analysis (CFA) includes many methodological advances that the former does not. To create a synergy of the two, exploratory structural equation modeling (ESEM) was proposed as an alternative solution, incorporating the advantages of EFA and CFA. The present investigation is thus an illustrative demonstration of the applicability and flexibility of ESEM. To achieve this goal, we compared CFA and ESEM models, then thoroughly tested measurement invariance and differential item functioning through multiple-indicators-multiple-causes (MIMIC) models on the Passion Scale, the only measure of the Dualistic Model of Passion (DMP) which differentiates between harmonious and obsessive forms of passion. Moreover, a hybrid model was also created to overcome the drawbacks of the two methods. Analyses of the first large community sample (N = 7,466; 67.7% females; Mage = 26.01) revealed the superiority of the ESEM model relative to CFA in terms of improved goodness-of-fit and less correlated factors, while at the same time retaining the high definition of the factors. However, this fit was only achieved with the inclusion of three correlated uniquenesses, two of which appeared in previous studies and one of which was specific to the current investigation. These findings were replicated on a second, comprehensive sample (N = 504; 51.8% females; Mage = 39.59). After combining the two samples, complete measurement invariance (factor loadings, item intercepts, item uniquenesses, factor variances-covariances, and latent means) was achieved across gender and partial invariance across age groups and their combination. Only one item intercept was non-invariant across both multigroup and MIMIC approaches, an observation that was further corroborated by the hybrid model. While obsessive passion showed a slight decline in the hybrid model, harmonious passion did not. Overall, the ESEM framework is a viable alternative of CFA that could be used and even extended to address substantially important questions and researchers should systematically compare these two approaches to identify the most suitable one. PMID:29163325

An Illustration of the Exploratory Structural Equation Modeling (ESEM) Framework on the Passion Scale.

PubMed

Tóth-Király, István; Bõthe, Beáta; Rigó, Adrien; Orosz, Gábor

2017-01-01

While exploratory factor analysis (EFA) provides a more realistic presentation of the data with the allowance of item cross-loadings, confirmatory factor analysis (CFA) includes many methodological advances that the former does not. To create a synergy of the two, exploratory structural equation modeling (ESEM) was proposed as an alternative solution, incorporating the advantages of EFA and CFA. The present investigation is thus an illustrative demonstration of the applicability and flexibility of ESEM. To achieve this goal, we compared CFA and ESEM models, then thoroughly tested measurement invariance and differential item functioning through multiple-indicators-multiple-causes (MIMIC) models on the Passion Scale, the only measure of the Dualistic Model of Passion (DMP) which differentiates between harmonious and obsessive forms of passion. Moreover, a hybrid model was also created to overcome the drawbacks of the two methods. Analyses of the first large community sample ( N = 7,466; 67.7% females; M age = 26.01) revealed the superiority of the ESEM model relative to CFA in terms of improved goodness-of-fit and less correlated factors, while at the same time retaining the high definition of the factors. However, this fit was only achieved with the inclusion of three correlated uniquenesses, two of which appeared in previous studies and one of which was specific to the current investigation. These findings were replicated on a second, comprehensive sample ( N = 504; 51.8% females; M age = 39.59). After combining the two samples, complete measurement invariance (factor loadings, item intercepts, item uniquenesses, factor variances-covariances, and latent means) was achieved across gender and partial invariance across age groups and their combination. Only one item intercept was non-invariant across both multigroup and MIMIC approaches, an observation that was further corroborated by the hybrid model. While obsessive passion showed a slight decline in the hybrid model, harmonious passion did not. Overall, the ESEM framework is a viable alternative of CFA that could be used and even extended to address substantially important questions and researchers should systematically compare these two approaches to identify the most suitable one.

Validation of the Social Appearance Anxiety Scale in Patients with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network Cohort Study.

PubMed

Mills, Sarah D; Kwakkenbos, Linda; Carrier, Marie-Eve; Gholizadeh, Shadi; Fox, Rina S; Jewett, Lisa R; Gottesman, Karen; Roesch, Scott C; Thombs, Brett D; Malcarne, Vanessa L

2018-01-17

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes. Patients enrolled in the Scleroderma Patient-centered Intervention Network Cohort completed the SAAS and measures of appearance-related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple-group CFA was used to determine if SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size. A total of 938 patients with SSc were included. CFA supported a one-factor structure (CFI: .92; SRMR: .04; RMSEA: .08), and multiple-group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = .96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression. The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Poly(I:C) adjuvant strongly enhances parasite-inhibitory antibodies and Th1 response against Plasmodium falciparum merozoite surface protein-1 (42-kDa fragment) in BALB/c mice.

PubMed

Mehrizi, Akram Abouie; Rezvani, Niloufar; Zakeri, Sedigheh; Gholami, Atefeh; Babaeekhou, Laleh

2018-04-01

Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 1 42 (PfMSP-1 42 ) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-1 42 , when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-1 42 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-1 42 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-1 42 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-1 42 -based vaccine formulations.

Canine urothelial carcinoma: genomically aberrant and comparatively relevant

PubMed Central

Shapiro, S. G.; Raghunath, S.; Williams, C.; Motsinger-Reif, A. A.; Cullen, J. M.; Liu, T.; Albertson, D.; Ruvolo, M.; Lucas, A. Bergstrom; Jin, J.; Knapp, D. W.; Schiffman, J. D.

2015-01-01

Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97% and 84% of cases, respectively, and losses on CFA 19 were present in 77% of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications. PMID:25783786

Canine urothelial carcinoma: genomically aberrant and comparatively relevant.

PubMed

Shapiro, S G; Raghunath, S; Williams, C; Motsinger-Reif, A A; Cullen, J M; Liu, T; Albertson, D; Ruvolo, M; Bergstrom Lucas, A; Jin, J; Knapp, D W; Schiffman, J D; Breen, M

2015-06-01

Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 % and 84 % of cases, respectively, and losses on CFA 19 were present in 77 % of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications.

Measurement invariance of big-five factors over the life span: ESEM tests of gender, age, plasticity, maturity, and la dolce vita effects.

PubMed

Marsh, Herbert W; Nagengast, Benjamin; Morin, Alexandre J S

2013-06-01

This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due in part to the overly restrictive assumptions of CFA models. Here we demonstrate that exploratory structural equation modeling (ESEM), an integration of CFA and exploratory factor analysis, overcomes these problems with the 15-item Big Five Inventory administered as part of the nationally representative British Household Panel Study (N = 14,021; age: 15-99 years, Mage = 47.1). ESEM fitted the data substantially better and resulted in much more differentiated (less correlated) factors than did CFA. Methodologically, we extended ESEM (introducing ESEM-within-CFA models and a hybrid of multiple groups and multiple indicators multiple causes models), evaluating full measurement invariance and latent mean differences over age, gender, and their interaction. Substantively the results showed that women had higher latent scores for all Big Five factors except for Openness and that these gender differences were consistent over the entire life span. Substantial nonlinear age effects led to the rejection of the plaster hypothesis and the maturity principle but did support a newly proposed la dolce vita effect in old age. In later years, individuals become happier (more agreeable and less neurotic), more self-content and self-centered (less extroverted and open), more laid back and satisfied with what they have (less conscientious, open, outgoing and extroverted), and less preoccupied with productivity. PsycINFO Database Record (c) 2013 APA, all rights reserved

Evaluation of microRNA Stability in Plasma and Serum from Healthy Dogs.

PubMed

Enelund, Lars; Nielsen, Lise N; Cirera, Susanna

2017-01-01

Early and specific detection of cancer is of great importance for successful treatment of the disease. New biomarkers, such as microRNAs, could improve treatment efficiency and survival ratio. In human medicine, deregulation of microRNA profiles in circulation has shown great potential as a new type of biomarker for cancer diagnostics. There are, however, few studies of circulating microRNAs in dogs. Extracellular circulating microRNAs have shown a high level of stability in human blood and other body fluids. Nevertheless, there are still important issues to be solved before microRNAs can be applied routinely as a clinical tool, one of them being their stability over time in media commonly used for blood sampling. Evaluation of the stability of microRNA levels in plasma and serum from healthy dogs after storage at room temperature for different time points before being processed. The levels of four microRNAs (cfa-let-7a, cfa-miR-16, cfa-miR-23a and cfa-miR-26a) known to be stably expressed from other canine studies, have been measured by quantitative real-time PCR (qPCR). MicroRNA levels were found sufficiently stable for gene profiling in serum- and plasma stored at room temperature for 1 hour but not for samples stored at room temperature for 24 hours. Storage at room temperature of serum and plasma samples intended for microRNA profiling should be kept for a minimum period of time before proceeding with RNA isolation. For the four microRNAs investigated in the present study, we did not find significant differences in microRNA levels between serum and plasma samples from the same time point. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluating WAIS-IV structure through a different psychometric lens: structural causal model discovery as an alternative to confirmatory factor analysis.

PubMed

van Dijk, Marjolein J A M; Claassen, Tom; Suwartono, Christiany; van der Veld, William M; van der Heijden, Paul T; Hendriks, Marc P H

Since the publication of the WAIS-IV in the U.S. in 2008, efforts have been made to explore the structural validity by applying factor analysis to various samples. This study aims to achieve a more fine-grained understanding of the structure of the Dutch language version of the WAIS-IV (WAIS-IV-NL) by applying an alternative analysis based on causal modeling in addition to confirmatory factor analysis (CFA). The Bayesian Constraint-based Causal Discovery (BCCD) algorithm learns underlying network structures directly from data and assesses more complex structures than is possible with factor analysis. WAIS-IV-NL profiles of two clinical samples of 202 patients (i.e. patients with temporal lobe epilepsy and a mixed psychiatric outpatient group) were analyzed and contrasted with a matched control group (N = 202) selected from the Dutch standardization sample of the WAIS-IV-NL to investigate internal structure by means of CFA and BCCD. With CFA, the four-factor structure as proposed by Wechsler demonstrates acceptable fit in all three subsamples. However, BCCD revealed three consistent clusters (verbal comprehension, visual processing, and processing speed) in all three subsamples. The combination of Arithmetic and Digit Span as a coherent working memory factor could not be verified, and Matrix Reasoning appeared to be isolated. With BCCD, some discrepancies from the proposed four-factor structure are exemplified. Furthermore, these results fit CHC theory of intelligence more clearly. Consistent clustering patterns indicate these results are robust. The structural causal discovery approach may be helpful in better interpreting existing tests, the development of new tests, and aid in diagnostic instruments.

Utilisation of Quartz Crystal Microbalance Sensors with Dissipation (QCM-D) for a Clauss Fibrinogen Assay in Comparison with Common Coagulation Reference Methods.

PubMed

Oberfrank, Stephanie; Drechsel, Hartmut; Sinn, Stefan; Northoff, Hinnak; Gehring, Frank K

2016-02-24

The determination of fibrinogen levels is one of the most important coagulation measurements in medicine. It plays a crucial part in diagnostic and therapeutic decisions, often associated with time-critical conditions. The commonly used measurement is the Clauss fibrinogen assay (CFA) where plasma is activated by thrombin reagent and which is conducted by mechanical/turbidimetric devices. As quartz crystal microbalance sensors with dissipation (QCM-D) based devices have a small footprint, can be operated easily and allow measurements independently from sample transportation time, laboratory location, availability and opening hours, they offer a great opportunity to complement laboratory CFA measurements. Therefore, the objective of the work was to (1) transfer the CFA to the QCM-D method; (2) develop an easy, time- and cost-effective procedure and (3) compare the results with references. Different sensor coatings (donor's own plasma; gold surface) and different QCM-D parameters (frequency signal shift; its calculated turning point; dissipation signal shift) were sampled. The results demonstrate the suitability for a QCM-D-based CFA in physiological fibrinogen ranges. Results were obtained in less than 1 min and in very good agreement with a standardized reference (Merlin coagulometer). The results provide a good basis for further investigation and pave the way to a possible application of QCM-D in clinical and non-clinical routine in the medical field.

Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer

PubMed Central

Chesnais, Cédric B.; Vlaminck, Johnny; Kunyu-Shako, Billy; Pion, Sébastien D.; Awaca-Uvon, Naomi-Pitchouna; Weil, Gary J.; Mumba, Dieudonné; Boussinesq, Michel

2016-01-01

The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities. PMID:27114288

Using iMCFA to Perform the CFA, Multilevel CFA, and Maximum Model for Analyzing Complex Survey Data.

PubMed

Wu, Jiun-Yu; Lee, Yuan-Hsuan; Lin, John J H

2018-01-01

To construct CFA, MCFA, and maximum MCFA with LISREL v.8 and below, we provide iMCFA (integrated Multilevel Confirmatory Analysis) to examine the potential multilevel factorial structure in the complex survey data. Modeling multilevel structure for complex survey data is complicated because building a multilevel model is not an infallible statistical strategy unless the hypothesized model is close to the real data structure. Methodologists have suggested using different modeling techniques to investigate potential multilevel structure of survey data. Using iMCFA, researchers can visually set the between- and within-level factorial structure to fit MCFA, CFA and/or MAX MCFA models for complex survey data. iMCFA can then yield between- and within-level variance-covariance matrices, calculate intraclass correlations, perform the analyses and generate the outputs for respective models. The summary of the analytical outputs from LISREL is gathered and tabulated for further model comparison and interpretation. iMCFA also provides LISREL syntax of different models for researchers' future use. An empirical and a simulated multilevel dataset with complex and simple structures in the within or between level was used to illustrate the usability and the effectiveness of the iMCFA procedure on analyzing complex survey data. The analytic results of iMCFA using Muthen's limited information estimator were compared with those of Mplus using Full Information Maximum Likelihood regarding the effectiveness of different estimation methods.

Utilisation of Quartz Crystal Microbalance Sensors with Dissipation (QCM-D) for a Clauss Fibrinogen Assay in Comparison with Common Coagulation Reference Methods

PubMed Central

Oberfrank, Stephanie; Drechsel, Hartmut; Sinn, Stefan; Northoff, Hinnak; Gehring, Frank K.

2016-01-01

The determination of fibrinogen levels is one of the most important coagulation measurements in medicine. It plays a crucial part in diagnostic and therapeutic decisions, often associated with time-critical conditions. The commonly used measurement is the Clauss fibrinogen assay (CFA) where plasma is activated by thrombin reagent and which is conducted by mechanical/turbidimetric devices. As quartz crystal microbalance sensors with dissipation (QCM-D) based devices have a small footprint, can be operated easily and allow measurements independently from sample transportation time, laboratory location, availability and opening hours, they offer a great opportunity to complement laboratory CFA measurements. Therefore, the objective of the work was to (1) transfer the CFA to the QCM-D method; (2) develop an easy, time- and cost-effective procedure and (3) compare the results with references. Different sensor coatings (donor’s own plasma; gold surface) and different QCM-D parameters (frequency signal shift; its calculated turning point; dissipation signal shift) were sampled. The results demonstrate the suitability for a QCM-D-based CFA in physiological fibrinogen ranges. Results were obtained in less than 1 min and in very good agreement with a standardized reference (Merlin coagulometer). The results provide a good basis for further investigation and pave the way to a possible application of QCM-D in clinical and non-clinical routine in the medical field. PMID:26927107

SAO/NASA ADS at SAO: Mirror Sites

Science.gov Websites

, Garching, Germany Astronomisches Rechen-Institut, Heidelberg, Germany Institute of Astronomy of the Russian Observatory, Chinese Academy of Science, Beijing, China Inter-University Centre for Astronomy and Astrophysics Intensive Astronomy, South Africa [ADS] ADS [CfA] CfA [NASA] NASA ads at cfa.harvard.edu

Confirmatory factor analysis using Microsoft Excel.

PubMed

Miles, Jeremy N V

2005-11-01

This article presents a method for using Microsoft (MS) Excel for confirmatory factor analysis (CFA). CFA is often seen as an impenetrable technique, and thus, when it is taught, there is frequently little explanation of the mechanisms or underlying calculations. The aim of this article is to demonstrate that this is not the case; it is relatively straightforward to produce a spreadsheet in MS Excel that can carry out simple CFA. It is possible, with few or no programming skills, to effectively program a CFA analysis and, thus, to gain insight into the workings of the procedure.

Antigenicity and immunogenicity of fused B-subunit of heat labile toxin of Escherichia coli and colonization factor antigen I polyepitopes.

PubMed

Savar, Nastaran Sadat; Dashti, Amir; Darzi Eslam, Elham; Jahanian-Najafabadi, Ali; Jafari, Anis

2014-11-01

Linear B-cell epitopes ((93)AKEFEAAAL(101) and (66)PQLTDVLN(73)) of CfaB were genetically fused to ltb-(gly)5-cfaB(1-25). Sera of rabbits immunized with fusion proteins reacted strongly with solid-phase bound ETEC bacteria bearing CFA/I fimbriae. Sera failed to agglutinate or inhibit hemagglutination promoted by CFA/I-positive strain which may be due to solvent inaccessibility of epitope residues on intact fimbriae. Copyright © 2014 Elsevier B.V. All rights reserved.

Adsorption and separation of proteins by collagen fiber adsorbent.

PubMed

Li, Juan; Liao, Xue-pin; Zhang, Qi-xian; Shi, Bi

2013-06-01

The separation of proteins is a key step in biomedical and pharmaceutical industries. In the present investigation, the collagen fiber adsorbent (CFA) was exploited as column packing material to separate proteins. Bovine serum albumin (BSA), bovine hemoglobin (Hb) and lysozyme (LYS) that have different isoelectric points (pIs) were selected as model proteins to investigate the separation ability of CFA to proteins. In batch adsorption, the adsorption behaviors of these proteins on CFA under different pHs and ionic strengths indicated that the electrostatic interaction plays a predominant role in the adsorption of proteins on CFA. CFA exhibited high adsorption capacity to Hb and LYS. In column separation, the proteins were completely separated by adjusting pH and ionic strength of the eluent. The increase of flow rate could reduce the separation time with no influence on the recovery of protein in the experimental range. The protein recovery was higher than 90% even when the CFA column was re-used for 4 times in separation of BSA and LYS, and the retention time of BSA or LYS was almost constant during the repeated applications. In addition, as a practical application, LYS was successfully separated from chicken egg white powder by CFA column. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age.

PubMed

Corvino, Silvana B; Damasceno, Débora C; Sinzato, Yuri K; Netto, Aline O; Macedo, Nathália C D; Zambrano, Elena; Volpato, Gustavo T

2017-01-01

The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2) was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

GluN2B/CaMKII mediates CFA-induced hyperalgesia via HDAC4-modified spinal COX2 transcription.

PubMed

Lai, Cheng-Yuan; Hsieh, Ming-Chun; Ho, Yu-Cheng; Chen, Gin-Den; Chou, Dylan; Ruan, Ting; Lee, An-Sheng; Wang, Hsueh-Hsiao; Chau, Yat-Pang; Peng, Hsien-Yu; Lai, Cheng-Hung

2018-06-01

Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons. Cytoplasmic HDAC4 retention led to its uncoupling with the COX2 promoter, hence prompting spinal COX2 transcription and expression in the dorsal horn. Moreover, the GluN2B-bearing N-methyl-d-aspartate receptor (GluN2B-NMDAR)/calmodulin-dependent protein kinase II (CaMKII) acted as an upstream cascade to facilitate HDAC4 phosphorylation/redistribution-associated spinal COX2 expression after inflammatory insults. The results of this pilot study demonstrated that the development and/or maintenance of inflammatory pain involved the spinal HDAC4-dependent epigenetic mechanisms. Our findings open up a new avenue for the development of a novel medical strategy for the relief of inflammatory pain. Copyright © 2018 Elsevier Ltd. All rights reserved.

Defining the common femoral artery: Insights from the femoral arterial access with ultrasound trial.

PubMed

Seto, Arnold H; Tyler, Jeffrey; Suh, William M; Harrison, Alexander T; Vera, Jesus A; Zacharias, Soni J; Daly, Timothy S; Sparling, Jeffrey M; Patel, Pranav M; Kern, Morton J; Abu-Fadel, Mazen

2017-06-01

We sought to establish the typical location of the common femoral artery (CFA) bifurcation, the origin and most inferior reflection of the inferior epigastric artery (IEA) relative to the femoral head (FH) and whether patient demographics predicted anatomical variations. In the absence of ultrasound guidance or prior imaging, the precise location of the CFA bifurcation and IEA can only be determined following access site angiography. Fluoroscopic landmarks are commonly used to estimate the location of the CFA bifurcation, but the position of the IEA is less well characterized. Prospectively collected data on 989 patients with femoral angiography in the FAUST trial were analyzed. The level of CFA bifurcation and the origin and most inferior reflection of the IEA were classified by angiography. Logistic regression was used to explore whether baseline demographics were associated with anatomic variations. The CFA bifurcation occurs below the middle 1/3 rd of the femoral head in 95% of patients, and no patient factors are predictive of a high bifurcation. The IEA origin has a more variable anatomically pattern, with high BSA, male gender, and white race associated with a low IEA origin. Operators should attempt to access the CFA at the level of the middle 1/3 rd of the FH to maximize the chance of CFA cannulation. However, this location carries an 11% risk of being at or above the IEA origin. Baseline demographics were of limited utility for predicting anatomic variants of the CFA bifurcation and the course of the IEA. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Preliminary X-ray diffraction analysis of CfaA, a molecular chaperone essential for the assembly of CFA/I fimbriae of human enterotoxigenic Escherichia coli.

PubMed

Bao, Rui; Esser, Lothar; Poole, Steven; McVeigh, Annette; Chen, Yu Xing; Savarino, Stephen J; Xia, Di

2014-02-01

Understanding of pilus bioassembly in Gram-negative bacteria stems mainly from studies of P pili and type 1 fimbriae of uropathogenic Escherichia coli, which are mediated by the classic chaperone-usher pathway (CUP). However, CFA/I fimbriae, a class 5 fimbria and intestinal colonization factor for enterotoxigenic E. coli (ETEC), are proposed to assemble via the alternate chaperone pathway (ACP). Both CUP and ACP fimbrial bioassembly pathways require the function of a periplasmic chaperone, but their corresponding proteins share very low similarity in primary sequence. Here, the crystallization of the CFA/I periplasmic chaperone CfaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected from a native CfaA crystal to 2 Å resolution and to 1.8 and 2.8 Å resolution, respectively, from a lead and a platinum derivative. These crystals displayed the symmetry of space group C2, with unit-cell parameters a = 103.6, b = 28.68, c = 90.60 Å, β = 119.7°. Initial phases were derived from multiple isomorphous replacement with anomalous scattering experiments using the data from the platinum and lead derivatives. This resulted in an interpretable electron-density map showing one CfaA molecule in an asymmetric unit. Sequence assignments were aided by anomalous signals from the heavy-atom derivatives. Refinement of the atomic model of CfaA is ongoing, which is expected to further understanding of the essential aspects and allowable variations in tertiary structure of the greater family of chaperones involved in chaperone-usher mediated bioassembly.

A Cross-Classified CFA-MTMM Model for Structurally Different and Nonindependent Interchangeable Methods.

PubMed

Koch, Tobias; Schultze, Martin; Jeon, Minjeong; Nussbeck, Fridtjof W; Praetorius, Anna-Katharina; Eid, Michael

2016-01-01

Multirater (multimethod, multisource) studies are increasingly applied in psychology. Eid and colleagues (2008) proposed a multilevel confirmatory factor model for multitrait-multimethod (MTMM) data combining structurally different and multiple independent interchangeable methods (raters). In many studies, however, different interchangeable raters (e.g., peers, subordinates) are asked to rate different targets (students, supervisors), leading to violations of the independence assumption and to cross-classified data structures. In the present work, we extend the ML-CFA-MTMM model by Eid and colleagues (2008) to cross-classified multirater designs. The new C4 model (Cross-Classified CTC[M-1] Combination of Methods) accounts for nonindependent interchangeable raters and enables researchers to explicitly model the interaction between targets and raters as a latent variable. Using a real data application, it is shown how credibility intervals of model parameters and different variance components can be obtained using Bayesian estimation techniques.

Determination of the second sectorial harmonic parameters of the geopotential using the positional observations of the geosynchronous satellites

NASA Astrophysics Data System (ADS)

Kuznetsov, E.; Kaiser, G.

2003-04-01

The paper is concerned with the determination of the second sectorial harmonic parameters of geopotential using the positional observations of the geosynchronous satellites at the Kourovka Astronomical Observatory. The calculated corrections Delta C_{22} and Delta S_{22} for the geopotential model JGM-3 are equal to Delta C_{22}=(-2.6 ± 1.4) * 10(-10) , Delta S_{22}=(-3.1 ± 0.9) * 10(-10) . From ads Wed Jan 12 06:25:03 2005 Return-Path: Received: (from ads@localhost) by head.cfa.harvard.edu (d/w) id j0CBP3DC007102; Wed, 12 Jan 2005 06:25:03 -0500 (EST) Received: from cfa.harvard.edu (cfa.harvard.edu [131.142.10.1]) by head.cfa.harvard.edu (d/w) with ESMTP id j0CBOeKD007030 for ; Wed, 12 Jan 2005 06:24:41 -0500 (EST) Received: from uqbar.mao.kiev.ua (mao.gluk.org [194.183.183.193]) by cfa.harvard.edu (8.12.9-20030924/8.12.9/cfunix Mast-Sol 1.0) with ESMTP id j0CBOXgu026863 for ; Wed, 12 Jan 2005 06:24:35 -0500 (EST) Received: from maoling.mao.kiev.ua (root@maoling.mao.kiev.ua [194.44.216.101]) by uqbar.mao.kiev.ua (8.11.6/8.11.6) with ESMTP id j0CBOVv08377 for ; Wed, 12 Jan 2005 13:24:31 +0200 Received: from maoling.mao.kiev.ua (gallaz@localhost [127.0.0.1]) by maoling.mao.kiev.ua (8.12.3/8.12.3/Debian-7.1) with ESMTP id j0CBOTPb014668 for ; Wed, 12 Jan 2005 13:24:29 +0200 Received: (from gallaz@localhost) by maoling.mao.kiev.ua (8.12.3/8.12.3/Debian-7.1) id j0CBOTgq014666 for ads@cfa.harvard.edu; Wed, 12 Jan 2005 13:24:29 +0200 Date: Wed, 12 Jan 2005 13:24:29 +0200 From: "Galina A. Lazorenko" Message-Id: <200501121124.j0CBOTgq014666@maoling.mao.kiev.ua> To: ads@cfa.harvard.edu X-Virus-Scanned: ClamAV 0.80/650/Mon Jan 3 05:00:02 2005 clamav-milter version 0.80j on maoling.mao.kiev.ua X-Virus-Status: Clean X-Loop: ads@cfa.harvard.edu X-Loop: ads@head.cfa.harvard.edu X-Spam-Checker-Version: SpamAssassin 2.64 (2004-01-11) on head.cfa.harvard.edu X-Spam-Level: * X-Spam-Status: No, hits=1.3 required=5.0 tests=J_CHICKENPOX_13, J_CHICKENPOX_14,J_CHICKENPOX_15,J_CHICKENPOX_16,J_CHICKENPOX_19, J_CHICKENPOX_23,J_CHICKENPOX_27,J_CHICKENPOX_33,J_CHICKENPOX_34, J_CHICKENPOX_36,J_CHICKENPOX_37,J_CHICKENPOX_38,J_CHICKENPOX_39, J_CHICKENPOX_71,OACYS_SINGLE autolearn=no version=2.64 Status: R Content-Length: 13739

48 CFR 352.234-3 - Full earned value management system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Federal Agency (CFA) as being compliant with the guidelines in ANSI/EIA Standard-748 (current version at... and accepted by the CFA at the time of award, see paragraph (b) of this clause. The Contractor shall..., the Contractor's EVM system has not been validated and accepted by the CFA as complying with EVMS...

[Dimensional structure of the Brazilian version of the Scale of Satisfaction with Interpersonal Processes of General Medical Care].

PubMed

Nascimento, Maria Isabel do; Reichenheim, Michael Eduardo; Monteiro, Gina Torres Rego

2011-12-01

The objective of this study was to reassess the dimensional structure of a Brazilian version of the Scale of Satisfaction with Interpersonal Processes of General Medical Care, proposed originally as a one-dimensional instrument. Strict confirmatory factor analysis (CFA) and exploratory factor analysis modeled within a CFA framework (E/CFA) were used to identify the best model. An initial CFA rejected the one-dimensional structure, while an E/CFA suggested a two-dimensional structure. The latter structure was followed by a new CFA, which showed that the model without cross-loading was the most parsimonious, with adequate fit indices (CFI = 0.982 and TLI = 0.988), except for RMSEA (0.062). Although the model achieved convergent validity, discriminant validity was questionable, with the square-root of the mean variance extracted from dimension 1 estimates falling below the respective factor correlation. According to these results, there is not sufficient evidence to recommend the immediate use of the instrument, and further studies are needed for a more in-depth analysis of the postulated structures.

The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

PubMed

Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

2009-01-15

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

Nature of fly ash amendments differently influences oxidative stress alleviation in four forest tree species and metal trace element phytostabilization in aged contaminated soil: A long-term field experiment.

PubMed

Labidi, Sonia; Firmin, Stéphane; Verdin, Anthony; Bidar, Géraldine; Laruelle, Frédéric; Douay, Francis; Shirali, Pirouz; Fontaine, Joël; Lounès-Hadj Sahraoui, Anissa

2017-04-01

Aided phytostabilization using coal fly ashes (CFAs) is an interesting technique to clean-up polluted soils and valorizing industrial wastes. In this context, our work aims to study the effect of two CFAs: silico-aluminous (CFA1) and sulfo-calcic (CFA2) ones, 10 years after their addition, on the phytostabilization of a highly Cd (cadmium), Pb (lead) and Zn (zinc) contaminated agricultural soil, with four forest tree species: Robinia pseudoacacia, Alnus glutinosa, Acer pseudoplatanus and Salix alba. To assess the effect of CFAs on trees, leaf fatty acid composition, malondialdehyde (MDA), oxidized and reduced glutathione contents ratio (GSSG: GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), Peroxidase (PO) and Superoxide dismutase (SOD) activities were examined. Our results showed that CFA amendments decreased the CaCl 2- extractable fraction of Cd and Zn from the soil. However, no significant effect was observed on metal trace element (MTE) concentrations in leaves. Fatty acid percentages were only affected by the addition of sulfo-calcic CFA. The most affected species were A. glutinosa and R. pseudoacacia in which C16:0, C18:0 and C18:2 percentages increased significantly whereas the C18:3 decreased. The addition of sulfo-calcic CFA induced the antioxidant systems response in tree leaves. An increase of SOD and POD activities in leaves of trees planted on the CFA2-amended plot was recorded. Conversely, silico-aluminous CFA generated a reduction of lipid and DNA oxidation associated with the absence or low induction of anti-oxidative processes. Our study evidenced oxidative stress alleviation in tree leaves due to CFA amendments. MTE mobility in contaminated soil and their accumulation in leaves differed with the nature of CFA amendments and the selected tree species. Copyright © 2016 Elsevier Inc. All rights reserved.

The luminosity function for different morphological types in the CfA Redshift Survey

NASA Technical Reports Server (NTRS)

Marzke, Ronald O.; Geller, Margaret J.; Huchra, John P.; Corwin, Harold G., Jr.

1994-01-01

We derive the luminosity function for different morphological types in the original CfA Redshift Survey (CfA1) and in the first two slices of the CfA Redshift Survey Extension (CfA2). CfA1 is a complete sample containing 2397 galaxies distributed over 2.7 steradians with m(sub z) less than or equal 14.5. The first two complete slices of CfA2 contain 1862 galaxies distributed over 0.42 steradians with m(sub z)=15.5. The shapes of the E-S0 and spiral luminosity functions (LF) are indistinguishable. We do not confirm the steeply decreasing faint end in the E-S0 luminosity function found by Loveday et al. for an independent sample in the southern hemisphere. We demonstrate that incomplete classification in deep redshift surveys can lead to underestimates of the faint end of the elliptical luminosity function and could be partially responsible for the difference between the CfA survey and other local field surveys. The faint end of the LF for the Magellanic spirals and irregulars is very steep. The Sm-Im luminosity function is well fit by a Schechter function with M*=-18.79, alpha=-1.87, and phi*=0.6x10(exp -3) for M(sub z) less than or equal to -13. These galaxies are largely responsible for the excess at the faint end of the general CfA luminosity function. The abundance of intrinsically faint, blue galaxies nearby affects the interpretation of deep number counts. The dwarf population increases the expected counts at B=25 in a no-evolution, q(sub 0)=0.05 model by a factor of two over standard no-evolution estimates. These dwarfs change the expected median redshift in deep redshift surveys by less than 10 percent . Thus the steep Sm-Im LF may contribute to the reconciliation of deep number counts with deep redshift surveys.

Subchronic Infection of Porphyromonas gingivalis and Tannerella forsythia Stimulates an Immune Response but Not Arthritis in Experimental Murine Model

PubMed Central

Hernández-Aguas, Jorday; Montiel-Hernández, José Luis; Ruiz-Ramos, Rosa Velia; Escamilla García, Erandi; Guzmán-García, Mario Alberto; Ayón-Haro, Esperanza Raquel; Garza-Elizondo, Mario Alberto

2017-01-01

Studies have proposed that Porphyromonas gingivalis (Pg) and Tannerella forsythia (Tf) promote a nonspecific inflammatory response that could produce systemic disease. Oral inoculation of Pg and Tf on the immune and arthritis response was evaluated in BALB/C mice divided into four groups: (1) sham; (2) food contaminated with Pg/Tf; (3) complete Freund's adjuvant (CFA) + Pg/Tf; and (4) CFA alone. CFA was administered subcutaneously on days 1 and 14. The arthritis response was monitored for 21 days after day 14 of CFA administration. IL-1β and IL-6 were determined in serum. T cell activation was evaluated by CD25 in salivary lymph nodes or mouse spleen. Pad inflammation appeared by day 19 in the CFA group, but animals with bacteria inoculation presented a delay. A significant increase in IL-6 was found in Groups 3 and 4, but not with respect to IL-1β. We observed an increase in CD25 in cells derived from cervical nodes and in animals with bacteria inoculation and CFA. A local immune response was observed in mice inoculated with Pg and Tf (T cell activation); a systemic response was observed with CFA. Since pad inflammation was delayed by bacterial inoculation this suggests that local T cell activation could decrease pad inflammation. PMID:28676826

A 3' UTR-derived non-coding RNA RibS increases expression of cfa and promotes biofilm formation of Salmonella enterica serovar Typhi.

PubMed

Zhao, Xin; Liu, Rui; Tang, Hao; Osei-Adjei, George; Xu, Shungao; Zhang, Ying; Huang, Xinxiang

2018-05-08

Bacterial non-coding RNAs (ncRNAs) are widely studied and found to play important roles in regulating various cellular processes. Recently, many ncRNAs have been discovered to be transcribed or processed from 3' untranslated regions (3' UTRs). Here we reported a novel 3' UTR-derived ncRNA, RibS, which could influence biofilm formation of Salmonella enterica serovar Typhi (S. Typhi). RibS was confirmed to be a ∼700 nt processed product produced by RNase III-catalyzed cleavage from the 3' UTR of riboflavin synthase subunit alpha mRNA, RibE. Overexpression of RibS increased the expression of the cyclopropane fatty acid synthase gene, cfa, which was located at the antisense strand. Biofilm formation of S. Typhi was enhanced by overexpressing RibS both in the wild type strain and cfa deletion mutant. Deletion of cfa attenuated biofilm formation of S. Typhi, while complementation of cfa partly restored the phenotype. Moreover, overexpressing cfa enhanced the biofilm formation of S. Typhi. In summary, RibS has been identified as a novel ncRNA derived from the 3' UTR of RibE that promotes biofilm formation of S. Typhi, and it appears to do so, at least in part, by increasing the expression of cfa. Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Construction and expression of immunogenic hybrid enterotoxigenic Escherichia coli CFA/I and CS2 colonization fimbriae for use in vaccines.

PubMed

Tobias, Joshua; Svennerholm, Ann-Mari; Holmgren, Jan; Lebens, Michael

2010-07-01

Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrheal morbidity in developing countries, especially in children and also of traveler's diarrhea. Colonization factors (CFs) of ETEC, like CFA/I and CS2 which are genetically and structurally related, play a substantial role in pathogenicity, and since intestinal-mucosal immune responses against CFs appear to be protective, much effort has focused on the development of a CF-based ETEC vaccine. We have constructed hybrid operons in which the major CS2 subunit-encoding cotA gene was inserted into the CFA/I operon, either replacing (hybrid I) or being added to the major CFA/I subunit-encoding cfaB gene (hybrid II). Using specific monoclonal antibodies against the major subunits of CFA/I and CS2, high levels of surface expression of both fimbrial subunits were shown in E. coli carrying the hybrid II operon. Oral immunization of mice with formalin-killed bacteria expressing hybrid II fimbriae induced strong CFA/I- and CS2-specific serum IgG + IgM and fecal IgA antibody responses, which were higher than those achieved by similar immunization with the reference strains. Bacteria expressing hybrid fimbriae are potential candidate strains in an oral-killed CF-ETEC vaccine, and the approach represents an attractive and novel means of producing a broad-spectrum ETEC vaccine.

Fly ashes from coal and petroleum coke combustion: current and innovative potential applications.

PubMed

González, Aixa; Navia, Rodrigo; Moreno, Natalia

2009-12-01

Coal fly ashes (CFA) are generated in large amounts worldwide. Current combustion technologies allow the burning of fuels with high sulfur content such as petroleum coke, generating non-CFA, such as petroleum coke fly ash (PCFA), mainly from fluidized bed combustion processes. The disposal of CFA and PCFA fly ashes can have severe impacts in the environment such as a potential groundwater contamination by the leaching of heavy metals and/or particulate matter emissions; making it necessary to treat or reuse them. At present CFA are utilized in several applications fields such as cement and concrete production, agriculture and soil stabilization. However, their reuse is restricted by the quality parameters of the end-product or requirements defined by the production process. Therefore, secondary material markets can use a limited amount of CFA, which implies the necessity of new markets for the unused CFA. Some potential future utilization options reviewed herein are zeolite synthesis and valuable metals extraction. In comparison to CFA, PCFA are characterized by a high Ca content, suggesting a possible use as neutralizers of acid wastewaters from mining operations, opening a new potential application area for PCFA that could solve contamination problems in emergent and mining countries such as Chile. However, this potential application may be limited by PCFA heavy metals leaching, mainly V and Ni, which are present in PCFA in high concentrations.

The Development of the Problematic Online Gaming Questionnaire (POGQ)

PubMed Central

Demetrovics, Zsolt; Urbán, Róbert; Nagygyörgy, Katalin; Farkas, Judit; Griffiths, Mark D.; Pápay, Orsolya; Kökönyei, Gyöngyi; Felvinczi, Katalin; Oláh, Attila

2012-01-01

Background Online gaming has become increasingly popular. However, this has led to concerns that these games might induce serious problems and/or lead to dependence for a minority of players. Aim: The aim of this study was to uncover and operationalize the components of problematic online gaming. Methods A total of 3415 gamers (90% males; mean age 21 years), were recruited through online gaming websites. A combined method of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) was applied. Latent profile analysis was applied to identify persons at-risk. Results EFA revealed a six-factor structure in the background of problematic online gaming that was also confirmed by a CFA. For the assessment of the identified six dimensions – preoccupation, overuse, immersion, social isolation, interpersonal conflicts, and withdrawal – the 18-item Problematic Online Gaming Questionnaire (POGQ) proved to be exceedingly suitable. Based on the latent profile analysis, 3.4% of the gamer population was considered to be at high risk, while another 15.2% was moderately problematic. Conclusions The POGQ seems to be an adequate measurement tool for the differentiated assessment of gaming related problems on six subscales. PMID:22590541

CFA or CFP: A Guide for Professors

ERIC Educational Resources Information Center

Moy, Ronald L.

2011-01-01

The CFA Institute and the CFP Board of Standards provide professional certifications in the field of finance. In this paper, I provide my experience with the CFA and CFP programs in order to give other professors some insight into the process of attaining the designations. I hope to provide answers to some of the questions that other faculty…

48 CFR 352.234-4 - Partial earned value management system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Cognizant Federal Agency (CFA) as being compliant with the schedule-related guidelines in ANSI/EIA Standard... has not been validated and accepted by the CFA at the time of award, see paragraph (b) of this clause..., at the time of award, the Contractor's EVM system has not been validated and accepted by the CFA as...

On the generation of a bubbly universe - A quantitative assessment of the CfA slice

NASA Technical Reports Server (NTRS)

Ostriker, J. P.; Strassler, M. J.

1989-01-01

A first attempt is made to calculate the properties of the matter distribution in a universe filled with overlapping bubbles produced by multiple explosions. Each spherical shell follows the cosmological Sedov-Taylor solution until it encounters another shell. Thereafter, mergers are allowed to occur in pairs on the basis of N-body results. At the final epoch, the matrix of overlapping shells is populated with 'galaxies' and the properties of slices through the numerically constructed cube compare well with CfA survey results for specified initial conditions. A statistic is found which measures the distance distribution from uniformly distributed points to the nearest galaxies on the projected plane which appears to provide a good measure of the bubbly character of the galaxy distribution. In a quantitative analysis of the CfA 'slice of the universe', a very good match is found between simulation and the real data for final average bubble radii of (13.5 + or - 1.5)/h Mpc with formal filling factor 1.0-1.5 or actual filling factor of 65-80 percent.

Gravitational lensing by globular clusters and dwarf galaxies-- the explanation of quasar-galaxy associations

NASA Astrophysics Data System (ADS)

Yushchenko, A.; Kim, C.; Sergeev, A.

2003-04-01

Quasar-galaxy associations can be explained as gravitational lensing by globular clusters, located in the halos of the foreground galaxies and dwarf galaxies in small groups of galaxies. We propose an observational test for checking this hypothesis. We used the SUPERCOSMOS sky survey to find the overdensities of star-like sources with zero proper motions in the vicinities of the~foreground galaxies from the CfA3 catalog. The results obtained for 19413 galaxies are presented. We show the results of calculations of number densities of star-like sources with zero proper motions in the vicinity of 19413 galaxies. Two different effects can explain the observational data: lensing by globular clusters and lensing by dwarf galaxies. We carried out the CCD 3-color photometry with the 2.0-m telescope of the~Terskol Observatory and the 1.8-m telescope of the Bohyunsan Observatory (South Korea) to select extremely lensed objects around several galaxies for future spectroscopic observations. From ads Wed Jan 12 06:25:17 2005 Return-Path: Received: (from ads@localhost) by head.cfa.harvard.edu (d/w) id j0CBPHjt007159; Wed, 12 Jan 2005 06:25:17 -0500 (EST) Received: from cfa.harvard.edu (cfa.harvard.edu [131.142.10.1]) by head.cfa.harvard.edu (d/w) with ESMTP id j0CBOuKD007095 for ; Wed, 12 Jan 2005 06:24:56 -0500 (EST) Received: from uqbar.mao.kiev.ua (mao.gluk.org [194.183.183.193]) by cfa.harvard.edu (8.12.9-20030924/8.12.9/cfunix Mast-Sol 1.0) with ESMTP id j0CBOgRv026875 for ; Wed, 12 Jan 2005 06:24:51 -0500 (EST) Received: from maoling.mao.kiev.ua (root@maoling.mao.kiev.ua [194.44.216.101]) by uqbar.mao.kiev.ua (8.11.6/8.11.6) with ESMTP id j0CBOdv08381 for ; Wed, 12 Jan 2005 13:24:39 +0200 Received: from maoling.mao.kiev.ua (gallaz@localhost [127.0.0.1]) by maoling.mao.kiev.ua (8.12.3/8.12.3/Debian-7.1) with ESMTP id j0CBObPb014682 for ; Wed, 12 Jan 2005 13:24:37 +0200 Received: (from gallaz@localhost) by maoling.mao.kiev.ua (8.12.3/8.12.3/Debian-7.1) id j0CBObwQ014680 for ads@cfa.harvard.edu; Wed, 12 Jan 2005 13:24:37 +0200 Date: Wed, 12 Jan 2005 13:24:37 +0200 From: "Galina A. Lazorenko" Message-Id: <200501121124.j0CBObwQ014680@maoling.mao.kiev.ua> To: ads@cfa.harvard.edu X-Virus-Scanned: ClamAV 0.80/650/Mon Jan 3 05:00:02 2005 clamav-milter version 0.80j on maoling.mao.kiev.ua X-Virus-Status: Clean X-Loop: ads@cfa.harvard.edu X-Loop: ads@head.cfa.harvard.edu X-Spam-Checker-Version: SpamAssassin 2.64 (2004-01-11) on head.cfa.harvard.edu X-Spam-Level: X-Spam-Status: No, hits=0.5 required=5.0 tests=J_CHICKENPOX_14, J_CHICKENPOX_16,J_CHICKENPOX_33,J_CHICKENPOX_34,J_CHICKENPOX_35, J_CHICKENPOX_36,J_CHICKENPOX_37,J_CHICKENPOX_38,J_CHICKENPOX_39 autolearn=no version=2.64 Status: R Content-Length: 12095

Impacts of coal fly ash on plant growth and accumulation of essential nutrients and trace elements by alfalfa (Medicago sativa) grown in a loessial soil.

PubMed

He, Honghua; Dong, Zhigang; Peng, Qi; Wang, Xia; Fan, Chenbin; Zhang, Xingchang

2017-07-15

Coal fly ash (CFA) is a problematic solid waste all over the world. One distinct beneficial reuse of CFA is its utilization in land application as a soil amendment. A pot experiment was carried out to assess the feasibility of using CFA to improve plant growth and increase the supply of plant-essential elements and selenium (Se) of a loessial soil for agricultural purpose. Plants of alfalfa (Medicago sativa) were grown in a loessial soil amended with different rates (5%, 10%, 20% and 40%) of CFA for two years and subjected to four successive cuttings. Dry mass of shoots and roots, concentrations of plant-essential elements and Se in plants were measured. Shoot dry mass and root dry mass were always significantly increased by 5%, 10% and 20% CFA treatments, and by 40% CFA treatment in all harvests except the first one. The CFA had a higher supply of exchangeable phosphorus (P), magnesium (Mg), copper (Cu), zinc (Zn), molybdenum (Mo), and Se than the loessial soil. Shoot P, calcium (Ca), Mg, Mo, boron (B), and Se concentrations were generally markedly increased, but shoot potassium (K), Cu, and Zn concentrations were generally reduced. The CFA can be a promising source of some essential elements and Se for plants grown in the loessial soil, and an application rate of not higher than 5% should be safe for agricultural purpose without causing plant toxicity symptoms in the studied loessial soil and similar soils. Field trials will be carried out to confirm the results of the pot experiment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice.

PubMed

Omorogbe, Osarume; Ajayi, Abayomi M; Ben-Azu, Benneth; Oghwere, Ejiroghene E; Adebesin, Adaeze; Aderibigbe, Adegbuyi O; Okubena, Olajuwon; Umukoro, Solomon

2018-02-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn ® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn ® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.

PubMed

Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V

2001-01-01

In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.

Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint.

PubMed

Lemos, George Azevedo; Rissi, Renato; de Souza Pires, Ivan Luiz; de Oliveira, Letícia Prado; de Aro, Andrea Aparecida; Pimentel, Edson Rosa; Palomari, Evanisi Teresa

2016-08-01

The objective of this study was to characterize morphological and biochemistry action of low-level laser therapy (LLLT) on induced arthritis in the temporomandibular joint (TMJ) of rats. Twenty-four male Wistar rats were randomly divided into groups with 12 animals each: (AG) group with arthritis induced in the left TMJ and (LG) group with arthritis induced in the left TMJ and treated with LLLT (830 nm, 30 mW, 3 J/cm(2)). Right TMJs in the AG group were used as noninjected control group (CG). Arthritis was induced by intra-articular injection of 50 μl Complete Freund's Adjuvant (CFA) and LLLT began 1 week after arthritis induction. Histopathological analysis was performed using sections stained with hematoxylin-eosin, Toluidine Blue, and picrosirius. Biochemical analysis was determined by the total concentration of sulfated glycosaminoglycans (GAGs) and evaluation of matrix metalloproteinases (MMP-2 and MMP-9). Statistical analysis was performed using paired and unpaired t tests, with p < 0.05. Compared to AG, LG had minor histopathological changes in the TMJ, smaller thickness of the articular disc in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001), high birefringence of collagen fibers in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001) on the articular disc, and statistically lower activity of MMP-2 latent (p < 0.0001), MMP-2 active (P = 0.02), MMP-9 latent (p < 0.0001), and MMP-9 active (p < 0.0001). These results suggest that LLLT can increase the remodeling and enhancing tissue repair in TMJ with induced arthritis.

Increased magnetic damping in ultrathin films of Co2FeAl with perpendicular anisotropy

NASA Astrophysics Data System (ADS)

Takahashi, Y. K.; Miura, Y.; Choi, R.; Ohkubo, T.; Wen, Z. C.; Ishioka, K.; Mandal, R.; Medapalli, R.; Sukegawa, H.; Mitani, S.; Fullerton, E. E.; Hono, K.

2017-06-01

We estimated the magnetic damping constant α of Co2FeAl (CFA) Heusler alloy films of different thicknesses with an MgO capping layer by means of time-resolved magneto-optical Kerr effect and ferromagnetic resonance measurements. CFA films with thicknesses of 1.2 nm and below exhibited perpendicular magnetic anisotropy arising from the presence of the interface with MgO. While α increased gradually with decreasing CFA film thickness down to 1.2 nm, it was increased substantially when the thickness was reduced further to 1.0 nm. Based on the microstructure analyses and first-principles calculations, we attributed the origin of the large α in the ultrathin CFA film primarily to the Al deficiency in the CFA layer, which caused an increase in the density of states and thereby in the scatterings of their spins.

Development and Construct Validation of the Interprofessional Attitudes Scale

PubMed Central

Norris, Jeffrey; Carpenter, Joan G.; Eaton, Jacqueline; Guo, Jia-Wen; Lassche, Madeline; Pett, Marjorie A.; Blumenthal, Donald K.

2015-01-01

Purpose Training of health professionals requires development of interprofessional competencies and assessment of these competencies. No validated tools exist to assess all four competency domains described in the 2011 Core Competencies for Interprofessional Collaborative Practice (the IPEC Report). The purpose of this study was to develop and validate a scale based on the IPEC competency domains that assesses interprofessional attitudes of students in the health professions. Method In 2012, a survey tool was developed and administered to 1,549 students from the University of Utah Health Science Center, an academic health center composed of four schools and colleges (Health, Medicine, Nursing, and Pharmacy). Exploratory and confirmatory factor analyses (EFA and CFA) were performed to validate the assessment tool, eliminate redundant questions, and to identify subscales. Results The EFA and CFA focused on aligning subscales with IPEC core competencies, and demonstrating good construct validity and internal consistency reliability. A response rate of 45% (n = 701) was obtained. Responses with complete data (n=678) were randomly split into two datasets which were independently analyzed using EFA and CFA. The EFA produced a 27-item scale, with five subscales (Cronbach’s alpha coefficients: 0.62 to 0.92). CFA indicated the content of the five subscales was consistent with the EFA model. Conclusions The Interprofessional Attitudes Scale (IPAS) is a novel tool that, compared to previous tools, better reflects current trends in interprofessional competencies. The IPAS should be useful to health sciences educational institutions and others training people to work collaboratively in interprofessional teams. PMID:25993280

Removal of sulfuric acid mist from lead-acid battery plants by coal fly ash-based sorbents.

PubMed

Shu, Yuehong; Wei, Xiangyu; Fang, Yu; Lan, Bingyan; Chen, Hongyu

2015-04-09

Sorbents from coal fly ash (CFA) activated by NaOH, CaO and H2O were prepared for H2SO4 mist removal from lead-acid battery plants. The effects of parameters including temperature, time, the ratios of CFA/activator and water/solid during sorbent preparation were investigated. It is found that the synthesized sorbents exhibit much higher removal capacity for H2SO4 mist when compared with that of raw coal fly ash and CaO except for H2O activated sorbent and this sorbent was hence excluded from the study because of its low capacity. The H2SO4 mist removal efficiency increases with the increasing of preparation time length and temperature. In addition, the ratios of CFA/activator and water/solid also impact the removal efficiency, and the optimum preparation conditions are identified as: a water/solid ratio of 10:1 at 120 °C for 10h, a CFA:CaO weight ratio of 10:1, and a NaOH solution concentration of 3 mol/L. The formation of rough surface structure and an increased surface area after NaOH/CaO activation favor the sorption of H2SO4 mist and possible sorption mechanisms might be electrostatic attractions and chemical precipitation between the surface of sorbents and H2SO4 mist. Copyright © 2015 Elsevier B.V. All rights reserved.

Hedonic and motivational responses to food reward are unchanged in rats with neuropathic pain

PubMed Central

Okun, Alec; McKinzie, David L.; Witkin, Jeffrey M.; Remeniuk, Bethany; Husein, Omar; Gleason, Scott D.; Oyarzo, Janice; Navratilova, Edita; McElroy, Brian; Cowen, Stephen; Kennedy, Jeffrey D.; Porreca, Frank

2016-01-01

Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. Here, we independently evaluated hedonic qualities of sweet or bitter tastants as well as motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation (SNL). Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions and “liking/disliking” responses were scored according to a facial reactivity scale. SNL rats did not differ from controls in either “liking” or “disliking” reactions to intraoral sucrose or quinine, respectively, at post-surgery day 21, suggesting no differences in perceived hedonic value of sweet or bitter tastants. To assess possible motivational deficits during acute and chronic pain, we employed fixed- and progressive-ratio response paradigms of sucrose pellet presentation in rats with transient inflammatory or chronic neuropathic pain. Assessment of response acquisition and break points under the progressive ratio schedule revealed no differences between sham and SNL rats for up to 120 days post-injury. However, rats with inflammation showed decrements in lever pressing and break points on post-CFA days 1 and 2 that normalized by day 4, consistent with transient ongoing pain. Thus, while acute, ongoing inflammatory pain may transiently reduce reward motivation, we did not detect influences of chronic neuropathic pain on hedonic or motivational responses to food rewards. Adaptations that allow normal reward responding to food regardless of chronic pain may be of evolutionary benefit to promote survival. PMID:27548047

Percolation analyses of observed and simulated galaxy clustering

NASA Astrophysics Data System (ADS)

Bhavsar, S. P.; Barrow, J. D.

1983-11-01

A percolation cluster analysis is performed on equivalent regions of the CFA redshift survey of galaxies and the 4000 body simulations of gravitational clustering made by Aarseth, Gott and Turner (1979). The observed and simulated percolation properties are compared and, unlike correlation and multiplicity function analyses, favour high density (Omega = 1) models with n = - 1 initial data. The present results show that the three-dimensional data are consistent with the degree of filamentary structure present in isothermal models of galaxy formation at the level of percolation analysis. It is also found that the percolation structure of the CFA data is a function of depth. Percolation structure does not appear to be a sensitive probe of intrinsic filamentary structure.

Are groups of galaxies virialized systems?

NASA Technical Reports Server (NTRS)

Diaferio, Antonaldo; Ramella, Massimo; Geller, Margaret J.; Ferrari, Attilio

1993-01-01

Groups are systems of galaxies with crossing times t(cr) much smaller than the Hubble time. Most of them have t(cr) less than 0.1/H0. The usual interpretation is that they are in virial equilibrium. We compare the data of the group catalog selected from the CfA redshift survey extension with different N-body models. We show that the distributions of kinematic and dynamical quantities of the groups in the CfA catalog can be reproduced by a single collapsing group observed along different line of sights. This result shows that (1) projection effects dominate the statistics of these systems, and (2) observed groups of galaxies are probably still in the collapse phase.

Neglect the Structure of Multitrait-Multimethod Data at Your Peril: Implications for Associations with External Variables

ERIC Educational Resources Information Center

Castro-Schilo, Laura; Widaman, Keith F.; Grimm, Kevin J.

2013-01-01

In 1959, Campbell and Fiske introduced the use of multitrait-multimethod (MTMM) matrices in psychology, and for the past 4 decades confirmatory factor analysis (CFA) has commonly been used to analyze MTMM data. However, researchers do not always fit CFA models when MTMM data are available; when CFA modeling is used, multiple models are available…

IscR Regulates Synthesis of Colonization Factor Antigen I Fimbriae in Response to Iron Starvation in Enterotoxigenic Escherichia coli

PubMed Central

Arnaud-Barbe, Nadège; Poncet, David; Reverchon, Sylvie; Wawrzyniak, Julien; Nasser, William

2015-01-01

ABSTRACT Iron availability functions as an environmental cue for enteropathogenic bacteria, signaling arrival within the human host. As enterotoxigenic Escherichia coli (ETEC) is a major cause of human diarrhea, the effect of iron on ETEC virulence factors was evaluated here. ETEC pathogenicity is directly linked to production of fimbrial colonization factors and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). Efficient colonization of the small intestine further requires at least the flagellin binding adhesin EtpA. Under iron starvation, production of the CFA/I fimbriae was increased in the ETEC H10407 prototype strain. In contrast, LT secretion was inhibited. Furthermore, under iron starvation, gene expression of the cfa (CFA/I) and etp (EtpBAC) operons was induced, whereas transcription of toxin genes was either unchanged or repressed. Transcriptional reporter fusion experiments focusing on the cfa operon further showed that iron starvation stimulated cfaA promoter activity in ETEC, indicating that the impact of iron on CFA/I production was mediated by transcriptional regulation. Evaluation of cfaA promoter activity in heterologous E. coli single mutant knockout strains identified IscR as the regulator responsible for inducing cfa fimbrial gene expression in response to iron starvation, and this was confirmed in an ETEC ΔiscR strain. The global iron response regulator, Fur, was not implicated. IscR binding sites were identified in silico within the cfaA promoter and fixation confirmed by DNase I footprinting, indicating that IscR directly binds the promoter region to induce CFA/I. IMPORTANCE Pathogenic enterobacteria modulate expression of virulence genes in response to iron availability. Although the Fur transcription factor represents the global regulator of iron homeostasis in Escherichia coli, we show that several ETEC virulence factors are modulated by iron, with expression of the major fimbriae under the control of the iron-sulfur cluster regulator, IscR. Furthermore, we demonstrate that the apo form of IscR, lacking an Fe-S cluster, is able to directly fix the corresponding promoter region. These results provide further evidence implicating IscR in bacterial virulence and suggest that IscR may represent a more general regulator mediating the iron response in enteropathogens. PMID:26124243

Role of interleukin-1beta and tumor necrosis factor-alpha-dependent expression of cyclooxygenase-2 mRNA in thermal hyperalgesia induced by chronic inflammation in mice.

PubMed

Narita, M; Shimamura, M; Imai, S; Kubota, C; Yajima, Y; Takagi, T; Shiokawa, M; Inoue, T; Suzuki, M; Suzuki, T

2008-03-18

The present study investigated whether the endogenous pro-inflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha)]-dependent expression of cyclooxygenase-2 (COX-2) mRNA within the spinal cord could be involved in the development of chronic inflammatory pain-like behaviors in mice. We demonstrated that the expression of COX-2 mRNA on the ipsilateral side of the spinal cord was significantly increased 6 h and 3 days after intraplantar injection of complete Freund's adjuvant (CFA), compared with the expression in saline-treated mice. In addition, the chronic pain-like behaviors following CFA injection were markedly suppressed by repeated intrathecal (i.t.) pre-treatment with the COX-2 inhibitor etodolac, but not with the COX-1 inhibitor mofezolac. The cytosolic level of the activated form of nuclear factor-kappa B (NF-kappaB), which is a major contributor to the induction of COX-2, on the ipsilateral side of the mouse spinal cord was also increased compared with that in the saline-treated mice. The key finding in the present study was that a single i.t. injection with either IL-1beta or TNF-alpha induced a marked increase in spinal COX-2 mRNA and persistent thermal hyperalgesia in mice. Furthermore, CFA-induced hypersensitivity to inflammatory pain was significantly reduced by repeated i.t. pre-injection of the recombinant Fc chimera of IL-1 receptor I or soluble TNF receptor I, which sequesters endogenous IL-1beta or TNF-alpha, respectively. In contrast, the expression of spinal COX-2 mRNA in CFA-treated mice was similar to that in saline-treated mice at 7 days after CFA injection. The present findings strongly indicate the early intrathecal use of the COX-2 inhibitor for the relief of chronic inflammatory pain. Furthermore, together with the result in a previous study that pro-inflammatory cytokines lead to stimulation of a NF-kappaB-dependent transcriptional pathway, these findings suggest that a spinal cytokine/NF-kappaB/COX-2 pathway may play an important role in the development, but not maintenance, of chronic pain following peripheral tissue inflammation.

A single factor underlies the metabolic syndrome: a confirmatory factor analysis.

PubMed

Pladevall, Manel; Singal, Bonita; Williams, L Keoki; Brotons, Carlos; Guyer, Heidi; Sadurni, Josep; Falces, Carles; Serrano-Rios, Manuel; Gabriel, Rafael; Shaw, Jonathan E; Zimmet, Paul Z; Haffner, Steven

2006-01-01

Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.

Family Engagement in Literacy Activities: Revised Factor Structure for the Familia--An Instrument Examining Family Support for Early Literacy Development

ERIC Educational Resources Information Center

Buhs, Eric S.; Welch, Greg; Burt, Jennifer; Knoche, Lisa

2011-01-01

This study evaluated a data-set drawn using "The Familia"--a measure originally developed to evaluate shared-reading activities. A newly developed set of conceptual supports and a confirmatory factor analysis (CFA) were applied to a new factor structure/model. Data were drawn from 219 young children and their families (mean age = 43…

ACE/AACE Inspection and Analysis Handbook. Part 3. Profiling

DTIC Science & Technology

1985-06-30

Peso Liberia Dollar Australia Dollar Libya Dinar Austria Schilling Liechtenstein Franc Bahamas Dollar Luxembourg Franc Bahrain Dinar Madagascar Franc...Dollar Mauritania Ouguiya Bolivia Peso Mauritius Rupee Botswana Pula Mexico Peso Brazil Cruzeiro Monaco Franc Bulgaria Lev Mongolia Tugrik Burma Kyat...Zealand Dollar Chad CFA Franc Nicaragua Cordoba Chile Peso Niger CFA Franc China Yuan Nigeria Naira Colombia Peso Norway Krone Congo CFA Franc Chan Rial

Topically applied standardized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced uveal inflammation in rats.

PubMed

Agarwal, Renu; Gupta, S K; Agarwal, Puneet; Srivastava, Sushma

2013-10-01

Aqueous extract of C. longa when administered 4 h after induction of E. coli lipopolysaccharide-induced uveitis in rats showed significantly suppressed inflammation with a significantly lower mean clinical grade, histopathological grade and aqueous humor (AH) protein level compared to vehicle treated group. Although, prednisolone group showed significantly lower clinical grade, histopathological grades and AH protein levels compared to C. longa group, TNF-alpha levels did not differ significantly. Moreover, when the aqueous extract was administered starting from 3 days before induction of uveitis, the mean clinical and histopathological grade as well as AH protein and TNF-alpha levels were comparable to C. longa group when treatment was administered 4 h after induction of uveitis. It is concluded that topically applied standardized aqueous extract of C. longa suppresses endotoxin-induced uveitis in rats by reducing TNF-alpha activity.

Floating cultivation of marine cyanobacteria using coal fly ash.

PubMed

Matsumoto, M; Yoshida, E; Takeyama, H; Matsunaga, T

2000-01-01

The aim of this study was to develop improved methodologies for bulk culturing of biotechnologically useful marine cyanobacteria in the open ocean. We have investigated the viability of using coal fly ash (CFA) blocks as the support medium in a novel floating culture system for marine micro-algae. The marine cyanobacterium Synechococcus sp. NKBG 040607 was found to adhere to floating CFA blocks in liquid culture medium. Maximum density of attached cells of 2.0 x 10(8) cells/cm2 was achieved using seawater. The marine cyanobacterium Synechococcus sp. NKBG 042902 weakly adhered to floating CFA blocks in BG-11 medium. Increasing the concentration of calcium ion in the culture medium enhanced adherence to CFA blocks.

Preliminary CFA measurements of Al and Fe "available" fraction in EPICA-Dome C ice core (East Antarctica)

NASA Astrophysics Data System (ADS)

Udisti, R.; Barbante, C.; Cozzi, G.; Fattori, I.; Largiuni, O.; Magaldi, L.; Traversi, R.

2003-04-01

Aerosol load of Al and Fe allows estimating the crustal contribution to the primary aerosol sources. While continental dust is the only significant source for Al, Fe takes part also to metabolic processes of living species as an essential oligo-element. For this reason, it has been assumed that atmospheric deposition of desert dust on the oceanic surface can constitute a phytoplanktonic growth factor. Besides, Fe content in aerosol during glacial/interglacial transitions is believed to play a relevant role in controlling oceanic phytoplanktonic uptake of atmospheric CO2. A detailed stratigraphy of Al and Fe in ice cores is basic in understanding the correlation between environmental and climatic changes. Here we report preliminary results of CFA methods able to determine, in field, the "available" (free form and labile complexes) fraction of Al and Fe in ice cores with high sensitivity (D.L. of 10 ppt for Al and 300 ppt for Fe) and reproducibility (around 2 % at ppb level). The two methods were applied to 32 selected sections coming from the EPICA-Dome C ice core (EDC96): 10 sections belonging to Holocene, 10 to the transition and 12 to the LGM. Though Al and Fe determined by CFA is representative of the only soluble fraction (or "available" in the measurement conditions after filtration on 5.0 um), a comparison with the Al and Fe "total" content, as measured by ICP-MS, was made. "Available" fractions represent a minor contribution to the ICP-MS Fe and Al content in the LGM, but this contribution increases during the transition. In the Holocene, the two different analytical methods give similar values. Anyway, also CFA Fe and Al profiles show a sharp concentration decrease in the glacial/interglacial transition, reflecting the lowering dust aerosol load. Fe, especially, shows a very high sensitivity for the ACR climatic change. Whereas CFA-Fe in the LGM is more than 10 times lower than ICP-MS-Fe, ACR values are similar. This evidence could be explained considering that during the LGM the insoluble continental dust is the main Fe source, while a sort of oceanic-recycled Fe, mainly distributed in the fine particles and as more soluble species, becomes more important during the ACR and in the Holocene. Further measurements, with a very higher temporal resolution, are necessary to confirm the observed behaviour.

Validation of patient health questionnaire (PHQ) for major depression in Chinese outpatients with multiple somatic symptoms: a multicenter cross-sectional study.

PubMed

Xiong, Nana; Fritzsche, Kurt; Wei, Jing; Hong, Xia; Leonhart, Rainer; Zhao, Xudong; Zhang, Lan; Zhu, Liming; Tian, Guoqing; Nolte, Sandra; Fischer, Felix

2015-03-15

Despite the high co-morbidity of depressive symptoms in patients with multiple somatic symptoms, the validity of the 9-item Patient Health Questionnaire (PHQ-9) has not yet been investigated in Chinese patients with multiple somatic symptoms. The multicenter cross-sectional study was conducted in ten outpatient departments located in four cities in China. The psychometric properties of the PHQ-9 were examined by confirmative factor analysis (CFA). Criterion validation was undertaken by comparing results with depression diagnoses obtained from the Mini International Neuropsychiatric Interview (MINI) as the gold standard. Overall, 491 patients were recruited of whom 237 had multiple somatic symptoms (SOM+ group, PHQ-15≥10). Cronbach׳s α of the PHQ-9 was 0.87, 0.87, and 0.90 for SOM+ patients, SOM- patients, and total sample respectively. All items and the total score were moderately correlated. The factor models of PHQ-9 tested by CFA yielded similar diagnostic performance when compared to sum score estimation. Multi-group confirmatory factor analysis based on unidimensional model showed similar psychometric properties over the groups with low and high somatic symptom burden. The optimal cut-off point to detect depression in Chinese outpatients was 10 for PHQ-9 (sensitivity=0.77, specificity=0.76) and 3 for PHQ-2 (sensitivity=0.77, specificity=0.74). Potential selection bias and nonresponse bias with applied sampling method. PHQ-9 (cut-off point=10) and PHQ-2 (cut-off point=3) were reliable and valid to detect major depression in Chinese patients with multiple somatic symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

The internal microstructure and fibrous mineralogy of fly ash from coal-burning power stations.

PubMed

Brown, Patrick; Jones, Tim; BéruBé, Kelly

2011-12-01

Coal fly ash (CFA) is a significant environmental pollutant that presents a respiratory hazard when airborne. Although previous studies have identified the mineral components of CFA, there is a paucity of information on the structural habits of these minerals. Samples from UK, Polish and Chinese power stations were studied to further our understanding of the factors that affect CFA geochemistry and mineralogy. ICP-MS, FE-SEM/EDX, XRD, and laser diffraction were used to study physicochemical characteristics. Analysis revealed important differences in the elemental compositions and particle size distributions of samples between sites. Microscopy of HF acid-etched CFA revealed the mullite present possesses a fibrous habit; fibres ranged in length between 1 and 10 μm. Respirable particles (<10 μm) were frequently observed to contain fibrous mullite. We propose that the biopersistence of these refractory fibres in the lung environment could be contributing towards chronic lung diseases seen in communities and individuals continually exposed to high levels of CFA. Copyright © 2011 Elsevier Ltd. All rights reserved.

CFA-1: the first chiral metal-organic framework containing Kuratowski-type secondary building units.

PubMed

Schmieder, Phillip; Denysenko, Dmytro; Grzywa, Maciej; Baumgärtner, Benjamin; Senkovska, Irena; Kaskel, Stefan; Sastre, German; van Wüllen, Leo; Volkmer, Dirk

2013-08-14

The novel homochiral metal-organic framework CFA-1 (Coordination Framework Augsburg-1), [Zn5(OAc)4(bibta)3], containing the achiral linker {H2-bibta = 1H,1'H-5,5'-bibenzo[d][1,2,3]triazole}, has been synthesised. The reaction of H2-bibta and Zn(OAc)2·2H2O in N-methylformamide (NMF) (90 °C, 3 d) yields CFA-1 as trigonal prismatic single crystals. CFA-1 serves as a convenient precursor for the synthesis of isostructural frameworks with redox-active metal centres, which is demonstrated by the postsynthetic exchange of Zn(2+) by Co(2+) ions. The framework is robust to solvent removal and has been structurally characterized by synchrotron single-crystal X-ray diffraction and solid state NMR measurements ((13)C MAS- and (1)H MAS-NMR at 10 kHz). Results from MAS-NMR and IR spectroscopy studies are corroborated by cluster and periodic DFT calculations performed on CFA-1 cluster fragments.

Factor Structure of the Student-Teacher Relationship Scale for Norwegian School-Age Children Explored with Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Drugli, May Britt; Hjemdal, Odin

2013-01-01

The validity of the Student-Teacher Relationship Scale (STRS) was examined in a national sample of 863 Norwegian schoolchildren in grades 1-7 (aged 6-13). The original factor structure of the STRS was tested by confirmatory factor analysis (CFA). The CFA results did not support the original three-factor structure of the STRS. Subsequent CFA of the…

The three-dimensional structure of CFA/I adhesion pili: traveler's diarrhea bacteria hang on by a spring.

PubMed

Mu, Xiang-Qi; Savarino, Stephen J; Bullitt, Esther

2008-02-22

To survive the harsh environment of a churning intestinal tract, bacteria attach to the host epithelium via thin fibers called pili (or fimbriae). Enterotoxigenic Escherichia coli bacteria expressing colonization factor antigen I (CFA/I) pili and related pili are the most common known bacterial cause of diarrheal disease, including traveler's diarrhea. CFA/I pili, assembled via the alternate chaperone pathway, are essential for binding and colonization of the small bowel by these pathogenic bacteria. Herein, we elucidate unique structural features of CFA/I pili that appear to optimize their function as bacterial tethers in the intestinal tract. Using transmission electron microscopy of negatively stained samples in combination with iterative three-dimensional helical reconstruction methods for image processing, we determined the structure of the CFA/I pilus filament. Our results indicate that strong end-to-end protein interactions and weak interactions between the coils of a sturdy spring-like helix provide the combination of strength, stability, and flexibility required to sustain bacterial adhesion and incite intestinal disease. We propose that CFA/I pili behave like a spring to maintain attachment to the gut lining during vortex mixing and downward flow of the intestinal contents, thereby persisting long enough for these bacteria to colonize the host epithelium and cause enteric disease.

Risk factor of contralateral radiculopathy following microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion.

PubMed

Yang, Yang; Liu, Zhong-Yu; Zhang, Liang-Ming; Dong, Jian-Wen; Xie, Pei-Gen; Chen, Rui-Qiang; Yang, Bu; Liu, Chang; Liu, Bin; Rong, Li-Min

2017-12-08

Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed statistical association with this complication (both P > 0.05). Based on ROC curve, the optimal threshold of preoperative CFA was 0.76 cm 2 . At final follow-up, significant improvement in VAS (back and leg), JOA and ODI was observed in both groups compared with preoperative baseline (all P < 0.05), while no difference was found between the two groups (all P > 0.05). Preoperative contralateral foramen stenosis is the risk factor of contralateral radiculopathy following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is not larger than 0.76 cm 2 , prophylactic measures, including both indirect and direct decompression of contralateral foramen, are recommended.

Characterization of upgraded hydrogel biochar from blended rice husk with coal fly ash

NASA Astrophysics Data System (ADS)

Ahmad, Nurul Farhana; Alias, Azil Bahari; Talib, Norhayati; Rashid, Zulkifli Abd; Ghani, Wan Azlina Wan Ab Karim

2017-12-01

Rice husk biochar (RB) blended with coal fly ash (CFA) is used as a material to develop hydrogel for heavy metal removal. This combination, namely hydrogel rice husk biochar-coal fly ash (HRB-CFA) composite is synthesized by embedding the biochar into acrylamide (AAM) as monomer, with N,N'-Methylenebisacrylamide (MBA) as crosslinker and ammonium persulfate (APS) as initiator. While activated carbon (AC) remains an expensive material, HRB-CFA is attracting great interest for its use in the absorption of organic contaminants due to its low material cost and importance as renewable source for securing future energy supply in the environmental system. Although the CFA does not have the surface area as high as AC, certain metallic components that are naturally present in the CFA can play the catalytic role in the removal of heavy metal from wastewater. The percentage of heavy metal removal is depends on the parameters that influence the sorption process; the effect of pH solution, dosage of adsorbent, initial concentration of solution, and contact time. The aim of this study is to characterize HRB-CFA by performing several analyses such as the Brunauer-Emmett-Teller (BET), thermogravimetric (TGA) and field emission scanning electron microscopy (FESEM) methods. The results obtained revealed that the best hydrogel ratio is 0.5:0.5 of blended RB and CFA, as proven by BET surface area, pore volume and pore size of 3.5392 m2/g, 0.00849 cm3/g and 90.566 Å, and the surface morphology showed an increase in porosity size.

Cyclopropanation of membrane unsaturated fatty acids is not essential to the acid stress response of Lactococcus lactis subsp. cremoris.

PubMed

To, Thi Mai Huong; Grandvalet, Cosette; Tourdot-Maréchal, Raphaëlle

2011-05-01

Cyclopropane fatty acids (CFAs) are synthetized in situ by the transfer of a methylene group from S-adenosyl-L-methionine to a double bond of unsaturated fatty acid chains of membrane phospholipids. This conversion, catalyzed by the Cfa synthase enzyme, occurs in many bacteria and is recognized to play a key role in the adaptation of bacteria in response to a drastic perturbation of the environment. The role of CFAs in the acid tolerance response was investigated in the lactic acid bacterium Lactococcus lactis MG1363. A mutant of the cfa gene was constructed by allelic exchange. The cfa gene encoding the Cfa synthase was cloned and introduced into the mutant to obtain the complemented strain for homologous system studies. Data obtained by gas chromatography (GC) and GC-mass spectrometry (GC-MS) validated that the mutant could not produce CFA. The CFA levels in both the wild-type and complemented strains increased upon their entry to stationary phase, especially with acid-adapted cells or, more surprisingly, with ethanol-adapted cells. The results obtained by performing quantitative reverse transcription-PCR (qRT-PCR) experiments showed that transcription of the cfa gene was highly induced by acidity (by 10-fold with cells grown at pH 5.0) and by ethanol (by 9-fold with cells grown with 6% ethanol) in comparison with that in stationary phase. Cell viability experiments were performed after an acidic shock on the mutant strain, the wild-type strain, and the complemented strain, as a control. The higher viability level of the acid-adapted cells of the three strains after 3 h of shock proved that the cyclopropanation of unsaturated fatty acids is not essential for L. lactis subsp. cremoris survival under acidic conditions. Moreover, fluorescence anisotropy data showed that CFA itself could not maintain the membrane fluidity level, particularly with ethanol-grown cells.

Influence of cyclopropane fatty acids on heat, high pressure, acid and oxidative resistance in Escherichia coli.

PubMed

Chen, Yuan Yao; Gänzle, Michael G

2016-04-02

Heat and high pressure resistant strains of Escherichia coli are a challenge to food safety. This study investigated effects of cyclopropane fatty acids (CFAs) on stress tolerance in the heat- and pressure-resistant strain E. coli AW1.7 and the sensitive strain E. coli MG1655. The role of CFAs was explored by disruption of cfa coding for CFA synthase with an in-frame, unmarked deletion method. Both wild-type strains consumed all the unsaturated fatty acids (C16:1 and C18:1) that were mostly converted to CFAs and a low proportion to saturated fatty acid (C16:0). Moreover, E. coli AW1.7 contained a higher proportion of membrane C19:0 cyclopropane fatty acid than E. coli MG1655 (P<0.05). The Δcfa mutant strains did not produce CFAs, and the corresponding substrates C16:1 and C18:1 accumulated in membrane lipids. The deletion of cfa did not alter resistance to H2O2 but increased the lethality of heat, high pressure and acid treatments in E. coli AW1.7, and E. coli MG1655. E. coli AW1.7 and its Δcfa mutant were more resistant to pressure and heat but less resistant to acid stress than E. coli MG1655. Heat resistance of wild-type strains and their Δcfa mutant was also assessed in beef patties grilled to an internal temperature of 71 °C. After treatment, cell counts of wild type strains were higher than those of the Δcfa mutant strains. In conclusion, CFA synthesis in E. coli increases heat, high pressure and acid resistance, and increases heat resistance in food. This knowledge on mechanisms of stress resistance will facilitate the design of intervention methods for improved pathogen control in food production. Copyright © 2016 Elsevier B.V. All rights reserved.

Cyclopropanation of Membrane Unsaturated Fatty Acids Is Not Essential to the Acid Stress Response of Lactococcus lactis subsp. cremoris ▿

PubMed Central

To, Thi Mai Huong; Grandvalet, Cosette; Tourdot-Maréchal, Raphaëlle

2011-01-01

Cyclopropane fatty acids (CFAs) are synthetized in situ by the transfer of a methylene group from S-adenosyl-l-methionine to a double bond of unsaturated fatty acid chains of membrane phospholipids. This conversion, catalyzed by the Cfa synthase enzyme, occurs in many bacteria and is recognized to play a key role in the adaptation of bacteria in response to a drastic perturbation of the environment. The role of CFAs in the acid tolerance response was investigated in the lactic acid bacterium Lactococcus lactis MG1363. A mutant of the cfa gene was constructed by allelic exchange. The cfa gene encoding the Cfa synthase was cloned and introduced into the mutant to obtain the complemented strain for homologous system studies. Data obtained by gas chromatography (GC) and GC-mass spectrometry (GC-MS) validated that the mutant could not produce CFA. The CFA levels in both the wild-type and complemented strains increased upon their entry to stationary phase, especially with acid-adapted cells or, more surprisingly, with ethanol-adapted cells. The results obtained by performing quantitative reverse transcription-PCR (qRT-PCR) experiments showed that transcription of the cfa gene was highly induced by acidity (by 10-fold with cells grown at pH 5.0) and by ethanol (by 9-fold with cells grown with 6% ethanol) in comparison with that in stationary phase. Cell viability experiments were performed after an acidic shock on the mutant strain, the wild-type strain, and the complemented strain, as a control. The higher viability level of the acid-adapted cells of the three strains after 3 h of shock proved that the cyclopropanation of unsaturated fatty acids is not essential for L. lactis subsp. cremoris survival under acidic conditions. Moreover, fluorescence anisotropy data showed that CFA itself could not maintain the membrane fluidity level, particularly with ethanol-grown cells. PMID:21421775

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis

PubMed Central

Srivastava, Niraj Kumar; Sharma, Shikha; Sharma, Rajkumar; Sinha, Neeraj; Mandal, Sudhir Kumar; Sharma, Deepak

2018-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA. PMID:29743863

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis.

PubMed

Srivastava, Niraj Kumar; Sharma, Shikha; Sharma, Rajkumar; Sinha, Neeraj; Mandal, Sudhir Kumar; Sharma, Deepak

2018-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA.

Effect of inflammation stimulation on energy and nutrient utilization in piglets selected for low and high residual feed intake.

PubMed

Labussière, E; Dubois, S; Gilbert, H; Thibault, J N; Le Floc'h, N; Noblet, J; van Milgen, J

2015-10-01

Selection of animals for improved feed efficiency can affect sustainability of animal production because the most efficient animals may face difficulties coping with challenges. The objective of this study was to determine the effects of an inflammatory challenge (using an intravenous injection of complete Freund's adjuvant - CFA) in piglets from two lines of pigs divergently selected during the fattening period for a low (RFI-) or a high (RFI+) residual feed intake (RFI; difference between actual feed intake and theoretical feed requirements). Nitrogen and energy balances (including heat production - HP - and its components: activity-related HP - AHP, thermic effect of feeding, and resting HP) were measured individually in thirteen 20-kg BW castrated male piglets (six and seven from RFI+ and RFI- line, respectively) fed at the same level (1.72 MJ ME/kg BW0.60 per day) from 3 days before to 3 days after CFA injection. Dynamics of dietary U-13C-glucose oxidation were estimated from measurements of 13CO2 production on the day before and 3 days after the CFA injection. Oxidation of dietary nutrients and lipogenesis were calculated based on HP and O2 consumption and CO2 production. The data were analyzed as repeated measurements within piglets in a mixed model. Before CFA injection, RFI- piglets had a lower resting energy expenditure than RFI+ piglets, which tended to increase energy retention because of a higher energy retention as fat. The CFA injection did not affect feed intake from the day following CFA injection onwards but it increased energy retention (P=0.04). Time to recover 50% of 13C from dietary glucose as expired 13CO2 was higher in RFI+ piglets before inducing inflammation but decreased after to the level of RFI- piglets (P<0.01). Oxidation of U-13C-glucose tended to slightly increased in RFI- piglets and to decreased in RFI+ piglets (P=0.10) because of CFA. Additionally, RFI- piglets had a lower respiratory quotient during the 1st day following the CFA injection whereas RFI+ piglets tended to have a higher respiratory quotient. In conclusion, selection for RFI during the fattening period also affected the energy metabolism of pigs during earlier stages of growth. The effects of CFA injection were moderated in both lines but the most efficient animals (RFI-) exhibited a marked re-orientation of nutrients only during the 1st day after CFA, and seemed to recover thereafter, whereas the less efficient piglets expressed a more prolonged alteration of their metabolism.

Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood.

PubMed

Boecker-Schlier, Regina; Holz, Nathalie E; Buchmann, Arlette F; Blomeyer, Dorothea; Plichta, Michael M; Jennen-Steinmetz, Christine; Wolf, Isabella; Baumeister, Sarah; Treutlein, Jens; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2016-05-15

Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation.

PubMed

Wei, F; Dubner, R; Ren, K

1999-03-01

Previous findings indicate that the brain stem descending system becomes more active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal sites that mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were produced in the nucleus raphe magnus (NRM), the nuclei reticularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). Compared to vehicle-injected animals with injection of vehicle alone, microinjection of a serotoninergic neurotoxin 5,7-dihydroxytryptamine into the NRM significantly increased thermal hyperalgesia and Fos protein expression in lumbar spinal cord after hindpaw inflammation. In contrast, the selective bilateral destruction of the NGC with a soma-selective excitotoxic neurotoxin, ibotenic acid, led to an attenuation of hyperalgesia and a reduction of inflammation-induced spinal Fos expression. Furthermore, if the NGC lesion was extended to involve the NRM, the behavioral hyperalgesia and CFA-induced Fos expression were similar to that in vehicle-injected rats. Bilateral LC/SC lesions were produced by microinjections of a noradrenergic neurotoxin, DSP-4. There was a significant increase in inflammation-induced spinal Fos expression, especially in the ipsilateral superficial dorsal horn following LC/SC lesions. These results demonstrated that multiple specific brain stem sites are involved in descending modulation of inflammatory hyperalgesia. Both NRM and LC/SC descending pathways are major sources of enhanced inhibitory modulation in inflamed animals. The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain and hyperalgesia is fine-tuned by descending pathways. The imbalance of these modulating systems may be one mechanism underlying variability in acute and chronic pain conditions.

Latent dimensions of posttraumatic stress disorder and their relations with alcohol use disorder.

PubMed

Biehn, Tracey L; Contractor, Ateka A; Elhai, Jon D; Tamburrino, Marijo; Fine, Thomas H; Cohen, Gregory; Shirley, Edwin; Chan, Philip K; Liberzon, Israel; Calabrese, Joseph R; Galea, Sandro

2016-03-01

The objective of this study was to evaluate the relationship between factors of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) using confirmatory factor analysis (CFA) in order to further our understanding of the substantial comorbidity between these two disorders. CFA was used to examine which factors of PTSD's dysphoria model were most related to AUD in a military sample. Ohio National Guard soldiers with a history of overseas deployment participated in the survey (n = 1215). Participants completed the PTSD Checklist and a 12-item survey from the National Survey on Drug Use used to diagnosis AUD. The results of the CFA indicated that a combined model of PTSD's four factors and a single AUD factor fit the data very well. Correlations between PTSD's factors and a latent AUD factor ranged from correlation coefficients of 0.258-0.285, with PTSD's dysphoria factor demonstrating the strongest correlation. However, Wald tests of parameter constraints revealed that AUD was not more correlated with PTSD's dysphoria than other PTSD factors. All four factors of PTSD's dysphoria model demonstrate comparable correlations with AUD. The role of dysphoria to the construct of PTSD is discussed.

Mimic Carbonic Anhydrase Using Metal-Organic Frameworks for CO2 Capture and Conversion.

PubMed

Jin, Chaonan; Zhang, Sainan; Zhang, Zhenjie; Chen, Yao

2018-02-19

Carbonic anhydrase (CA) is a zinc-containing metalloprotein, in which the Zn active center plays the key role to transform CO 2 into carbonate. Inspired by nature, herein we used metal-organic frameworks (MOFs) to mimic CA for CO 2 conversion, on the basis of the structural similarity between the Zn coordination in MOFs and CA active center. The biomimetic activity of MOFs was investigated by detecting the hydrolysis of para-nitrophenyl acetate, which is a model reaction used to evaluate CA activity. The biomimetic materials (e.g., CFA-1) showed good catalytic activity, and excellent reusability, and solvent and thermal stability, which is very important for practical applications. In addition, ZIF-100 and CFA-1 were used to mimic CA to convert CO 2 gas, and exhibited good efficiency on CO 2 conversion compared with those of other porous materials (e.g., MCM-41, active carbon). This biomimetic study revealed a novel CO 2 treatment method. Instead of simply using MOFs to absorb CO 2 , ZIF-100 and CFA-1 were used to mimic CA for in situ CO 2 conversion, which provides a new prospect in the biological and industrial applications of MOFs.

N-point correlation functions in the CfA and SSRS redshift distribution of galaxies

NASA Technical Reports Server (NTRS)

Gaztanaga, Enrique

1992-01-01

Using counts in cells, we estimate the volume-average N-point galaxy correlation functions for N = 2, 3, and 4, in redshift samples of the CfA and SSRS catalogs. Volume-limited samples of different sizes are used to study the uncertainties at different scales, the shot noise, and the problem with the boundaries. The hierarchical constants S3 and S4 agree well in all samples in CfA and SSRS, with average S3 = 194 +/- 0.07 and S4 = 4.56 +/- 0.53. We compare these results with estimates obtained from angular catalogs and recent analysis over IRAS samples. The amplitudes SJ seem larger in real space than in redshift space, although the values from the angular analysis correspond to smaller scales, where we might expect larger nonperturbative effects. It is also found that S3 and S4 are smaller for IRAS than for optical galaxies. This, together with the fact that IRAS galaxies have smaller amplitude for the above correlation functions, indicates that the density fluctuations of IRAS galaxies cannot be simply proportional to the density fluctuations of optical galaxies, i.e., biasing has to be nonlinear between them.

Serologic Correlates of Protection against Enterotoxigenic Escherichia coli Diarrhea

DTIC Science & Technology

2005-01-14

strain expressed either LT, CFA/I, CFA/II, or CFA/IV. Episodes in which Shigella spe- cies, Campylobacter species, rotavirus , or astrovirus were iso- lated...serum antibody levels cor- relate with protection against diarrheal illness caused by cholera and rotavirus [29–33]. Serum vibriocidal antibodies...cholera. J Infect Dis 1991; 163:1235–42. 31. Clemens JD, Ward RL, Rao MR, et al. Seroepidemiologic evaluation of antibodies to rotavirus as correlates of

Continuous analysis of phosphate in a Greenland shallow ice core

NASA Astrophysics Data System (ADS)

Kjær, Helle Astrid; Svensson, Anders; Bigler, Matthias; Vallelonga, Paul; Kettner, Ernesto; Dahl-Jensen, Dorthe

2010-05-01

Phosphate is an important and sometimes limiting nutrient for primary production in the oceans. Because of deforestation and the use of phosphate as a fertilizer changes in the phosphate cycle have occurred over the last centuries. On longer time scales, sea level changes are thought to have also caused changes in the phosphate cycle. Analyzing phosphate concentrations in ice cores may help to gain important knowledge about those processes. In the present study, we attach a phosphate detection line to an existing continuous flow analysis (CFA) setup for ice core analysis at the University of Copenhagen. The CFA system is optimized for high-resolution measurements of insoluble dust particles, electrolytic melt water conductivity, and the concentrations of ammonium and sodium. For the phosphate analysis we apply a continuous and highly sensitive absorption method that has been successfully applied to determine phosphate concentrations of sea water (Zhang and Chi, 2002). A line of melt water from the CFA melt head (1.01 ml per minute) is combined with a molybdate blue reagent and an ascorbic acid buffer. An uncompleted reaction takes place in five meters of heated mixing coils before the absorption measurement at a wavelength of 710 nanometer takes place in a 2 m long liquid waveguide cell (LWCC) with an inner volume of 0.5 ml. The method has a detection limit of around 0.1 ppb and we are currently investigating a possible interference from molybdate reacting with silicates that are present in low amounts in the ice. Preliminary analysis of early Holocene samples from the NGRIP ice core show phosphate concentration values of a few ppb. In this study, we will attempt to determine past levels of phosphate in a shallow Northern Greenland firn core with an annual layer thickness of about 20 cm ice equivalent. With a melt speed of 2.5 cm ice per minute our method should allow the resolution of any seasonal variability in phosphate concentrations.

Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease

PubMed Central

Karl, Franziska; Sommer, Claudia; Üçeyler, Nurcan

2017-01-01

Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. PMID:28662189

Uncertainties in the cluster-cluster correlation function

NASA Astrophysics Data System (ADS)

Ling, E. N.; Frenk, C. S.; Barrow, J. D.

1986-12-01

The bootstrap resampling technique is applied to estimate sampling errors and significance levels of the two-point correlation functions determined for a subset of the CfA redshift survey of galaxies and a redshift sample of 104 Abell clusters. The angular correlation function for a sample of 1664 Abell clusters is also calculated. The standard errors in xi(r) for the Abell data are found to be considerably larger than quoted 'Poisson errors'. The best estimate for the ratio of the correlation length of Abell clusters (richness class R greater than or equal to 1, distance class D less than or equal to 4) to that of CfA galaxies is 4.2 + 1.4 or - 1.0 (68 percentile error). The enhancement of cluster clustering over galaxy clustering is statistically significant in the presence of resampling errors. The uncertainties found do not include the effects of possible systematic biases in the galaxy and cluster catalogs and could be regarded as lower bounds on the true uncertainty range.

Confirmatory factor analysis applied to the Force Concept Inventory

NASA Astrophysics Data System (ADS)

Eaton, Philip; Willoughby, Shannon D.

2018-06-01

In 1995, Huffman and Heller used exploratory factor analysis to draw into question the factors of the Force Concept Inventory (FCI). Since then several papers have been published examining the factors of the FCI on larger sets of student responses and understandable factors were extracted as a result. However, none of these proposed factor models have been verified to not be unique to their original sample through the use of independent sets of data. This paper seeks to confirm the factor models proposed by Scott et al. in 2012, and Hestenes et al. in 1992, as well as another expert model proposed within this study through the use of confirmatory factor analysis (CFA) and a sample of 20 822 postinstruction student responses to the FCI. Upon application of CFA using the full sample, all three models were found to fit the data with acceptable global fit statistics. However, when CFA was performed using these models on smaller sample sizes the models proposed by Scott et al. and Eaton and Willoughby were found to be far more stable than the model proposed by Hestenes et al. The goodness of fit of these models to the data suggests that the FCI can be scored on factors that are not unique to a single class. These scores could then be used to comment on how instruction methods effect the performance of students along a single factor and more in-depth analyses of curriculum changes may be possible as a result.

Modelling and analysis of FMS productivity variables by ISM, SEM and GTMA approach

NASA Astrophysics Data System (ADS)

Jain, Vineet; Raj, Tilak

2014-09-01

Productivity has often been cited as a key factor in a flexible manufacturing system (FMS) performance, and actions to increase it are said to improve profitability and the wage earning capacity of employees. Improving productivity is seen as a key issue for survival and success in the long term of a manufacturing system. The purpose of this paper is to make a model and analysis of the productivity variables of FMS. This study was performed by different approaches viz. interpretive structural modelling (ISM), structural equation modelling (SEM), graph theory and matrix approach (GTMA) and a cross-sectional survey within manufacturing firms in India. ISM has been used to develop a model of productivity variables, and then it has been analyzed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) are powerful statistical techniques. CFA is carried by SEM. EFA is applied to extract the factors in FMS by the statistical package for social sciences (SPSS 20) software and confirming these factors by CFA through analysis of moment structures (AMOS 20) software. The twenty productivity variables are identified through literature and four factors extracted, which involves the productivity of FMS. The four factors are people, quality, machine and flexibility. SEM using AMOS 20 was used to perform the first order four-factor structures. GTMA is a multiple attribute decision making (MADM) methodology used to find intensity/quantification of productivity variables in an organization. The FMS productivity index has purposed to intensify the factors which affect FMS.

The effect of 1800MHz radio-frequency radiation on NMDA receptor subunit NR1 expression and peroxidation in the rat brain in healthy and inflammatory states.

PubMed

Bodera, Paweł; Makarova, Katerina; Zawada, Katarzyna; Antkowiak, Bożena; Paluch, Małgorzata; Sobiczewska, Elżbieta; Sirav, Bahriye; Siwicki, Andrzej K; Stankiewicz, Wanda

2017-08-01

The aim of this study was to evaluate the effect of repeated exposure (5 times for 15min) of 1800MHz radio-frequency radiation (RFR) on N-methyl-d-aspartate receptor subunit NR1 (NMDA-NR1) expression in the brains of rats in a persistent inflammatory state. We also measured the effect of RFR combined with tramadol (TRAM) to determine the potential antioxidant capacity of this agent. The effects of the Global System for Mobile Communication (GSM) modulated 1800MHz RFR exposure on the expression and activity of glutamate receptor channels with antioxidative activity in brain tissue was measured using oxygen radical absorbance capacity (ORAC) and electron spin resonance (ESR) detection of the hydroxyl radical generated by the Fenton reaction. NMDA-NR1 was measured in the cerebral tissue of rats with inflammation (complete Freund's adjuvent) and those injected with tramadol after RFR exposure (RFR, RFR/TRAM) and in non-exposed (baseline, TRAM) rats. No differences between the baseline group and the exposed group (RFR) were observed. NMDA-NR1 expression decreased after CFA injection and RFR exposure, and an elevated expression of NMDA-NR1 was observed in healthy control rats of both groups: TRAM/RFR and RFR. ORAC assessment revealed a robust effect of RFR, however the other experiments revealed equivocal effects. Further studies examining the combination of ORAC with NMDA are warranted to elucidate more clearly the effect of RFR on the brain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

PubMed Central

Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

Intratracheal instillation of coal and coal fly ash particles in mice induces DNA damage and translocation of metals to extrapulmonary tissues.

PubMed

León-Mejía, Grethel; Machado, Mariana Nascimento; Okuro, Renata Tiemi; Silva, Luis F O; Telles, Claudia; Dias, Johnny; Niekraszewicz, Liana; Da Silva, Juliana; Henriques, João Antônio Pêgas; Zin, Walter Araujo

2018-06-01

Continuous exposure to coal mining particles can cause a variety of lung diseases. We aimed to evaluate the outcomes of exposure to detailed characterized coal and coal fly ash (CFA) particles on DNA, lung and extrapulmonary tissues. Coal samples (COAL11 and COAL16) and CFA samples (CFA11 and CFA16) were included in this study. Intending to enhance the combustion process COAL16 was co-fired with a mixture of fuel oil and diesel oil, producing CFA16. Male BALB/c mice were intratracheally instilled with coal and CFA particles. Measurements were done 24h later. Results showed significant rigidity and obstruction of the central airways only for animals acutely exposed to coal particles. The COAL16 group also showed obstruction of the peripheral airways. Mononuclear cells were recruited in all treatment groups and expression of cytokines, particularly TNF-α and IL-1β, was observed. Only animals exposed to COAL16 showed a significant expression of IL-6 and recruitment of polymorphonuclear cells. DNA damage was demonstrated by Comet assay for all groups. Cr, Fe and Ni were detected in liver, spleen and brain, showing the efficient translocation of metals from the bloodstream to extrapulmonary organs. These effects were associated with particle composition (oxides, hydroxides, phosphates, sulfides, sulphates, silciates, organic-metalic compounds, and polycyclic aromatic hidrocarbons) rather than their size. This work provides state of knowledge on the effects of acute exposure to coal and CFA particles on respiratory mechanics, DNA damage, translocation of metals to other organs and related inflammatory processes. Copyright © 2018 Elsevier B.V. All rights reserved.

A structural basis for sustained bacterial adhesion: biomechanical properties of CFA/I pili.

PubMed

Andersson, Magnus; Björnham, Oscar; Svantesson, Mats; Badahdah, Arwa; Uhlin, Bernt Eric; Bullitt, Esther

2012-02-03

Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal disease worldwide. Adhesion pili (or fimbriae), such as the CFA/I (colonization factor antigen I) organelles that enable ETEC to attach efficiently to the host intestinal tract epithelium, are critical virulence factors for initiation of infection. We characterized the intrinsic biomechanical properties and kinetics of individual CFA/I pili at the single-organelle level, demonstrating that weak external forces (7.5 pN) are sufficient to unwind the intact helical filament of this prototypical ETEC pilus and that it quickly regains its original structure when the force is removed. While the general relationship between exertion of force and an increase in the filament length for CFA/I pili associated with diarrheal disease is analogous to that of P pili and type 1 pili, associated with urinary tract and other infections, the biomechanical properties of these different pili differ in key quantitative details. Unique features of CFA/I pili, including the significantly lower force required for unwinding, the higher extension speed at which the pili enter a dynamic range of unwinding, and the appearance of sudden force drops during unwinding, can be attributed to morphological features of CFA/I pili including weak layer-to-layer interactions between subunits on adjacent turns of the helix and the approximately horizontal orientation of pilin subunits with respect to the filament axis. Our results indicate that ETEC CFA/I pili are flexible organelles optimized to withstand harsh motion without breaking, resulting in continued attachment to the intestinal epithelium by the pathogenic bacteria that express these pili. Copyright © 2011 Elsevier Ltd. All rights reserved.

Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

PubMed Central

FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

2016-01-01

Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

Comparison of Ultrasound-Guided and Fluoroscopy-Assisted Antegrade Common Femoral Artery Puncture Techniques

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

Slattery, Michael M.; Goh, Gerard S.; Power, Sarah

PurposeTo prospectively compare the procedural time and complication rates of ultrasound-guided and fluoroscopy-assisted antegrade common femoral artery (CFA) puncture techniques.Materials and MethodsHundred consecutive patients, undergoing a vascular procedure for which an antegrade approach was deemed necessary/desirable, were randomly assigned to undergo either ultrasound-guided or fluoroscopy-assisted CFA puncture. Time taken from administration of local anaesthetic to vascular sheath insertion in the superficial femoral artery (SFA), patients’ age, body mass index (BMI), fluoroscopy radiation dose, haemostasis method and immediate complications were recorded. Mean and median values were calculated and statistically analysed with unpaired t tests.ResultsSixty-nine male and 31 female patients underwent antegrademore » puncture (mean age 66.7 years). The mean BMI was 25.7 for the ultrasound-guided (n = 53) and 25.3 for the fluoroscopy-assisted (n = 47) groups. The mean time taken for the ultrasound-guided puncture was 7 min 46 s and for the fluoroscopy-assisted technique was 9 min 41 s (p = 0.021). Mean fluoroscopy dose area product in the fluoroscopy group was 199 cGy cm{sup 2}. Complications included two groin haematomas in the ultrasound-guided group and two retroperitoneal haematomas and one direct SFA puncture in the fluoroscopy-assisted group.ConclusionUltrasound-guided technique is faster and safer for antegrade CFA puncture when compared to the fluoroscopic-assisted technique alone.« less

Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

PubMed

Jeffrey-Gauthier, Renaud; Piché, Mathieu; Leblond, Hugues

2017-09-17

Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI. Lower limb kinematics during treadmill training was assessed before and after complete SCI at T8 (2, 7, 14, 21 and 28days post-injury). Locomotor recovery was compared in 4 groups of CD1 mice: control spinal mice; spinal mice with daily locomotor training; spinal mice with lumbar muscle inflammation (Complete Freund's Adjuvant (CFA) injection); and spinal mice with locomotor training and CFA. On day 28, H-reflex excitability and its inhibition at high-frequency stimulation (frequency-dependent depression: FDD) were compared between groups, all of which showed locomotor recovery. Recovery was enhanced by training, whereas lumbar muscle inflammation hindered these effects (knee angular excursion and paw drag: p's<0.05). In addition, lumbar muscle inflammation impaired hind limb coupling during locomotion (p<0.05) throughout recovery. Also, H-reflex disinhibition was prevented by training, with or without CFA injection (p's<0.05). Altogether, these results indicate that back muscle inflammation modulates spinally mediated locomotor recovery in mice with complete SCI, in part, by reducing adaptive changes induced by training. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Cloning and expression of colonization factor antigen I (CFA/I) epitopes of enterotoxigenic Escherichia coli (ETEC) in Salmonella flagellin.

PubMed

Luna, M G; Martins, M M; Newton, S M; Costa, S O; Almeida, D F; Ferreira, L C

1997-01-01

Oligonucleotides coding for linear epitopes of the fimbrial colonization factor antigen I (CFA/I) of enterotoxigenic Escherichia coli (ETEC) were cloned and expressed in a deleted form of the Salmonella muenchen flagellin fliC (H1-d) gene. Four synthetic oligonucleotide pairs coding for regions corresponding to amino acids 1 to 15 (region I), amino acids 11 to 25 (region II), amino acids 32 to 45 (region III) and amino acids 88 to 102 (region IV) were synthesized and cloned in the Salmonella flagellin-coding gene. All four hybrid flagellins were exported to the bacterial surface where they produced flagella, but only three constructs were fully motile. Sera recovered from mice immunized with intraperitoneal injections of purified flagella containing region II (FlaII) or region IV (FlaIV) showed high titres against dissociated solid-phase-bound CFA/I subunits. Hybrid flagellins containing region I (FlaI) or region III (FlaIII) elicited a weak immune response as measured in enzyme-linked immunosorbent assay (ELISA) with dissociated CFA/I subunits. None of the sera prepared with purified hybrid flagella were able to agglutinate or inhibit haemagglutination promoted by CFA/I-positive strains. Moreover, inhibition ELISA tests indicated that antisera directed against region I, II, III or IV cloned in flagellin were not able to recognize surface-exposed regions on the intact CFA/I fimbriae.

Peripheral inflammation increased the synaptic expression of NMDA receptors in spinal dorsal horn.

PubMed

Yang, Xian; Yang, Hong-Bin; Xie, Qin-Jian; Liu, Xiao-Hua; Hu, Xiao-Dong

2009-07-01

Considerable evidence has indicated that the aberrant, sustained enhancement of spinal NMDA receptors (NMDARs) function is closely associated with behavioral sensitization during inflammatory pain. However, the molecular mechanisms underlying inflammation-induced NMDARs hyperfunction remain poorly understood. The present study performed immunoblotting analysis to evaluate the possible changes in the protein expression of spinal NMDARs after injection of complete Freund's adjuvant (CFA) in mice. We found that CFA did not affect the total protein level of NMDARs subunit NR1 in spinal dorsal horn. However, NR1 immunoreactivity at synapses significantly increased after CFA injection, which was correlated in the time course with the development of mechanical allodynia. Inhibition of spinal NMDARs with D-APV completely eliminated the CFA-induced increase in NR1 immunoreactive density at synapses, and direct application of NMDA onto the spinal cord of naïve mice mimicked the effects of CFA, suggesting the importance of NMDARs activity in regulating the synaptic content of NR1 during inflammatory pain. Moreover, cAMP-dependent protein kinase (PKA) downstream to NMDARs was also required for NR1 synaptic expression because inhibition of PKA activity abolished the enhancement of synaptic NR1 immunoreactivity evoked by either CFA or NMDA. Thus, our data suggested that NMDARs- and PKA-dependent increase in NR1 synaptic expression represented an important mechanism for the hyperfunction of spinal NMDARs following peripheral inflammation.

Common factor analysis versus principal component analysis: choice for symptom cluster research.

PubMed

Kim, Hee-Ju

2008-03-01

The purpose of this paper is to examine differences between two factor analytical methods and their relevance for symptom cluster research: common factor analysis (CFA) versus principal component analysis (PCA). Literature was critically reviewed to elucidate the differences between CFA and PCA. A secondary analysis (N = 84) was utilized to show the actual result differences from the two methods. CFA analyzes only the reliable common variance of data, while PCA analyzes all the variance of data. An underlying hypothetical process or construct is involved in CFA but not in PCA. PCA tends to increase factor loadings especially in a study with a small number of variables and/or low estimated communality. Thus, PCA is not appropriate for examining the structure of data. If the study purpose is to explain correlations among variables and to examine the structure of the data (this is usual for most cases in symptom cluster research), CFA provides a more accurate result. If the purpose of a study is to summarize data with a smaller number of variables, PCA is the choice. PCA can also be used as an initial step in CFA because it provides information regarding the maximum number and nature of factors. In using factor analysis for symptom cluster research, several issues need to be considered, including subjectivity of solution, sample size, symptom selection, and level of measure.

PCA-based spatially adaptive denoising of CFA images for single-sensor digital cameras.

PubMed

Zheng, Lei; Lukac, Rastislav; Wu, Xiaolin; Zhang, David

2009-04-01

Single-sensor digital color cameras use a process called color demosiacking to produce full color images from the data captured by a color filter array (CAF). The quality of demosiacked images is degraded due to the sensor noise introduced during the image acquisition process. The conventional solution to combating CFA sensor noise is demosiacking first, followed by a separate denoising processing. This strategy will generate many noise-caused color artifacts in the demosiacking process, which are hard to remove in the denoising process. Few denoising schemes that work directly on the CFA images have been presented because of the difficulties arisen from the red, green and blue interlaced mosaic pattern, yet a well-designed "denoising first and demosiacking later" scheme can have advantages such as less noise-caused color artifacts and cost-effective implementation. This paper presents a principle component analysis (PCA)-based spatially-adaptive denoising algorithm, which works directly on the CFA data using a supporting window to analyze the local image statistics. By exploiting the spatial and spectral correlations existing in the CFA image, the proposed method can effectively suppress noise while preserving color edges and details. Experiments using both simulated and real CFA images indicate that the proposed scheme outperforms many existing approaches, including those sophisticated demosiacking and denoising schemes, in terms of both objective measurement and visual evaluation.

Correlation between basalt flows and radiochemical and chemical constituents in selected wells in the southwestern part of the Idaho National Laboratory, Idaho

USGS Publications Warehouse

Bartholomay, Roy C.; Hodges, Mary K. V.; Champion, Duane E.

2017-12-21

Wastewater discharged to wells and ponds and wastes buried in shallow pits and trenches at facilities at the Idaho National Laboratory (INL) have contributed contaminants to the eastern Snake River Plain (ESRP) aquifer in the southwestern part of the INL. This report describes the correlation between subsurface stratigraphy in the southwestern part of the INL with information on the presence or absence of wastewater constituents to better understand how flow pathways in the aquifer control the movement of wastewater discharged at INL facilities. Paleomagnetic inclination was used to identify subsurface basalt flows based on similar inclination measurements, polarity, and stratigraphic position. Tritium concentrations, along with other chemical information for wells where tritium concentrations were lacking, were used as an indicator of which wells were influenced by wastewater disposal.The basalt lava flows in the upper 150 feet of the ESRP aquifer where wastewater was discharged at the Idaho Nuclear Technology and Engineering Center (INTEC) consisted of the Central Facilities Area (CFA) Buried Vent flow and the AEC Butte flow. At the Advanced Test Reactor (ATR) Complex, where wastewater would presumably pond on the surface of the water table, the CFA Buried Vent flow probably occurs as the primary stratigraphic unit present; however, AEC Butte flow also could be present at some of the locations. At the Radioactive Waste Management Complex (RWMC), where contamination from buried wastes would presumably move down through the unsaturated zone and pond on the surface of the water table, the CFA Buried Vent; Late Basal Brunhes; or Early Basal Brunhes basalt flows are the flow unit at or near the water table in different cores.In the wells closer to where wastewater disposal occurred at INTEC and the ATR-Complex, almost all the wells show wastewater influence in the upper part of the ESRP aquifer and wastewater is present in both the CFA Buried Vent flow and AEC Butte flow. The CFA Buried Vent flow and AEC Butte flow are also present in wells at and north of CFA and are all influenced by wastewater contamination. All wells with the AEC Butte flow present have wastewater influence and 83 percent of the wells with the more prevalent CFA Buried Vent flow have wastewater influence. South and southeast of CFA, most wells are not influenced by wastewater disposal and are completed in the Big Lost Flow and the CFA Buried Vent flow. Wells southwest of CFA are influenced by wastewater disposal and are completed in the Big Lost flow and CFA Buried Vent flow at the top of the aquifer. Basalt stratigraphy indicates that the CFA Buried Vent flow is the predominant flow in the upper part of the ESRP aquifer at and near the RWMC as it is present in all the wells in this area. The Late Basal Brunhes flow, Middle Basal Brunhes flow, Early Basal Brunhes flow, South Late Matuyama flow, and Matuyama flow are also present in various wells influenced by waste disposal.Some wells south of RWMC do not show wastewater influence, and the lack of wastewater influence could be due to low hydraulic conductivities. Several wells south and southeast of CFA also do not show wastewater influence. Low hydraulic conductivities or ESRP subsidence are possible causes for lack of wastewater south of CFA.Multilevel monitoring wells completed much deeper in the aquifer show influence of wastewater in numerous basalt flows. Well Middle 2051 (northwest of RWMC) does not show wastewater influence in its upper three basalt flows (CFA Buried Vent, Late Basal Brunhes, and Middle Basal Brunhes); however, wastewater is present in two deeper flows (the Matuyama and Jaramillo flows). Well USGS 131A (southwest of CFA) and USGS132 (south of RWMC) both show wastewater influence in all the basalt flows sampled in the upper 600 feet of the aquifer. Wells USGS 137A, 105, 108, and 103 completed along the southern boundary of the INL all show wastewater influence in several basalt flows including the G flow, Middle and Early Basal Brunhes flows, the South Late Matuyama flow and the Matuyama flow; however, the strongest wastewater influence appears to be in the South Late Matuyama flow. The concentrations of wastewater constituents in deeper parts of these wells support the concept of groundwater flow deepening in the southwestern part of the INL.

Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats

PubMed Central

Kim, Hye-Jin; Lee, Geun-Woo; Kim, Min-Ji; Yang, Kui-Ye; Kim, Seong-Taek; Bae, Yong-Cheol

2015-01-01

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions. PMID:26170739

Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

PubMed

Thornton, Judith; Rangaraj, Satyapal

2016-01-21

Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis. Studies should also better define the two conditions. A study has recently been conducted in CFA and may help fill this gap when analysed and published.There are no trials included in the review up to January 2016. We will continue to run searches to identify any potentially relevant studies; however, we do not plan to update other sections of the review until new studies are published.

Psychometric Evaluation of the 6-item Version of the Multigroup Ethnic Identity Measure with East Asian Adolescents in Canada

PubMed Central

Homma, Yuko; Zumbo, Bruno D.; Saewyc, Elizabeth M.; Wong, Sabrina T.

2016-01-01

We examined the psychometric properties of scores on a 6-item version of the Multigroup Ethnic Identity Measure (MEIM) among East Asian adolescents in Canada. A series of confirmatory factor analysis (CFA) was conducted for 4,190 East Asians who completed a provincial survey of students in grades 7 to 12. The MEIM measured highly correlated dimensions of ethnic identity (exploration and commitment). Further, multi-group CFA indicated that the scale measured the same constructs on the same metric across three age groups and across four groups with varying degrees of exposure to Canadian and East Asian cultures. The findings suggest the short version of the MEIM can be used to compare levels of ethnic identity across different age or acculturation groups. PMID:27833471

The Strengths and Difficulties Questionnaire (SDQ): Factor Structure and Gender Equivalence in Norwegian Adolescents.

PubMed

Bøe, Tormod; Hysing, Mari; Skogen, Jens Christoffer; Breivik, Kyrre

2016-01-01

Although frequently used with older adolescents, few studies of the factor structure, internal consistency and gender equivalence of the SDQ exists for this age group, with inconsistent findings. In the present study, confirmatory factor analysis (CFA) was used to evaluate the five-factor structure of the SDQ in a population sample of 10,254 16-18 year-olds from the youth@hordaland study. Measurement invariance across gender was assessed using multigroup CFA. A modestly modified five-factor solution fitted the data acceptably, accounting for one cross loading and some local dependencies. Importantly, partial measurement non-invariance was identified, with differential item functioning in eight items, and higher correlations between emotional and conduct problems for boys compared to girls. Implications for use clinically and in research are discussed.

Testing CMAQ chemistry sensitivities in base case and emissions control runs at SEARCH and SOS99 surface sites in the southeastern US

NASA Astrophysics Data System (ADS)

Arnold, J. R.; Dennis, Robin L.

CMAQ was run to simulate urban and regional tropospheric conditions in the southeastern US over 14 days in July 1999 at 32, 8 and 2 km grid spacings. Runs were made with either of two older mechanisms, Carbon Bond IV (CB4) and the Regional Acid Deposition Model, version 2 (RADM2), and with the more recent and complete California Statewide Air Pollution Research Center, version 1999 mechanism (SAPRC99) in a sensitivity matrix with a full emissions base case and separate 50% control scenarios for emissions of nitrogen oxides (NO X) and volatile organic compounds (VOC). Results from the base case were compared to observations at the Southeastern Aerosol Research and Characterization Study (SEARCH) site at Jefferson Street in Atlanta, GA (JST) and the Southern Oxidant Study (SOS) Cornelia Fort Airpark (CFA) site downwind of Nashville, TN. In the base case, SAPRC99 predicted more ozone (O 3) than CB4 or RADM2 almost every hour and especially for afternoon maxima at both JST and CFA. Performance of the 8 km models at JST was better than that of the 32 km ones for all chemistries, reducing the 1 h peak bias by as much as 30 percentage points; at CFA only the RADM2 8 km model improved. The 2 km solutions did not show improved performance over the 8 km ones at either site, with normalized 1 h bias in the peak O 3 ranging from 21% at CFA to 43% at JST. In the emissions control cases, SAPRC99 was generally more responsive than CB4 and RADM2 to NO X and VOC controls, excepting hours at JST with predicted increased O 3 from NO X control. Differential sensitivity to chemical mechanism varied by more than ±10% for NO X control at JST and CFA, and in a similar range for VOC control at JST. VOC control at the more strongly NO X- limited urban CFA site produced a differential sensitivity response of <5%. However, even when differential sensitivities in control cases were small, neither their sign nor their magnitude could be reliably determined from model performance in the full emissions case, meaning that the degree of O 3 response to a change in chemical mechanism can differ substantially with the level of precursor emissions. Hence we conclude that properly understanding the effects of changes in a model's chemical mechanism always requires emissions control cases as part of model sensitivity analysis.

Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses.

PubMed

Menetski, J; Mistry, S; Lu, M; Mudgett, J S; Ransohoff, R M; Demartino, J A; Macintyre, D E; Abbadie, C

2007-11-09

Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. There were no differences in mechanical allodynia in the partial sciatic nerve ligation model, in terms of either magnitude or duration of the allodynic response; however, both groups responded to the maximal extent measurable. In a model of inflammatory pain, elicited by intraplantar administration of complete Freund's adjuvant (CFA), CCL2 tg mice displayed both greater edema and thermal hyperalgesia compared with control mice. In control mice, edema and hyperalgesia returned to baseline values 5-7 days post CFA. However, in CCL2 tg mice, thermal hyperalgesia was significantly different from baseline up to 3 weeks post CFA. Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflammatory cytokine mRNA expression (IL-1beta, IL-6, and TNFalpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies.

Psychometric evaluation of Persian Nomophobia Questionnaire: Differential item functioning and measurement invariance across gender.

PubMed

Lin, Chung-Ying; Griffiths, Mark D; Pakpour, Amir H

2018-03-01

Background and aims Research examining problematic mobile phone use has increased markedly over the past 5 years and has been related to "no mobile phone phobia" (so-called nomophobia). The 20-item Nomophobia Questionnaire (NMP-Q) is the only instrument that assesses nomophobia with an underlying theoretical structure and robust psychometric testing. This study aimed to confirm the construct validity of the Persian NMP-Q using Rasch and confirmatory factor analysis (CFA) models. Methods After ensuring the linguistic validity, Rasch models were used to examine the unidimensionality of each Persian NMP-Q factor among 3,216 Iranian adolescents and CFAs were used to confirm its four-factor structure. Differential item functioning (DIF) and multigroup CFA were used to examine whether males and females interpreted the NMP-Q similarly, including item content and NMP-Q structure. Results Each factor was unidimensional according to the Rach findings, and the four-factor structure was supported by CFA. Two items did not quite fit the Rasch models (Item 14: "I would be nervous because I could not know if someone had tried to get a hold of me;" Item 9: "If I could not check my smartphone for a while, I would feel a desire to check it"). No DIF items were found across gender and measurement invariance was supported in multigroup CFA across gender. Conclusions Due to the satisfactory psychometric properties, it is concluded that the Persian NMP-Q can be used to assess nomophobia among adolescents. Moreover, NMP-Q users may compare its scores between genders in the knowledge that there are no score differences contributed by different understandings of NMP-Q items.

Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels.

PubMed

Corcoran, Jenna; Winter, Matthew J; Lange, Anke; Cumming, Rob; Owen, Stewart F; Tyler, Charles R

2015-04-01

In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20mg/L) and for an environmentally relevant concentration (4μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

A validated model for the 22-item Sino-Nasal Outcome Test subdomain structure in chronic rhinosinusitis.

PubMed

Feng, Allen L; Wesely, Nicholas C; Hoehle, Lloyd P; Phillips, Katie M; Yamasaki, Alisa; Campbell, Adam P; Gregorio, Luciano L; Killeen, Thomas E; Caradonna, David S; Meier, Josh C; Gray, Stacey T; Sedaghat, Ahmad R

2017-12-01

Previous studies have identified subdomains of the 22-item Sino-Nasal Outcome Test (SNOT-22), reflecting distinct and largely independent categories of chronic rhinosinusitis (CRS) symptoms. However, no study has validated the subdomain structure of the SNOT-22. This study aims to validate the existence of underlying symptom subdomains of the SNOT-22 using confirmatory factor analysis (CFA) and to develop a subdomain model that practitioners and researchers can use to describe CRS symptomatology. A total of 800 patients with CRS were included into this cross-sectional study (400 CRS patients from Boston, MA, and 400 CRS patients from Reno, NV). Their SNOT-22 responses were analyzed using exploratory factor analysis (EFA) to determine the number of symptom subdomains. A CFA was performed to develop a validated measurement model for the underlying SNOT-22 subdomains along with various tests of validity and goodness of fit. EFA demonstrated 4 distinct factors reflecting: sleep, nasal, otologic/facial pain, and emotional symptoms (Cronbach's alpha, >0.7; Bartlett's test of sphericity, p < 0.001; Kaiser-Meyer-Olkin >0.90), independent of geographic locale. The corresponding CFA measurement model demonstrated excellent measures of fit (root mean square error of approximation, <0.06; standardized root mean square residual, <0.08; comparative fit index, >0.95; Tucker-Lewis index, >0.95) and measures of construct validity (heterotrait-monotrait [HTMT] ratio, <0.85; composite reliability, >0.7), again independent of geographic locale. The use of the 4-subdomain structure for SNOT-22 (reflecting sleep, nasal, otologic/facial pain, and emotional symptoms of CRS) was validated as the most appropriate to calculate SNOT-22 subdomain scores for patients from different geographic regions using CFA. © 2017 ARS-AAOA, LLC.

Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

PubMed Central

Corcoran, Jenna; Winter, Matthew J.; Lange, Anke; Cumming, Rob; Owen, Stewart F.; Tyler, Charles R.

2015-01-01

In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA is pharmacologically active in carp and has the potential to invoke PPARα-related responses in fish exposed in the environment, particularly considering that CFA may represent just one of a number of PPAR-active compounds present to which wild fish may be exposed. PMID:25749508

78 FR 26324 - Notice of Meeting

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78 FR 54242 - Notice of Meeting

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CFA-7: an interpenetrated metal-organic framework of the MFU-4 family.

PubMed

Schmieder, Phillip; Grzywa, Maciej; Denysenko, Dmytro; Hambach, Manuel; Volkmer, Dirk

2015-08-07

The novel interpenetrated metal-organic framework CFA-7 (Coordination Framework Augsburg University-7), [Zn5Cl4(tqpt)3], has been synthesized containing the organic linker {H2-tqpt = 6,6,14,14-tetramethyl-6,14-dihydroquinoxalino[2,3-b]phenazinebistriazole}. Reaction of H2-tqpt and anhydrous ZnCl2 in N,N-dimethylformamide (DMF) yields CFA-7 as pseudo-cubic crystals. CFA-7 serves as precursor for the synthesis of isostructural frameworks with redox-active metal centers, which is demonstrated by postsynthetic metal exchange of Zn(2+) by different M(2+) (M = Co, Ni, Cu) ions. The novel framework is robust upon solvent removal and has been structurally characterized by single-crystal X-ray diffraction, TGA and IR spectroscopy, as well as gas sorption (Ar, CO2 and H2).

Teaching Confirmatory Factor Analysis to Non-Statisticians: A Case Study for Estimating Composite Reliability of Psychometric Instruments

PubMed Central

Gajewski, Byron J.; Jiang, Yu; Yeh, Hung-Wen; Engelman, Kimberly; Teel, Cynthia; Choi, Won S.; Greiner, K. Allen; Daley, Christine Makosky

2013-01-01

Texts and software that we are currently using for teaching multivariate analysis to non-statisticians lack in the delivery of confirmatory factor analysis (CFA). The purpose of this paper is to provide educators with a complement to these resources that includes CFA and its computation. We focus on how to use CFA to estimate a “composite reliability” of a psychometric instrument. This paper provides guidance for introducing, via a case-study, the non-statistician to CFA. As a complement to our instruction about the more traditional SPSS, we successfully piloted the software R for estimating CFA on nine non-statisticians. This approach can be used with healthcare graduate students taking a multivariate course, as well as modified for community stakeholders of our Center for American Indian Community Health (e.g. community advisory boards, summer interns, & research team members). The placement of CFA at the end of the class is strategic and gives us an opportunity to do some innovative teaching: (1) build ideas for understanding the case study using previous course work (such as ANOVA); (2) incorporate multi-dimensional scaling (that students already learned) into the selection of a factor structure (new concept); (3) use interactive data from the students (active learning); (4) review matrix algebra and its importance to psychometric evaluation; (5) show students how to do the calculation on their own; and (6) give students access to an actual recent research project. PMID:24772373

Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

PubMed

Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

2009-11-01

IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn.

PubMed

Cheng, H T; Suzuki, M; Hegarty, D M; Xu, Q; Weyerbacher, A R; South, S M; Ohata, M; Inturrisi, C E

2008-08-26

The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKCgamma and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH.

Simulation Study on Fit Indexes in CFA Based on Data with Slightly Distorted Simple Structure

ERIC Educational Resources Information Center

Beauducel, Andre; Wittmann, Werner W.

2005-01-01

Fit indexes were compared with respect to a specific type of model misspecification. Simple structure was violated with some secondary loadings that were present in the true models that were not specified in the estimated models. The c2 test, Comparative Fit Index, Goodness-of-Fit Index, Incremental Fit Index, Nonnormed Fit Index, root mean…

Binding of caffeine with caffeic acid and chlorogenic acid using fluorescence quenching, UV/vis and FTIR spectroscopic techniques.

PubMed

Belay, Abebe; Kim, Hyung Kook; Hwang, Yoon-Hwae

2016-03-01

The interactions of caffeine (CF) with chlorogenic acid (CGA) and caffeic acid (CFA) were investigated by fluorescence quenching, UV/vis and Fourier transform infrared (FTIR) spectroscopic techniques. The results of the study indicated that the fluorescence quenching between caffeine and hydroxycinnamic acids could be rationalized in terms of static quenching or the formation of non-fluorescent CF-CFA and CF-CGA complexes. From fluorescence quenching spectral analysis, the quenching constant (KSV), quenching rate constant (kq), number of binding sites (n), thermodynamic properties and conformational changes of the interaction were determined. The quenching constants (KSV) between CF and CGA, CFA are 1.84 × 10(4) and 1.04 × 10(4) L/mol at 298 K and their binding site n is ~ 1. Thermodynamic parameters determined using the Van't Hoff equation indicated that hydrogen bonds and van der Waal's forces have a major role in the reaction of caffeine with caffeic acid and chlorogenic acid. The 3D fluorescence, UV/vis and FTIR spectra also showed that the binding of CF with CFA and CGA induces conformational changes in CFA and CGA. Copyright © 2015 John Wiley & Sons, Ltd.

Voltage control of magnetic anisotropy in epitaxial Ru/Co2FeAl/MgO heterostructures

NASA Astrophysics Data System (ADS)

Wen, Zhenchao; Sukegawa, Hiroaki; Seki, Takeshi; Kubota, Takahide; Takanashi, Koki; Mitani, Seiji

2017-03-01

Voltage control of magnetic anisotropy (VCMA) in magnetic heterostructures is a key technology for achieving energy-efficiency electronic devices with ultralow power consumption. Here, we report the first demonstration of the VCMA effect in novel epitaxial Ru/Co2FeAl(CFA)/MgO heterostructures with interfacial perpendicular magnetic anisotropy (PMA). Perpendicularly magnetized tunnel junctions with the structure of Ru/CFA/MgO were fabricated and exhibited an effective voltage control on switching fields for the CFA free layer. Large VCMA coefficients of 108 and 139 fJ/Vm for the CFA film were achieved at room temperature and 4 K, respectively. The interfacial stability in the heterostructure was confirmed by repeating measurements. Temperature dependences of both the interfacial PMA and the VCMA effect were also investigated. It is found that the temperature dependences follow power laws of the saturation magnetization with an exponent of ~2, where the latter is definitely weaker than that of conventional Ta/CoFeB/MgO. The significant VCMA effect observed in this work indicates that the Ru/CFA/MgO heterostructure could be one of the promising candidates for spintronic devices with voltage control.

10. Historic American Buildings Survey CFA Staff, Photographer, 1972 FIRST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. Historic American Buildings Survey CFA Staff, Photographer, 1972 FIRST- SECOND- FLOOR PLAN J. L. S. Jennings, Jr., Delineator - Edward H. Everett House, 1606 Twenty-third Street Northwest, Washington, District of Columbia, DC

76 FR 2087 - Notice of Meeting

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2011-01-12

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78 FR 40727 - Notice of Meeting

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2013-07-08

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75 FR 67348 - Notice of Meeting

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2010-11-02

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75 FR 9587 - Notice of Meeting

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2010-03-03

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76 FR 9328 - Notice of Meeting

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2011-02-17

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78 FR 15357 - Notice of Meeting

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2013-03-11

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78 FR 34654 - Notice of Meeting

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2013-06-10

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2011-07-07

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2010-09-28

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76 FR 28424 - Notice of Meeting

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2011-05-17

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2010-07-21

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78 FR 20094 - Notice of Meeting

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2013-04-03

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Streptomyces scabies 87-22 contains a coronafacic acid-like biosynthetic cluster that contributes to plant-microbe interactions.

PubMed

Bignell, Dawn R D; Seipke, Ryan F; Huguet-Tapia, José C; Chambers, Alan H; Parry, Ronald J; Loria, Rosemary

2010-02-01

Plant-pathogenic Streptomyces spp. cause scab disease on economically important root and tuber crops, the most important of which is potato. Key virulence determinants produced by these species include the cellulose synthesis inhibitor, thaxtomin A, and the secreted Nec1 protein that is required for colonization of the plant host. Recently, the genome sequence of Streptomyces scabies 87-22 was completed, and a biosynthetic cluster was identified that is predicted to synthesize a novel compound similar to coronafacic acid (CFA), a component of the virulence-associated coronatine phytotoxin produced by the plant-pathogenic bacterium Pseudomonas syringae. Southern analysis indicated that the cfa-like cluster in S. scabies 87-22 is likely conserved in other strains of S. scabies but is absent from two other pathogenic streptomycetes, S. turgidiscabies and S. acidiscabies. Transcriptional analyses demonstrated that the cluster is expressed during plant-microbe interactions and that expression requires a transcriptional regulator embedded in the cluster as well as the bldA tRNA. A knockout strain of the biosynthetic cluster displayed a reduced virulence phenotype on tobacco seedlings compared with the wild-type strain. Thus, the cfa-like biosynthetic cluster is a newly discovered locus in S. scabies that contributes to host-pathogen interactions.

Hidden Broad-Line Seyfert 2 Galaxies in the CFA and 12 μM Samples

NASA Astrophysics Data System (ADS)

Tran, Hien D.

2001-06-01

We report the results of a spectropolarimetric survey of the CfA and 12 μm samples of Seyfert 2 (S2) galaxies. Polarized (hidden) broad-line regions (HBLRs) are confirmed in a number of galaxies, and several new cases (F02581-1136, MCG -3-58-7, NGC 5995, NGC 6552, NGC 7682) are reported. The 12 μm S2 galaxy sample shows a significantly higher incidence of HBLRs (50%) than its CfA counterpart (30%), suggesting that the latter may be incomplete in hidden active galactic nuclei. Compared to the non-HBLR S2 galaxies, the HBLR S2 galaxies display distinctly higher radio power relative to their far-infrared output and hotter dust temperature as indicated by the f25/f60 color. However, the level of obscuration is indistinguishable between the two types of S2 galaxies. These results strongly support the existence of two intrinsically different populations of S2 galaxies: one harboring an energetic, hidden S1 nucleus with a broad-line region and the other a ``pure'' S2 galaxy, with a weak or absent S1 nucleus and a strong, perhaps dominating starburst component. Thus, the simple purely orientation-based unification model is not applicable to all Seyfert galaxies.

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

Comparison of corifollitropin alfa and daily recombinant follicle-stimulating hormone in poor responder patients undergoing in vitro fertilization cycles.

PubMed

Akarsu, Süleyman; Demir, Sibel; Gode, Funda; Işık, Ahmet Zeki

2017-12-01

The aim of this study was to compare the effect of corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder patients undergoing antagonist cycles. The study was a retrospective analysis of the treatment results of 214 poor responder patients who had been admitted to the In Vitro Fertilization Unit of İzmir Medical Park Hospital between November 2014 and November 2016. Intracytoplasmic sperm injections were performed in 38 patients (group 1) with CFA, and the remaining 176 (group 2) with rFSH for controlled ovarian hyperstimulation. The age, body mass index, anti-müllerian hormone level, duration of infertility, duration of induction and antral follicle number were similar in the two groups. There was no difference in the total aspirated oocyte counts, mature oocyte ratio, fertilization rate, implantation rate, and clinical pregnancy rates between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and 42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and 17.2%, respectively. No difference was found in terms of oocyte count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA or rFSH use in the antagonist cycles in poor-responder patients.

Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

PubMed Central

Ortiz, Andrea N.; Osterhaus, Gregory L.; Lauderdale, Kelli; Mahoney, Luke; Fowler, Stephen C.; von Hörsten, Stephan; Riess, Olaf; Johnson, Michael A.

2013-01-01

Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats. PMID:22418060

Multiple Loci are associated with dilated cardiomyopathy in Irish wolfhounds.

PubMed

Philipp, Ute; Vollmar, Andrea; Häggström, Jens; Thomas, Anne; Distl, Ottmar

2012-01-01

Dilated cardiomyopathy (DCM) is a highly prevalent and often lethal disease in Irish wolfhounds. Complex segregation analysis indicated different loci involved in pathogenesis. Linear fixed and mixed models were used for the genome-wide association study. Using 106 DCM cases and 84 controls we identified one SNP significantly associated with DCM on CFA37 and five SNPs suggestively associated with DCM on CFA1, 10, 15, 21 and 17. On CFA37 MOGAT1 and ACSL3 two enzymes of the lipid metabolism were located near the identified SNP.

Multiple Loci Are Associated with Dilated Cardiomyopathy in Irish Wolfhounds

PubMed Central

Philipp, Ute; Vollmar, Andrea; Häggström, Jens; Thomas, Anne; Distl, Ottmar

2012-01-01

Dilated cardiomyopathy (DCM) is a highly prevalent and often lethal disease in Irish wolfhounds. Complex segregation analysis indicated different loci involved in pathogenesis. Linear fixed and mixed models were used for the genome-wide association study. Using 106 DCM cases and 84 controls we identified one SNP significantly associated with DCM on CFA37 and five SNPs suggestively associated with DCM on CFA1, 10, 15, 21 and 17. On CFA37 MOGAT1 and ACSL3 two enzymes of the lipid metabolism were located near the identified SNP. PMID:22761652

Anti-Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro-Inflammatory Mediators.

PubMed

Singh, Ajeet Kumar; Vinayak, Manjula

2016-07-01

Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti-hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c-Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL-1β, TNF-α and IL-6 as well as inflammatory enzymes COX-2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX-2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti-nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Psychometric properties of the Persian version of the “Hospital Ethical Climate Survey”

PubMed Central

Khalesi, Nader; Arabloo, Jalal; Khosravizadeh, Omid; Taghizadeh, Sanaz; Heyrani, Ali; Ebrahimian, Abbasali

2014-01-01

In order to improve the ethical climate in health care organizations, it is important to apply a valid measure. This study aimed to investigate the psychometric properties of the Persian version of the Hospital Ethical Climate Survey (HECS) and to assess nurses’ perceptions of the ethical climate in teaching hospitals of Iran. A cross-sectional study of randomly selected nurses (n = 187) was conducted in three teaching general hospitals of Tehran, capital of Iran. Olson’s Hospital Ethical Climate Survey (HECS), a self-administered questionnaire, was used to assess the nurses’ perceptions of the hospital ethical climate. Descriptive statistics, confirmatory factor analysis (CFA), internal consistency, and correlation were used to analyze the data. CFA showed acceptable model fit: an standardized root mean square residual (SRMR) of 0.064, an non-normalized fit index (NNFI) of 0.96, a comparative fit index (CFI) of 0.96, and an root mean square error of approximation (RMSEA) of 0.075. The Cronbach’s alpha values were acceptable and ranging from 0.69 to 0.85. The overall Cronbach’s alpha coefficient was 0.94. The factor loadings for all ethical climate items were between 0.50 and 0.80, which revealed good structure of the Persian version of the HECS. Survey findings showed that the “managers” subscale had the highest score and the subscale of “doctors” had the lowest score. This study shows that the Persian version of the HECS is a valid and reliable instrument for measuring nurses’ perceptions of the ethical climate in hospitals of Iran PMID:25512834

Interpreting the Coulomb-field approximation for generalized-Born electrostatics using boundary-integral equation theory.

PubMed

Bardhan, Jaydeep P

2008-10-14

The importance of molecular electrostatic interactions in aqueous solution has motivated extensive research into physical models and numerical methods for their estimation. The computational costs associated with simulations that include many explicit water molecules have driven the development of implicit-solvent models, with generalized-Born (GB) models among the most popular of these. In this paper, we analyze a boundary-integral equation interpretation for the Coulomb-field approximation (CFA), which plays a central role in most GB models. This interpretation offers new insights into the nature of the CFA, which traditionally has been assessed using only a single point charge in the solute. The boundary-integral interpretation of the CFA allows the use of multiple point charges, or even continuous charge distributions, leading naturally to methods that eliminate the interpolation inaccuracies associated with the Still equation. This approach, which we call boundary-integral-based electrostatic estimation by the CFA (BIBEE/CFA), is most accurate when the molecular charge distribution generates a smooth normal displacement field at the solute-solvent boundary, and CFA-based GB methods perform similarly. Conversely, both methods are least accurate for charge distributions that give rise to rapidly varying or highly localized normal displacement fields. Supporting this analysis are comparisons of the reaction-potential matrices calculated using GB methods and boundary-element-method (BEM) simulations. An approximation similar to BIBEE/CFA exhibits complementary behavior, with superior accuracy for charge distributions that generate rapidly varying normal fields and poorer accuracy for distributions that produce smooth fields. This approximation, BIBEE by preconditioning (BIBEE/P), essentially generates initial guesses for preconditioned Krylov-subspace iterative BEMs. Thus, iterative refinement of the BIBEE/P results recovers the BEM solution; excellent agreement is obtained in only a few iterations. The boundary-integral-equation framework may also provide a means to derive rigorous results explaining how the empirical correction terms in many modern GB models significantly improve accuracy despite their simple analytical forms.

Thickness Dependence of the Dzyaloshinskii-Moriya Interaction in Co2 FeAl Ultrathin Films: Effects of Annealing Temperature and Heavy-Metal Material

NASA Astrophysics Data System (ADS)

Belmeguenai, M.; Roussigné, Y.; Bouloussa, H.; Chérif, S. M.; Stashkevich, A.; Nasui, M.; Gabor, M. S.; Mora-Hernández, A.; Nicholson, B.; Inyang, O.-O.; Hindmarch, A. T.; Bouchenoire, L.

2018-04-01

The interfacial Dzyaloshinskii-Moriya interaction (IDMI) is investigated in Co2FeAl (CFA) ultrathin films of various thicknesses (0.8 nm ≤tCFA≤2 nm ) grown by sputtering on Si substrates, using Pt, W, Ir, and MgO buffer or/and capping layers. Vibrating sample magnetometry reveals that the magnetization at saturation (Ms ) for the Pt- and Ir-buffered films is higher than the usual Ms of CFA due to the proximity-induced magnetization (PIM) in Ir and Pt estimated to be 19% and 27%, respectively. The presence of PIM in these materials is confirmed using x-ray resonant magnetic reflectivity. Moreover, while no PIM is induced in W, higher PIM is obtained with Pt when it is used as a buffer layer rather than a capping layer. Brillouin light scattering in the Damon-Eshbach geometry is used to investigate the thickness dependences of the IDMI constants from the spin-wave nonreciprocity and the perpendicular anisotropy field versus the annealing temperature. The IDMI sign is found to be negative for Pt /CFA and Ir /CFA , while it is positive for W /CFA . The thickness dependence of the effective IDMI constant for stacks involving Pt and W shows the existence of two regimes similar to that of the perpendicular anisotropy constant due to the degradation of the interfaces as the CFA thickness approaches a critical thickness. The surface IDMI and anisotropy constants of each stack are determined for the thickest samples where a linear thickness dependence of the effective IDMI constant and the effective magnetization are observed. The interface anisotropy and IDMI constants investigated for the Pt /CFA /MgO system show different trends with the annealing temperature. The decrease of the IDMI constant with increasing annealing temperature is probably due to the electronic structure changes at the interfaces, while the increase of the interface anisotropy constant is coherent with the interface quality and disorder enhancement.

Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

PubMed

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty acids might have an important role in this pain control system.

Analysis of colonization factor antigen I, an adhesin of enterotoxigenic Escherichia coli O78:H11: fimbrial morphology and location of the receptor-binding site.

PubMed Central

Bühler, T; Hoschützky, H; Jann, K

1991-01-01

Colonization factor antigen I (CFA/I) of enterotoxigenic Escherichia coli was dissociated into one type of subunit (15 kDa). The dissociation was achieved either by heating CFA/I in sodium dodecyl sulfate at 100 degrees C or by heating it for 20 min in water. Heating in water to 100 degrees C yielded only in the 15-kDa subunit, but heating to 85 degree C yielded small amounts of oligomers in addition. The monomeric subunits obtained after heating in water are stable, as demonstrated by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis without heating prior to the electrophoretic run. These subunits inhibited CFA/I-induced hemagglutination, indicating that they had maintained their receptor-binding properties. When the hybridoma technique was used, two types of monoclonal anti-CFA/I antibodies were obtained. Antibodies obtained by immunization with the purified subunits were more reactive with subunits than with fimbriae, as shown by enzyme-linked immunosorbent assay. These antibodies strongly inhibited CFA/I-induced hemagglutination. When examined by immunoelectron microscopy, these antibodies seemed to label the fimbrial tips. A similar labeling pattern was obtained with gold particles modified with the receptor ganglioside GM2. Antibodies obtained by immunization with fimbriae reacted in enzyme-linked immunosorbent assays equally well with fimbriae and subunits. They inhibited CFA/I-induced hemagglutination only slightly. Immunoelectron microscopy revealed that these antibodies labeled the fimbriae densely and regularly over their entire lengths. In a coagglutination experiment with Staphylococcus aureus and monoclonal antibodies, the subunits retained their receptor-binding properties. From these results, we conclude that CFA/I fimbriae consist entirely of one type of adhesive subunit, of which only the one at the tip is accessible to the receptor. Images PMID:1682253

Radiological outcomes of pinless navigation in total knee arthroplasty: a randomized controlled trial.

PubMed

Chen, Jerry Yongqiang; Chin, Pak Lin; Li, Zongxian; Yew, Andy Khye Soon; Tay, Darren Keng Jin; Chia, Shi-Lu; Lo, Ngai Nung; Yeo, Seng Jin

2015-12-01

This study aimed to investigate the accuracy of pinless navigation (BrainLAB(®) VectorVision(®) Knee 2.5 Navigation System) as an intra-operative alignment guide in total knee arthroplasty (TKA). The authors hypothesized that pinless navigation would reduce the proportion of outliers in conventional TKA, without a significant increase in the duration of surgery. Between 2011 and 2012, 100 patients scheduled for a unilateral primary TKA were randomized into two groups: pinless navigation and conventional surgery. All TKAs were performed with the surgical aim of achieving neutral coronal alignment with a 180° mechanical axis. The primary outcomes of this study were post-operative radiographic assessment of lower limb alignment using hip-knee-ankle angle (HKA) and components placement using coronal femoral-component angle (CFA) and coronal tibia-component angle (CTA). There was a smaller proportion of outliers for HKA, CFA and CTA at 10, 2 and 2 % respectively, in the pinless navigation group, compared to 32, 16 and 16 %, respectively, in the conventional group (p = 0.013, p = 0.032 and p = 0.032, respectively). The mean CFA was also more accurate at 90° in the pinless navigation group compared to 91° in the conventional group (p = 0.002). There was no difference in the duration of surgery between the two groups (n.s.). Pinless navigation improves lower limb alignment and components placement without a significant increase in the duration of surgery. The authors recommend the use of pinless navigation to verify the coronal alignments of conventional cutting blocks in TKA before the bone cuts are made. I.

Application of cranberry concentrate (Vaccinium macrocarpon) to control Escherichia coli O157:H7 in ground beef and its antimicrobial mechanism related to the downregulated slp, hdeA and cfa.

PubMed

Wu, Vivian C H; Qiu, Xujian; de los Reyes, Benildo G; Lin, Chih-Sheng; Pan, Yingjie

2009-02-01

The possible use of cranberry concentrate (CC) as a natural food preservative was studied by examining its antimicrobial effect on the growth of Escherichia coli O157:H7 inoculated in ground beef, its organoleptical effect on beef patties, and its antimicrobial mechanism on the gene regulation level. Inoculated ground beef was added with CC and stored at 4 degrees C for 5 days. Bacteria were detected on day 0, 1, 3, and 5. Cranberry concentrate (2.5%, 5%, and 7.5% w/w) reduced total aerobic bacteria 1.5 log, 2.1 log, and 2.7 log CFU/g and E. coli O157:H7 0.4 log, 0.7 log, and 2.4 log CFU/g, respectively, when compared to the control on day 5. Fifty panelists evaluated the burgers supplemented with CC. No differences in appearance, flavor, and taste were found among burgers with 0%, 2.5%, and 5% CC. The expression of E. coli O157:H7 cyclopropane fatty acyl phospholipid synthase (cfa), hypothetical protein (hdeA), outer membrane porin protein C (ompC), hyperosmotically inducible periplasmic protein (osmY), and outer membrane protein induced after carbon starvation (slp) genes with or without CC (2.5% v/v) treatment was investigated by quantitative real-time PCR. Compared to the control, slp, hdeA, and cfa were markedly downregulated, ompC was slightly downregulated, while osmY was slightly affected.

75 FR 31426 - Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... information regarding the Commission are available on our Web site: http://www.cfa.gov . Inquiries regarding..., Secretary, U.S. Commission of Fine Arts, at the above address; by e-mailing [email protected]cfa.gov ; or by calling...

Electroacupuncture alleviates affective pain in an inflammatory pain rat model

PubMed Central

Zhang, Yu; Meng, Xianze; Li, Aihui; Xin, Jiajia; Berman, Brian M.; Lao, Lixing; Tan, Ming; Ren, Ke; Zhang, Rui-Xin

2011-01-01

Pain has both sensory-discriminative and emotional-affective dimensions. Previous studies demonstrate that electroacupuncture (EA) alleviates the sensory dimension but do not address the affective. An inflammatory pain rat model, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a conditioned place avoidance (CPA) test to determine whether EA inhibits spontaneous pain-induced affective response and, if so, to study the possibility that rostral anterior cingulate cortex (rACC) opioids underlie this effect. Male Sprague-Dawley rats (250–275g, Harlan) were used. The rats showed place aversion (i.e. affective pain) by spending less time in a pain-paired compartment after conditioning than during a preconditioning test. Systemic non-analgesic morphine (0.5 and 1.0 mg/ kg, i.p.) inhibited the affective reaction, suggesting that the affective dimension is underpinned by mechanisms different from those of the sensory dimension of pain. Morphine at 0.5 and at 1 mg/kg did not induce reward. Rats given EA treatment before pain-paired conditioning at GB 30 showed no aversion to the pain-paired compartment, indicating that EA inhibited the affective dimension. EA treatment did not produce reward or aversive effect. Intra-rACC administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP), a selective mu opioid receptor antagonist, but not norbinaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist, blocked EA inhibition of the affective dimension. These data demonstrate that EA activates opioid receptors in the rACC to inhibit pain-induced affective responses and that EA may be an effective therapy for both the sensory-discriminative and the affective dimensions of pain. PMID:22323370

Morphological Differences Between Seyfert Hosts and Normal Galaxies

NASA Astrophysics Data System (ADS)

Shlosman, Isaac

Using new sub-arcsecond resolution imaging we compare large-scale stellar bar fraction in CfA sample of Seyferts and a closely matched control sample of normal galaxies. We find a difference between the samples on the 2.5σ level. We further compare the axial ratios of bars in all available samples quoted in the literature and find a deficiency of small axial ratio bars in Seyferts compared to normal galaxies.

The Strengths and Difficulties Questionnaire (SDQ): Factor Structure and Gender Equivalence in Norwegian Adolescents

PubMed Central

Hysing, Mari; Skogen, Jens Christoffer; Breivik, Kyrre

2016-01-01

Although frequently used with older adolescents, few studies of the factor structure, internal consistency and gender equivalence of the SDQ exists for this age group, with inconsistent findings. In the present study, confirmatory factor analysis (CFA) was used to evaluate the five-factor structure of the SDQ in a population sample of 10,254 16–18 year-olds from the youth@hordaland study. Measurement invariance across gender was assessed using multigroup CFA. A modestly modified five-factor solution fitted the data acceptably, accounting for one cross loading and some local dependencies. Importantly, partial measurement non-invariance was identified, with differential item functioning in eight items, and higher correlations between emotional and conduct problems for boys compared to girls. Implications for use clinically and in research are discussed. PMID:27138259

48 CFR 252.234-7001 - Notice of Earned Value Management System.

Code of Federal Regulations, 2010 CFR

2010-10-01

... documentation that the Cognizant Federal Agency (CFA) has determined that the proposed Earned Value Management... compliance with ANSI/EIA-748. (2) If the offeror proposes to use an EVMS that has been determined by the CFA...

A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

PubMed

Ancot, Frédéric; Lemay, Philippe; Knowler, Susan P; Kennedy, Karen; Griffiths, Sandra; Cherubini, Giunio Bruto; Sykes, Jane; Mandigers, Paul J J; Rouleau, Guy A; Rusbridge, Clare; Kibar, Zoha

2018-03-22

Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.

Human Immunodeficiency Virus, Antiretroviral Therapy and Markers of Lymphatic Filariasis Infection: A Cross-sectional Study in Rural Northern Malawi

PubMed Central

Tafatatha, Terence; Taegtmeyer, Miriam; Ngwira, Bagrey; Phiri, Amos; Kondowe, Mariot; Piston, Wilson; Molesworth, Anna; Kayuni, Ndoliwe; Koole, Olivier; Crampin, Amelia; Horton, John; French, Neil

2015-01-01

Background Lymphatic filariasis (LF) and human immunodeficiency virus (HIV) are major public health problems. Individuals may be co-infected, raising the possibility of important interactions between these two pathogens with consequences for LF elimination through annual mass drug administration (MDA). Methodology and Principal Findings We analysed circulating filarial antigenaemia (CFA) by HIV infection status among adults in two sites in northern Malawi, a region endemic for both LF and HIV. Stored blood samples and data from two geographically separate studies were used: one a recruitment phase of a clinical trial of anti-filarial agent dosing regimens, and the other a whole population annual HIV sero-survey. In study one, 1,851 consecutive adult volunteers were screened for HIV and LF infection. CFA prevalence was 25.4% (43/169) in HIV-positive and 23.6% (351/1487) in HIV-negative participants (p=0.57). Geometric mean CFA concentrations were 859 and 1660 antigen units per ml of blood (Ag/ml) respectively, geometric mean ratio (GMR) 0.85, 95%CI 0.49-1.50. In 7,863 adults in study two, CFA prevalence was 20.9% (86/411) in HIV-positive and 24.0% (1789/7452) in HIV–negative participants (p=0.15). Geometric mean CFA concentrations were 630 and 839 Ag/ml respectively (GMR 0.75, 95%CI 0.60-0.94). In the HIV-positive group, antiretroviral therapy (ART) use was associated with a lower CFA prevalence, 12.7% (18/142) vs. 25.3% (67/265), (OR 0.43, 95%CI 0.24-0.76). Prevalence of CFA decreased with duration of ART use, 15.2% 0-1 year (n=59), 13.6% >1-2 years (n=44), 10.0% >2-3 years (n=30) and 0% >3-4 years treatment (n=9), p<0.01 χ2 for linear trend. Conclusions/Significance In this large cross-sectional study of two distinct LF-exposed populations, there is no evidence that HIV infection has an impact on LF epidemiology that will interfere with LF control measures. A significant association of ART use with lower CFA prevalence merits further investigation to understand this apparent beneficial impact of ART. PMID:26042839

A curved surface micro-moiré method and its application in evaluating curved surface residual stress

NASA Astrophysics Data System (ADS)

Zhang, Hongye; Wu, Chenlong; Liu, Zhanwei; Xie, Huimin

2014-09-01

The moiré method is typically applied to the measurement of deformations of a flat surface while, for a curved surface, this method is rarely used other than for projection moiré or moiré interferometry. Here, a novel colour charge-coupled device (CCD) micro-moiré method has been developed, based on which a curved surface micro-moiré (CSMM) method is proposed with a colour CCD and optical microscope (OM). In the CSMM method, no additional reference grating is needed as a Bayer colour filter array (CFA) installed on the OM in front of the colour CCD image sensor performs this role. Micro-moiré fringes with high contrast are directly observed with the OM through the Bayer CFA under the special condition of observing a curved specimen grating. The principle of the CSMM method based on a colour CCD micro-moiré method and its application range and error analysis are all described in detail. In an experiment, the curved surface residual stress near a welded seam on a stainless steel tube was investigated using the CSMM method.

Psychometric properties of the Internet Addiction Test in Turkish

PubMed Central

Kaya, Fatih; Delen, Erhan; Young, Kimberly S.

2016-01-01

Background and aims In this study, the Internet Addiction Test (IAT) was adapted to Turkish language, which was originally developed by Young (1998) in English to measure the presence and severity of the Internet dependency. The main purpose was to ensure that the psychometric features and the factor structure of the test were suitable for Turkish university students. Method The study was conducted in two sequent phases. Participants were 990 undergraduate students from several public universities in Turkey. Results In the first phase, an exploratory factor analysis (EFA) was applied to figure out the factor structure of the Turkish version of the IAT. The EFA revealed four factors, which explained 46.02% of the total variance. In the following phase, a confirmatory factor analysis (CFA) was conducted with a different sample, to verify the factor structure that was found in the initial EFA. The CFA resulted four-factor model was satisfactory for the Turkish version of the IAT. These four factors were named as Mood, Relationship, Responsibilities, and Duration. Conclusions Based on the findings, the administration of Turkish version of the IAT provided acceptable results on undergraduate students. PMID:28092191

Locally applied simvastatin improves fracture healing at late period in osteoporotic rat

NASA Astrophysics Data System (ADS)

Tian, Faming; Zhang, Liu; Kang, Yuchuan; Zhang, Junshan; Ao, Jiao; Yang, Fang

effect of simvastatin locally applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. Methods:Femur fracture model was established on normal or osteotoporotic mature female SD rats, intramedullary stabilization was achieved with uncoated titanium Kirschnerwires in normal rats(group A),with polymer-only coated vs. polymer plus simvastatin coated titanium Kirschner wires in osteoporotic rats(group B and C, respectively).Femurs were harvested after 12 weeks, and underwent radiographic and histologic analysis, as well as immunohistochemical evaluation for BMP-2 expression. Results:Radiographic results demonstrated progressed callus in the simvastatin-treated groups compared to the uncoated group.The histologic analysis revealed a significantly processed callus with irregular-shaped newly formed bone trabeculae in simvastatin-treated group. Immunohistochemical evaluation showed markedly higher expression levels of B:MP-2 in simvastatin-treated group.Conclusions: The present study revealed a improved fracture healing under local application of simvastatin in osteoporotic rat,which might partially from upregulation of the B:MP-2 expression at fractured site.

Effect of Andrographis paniculata leaf extract on wound healing in rats.

PubMed

Al-Bayaty, Fouad Hussain; Abdulla, Mahmood Ameen; Abu Hassan, Mohamed Ibrahim; Ali, Hapipah Mohd

2012-01-01

This work was carried out to study the effect of topical application of Andrographis paniculata on the rate of wound enclosure and its histological features. A wound was created in four groups of rat in posterior neck region. Blank placebo was applied topically to the wounds of Group 1. Groups 2 and 3 were dressed with placebo containing 5% and 10% extracts of A. paniculata, respectively. Intrasite gel was applied topically to the wounds of Group 4. Macroscopical examination revealed that the rate of wound healing was significantly accelerated in the wound dressed with A. paniculata extract compared to the blank placebo. The wounds dressed with 10% extract or Intrasite gel healed earlier compared to the wounds dressed with placebo containing 5% A. paniculata extract. Histologically, wounds dressed with A. paniculata extracts showed markedly less scar width and contained large amounts of fibroblast proliferation. More collagen and less angiogenesis with absence of inflammatory cells were seen for wounds dressed with 10% A. paniculata compared to the blank placebo. Conclusion, A. paniculata extracts significantly enhanced rate of wound healing in rats.

Application of Bayesian configural frequency analysis (BCFA) to determine characteristics user and non-user motor X

NASA Astrophysics Data System (ADS)

Mawardi, Muhamad Iqbal; Padmadisastra, Septiadi; Tantular, Bertho

2018-03-01

Configural Frequency Analysis is a method for cell-wise testing in contingency tables for exploratory search type and antitype, that can see the existence of discrepancy on the model by existence of a significant difference between the frequency of observation and frequency of expectation. This analysis focuses on whether or not the interaction among categories from different variables, and not the interaction among variables. One of the extensions of CFA method is Bayesian CFA, this alternative method pursue the same goal as frequentist version of CFA with the advantage that adjustment of the experiment-wise significance level α is not necessary and test whether groups of types and antitypes form composite types or composite antitypes. Hence, this research will present the concept of the Bayesian CFA and how it works for the real data. The data on this paper is based on case studies in a company about decrease Brand Awareness & Image motor X on Top Of Mind Unit indicator in Cirebon City for user 30.8% and non user 9.8%. From the result of B-CFA have four characteristics from deviation, one of the four characteristics above that is the configuration 2212 need more attention by company to determine promotion strategy to maintain and improve Top Of Mind Unit in Cirebon City.

Development of the Internet addiction scale based on the Internet Gaming Disorder criteria suggested in DSM-5.

PubMed

Cho, Hyun; Kwon, Min; Choi, Ji-Hye; Lee, Sang-Kyu; Choi, Jung Seok; Choi, Sam-Wook; Kim, Dai-Jin

2014-09-01

This study was conducted to develop and validate a standardized self-diagnostic Internet addiction (IA) scale based on the diagnosis criteria for Internet Gaming Disorder (IGD) in the Diagnostic and Statistical Manual of Mental Disorder, 5th edition (DSM-5). Items based on the IGD diagnosis criteria were developed using items of the previous Internet addiction scales. Data were collected from a community sample. The data were divided into two sets, and confirmatory factor analysis (CFA) was performed repeatedly. The model was modified after discussion with professionals based on the first CFA results, after which the second CFA was performed. The internal consistency reliability was generally good. The items that showed significantly low correlation values based on the item-total correlation of each factor were excluded. After the first CFA was performed, some factors and items were excluded. Seven factors and 26 items were prepared for the final model. The second CFA results showed good general factor loading, Squared Multiple Correlation (SMC) and model fit. The model fit of the final model was good, but some factors were very highly correlated. It is recommended that some of the factors be refined through further studies. Copyright © 2014. Published by Elsevier Ltd.

Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes.

PubMed

Nikoopour, Enayat; Schwartz, Jordan A; Huszarik, Katrina; Sandrock, Christian; Krougly, Olga; Lee-Chan, Edwin; Singh, Bhagirath

2010-05-01

IL-17-producing T cells are regarded as potential pathogenic T cells in the induction of autoimmune diseases. Previously, we have shown that injection of adjuvants containing Mycobacterium, such as CFA or bacillus Calmette-Guérin, can prevent type 1 diabetes in NOD mice. We injected NOD mice with mycobacterial products s.c. and analyzed the IL-17-producing cells from the draining lymph nodes and spleen by restimulating whole-cell populations or CD4(+) T cells in vitro with or without IL-17-polarizing cytokines. Mice receiving CFA had a concomitant rise in the level of IL-17, IL-22, IL-10, and IFN-gamma in the draining lymph node and spleen. Adoptive transfer of splenocytes from CFA-injected NOD mice polarized with TGF-beta plus IL-6 or IL-23 delayed the development of diabetes in recipient mice. IL-17-producing cells induced by CFA maintained their IL-17-producing ability in the recipient mice. Injection of CFA also changed the cytokine profile of cells in pancreatic tissue by increasing IL-17, IL-10, and IFN-gamma cytokine gene expression. We suggest that the rise in the level of IL-17 after adjuvant therapy in NOD mice has a protective effect on type 1 diabetes development.

Cost-effective antigen testing for delimitation, monitoring and evaluation in bancroftian filariasis.

PubMed

Das, L K; Pani, S P; Vanamail, P; Vijayalakshmi, G; Debritto, L J

2012-01-31

This study was focussed on identifying a cost-effective method for delimitation, monitoring and evaluation in bancroftian filariasis. Finger prick blood samples were collected between 20.00 and 23.00 hours for the detection of microfilariae (mf) from the available population in a village which was endemic for lymphatic filariasis. Simultaneously, from each individual, four spots of 25-μl blood samples were collected on Whatman number 3 filter paper and air dried. Dried filter paper spots were pooled in quantities of 1, 5, 10, 15, 20 and 25 on unknown and simulated mf and antigen prevalence. Pooled samples were assayed for circulating filarial antigen (CFA) using TropBIO Og4C3 ELISA kits. The community mf and CFA rates were 3.4% and 25.9%, respectively. The pool sizes of 20 and 25 showed CFA positivity in all the above categories tested. The results of the pooled blood spot samples suggest that, in areas with mf and CFA prevalence rates between 1 and 10%, pools of 20 or 25 could be considered as the ideal pool size for the detection of filarial infection in the community. CFA prevalence at the level of 5-6% following desirable rounds of mass drug administration (MDA) indicates that the community mf prevalence is likely to be at the 1% level.

Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

PubMed

Obiri, David D; Osafo, Newman; Ayande, Patrick G; Antwi, Aaron O

2014-03-28

Xylopia aethiopica is used in a decoction of the dried fruit to treat bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain. The aim of the study is to evaluate the anti-arthritic effects of a 70% aqueous ethanol extract of the fruit of Xylopia aethiopica in a chronic inflammatory model. Adjuvant arthritis was induced in Sprague-Dawley rats by intraplantar injection of Complete Freund's adjuvant into the right hind paw. Foot volume was measured by water displacement plethysmometry. The oedema component of inflammation was evaluated as the percentage change in paw swelling and the total oedema induced calculated as area under the time course curves. In addition to X-ray radiography, histopathology of ankle joints supported by haematological analysis was used to assess the anti-arthritic action of the extract of Xylopia aethiopica (XAE). Xylopia aethiopica extract (100, 300 and 600 mg kg(-1)) modified the time course curve significantly reducing hind paw oedema in the ipsilateral paw at all dose levels when administered both prophylactically and therapeutically. In addition XAE significantly suppressed the systemic spread of the arthritis from the ipsilateral to the contralateral limbs. The radiological pictures of the joints particularly metatarsal, phalanges and the ankle joint space of rats in the XAE-treated group showed protective effect against adjuvant-induced arthritis while histopathology revealed significant reduction in mononuclear infiltration, pannus formation and bone erosion. The haematological analysis in the test animals revealed significant improvement relative to the CFA model group. Xylopia aethiopica XAE suppresses joint inflammation and destruction in arthritic rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Calculation of Protein Heat Capacity from Replica-Exchange Molecular Dynamics Simulations with Different Implicit Solvent Models

DTIC Science & Technology

2008-10-30

rigorous Poisson-based methods generally apply a Lee-Richards mo- lecular surface.9 This surface is considered the de facto description for continuum...definition and calculation of the Born radii. To evaluate the Born radii, two approximations are invoked. The first is the Coulomb field approximation (CFA...energy term, and depending on the particular GB formulation, higher-order non- Coulomb correction terms may be added to the Born radii to account for the

Prophylactic Efficacy of Hyperimmune Bovine Colostral Antiadhesin Antibodies Against Enterotoxigenic Escherichia coli Diarrhea: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial.

PubMed

Savarino, Stephen J; McKenzie, Robin; Tribble, David R; Porter, Chad K; O'Dowd, Aisling; Cantrell, Joyce A; Sincock, Stephanie A; Poole, Steven T; DeNearing, Barbara; Woods, Colleen M; Kim, Hye; Grahek, Shannon L; Brinkley, Carl; Crabb, Joseph H; Bourgeois, A Louis

2017-07-01

Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers. Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge. After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively. Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Structural characterization of CFA/III and Longus type IVb pili from enterotoxigenic Escherichia coli.

PubMed

Kolappan, Subramaniapillai; Roos, Justin; Yuen, Alex S W; Pierce, Owen M; Craig, Lisa

2012-05-01

The type IV pili are helical filaments found on many Gram-negative pathogenic bacteria, with multiple diverse roles in pathogenesis, including microcolony formation, adhesion, and twitching motility. Many pathogenic enterotoxigenic Escherichia coli (ETEC) isolates express one of two type IV pili belonging to the type IVb subclass: CFA/III or Longus. Here we show a direct correlation between CFA/III expression and ETEC aggregation, suggesting that these pili, like the Vibrio cholerae toxin-coregulated pili (TCP), mediate microcolony formation. We report a 1.26-Å resolution crystal structure of CofA, the major pilin subunit from CFA/III. CofA is very similar in structure to V. cholerae TcpA but possesses a 10-amino-acid insertion that replaces part of the α2-helix with an irregular loop containing a 3(10)-helix. Homology modeling suggests a very similar structure for the Longus LngA pilin. A model for the CFA/III pilus filament was generated using the TCP electron microscopy reconstruction as a template. The unique 3(10)-helix insert fits perfectly within the gap between CofA globular domains. This insert, together with differences in surface-exposed residues, produces a filament that is smoother and more negatively charged than TCP. To explore the specificity of the type IV pilus assembly apparatus, CofA was expressed heterologously in V. cholerae by replacing the tcpA gene with that of cofA within the tcp operon. Although CofA was synthesized and processed by V. cholerae, no CFA/III filaments were detected, suggesting that the components of the type IVb pilus assembly system are highly specific to their pilin substrates.

Improved methodologies for continuous-flow analysis of stable water isotopes in ice cores

NASA Astrophysics Data System (ADS)

Jones, Tyler R.; White, James W. C.; Steig, Eric J.; Vaughn, Bruce H.; Morris, Valerie; Gkinis, Vasileios; Markle, Bradley R.; Schoenemann, Spruce W.

2017-02-01

Water isotopes in ice cores are used as a climate proxy for local temperature and regional atmospheric circulation as well as evaporative conditions in moisture source regions. Traditional measurements of water isotopes have been achieved using magnetic sector isotope ratio mass spectrometry (IRMS). However, a number of recent studies have shown that laser absorption spectrometry (LAS) performs as well or better than IRMS. The new LAS technology has been combined with continuous-flow analysis (CFA) to improve data density and sample throughput in numerous prior ice coring projects. Here, we present a comparable semi-automated LAS-CFA system for measuring high-resolution water isotopes of ice cores. We outline new methods for partitioning both system precision and mixing length into liquid and vapor components - useful measures for defining and improving the overall performance of the system. Critically, these methods take into account the uncertainty of depth registration that is not present in IRMS nor fully accounted for in other CFA studies. These analyses are achieved using samples from a South Pole firn core, a Greenland ice core, and the West Antarctic Ice Sheet (WAIS) Divide ice core. The measurement system utilizes a 16-position carousel contained in a freezer to consecutively deliver ˜ 1 m × 1.3 cm2 ice sticks to a temperature-controlled melt head, where the ice is converted to a continuous liquid stream and eventually vaporized using a concentric nebulizer for isotopic analysis. An integrated delivery system for water isotope standards is used for calibration to the Vienna Standard Mean Ocean Water (VSMOW) scale, and depth registration is achieved using a precise overhead laser distance device with an uncertainty of ±0.2 mm. As an added check on the system, we perform inter-lab LAS comparisons using WAIS Divide ice samples, a corroboratory step not taken in prior CFA studies. The overall results are important for substantiating data obtained from LAS-CFA systems, including optimizing liquid and vapor mixing lengths, determining melt rates for ice cores with different accumulation and thinning histories, and removing system-wide mixing effects that are convolved with the natural diffusional signal that results primarily from water molecule diffusion in the firn column.

Microscopic spin Hamiltonian approaches for 3d8 and 3d2 ions in a trigonal crystal field - perturbation theory methods versus complete diagonalization methods

NASA Astrophysics Data System (ADS)

Rudowicz, Czeslaw; Yeung, Yau-yuen; Yang, Zi-Yuan; Qin, Jian

2002-06-01

In this paper, we critically review the existing microscopic spin Hamiltonian (MSH) approaches, namely the complete diagonalization method (CDM) and the perturbation theory method (PTM), for 3d8(3d2) ions in a trigonal (C3v, D3, D3d) symmetry crystal field (CF). A new CDM is presented and a CFA/MSH computer package based on our crystal-field analysis (CFA) package for 3dN ions is developed for numerical calculations. Our method takes into account the contribution to the SH parameters (D, g∥ and g⊥) from all 45 CF states for 3d8(3d2) ions and is based on the complete diagonalization of the Hamiltonian including the electrostatic interactions, the CF terms (in the intermediate CF scheme) and the spin-orbit coupling. The CFA/MSH package enables us to study not only the CF energy levels and wavefunctions but also the SH parameters as functions of the CF parameters (B20, B40 and B43 or alternatively Dq, v and v') for 3d8(3d2) ions in trigonal symmetry. Extensive comparative studies of other MSH approaches are carried out using the CFA/MSH package. First, we check the accuracy of the approximate PTM based on the `quasi-fourth-order' perturbation formulae developed by Petrosyan and Mirzakhanyan (PM). The present investigations indicate that the PM formulae for the g-factors (g∥ and g⊥) indeed work well, especially for the cases of small v and v' and large Dq, whereas the PM formula for the zero-field splitting (ZFS) exhibits serious shortcomings. Earlier criticism of the PM approach by Zhou et al (Zhou K W, Zhao S B, Wu P F and Xie J K 1990 Phys. Status Solidi b 162 193) is then revisited. Second, we carry out an extensive comparison of the results of the present CFA/MSH package and those of other CDMs based on the strong- and weak-CF schemes. The CF energy levels and the SH parameters for 3d2 and 3d8 ions at C3v symmetry sites in several crystals are calculated and analysed. Our investigations reveal serious inconsistencies in the CDM results of Zhou et al and Li (Li Y 1995 J. Phys.: Condens. Matter 7 4075) based on the strong-CF scheme for Ni2+ ions in LiNbO3 crystals. The correctness of our CFA/MSH package is verified by comparing our results with the predictions of Ma et al (Ma D P, Ma N, Ma X D and Zhang H M 1998 J. Phys. Chem. Solids 59 1211, Ma D P, Ma X D, Chen J R and Liu Y Y 1997 Phys. Rev. B 56 1780) and Macfarlane (Macfarlane R M 1964 J. Chem. Phys. 40 373) for α-Al2O3 : V3+(3d2) and MgO : Ni2+(3d8). It appears that the two independent approaches show perfect agreement with our approach, unlike those of Zhou et al and Li, which turn out to be unreliable. Our results reveal that the contributions to the ZFS parameter from the higher excited states cannot be neglected; also, the ZFS parameter is very sensitive to slight changes of the crystal structure. Hence our CFA/MSH package, which takes into account the contributions to the ZFS parameter from the higher excited states, can provide reliable results and proves to be a useful tool for the studies of the effect of the lattice distortions, defects and structural disorder on the spectroscopic properties of 3d2 and 3d8 ions at trigonal symmetry sites in crystals.

Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

PubMed

Hua, Susan; Cabot, Peter J

2013-01-01

The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein injection using liquid scintillation counting (LSC). Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund's Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions.

Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

PubMed

de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

2014-05-01

Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Boron deactivation in heavily boron-doped Czochralski silicon during rapid thermal anneal: Atomic level understanding

NASA Astrophysics Data System (ADS)

Gao, Chao; Lu, Yunhao; Dong, Peng; Yi, Jun; Ma, Xiangyang; Yang, Deren

2014-01-01

The changes in hole concentration of heavily boron (B)-doped Czochralski silicon subjected to high temperature rapid thermal anneal (RTA) and following conventional furnace anneal (CFA) have been investigated. It is found that decrease in hole concentration, namely, B deactivation, is observed starting from 1050 °C and increases with RTA temperature. The following CFA at 300-500 °C leads to further B deactivation, while that at 600-800 °C results in B reactivation. It is supposed that the interaction between B atoms and silicon interstitials (I) thus forming BI pairs leads to the B deactivation during the high temperature RTA, and, moreover, the formation of extended B2I complexes results in further B deactivation in the following CFA at 300-500 °C. On the contrary, the dissociation of BI pairs during the following CFA at 600-800 °C enables the B reactivation. Importantly, the first-principles calculation results can soundly account for the above-mentioned supposition.

Molecular cloning and expression of the gene encoding the kinetoplast-associated type II DNA topoisomerase of Crithidia fasciculata.

PubMed

Pasion, S G; Hines, J C; Aebersold, R; Ray, D S

1992-01-01

A type II DNA topoisomerase, topoIImt, was shown previously to be associated with the kinetoplast DNA of the trypanosomatid Crithidia fasciculata. The gene encoding this kinetoplast-associated topoisomerase has been cloned by immunological screening of a Crithidia genomic expression library with monoclonal antibodies raised against the purified enzyme. The gene CfaTOP2 is a single copy gene and is expressed as a 4.8-kb polyadenylated transcript. The nucleotide sequence of CfaTOP2 has been determined and encodes a predicted polypeptide of 1239 amino acids with a molecular mass of 138,445. The identification of the cloned gene is supported by immunoblot analysis of the beta-galactosidase-CfaTOP2 fusion protein expressed in Escherichia coli and by analysis of tryptic peptide sequences derived from purified topoIImt. CfaTOP2 shares significant homology with nuclear type II DNA topoisomerases of other eukaryotes suggesting that in Crithidia both nuclear and mitochondrial forms of topoisomerase II are encoded by the same gene.

Construct Equivalence of a National Certification Examination that Uses Dual Languages and Audio Assistance

ERIC Educational Resources Information Center

Wang, Shudong; Wang, Ning; Hoadley, David

2007-01-01

This study used confirmatory factor analysis (CFA) to examine the comparability of the National Nurse Aide Assessment Program (NNAAP[TM]) test scores across language and administration condition groups for calibration and validation samples that were randomly drawn from the same population. Fit statistics supported both the calibration and…

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Macaque Species

PubMed Central

Curtis, Alan D.; Taslim, Najla; Reece, Shaun P.; Grebenciucova, Elena; Ray, Richard H.; Rosenbaum, Matthew D.; Wardle, Robert L.; Van Scott, Michael R.; Mannie, Mark D.

2014-01-01

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction. PMID:25303101

The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

PubMed

Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

2014-01-01

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction.

The multidimensional inventory of hypochondriacal traits: factor structure, specificity, reliability, and validity in patients with hypochondriasis.

PubMed

Witthöft, Michael; Weck, Florian; Gropalis, Maria

2015-06-01

Severe health anxiety constitutes a disabling and costly clinical condition. The Multidimensional Inventory of Hypochondriacal Traits (MIHT) represents an innovative instrument that was developed according to cognitive-behavioral, cognitive-perceptual, interpersonal, and trait models of hypochondriasis. We aimed at evaluating the psychometric properties of the MIHT in a sample of patients with the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of hypochondriasis. Using confirmatory factor analysis (CFA), the postulated four-factor structure of the MIHT was found in a first CFA in patients with hypochondriasis (n = 178) and in a second CFA based on a mixed sample, with other somatoform disorders (n = 27), panic disorder (n = 25), and healthy controls (n = 31) added to the original group of patients with hypochondriasis (n = 178). In terms of specificity, patients with hypochondriasis showed larger scores on all four MIHT subscales (i.e., affective, cognitive, behavioral, and perceptual) compared to all other groups. Analyses of convergent and discriminant validity revealed promising results concerning the MIHT affective and perceptual scales but also point to certain problematic issues concerning the MIHT cognitive and behavioral scales. The findings suggest that the proposed structure of the MIHT is valid also in patients with hypochondriasis and demonstrate the specificity of the four hypochondriacal traits assessed in the MIHT. © The Author(s) 2014.

The cross-national structure of mental disorders: results from the World Mental Health Surveys.

PubMed

de Jonge, Peter; Wardenaar, Klaas J; Lim, Carmen C W; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Andrade, Laura Helena; Bunting, Brendan; Chatterji, Somnath; Ciutan, Marius; Gureje, Oye; Karam, Elie G; Lee, Sing; Medina-Mora, Maria Elena; Moskalewicz, Jacek; Navarro-Mateu, Fernando; Pennell, Beth-Ellen; Piazza, Marina; Posada-Villa, José; Torres, Yolanda; Kessler, Ronald C; Scott, Kate

2017-12-19

The patterns of comorbidity among mental disorders have led researchers to model the underlying structure of psychopathology. While studies have suggested a structure including internalizing and externalizing disorders, less is known with regard to the cross-national stability of this model. Moreover, little data are available on the placement of eating disorders, bipolar disorder and psychotic experiences (PEs) in this structure. We evaluated the structure of mental disorders with data from the World Health Organization Composite International Diagnostic Interview, including 15 lifetime mental disorders and six PEs. Respondents (n = 5478-15 499) were included from 10 high-, middle- and lower middle-income countries across the world aged 18 years or older. Confirmatory factor analyses (CFAs) were used to evaluate and compare the fit of different factor structures to the lifetime disorder data. Measurement invariance was evaluated with multigroup CFA (MG-CFA). A second-order model with internalizing and externalizing factors and fear and distress subfactors best described the structure of common mental disorders. MG-CFA showed that this model was stable across countries. Of the uncommon disorders, bipolar disorder and eating disorder were best grouped with the internalizing factor, and PEs with a separate factor. These results indicate that cross-national patterns of lifetime common mental-disorder comorbidity can be explained with a second-order underlying structure that is stable across countries and can be extended to also cover less common mental disorders.

Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

PubMed Central

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty acids might have an important role in this pain control system. PMID:24349089

Comparative pharmacokinetics of (S)-MP3950, a novel 5-HT4 receptor agonist, in normal and atropine-induced gastrointestinal motility disorders rats.

PubMed

Wang, Binjie; Sun, Xiaoyang; Wang, Shixiao; Guo, Ping; Li, Shujuan; Zhang, Meiyu; Zhao, Longshan; Chen, Xiaohui

2018-08-01

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT 4 receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, C max reduced by 73.8%, AUC 0-t decreased by 57.6% and AUC 0-∞ declined by 56.8% in model rats. Additionally, the elimination half-life (t 1/2 ) and T max were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Joint demosaicking and zooming using moderate spectral correlation and consistent edge map

NASA Astrophysics Data System (ADS)

Zhou, Dengwen; Dong, Weiming; Chen, Wengang

2014-07-01

The recently published joint demosaicking and zooming algorithms for single-sensor digital cameras all overfit the popular Kodak test images, which have been found to have higher spectral correlation than typical color images. Their performance perhaps significantly degrades on other datasets, such as the McMaster test images, which have weak spectral correlation. A new joint demosaicking and zooming algorithm is proposed for the Bayer color filter array (CFA) pattern, in which the edge direction information (edge map) extracted from the raw CFA data is consistently used in demosaicking and zooming. It also moderately utilizes the spectral correlation between color planes. The experimental results confirm that the proposed algorithm produces an excellent performance on both the Kodak and McMaster datasets in terms of both subjective and objective measures. Our algorithm also has high computational efficiency. It provides a better tradeoff among adaptability, performance, and computational cost compared to the existing algorithms.

Streptococcus faecium M 74 in control of diarrhoea induced by a human enterotoxigenic Escherichia coli strain in an infant rabbit model.

PubMed

Wadström, T

1984-08-01

Streptococcus faecium strain M 74 was evaluated as a prophylacticum for enterotoxigenic Escherichia coli (ETEC) diarrhoea with human isolates of E. coli with CFA/I and CFA/II surface fimbrial haemagglutinins (adhesins) in a rabbit model. Young rabbits (3 to 4 days old) were given S. faecium organisms (5 X 10(9)) 15 min before (group A), 6 h before (group B) and 12 h after (group C) challenge with ETEC organisms. Only 4 out of 26 rabbits in group A, 6 out of 21 in group B and 7 out of 23 in group C developed diarrhoea. In conclusion, this S. faecium strain M 74 seems efficiently to protect animals from ETEC diarrhoea when given as a prophylactic agent at a high dose. This animal model seems useful for comparative studies on new preventive methods for ETEC diarrhoea such as testing probiotics and antiadhesive drugs.

Factor analytical study of the short version of the World Health Organization Quality of Life Instrument.

PubMed

Ohaeri, Jude U; Olusina, Adewunmi K; Al-Abassi, Abdul-Hamid M

2004-01-01

The domains of the 26-item World Health Organization Quality of Life Instrument (WHOQOL-Bref) contain heterogeneous items and do not encompass the logical constructs of subjective quality of life (QOL). We compared the WHO 4-domain and 6-domain models of the WHOQOL-Bref with the 8-domain model that we obtained from factor analysis (FA). Data from 118 recently recovered Nigerian psychotic patients were used in confirmatory factor analysis (CFA) to assess goodness of fit and clarity of concept. Our FA model had superior goodness of fit for CFA and provided clarity of concept. Analysis of the WHOQOL-Bref should consider the domains from FA and include 'overall QOL' as an item and dependent variable. Subjective QOL is an aggregate of the following constructs: satisfaction with life circumstances; fulfillment of needs, and opportunity for experience in the milieu.

[Epidemic of gastroenteritis in Noumea (New Caledonia) caused by an enterotoxinogenic strain of Escherichia coli (0l26:B16) believed to be enteropathogenic].

PubMed

Germani, Y; Amat, F; Brethes, B; Begaud, E; Plassart, H

1985-01-01

A strain of enteropathogenic Escherichia coli 0126:B16 has been isolated in fifteen children and one adult during a severe outbreak. One infant is dead. The strain produced heat-stable enterotoxin, attach to rabbit enterocytes but did not have colonization factor antigen CFA/I or CFA/II. Its hemagglutination type was the same that the E. coli H10407, CFA/I+. It presented a resistance at eight antibiotics and, with the loss of enterotoxigenicity, there was a loss of resistance at ampicillin and of the capacity to attach to enterocytes.

Hybrid Fluorosilicones for Aircraft Fuel Tank Sealants. Part 4. Synthesis of Fluorocarbon and Fluorocarbon Ether Hybrid Fluorosilicone Polymers.

DTIC Science & Technology

1974-05-01

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The effects of tungstate on skin lesions caused by PPD in rats.

PubMed

Lee, Sang-Hee; Cho, Hyun-Gug; Lee, Sang-Il

2008-04-01

P-phenylenediamine (PPD) has been used as one of the ingredients in hair dye. The purpose of this study is to investigate the skin toxicity of PPD application in a tungstate-induced xanthine oxidase (XO) deficient animal model. PPD (2.5% PPD in 2% NH4OH) was applied to rat skin (25 mg/16.5 cm2) five times every other day in rats fed a standard diet (SD) or a tungstate supplemented diet (TD). The skin structure in the SD and the TD group was intact, whereas XO activity was not detected in the TD group during experimental periods. Furthermore, there were no differences between the SD and the TD group in dermal reactive oxygen species (ROS) scavenging enzymes. In these experimental conditions, although XO activity was not detected in the applied PPD rats fed a tungstate supplemented diet (PTD) group, it showed more severe tissue damage compared with the applied PPD rats fed a standard diet (PSD) group. In addition, the PTD group showed higher increased rates of ROS scavenging enzyme activity and lipid peroxide (LPO) content, and decreased glutathione (GSH) content than in the PSD group. In conclusion, the increase of PPD dermal toxicity in tungstate-induced XO deficient animals may be due to excessive ROS via ROS imbalance during PPD skin application.

Revisiting Executive Function Measurement: Implications for Lifespan Development

ERIC Educational Resources Information Center

Wiebe, Sandra A.; McFall, G. Peggy

2014-01-01

Since Miyake and his colleagues (2000) published their seminal paper on the use of confirmatory factor analysis (CFA) to parse executive function (EF), CFA methods have become ubiquitous in EF research. In their interesting and thoughtful Focus article, "Executive Function: Formative Versus Reflective Measurement," Willoughby and…

Coronafacoyl Phytotoxin Biosynthesis and Evolution in the Common Scab Pathogen Streptomyces scabiei

PubMed Central

Bown, Luke; Li, Yuting; Berrué, Fabrice; Verhoeven, Joost T. P.; Dufour, Suzanne C.

2017-01-01

ABSTRACT Coronafacoyl phytotoxins are an important family of plant toxins that are produced by several different phytopathogenic bacteria, including the gammaproteobacterium Pseudomonas syringae and the actinobacterium Streptomyces scabiei (formerly Streptomyces scabies). The phytotoxins consist of coronafacic acid (CFA) linked via an amide bond to different amino acids or amino acid derivatives. Previous work suggested that S. scabiei and P. syringae use distinct biosynthetic pathways for producing CFA, which is subsequently linked to its amino acid partner to form the complete phytotoxin. Here, we provide further evidence that the S. scabiei CFA biosynthetic pathway is novel by characterizing the role of CYP107AK1, a predicted cytochrome P450 that has no homologue in P. syringae. Deletion of the CYP107AK1 gene abolished production of coronafacoyl-isoleucine (CFA-Ile), the primary coronafacoyl phytotoxin produced by S. scabiei. Structural elucidation of accumulated biosynthetic intermediates in the ΔCYP107AK1 mutant indicated that CYP107AK1 is required for introducing the oxygen atom that ultimately forms the carbonyl group in the CFA backbone. The CYP107AK1 gene along with two additional genes involved in CFA-Ile biosynthesis in S. scabiei were found to be associated with putative CFA biosynthetic genes in other actinobacteria but not in other organisms. Analysis of the overall genetic content and organization of known and putative CFA biosynthetic gene clusters, together with phylogenetic analysis of the core biosynthetic genes, indicates that horizontal gene transfer has played an important role in the dissemination of the gene cluster and that rearrangement, insertion, and/or deletion events have likely contributed to the divergent biosynthetic evolution of coronafacoyl phytotoxins in bacteria. IMPORTANCE The ability of plants to defend themselves against invading pathogens relies on complex signaling pathways that are controlled by key phytohormones such as jasmonic acid (JA). Some phytopathogenic bacteria have evolved the ability to manipulate JA signaling in order to overcome host defenses by producing coronatine (COR), which functions as a potent JA mimic. COR and COR-like molecules, collectively referred to as coronafacoyl phytotoxins, are produced by several different plant-pathogenic bacteria, and this study provides supporting evidence that different biosynthetic pathways are utilized by different bacteria for production of these phytotoxins. In addition, our study provides a greater understanding of how coronafacoyl phytotoxin biosynthesis may have evolved in phylogenetically distinct bacteria, and we demonstrate that production of these compounds may be more widespread than previously recognized and that their role for the producing organism may not be limited to host-pathogen interactions. PMID:28754703

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa

PubMed Central

Chesnais, Cédric B.; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K.; Boussinesq, Michel; Fischer, Peter U.; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D.

2017-01-01

Background The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. Methodology The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Principal findings Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. Conclusions/Significance This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance. PMID:28892473

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa.

PubMed

Chesnais, Cédric B; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K; Boussinesq, Michel; Fischer, Peter U; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D; Weil, Gary J

2017-09-01

The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance.

Combined use of directional atherectomy and drug-coated balloon for the endovascular treatment of common femoral artery disease: immediate and one-year outcomes.

PubMed

Cioppa, Angelo; Stabile, Eugenio; Salemme, Luigi; Popusoi, Grigore; Pucciarelli, Armando; Iacovelli, Fortunato; Arcari, Antonella; Coscioni, Enrico; Trimarco, Bruno; Esposito, Giovanni; Tesorio, Tullio

2017-02-20

Surgical endarterectomy is the therapy of choice for atherosclerotic common femoral artery (CFA) obstruction. Recently, some large single-centre series have shown encouraging results for the percutaneous treatment of CFA obstructions. The purpose of this study was to evaluate the safety, feasibility, and one-year efficacy of the endovascular treatment of CFA obstructions with combined use of directional atherectomy (DA) and a paclitaxel-coated balloon (DCB). Between January 2012 and July 2014, 30 consecutive patients with severely calcified obstructions of the common femoral artery were treated in our centre using DA followed by DCB dilatation. Provisional stenting was allowed in the case of a suboptimal result. Twenty cases (66%) were isolated CFA interventions, whereas five (17%) and five (17%) also involved inflow and outflow vessels, respectively. Chronic total CFA occlusions (CTO) were recanalised in six cases (20%). Procedural success was achieved in all cases; stenting was needed in three cases (10%). At one year, restenosis and target lesion revascularisation were observed in two of 30 (6.6%) and one of 30 (3.3%) patients, respectively. The secondary patency rate was 96.7%. This single-centre prospective study suggests that the combined use of DA and DCB is a safe and effective alternative to surgery, a treatment option for common femoral artery lesions and provides encouraging results in this setting.

Development and construct validity of the Classroom Strategies Scale-Observer Form.

PubMed

Reddy, Linda A; Fabiano, Gregory; Dudek, Christopher M; Hsu, Louis

2013-12-01

Research on progress monitoring has almost exclusively focused on student behavior and not on teacher practices. This article presents the development and validation of a new teacher observational assessment (Classroom Strategies Scale) of classroom instructional and behavioral management practices. The theoretical underpinnings and empirical basis for the instructional and behavioral management scales are presented. The Classroom Strategies Scale (CSS) evidenced overall good reliability estimates including internal consistency, interrater reliability, test-retest reliability, and freedom from item bias on important teacher demographics (age, educational degree, years of teaching experience). Confirmatory factor analyses (CFAs) of CSS data from 317 classrooms were carried out to assess the level of empirical support for (a) a 4 first-order factor theory concerning teachers' instructional practices, and (b) a 4 first-order factor theory concerning teachers' behavior management practice. Several fit indices indicated acceptable fit of the (a) and (b) CFA models to the data, as well as acceptable fit of less parsimonious alternative CFA models that included 1 or 2 second-order factors. Information-theory-based indices generally suggested that the (a) and (b) CFA models fit better than some more parsimonious alternative CFA models that included constraints on relations of first-order factors. Overall, CFA first-order and higher order factor results support the CSS-Observer Total, Composite, and subscales. Suggestions for future measurement development efforts are outlined. PsycINFO Database Record (c) 2013 APA, all rights reserved.