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Sample records for alphav beta3 aggravates

  1. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich; Kjaer, Andreas

    2009-01-01

    molecules VEGF and integrin beta3 were lower in neuroendocrine tumors than in colorectal liver metastases and were highly variable. Therefore, individual selection of patients may be necessary if anti-angiogenesis treatment is to be successful in patients with neuroendocrine tumors......., in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver...

  2. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages

    DEFF Research Database (Denmark)

    von Wichert, Gotz; Jiang, Guoying; Kostic, Ana;

    2003-01-01

    -integrins at the leading edge during early spreading, and coimmunoprecipitates with alphav-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and...

  3. microPET Imaging of Glioma Integrin (alpha-v, beta-3) Expression Using Cu-64-Labeled Tetrameric RGD Peptide

    International Nuclear Information System (INIS)

    Integrins ?v?3 and ?v?5 play a critical role in tumor-induced angiogenesis and metastasis, and have become promising diagnostic indicators and therapeutic targets of tumors. Radiolabeled RGD peptides that are integrin-specific may be used for non-invasive imaging of integrin expression level as well as for integrin-targeted radionuclide therapy. We previously conjugated a series of mono- and dimeric RGD peptides with 1,4,7,10-tetraazacyclododecane-N, N?,N??,N???-tetraacetic acid (DOTA) and labeled these with copper-64 for microPET imaging in various mouse xenograft models. The copper-64 tracers showed ?v?3-selective tumor uptake, but the magnitude of tumor uptake was relatively low, the tumor washout was rapid, and non-target organ/tissue retention was high. In this study we developed a tetrameric RGD peptide tracer 64Cu-DOTA-E{E[c(RGDfK)]2}2 for positron emission tomography (PET) imaging of integrin ?v?3 expression in a subcutaneous U87MG glioma xenograft model in female athymic nude mice. The RGD tetramer showed significantly higher integrin binding affinity than the corresponding mono- and dimeric RGD analogs, most likely due to polyvalency effect. The radiolabeled peptide showed rapid blood clearance (0.61 - 0.01%ID/g at 30 min and 0.21 - 0.01 %ID/g at 4 h postinjection (p.i.), respectively) and predominantly renal excretion. Tumor uptake was rapid and high and the tumor washout was slow (9.93 - 1.05 %ID/g at 30 min p.i. and 4.56 - 0.51 %ID/g at 24 h post-injection). The metabolic stability of 64Cu-DOTA-E{E[c(RGDfK)]2}2 was determined in mouse blood, urine, and liver and kidney homogenates at different times after tracer injection. The average fractions of intact tracer in these organs at 1 h were approximately 70, 58, 51 and 26 percent, respectively. Non-invasive microPET imaging studies showed significant tumor uptake and good contrast in the subcutaneous tumor-bearing mice, which agreed well with the biodistribution results. Integrin ?v?3 specificity was demonstrated by successful blocking of tumor uptake of 64Cu-DOTA-E{E[c(RGDfK)]2}2 in the presence of excess amount of c(RGDyK) at 1 h postinjection. The highest absorbed radiation doses determined for the human reference adult were received by the urinary bladder wall (0.263 mGy/MBq), kidneys (0.0298 mGy/MBq), and liver (0.0244 mGy/MBq). Assuming 0.5-g U87MG glioma tumors in man, we calculated an absorbed dose of 65.3 mGy/MBq (242 rad/mCi) following a single injection of 64Cu-DOTA-E{E[c(RGDfK)]2}2. In conclusion, the high integrin avidity and favorable biokinetics make 64Cu-DOTA-E{E[c(RGDfK)]2}2 a promising agent for peptide receptor radionuclide imaging therapy of integrin-positive tumors

  4. microPET Imaging of Glioma Integrin (alpha-v, beta-3) Expression Using Cu-64-Labeled Tetrameric RGD Peptide

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yun; Zhang, , Xianzhong; Xiong, , Zhengming; Cheng, Zhen; Fisher, Darrell R.; Liu, Shu-hong; Gambhir, Sanjiv S.; Chen, Xiaoyuan

    2005-10-01

    Integrins ?v?3 and ?v?5 play a critical role in tumor-induced angiogenesis and metastasis, and have become promising diagnostic indicators and therapeutic targets of tumors. Radiolabeled RGD peptides that are integrin-specific may be used for non-invasive imaging of integrin expression level as well as for integrin-targeted radionuclide therapy. We previously conjugated a series of mono- and dimeric RGD peptides with 1,4,7,10-tetraazacyclododecane-N, N?,N??,N???-tetraacetic acid (DOTA) and labeled these with copper-64 for microPET imaging in various mouse xenograft models. The copper-64 tracers showed ?v?3-selective tumor uptake, but the magnitude of tumor uptake was relatively low, the tumor washout was rapid, and non-target organ/tissue retention was high. In this study we developed a tetrameric RGD peptide tracer 64Cu-DOTA-E{l_brace}E[c(RGDfK)]2{r_brace}2 for positron emission tomography (PET) imaging of integrin ?v?3 expression in a subcutaneous U87MG glioma xenograft model in female athymic nude mice. The RGD tetramer showed significantly higher integrin binding affinity than the corresponding mono- and dimeric RGD analogs, most likely due to polyvalency effect. The radiolabeled peptide showed rapid blood clearance (0.61 ? 0.01%ID/g at 30 min and 0.21 ? 0.01 %ID/g at 4 h postinjection (p.i.), respectively) and predominantly renal excretion. Tumor uptake was rapid and high and the tumor washout was slow (9.93 ? 1.05 %ID/g at 30 min p.i. and 4.56 ? 0.51 %ID/g at 24 h post-injection). The metabolic stability of 64Cu-DOTA-E{l_brace}E[c(RGDfK)]2{r_brace}2 was determined in mouse blood, urine, and liver and kidney homogenates at different times after tracer injection. The average fractions of intact tracer in these organs at 1 h were approximately 70, 58, 51 and 26 percent, respectively. Non-invasive microPET imaging studies showed significant tumor uptake and good contrast in the subcutaneous tumor-bearing mice, which agreed well with the biodistribution results. Integrin ?v?3 specificity was demonstrated by successful blocking of tumor uptake of 64Cu-DOTA-E{l_brace}E[c(RGDfK)]2{r_brace}2 in the presence of excess amount of c(RGDyK) at 1 h postinjection. The highest absorbed radiation doses determined for the human reference adult were received by the urinary bladder wall (0.263 mGy/MBq), kidneys (0.0298 mGy/MBq), and liver (0.0244 mGy/MBq). Assuming 0.5-g U87MG glioma tumors in man, we calculated an absorbed dose of 65.3 mGy/MBq (242 rad/mCi) following a single injection of 64Cu-DOTA-E{l_brace}E[c(RGDfK)]2{r_brace}2. In conclusion, the high integrin avidity and favorable biokinetics make 64Cu-DOTA-E{l_brace}E[c(RGDfK)]2{r_brace}2 a promising agent for peptide receptor radionuclide imaging therapy of integrin-positive tumors.

  5. Molecular characterization and expression analysis of the gene coding for the porcine beta(3) integrin subunit (CD61).

    Science.gov (United States)

    Jiménez-Marín, Angeles; Yubero, Noemí; Esteso, Gloria; Moreno, Angela; de las Mulas, Juana Martín; Morera, Luis; Llanes, Diego; Barbancho, Manuel; Garrido, Juan J

    2008-01-31

    Integrins are heterodimeric cell adhesion molecules with major roles in a variety of biological processes ranging from cell migration to tissue organization, immune and non-immune defense mechanisms and oncogenic transformation. Members of the beta(3) integrin subfamily are composed of a beta(3) subunit (CD61) non-covalently associated with two alpha subunits, alpha(IIb) (CD41) and alpha(v) (CD51), to constitute a group of transmembrane glycoproteins that participate in many physiologically important events. This investigation has focused on the molecular characterization of the cDNA encoding the porcine beta(3) integrin subunit. The deduced 762-amino acid sequence was 93, 92, 91, 89, 79 and 73% homologous to human, dog, rabbit, mouse, chicken and Xenopus laevis CD61 protein, respectively. Porcine CD61 molecule shares many structural features with human CD61, including a region containing a metal ion-dependent adhesion site (MIDAS) folding into an I domain-like structure. Through PCR-SSCP analysis and sequencing, six polymorphic positions were detected in the cDNA sequence of porcine CD61, and their frequencies were observed from a collection of 47 pigs. Expression analysis was done at two different levels: expression of the CD61 mRNA by RT-PCR and localization of the protein by immunohistochemistry. Our results show that CD61 transcripts were detected mainly in platelets and hematopoietic tissues. The immunohistochemical tissue localization of CD61 protein by a specific monoclonal antibody against CD61 recombinant protein showed that CD61 was expressed on vascular and non-vascular smooth muscle, epithelium and myeloid cells, being undetectable in cells of the lymphoid lineage. Furthermore, pulmonary intravascular macrophages (PIM), a subpopulation of macrophages which seem to play an important role in blood clearance, expressed much more CD61 when compared to pulmonary alveolar macrophages (PAM). The knowledge of the structure and distribution of the CD61 provides

  6. Genetics Home Reference: potassium-aggravated myotonia

    Science.gov (United States)

    ... myotonia Patient Support and Advocacy Resources (2 links) Muscular Dystrophy Association Resource list from the University of Kansas Medical Center Genetic Testing Registry (1 link) Potassium aggravated myotonia ClinicalTrials. ...

  7. Improved targeting of the alpha(v)beta (3) integrin by multimerisation of RGD peptides.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Kruijtzer, J.A.; Liu, S.; Soede, A.C.; Oyen, W.J.G.; Corstens, F.H.M.; Liskamp, R.M.; Boerman, O.C.

    2007-01-01

    PURPOSE: The integrin alpha(v)beta(3) is expressed on sprouting endothelial cells and on various tumour cell types. Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3) binding charac

  8. Role of Jumonji c-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) can utilize as many as three distinct groups of receptor molecules to attach and enter a susceptible host cell. Four integrin heterodimers (alphavBeta1, alphavBeta3, alphavBeta6, and alphavBeta8) can function as the primary receptor for FMDV field strains. FMDV ...

  9. Functional beta3-adrenoceptor in the human heart.

    OpenAIRE

    Gauthier, C.; Tavernier, G.; Charpentier, F.; Langin, D.; Le Marec, H

    1996-01-01

    Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also res...

  10. Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms.

    Science.gov (United States)

    Smyth, S S; Reis, E D; Väänänen, H; Zhang, W; Coller, B S

    2001-08-15

    Platelet integrin alpha IIb beta 3 (GPIIb/IIIa) plays a central role in the initiation of arterial thrombosis, but its contribution to disseminated microvascular thrombosis is less well defined. Therefore, wild-type mice (beta 3(+/+)), beta 3-integrin-deficient mice (beta 3(-/-)), and wild-type mice treated with a hamster monoclonal antibody (1B5) that blocks murine alpha IIb beta 3 function were tested in models of large-vessel and microvascular thrombosis. In the large-vessel model, ferric chloride was used to injure the carotid artery, and the time to thrombosis was measured. In beta 3(+/+) mice, the median time to occlusion was 6.7 minutes, whereas occlusion did not occur in any of the beta 3(-/-) mice tested (P <.001). Fab and F(ab')(2) fragments of 1B5 increased the median time to occlusion. To initiate systemic intravascular thrombosis, prothrombotic agents were administered intravenously, and platelet thrombus formation was monitored by the decrease in circulating platelet count. Three minutes after the injection of adenosine diphosphate (ADP), collagen + epinephrine, or tissue factor, the platelet counts in beta 3(+/+) mice decreased by 289, 424, and 429 x 10(3)/microL, respectively. beta 3(-/-) mice and wild-type mice pretreated with 1B5 Fab (1 mg/kg, IP) were nearly completely protected from the effects of ADP. In contrast, beta 3(-/-) mice were only partially protected from the effects of collagen + epinephrine and minimally protected from the effects of tissue factor. In all cases, less fibrin became deposited in the lungs of beta 3(-/-) mice than in wild-type mice. These results suggest that though alpha IIb beta 3 plays a dominant role in large-vessel thrombosis, it plays a variable role in systemic intravascular thrombosis. (Blood. 2001;98:1055-1062) PMID:11493451

  11. Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.

    Science.gov (United States)

    Rodriguez, M; Carillon, C; Coquerel, A; Le Fur, G; Ferrara, P; Caput, D; Shire, D

    1995-04-01

    The beta 3-adrenergic receptor (AR) is widely distributed in peripheral tissues, but up to now it has not been detected in the central nervous system. By using the polymerase chain reaction (PCR) technique, we found the beta 3-AR mRNA to be present in all the regions of the human brain we investigated. The quantities found were very low compared to those of the beta 1-AR and beta 2-AR mRNAs, being hardly detectable in adult brain. In contrast, the brain of very young infants contained about 100 times more beta 3-AR mRNA than the adult brain, whereas the amounts of beta 1-AR and beta 2-AR transcripts were essentially the same. In addition, using PCR we have cloned a central beta 3-AR coding region from a human frontal cortex cDNA library and have found it to be identical to the corresponding peripheral sequence. PMID:7609625

  12. 38 CFR 3.306 - Aggravation of preservice disability.

    Science.gov (United States)

    2010-07-01

    ... disability. 3.306 Section 3.306 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Connection § 3.306 Aggravation of preservice disability. (a) General. A preexisting injury or disease will be... disability during such service, unless there is a specific finding that the increase in disability is due...

  13. Aggravating andmitigating factors associated with cyclist injury severity in Denmark

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Vavatsoulas,, Konstantinos; Prato, Carlo Giacomo

    2014-01-01

    severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature of......Denmark is one of the leading cycling nations, where cycling trips constitute a large share of the total trips, and cycling safety assumes a top priority position in the agenda of policy makers. The current study sheds light on the aggravating and mitigating factors associated with cyclist injury...... severity while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

  14. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

    OpenAIRE

    Ken-Ichiro Inoue; Hirohisa Takano

    2011-01-01

    Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanop...

  15. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    OpenAIRE

    Maria de Fatima Guerreiro Godoy; Livia Maria Pereira de Godoy; Stelamarys Barufi; José Maria Pereira de Godoy

    2014-01-01

    The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb), i...

  16. The subjective meaning of xerostomia—an aggravating misery

    OpenAIRE

    Folke, Solgun; Paulsson, Gun; Fridlund, Bengt; Söderfeldt, Björn

    2010-01-01

    Xerostomia, the subjective sensation of dry mouth, is associated with qualitative and quantitative changes of saliva. Poor health, certain medications and radiation therapy constitute major risk factors. To gain further understanding of this condition the present study explored the main concern of xerostomia expressed by affl icted adults. Qualitative interviews were conducted with 15 participants and analysed according to the grounded theory method. An aggravating misery was identifi ed as t...

  17. 42 CFR 93.408 - Mitigating and aggravating factors in HHS administrative actions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Mitigating and aggravating factors in HHS... and Human Services Research Misconduct Issues § 93.408 Mitigating and aggravating factors in HHS... conserve public funds. HHS considers aggravating and mitigating factors in determining appropriate...

  18. Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?

    OpenAIRE

    2007-01-01

    The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the beta3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that...

  19. Beyond bullying: Aggravating elements of peer victimization episodes.

    Science.gov (United States)

    Turner, Heather A; Finkelhor, David; Shattuck, Anne; Hamby, Sherry; Mitchell, Kimberly

    2015-09-01

    This study sought to identify features of peer victimization that aggravate negative outcomes in children. The features that were assessed include "power imbalance," a commonly used criterion in defining bullying, and 5 other characteristics: injury, weapon involvement, Internet involvement, sexual content, and bias content. Three outcomes were assessed: level of fear, missing school, and trauma symptoms. A nationally representative sample of 3,164 children and youth ages 6-17 (51.8% male; 68.4% white, 12.5% black, 13.5% Hispanic, 5.7% other race) was obtained through Random Digit Dial and supplemented with an address-based sample to capture cell-phone-only households. One child was randomly selected from each household. Interviews were conducted with parents of children age 6-9 and with the youths themselves if they were age 10-17. Peer victimization was assessed with the Juvenile Victimization Questionnaire (JVQ). Almost half (48.4%) of the entire sample of school-age children experienced at least 1 form of peer victimization in the past year. Injury and power imbalance independently increased the impact on children for all 3 outcomes. Additionally, weapon involvement and sexual content were associated with trauma symptoms, with sexual content having the strongest effect (B = .23, p bullying with its exclusionary power imbalance definition as the central focus for prevention and intervention. We recommend a broader focus on peer victimization along with more research to identify the aggravating features that signal the greatest need for intervention. PMID:25330389

  20. Sizeable beta-strength in 31Ar (beta 3p) decay

    DEFF Research Database (Denmark)

    T. Koldste, G.; Blank, B.; J. G. Borge, M.;

    2014-01-01

    We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as...... much as 30% of the strength resides in the beta-3p decay mode. A simplified description of how the main decay modes evolve as the excitation energy increases in 31Cl is provided....

  1. Adaptive rewiring aggravates the effects of species loss in ecosystems.

    Science.gov (United States)

    Gilljam, David; Curtsdotter, Alva; Ebenman, Bo

    2015-01-01

    Loss of one species in an ecosystem can trigger extinctions of other dependent species. For instance, specialist predators will go extinct following the loss of their only prey unless they can change their diet. It has therefore been suggested that an ability of consumers to rewire to novel prey should mitigate the consequences of species loss by reducing the risk of cascading extinction. Using a new modelling approach on natural and computer-generated food webs we find that, on the contrary, rewiring often aggravates the effects of species loss. This is because rewiring can lead to overexploitation of resources, which eventually causes extinction cascades. Such a scenario is particularly likely if prey species cannot escape predation when rare and if predators are efficient in exploiting novel prey. Indeed, rewiring is a two-edged sword; it might be advantageous for individual predators in the short term, yet harmful for long-term system persistence. PMID:26400367

  2. Impaired platelet aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin alpha IIb beta 3.

    OpenAIRE

    Holmbäck, K; Danton, M J; Suh, T T; Daugherty, C. C.; Degen, J L

    1996-01-01

    Blood loss at sites of vascular rupture is controlled by the adhesion and aggregation of platelets and the formation of an insoluble fibrin matrix. Fibrinogen is considered to be critical in these processes by both providing an abundant dimeric ligand for alpha IIb beta 3-mediated platelet aggregation, and serving as the fundamental building block of the fibrin polymer. To establish an in vivo model system to examine in detail the importance of alpha IIb beta 3-fibrinogen interactions in plat...

  3. PET imaging of alpha(v)beta(3) integrin expression in tumours with Ga-68-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, Ingrid; Yim, Cheng-Bin; Franssen, Gerben M.; Schuit, Robert C.; Luurtsema, Gert; Liu, Shuang; Oyen, Wim J. G.; Boerman, Otto C.

    2011-01-01

    Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of Ga-68-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their I

  4. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  5. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  6. Imprecise methods may both obscure and aggravate a relation between fat and breast cancer

    DEFF Research Database (Denmark)

    Heitmann, B L; Frederiksen, Peder

    2007-01-01

    -protein energy has been found to be substantial, particularly among those who are obese or have high dietary intakes. Such a non-random bias on the group level would tend to aggravate associations between dietary non-protein and disease. Whether the net result of the random and non-random bias aggravates or...

  7. Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate-salt hypertensive mice.

    Science.gov (United States)

    Sheng, Li-Juan; Ruan, Cheng-Chao; Ma, Yu; Chen, Dong-Rui; Kong, Ling-Ran; Zhu, Ding-Liang; Gao, Ping-Jin

    2016-03-01

    Beta3 adrenergic receptor (ADRB3) mediates vessel relaxation in the endothelium while it modulates lipolysis in the adipose tissue. However, the function and regulation mechanism of ADRB3 in the perivascular adipose tissue (PVAT), especially in hypertension, is still unclear. We show that ADRB3 protein is upregulated in the PVAT of deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice, with the characteristics of PVAT browning and increased uncoupling protein 1 (UCP1) expression. Inhibition of ADRB3 with selective antagonist SR59230A caused serious vascular injury in vivo, even though UCP1 expression was downregulated. ADRB3 protein was regulated by let-7b, which was decreased in the PVAT of the DOCA-salt group. These data reveal that ADRB3 in PVAT contributes to vascular function in the progression of hypertension. PMID:26910302

  8. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy

    2014-01-01

    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  9. Vitamin D depletion aggravates hypertension and target-organ damage

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine; von Versen-Höynck, Frauke; Qadri, Fatimunnisa; Jørgensen, Jan Stener; Sorensen, Grith Lykke; Fruekilde, Palle; Poglitsch, Marko; Szijarto, István; Gollasch, Maik; Peters, Joerg; Muller, Dominik N; Christesen, Henrik Thybo; Dechend, Ralf

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0......, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter-regulatory breakdown product Ang 1 to 7, were significantly up-regulated in the vitamin D-depleted groups, while ACE-1...

  10. The contribution of IL-6 to beta 3 adrenergic receptor mediated adipose tissue remodeling.

    Science.gov (United States)

    Buzelle, Samyra L; MacPherson, Rebecca E K; Peppler, Willem T; Castellani, Laura; Wright, David C

    2015-02-01

    The chronic activation of beta 3 adrenergic receptors results in marked alterations in adipose tissue morphology and metabolism, including increases in mitochondrial content and the expression of enzymes involved in lipogenesis and glyceroneogenesis. Acute treatment with CL 316,243, a beta 3 adrenergic agonist, induces the expression of interleukin 6. Interestingly, IL-6 has been shown to induce mitochondrial genes in cultured adipocytes. Therefore, the purpose of this paper was to examine the role of interleukin 6 in mediating the in vivo effects of CL 316,243 in white adipose tissue. Circulating IL-6, and markers of IL-6 signaling in white adipose tissue were increased 4 h following a single injection of CL 316,243 in C57BL6/J mice. Once daily injections of CL 316,243 for 5 days increased the protein content of a number of mitochondrial proteins including CORE1, Cytochrome C, PDH, MCAD, and Citrate Synthase to a similar extent in adipose tissue from WT and IL-6(-/-) mice. Conversely, CL 316,243-induced increases in COXIV and phosphorylated AMPK were attenuated in IL-6(-/-) mice. Likewise, the slight, but significant, CL 316,243-induced increases in ATGL, PEPCK, and PPARγ, were reduced or absent in adipose tissue IL-6(-/-) mice. The attenuated response to CL 316,243 in white adipose tissue in IL-6(-/-) mice was associated with reductions in whole-body oxygen consumption and energy expenditure in the light phase. Our findings suggest that IL-6 plays a limited role in CL 316,243-mediated adipose tissue remodeling. PMID:25713332

  11. Studies on the interactions between glycosylated beta3-peptides and the lectin Vicia villosa by saturation transfer difference NMR spectroscopy.

    Science.gov (United States)

    Kaszowska, Marta; Norgren, Anna S; Arvidson, Per I; Sandström, Corine

    2009-12-14

    Saturation transfer difference (STD) NMR spectroscopy was used to study the interaction of the lectin Vicia villosa (VVLB(4)) with alpha-D-GalNAc glycosylated beta(3)-peptides. The data were compared to those obtained with the monosaccharides D-Gal, D-GalNAc, and D-Glc as well as with those obtained with the Tn antigen alpha-glycopeptide (D-GalNAc-alpha-O-Ser/Thr), molecule naturally recognized by V. villosa. Evidence that the lectin also recognizes glycosylated beta(3)-peptides and has close contact with both the sugar and amino acid moieties was obtained. PMID:19863951

  12. Naproxen aggravates doxorubicin-induced cardiomyopathy in rats

    Directory of Open Access Journals (Sweden)

    Pathan Rahila

    2010-01-01

    Full Text Available Background : The repercussion of the heated dispute on cyclooxygenase-2 (COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs led to the national and international withdrawal of several of the recently introduced coxibs. Further debate and research have highlighted risks of the classical NSAIDs too. There is much controversy about the cardiovascular safety of a nonselective NSAID naproxen (NAP and its possible cardioprotective effect. Objectives : The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats. Materials and Methods : Male albino rats received a single i.p. injection of normal saline (normal control group and doxorubicin (DOX 15 mg/kg (toxic control group. Naproxen was administered alone (50 mg/kg/day, p.o. and in combination with DOX and DOX + trimetazidine (TMZ (10 mg/kg/day, p.o. for 5 days after 24 h of DOX treatment. DOX-induced cardiomyopathy was assessed in terms of increased activities of serum lactate dehydrogenase (LDH, tissue thiobarbituric acid reactive substances (TBARS and decreased activities of myocardial glutathione, superoxide dismutase and catalase, followed by transmission electron microscopy of the cardiac tissue. Results : Doxorubicin significantly increased oxidative stress as evidenced by increased levels of LDH and TBARS and decreased antioxidant enzymes levels. Both biochemical and electron microscopic studies revealed that NAP itself was cardiotoxic and aggravated DOX-induced cardiomyopathy and abolished the protective effect of TMZ in rats. Conclusions : This study indicates that NAP has the potential to worsen the situation in patients with cardiovascular disease. Therefore, it should be used cautiously in patients with compromised cardiac function.

  13. Dietary hypercholesterolemia aggravates contrast media-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨定位; 贾汝汉; 杨定平; 丁国华; 黄从新

    2004-01-01

    Background Contrast media administration can result in severe nephrotoxicity under pathological conditions such as diabetic nephropathy, congestive heart failure, dehydration, et al. The purpose of this study was to evaluate the effects of dietary hypercholesterolemia on contrast media-induced changes in renal function, blood flow, and histopathology.Methods Rats were fed either on a normal rodent diet (group N) or a high-cholesterol supplemented diet (group H; 4% cholesterol and 1% cholic acid) for 8 weeks. Half of the animals (n =6) from each diet group were then given a tail vein injection of 60% diatrizoate (6 ml/kg; group NC and group HC)and the other half were administered saline. Total serum cholesterol, triglyceride, serum creatinine,creatinine clearance rate, fractional excretion of sodium and potassium, and cortical nitric oxide production were determined one day following contrast media administration. Renal blood flow was determined by color Doppler flow imaging and pulsed-mode Doppler. Renal histopathology was observed by light microscopy.Results Total serum cholesterol and resistance indices of renal blood vessels increased significantly,while creatinine clearance rate and production of nitric oxide in the renal cortex decreased markedly in group HC and group H when compared to group N and group NC. The creatinine clearance rate decreased significantly in group HC compared to group H. Serum creatinine levels and fractional excretion of sodium and potassium in group HC were significantly higher than those in the other three groups. Severe tubular degeneration and necrosis, protein cast accumulation, and medullary congestion were found in group HC.Conclusion Hypercholesterolemia is a risk factor for contrast media-induced nephropathy.Hypercholesterolemia aggravates contrast media-induced nephrotoxicity through the reduced production of nitric oxide.

  14. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity.

    Science.gov (United States)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou; Peng, Shuangqing; Wang, Weidong; Li, Rong

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT-/-) and corresponding wild-type (MT+/+) mice was investigated to determine any associations with MT. Each MT-/- or MT+/+ mouse was pretreated with a single dose of DU (10mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT-/- mice significantly increased than in MT+/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT-/- mice. The apoptosis rate in MT-/- mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT-/- mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT-/- mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. PMID:26148447

  15. Arterial hypertension aggravates innate immune responses after experimental stroke

    Directory of Open Access Journals (Sweden)

    Karoline Möller

    2015-11-01

    Full Text Available Arterial hypertension is not only the leading risk factor for stroke, but also attribute to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHR and normotensive Wistar Kyoto rats (WKY were subjected to photothrombotic stroke. One and three days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines, along with the post-stroke inflammatory response was analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains four days after stroke. Although comparable at day one, lesion volumes were significantly larger in SHR at day three. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion molecule 1 (VCAM-1 and P-selectin (CD62P was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may

  16. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Science, 20 Dongdajie Street, Fengtai District, Beijing 100071 (China); Wang, Weidong, E-mail: wwdwyl@sina.com [Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Li, Rong, E-mail: yuhui_hao@126.com [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China)

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  17. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    International Nuclear Information System (INIS)

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  18. External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas

    International Nuclear Information System (INIS)

    The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors. We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR) and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test. The gene and protein ITGB3 (Integrin beta 3) were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME. The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours

  19. External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Sundfeldt Karin

    2009-09-01

    Full Text Available Abstract Background The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors. Methods We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test. Results The gene and protein ITGB3 (Integrin beta 3 were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME. Conclusion The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours.

  20. Lateral mobility of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) in the plasma membrane of a human megakaryocyte.

    Science.gov (United States)

    Schootemeijer, A; van Willigen, G; van der Vuurst, H; Tertoolen, L G; De Laat, S W; Akkerman, J W

    1997-01-01

    The migration of integrins to sites of cell-cell and cell-matrix contact is thought to be important for adhesion strengthening. We studied the lateral diffusion of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) in the plasma membrane of a cultured human megakaryocyte by fluorescence recovery after photobleaching of FITC-labelled monovalent Fab fragments directed against the beta 3 subunit. The diffusion of beta 3 on the unstimulated megakaryocyte showed a lateral diffusion coefficient (D) of 0.37 x 10(-9) cm2/s and a mobile fraction of about 50%. Stimulation with ADP (20 microM) or alpha-thrombin (10 U/ml) at 22 degrees C induced transient decreases in both parameters reducing D to 0.21 x 10(-9) cm2/s and the mobile fraction to about 25%. The fall in D was observed within 1 min after stimulation but the fall in mobile fraction showed a lag phase of 5 min. The lag phase was absent in the presence of Calpain I inhibitor, where-as cytochalasin D completely abolished the decreased in mobile fraction. The data are compatible with the concept that cell activation induces anchorage of 50% of the mobile alpha IIb beta 3 (25% of the whole population of receptor) to the cytoplasmic actin filaments, although, as discussed, other rationals are not ruled out. PMID:9031465

  1. Sleep-related hypoxemia aggravates systematic inflammation in emphysematous rats

    Institute of Scientific and Technical Information of China (English)

    FENG Jing; Ambrose An-Po Chiang; WU Qi; CHEN Bao-yuan; CUI Lin-yang; LIANG Dong-chun; ZHANG Ze-li; YAO Wo

    2010-01-01

    mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (ail P <0.05). O2Sat in SRHStand rats when SRH exposure was (83.45±1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P <0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P <0.05)). MDA values were the highest in SRHStand group (all P <0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P <0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P <0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P <0.05).Conclusions With a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia,oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied.

  2. Integrin beta3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

    DEFF Research Database (Denmark)

    Tofteng, Charlotte L; Bach-Mortensen, Pernille; Bojesen, Stig E;

    2007-01-01

    integrin beta3 Leu33Pro polymorphism have a two-fold risk of hip fracture, mainly confined to postmenopausal women. Integrin beta3 Leu33Pro homozygosity could prove a useful marker for risk of future hip fracture and may contribute to pharmacogenetic variation in effects of integrin alphavbeta3 antagonists....

  3. 33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.

    Science.gov (United States)

    2010-07-01

    ... PROCEEDINGS OF THE COAST GUARD Supplementary Evidentiary Rules for Suspension and Revocation Hearings § 20... aware. The Coast Guard representative may offer evidence and argument in aggravation of any charge proved. The respondent may offer evidence of, and argument on, prior maritime service, including both...

  4. Street Life: Aggravated and Sexual Assaults among Homeless and Runaway Adolescents.

    Science.gov (United States)

    Terrell, Nathanial Eugene

    1997-01-01

    Examines aggravated and sexual assaults among 240 runaway and homeless adolescents (RHAs) in Des Moines (Iowa). Results suggest RHAs are at risk of life-threatening situations on the streets due to aggressive and abusive parents. Additionally, street life situations have significant impacts on the probability that RHAs will be victims of…

  5. 5 CFR 890.1016 - Aggravating and mitigating factors used to determine the length of permissive debarments.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Aggravating and mitigating factors used....1016 Aggravating and mitigating factors used to determine the length of permissive debarments. (a..., or impede official inquiries into the wrongful conduct underlying the debarment. (b)...

  6. Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity.

    Science.gov (United States)

    Valet, P; Grujic, D; Wade, J; Ito, M; Zingaretti, M C; Soloveva, V; Ross, S R; Graves, R A; Cinti, S; Lafontan, M; Lowell, B B

    2000-11-01

    Catecholamines play an important role in controlling white adipose tissue function and development. beta- and alpha 2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte alpha 2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs in adipose tissue with or without decreased beta-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta 3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha 2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass. PMID:10948198

  7. Postoperative neurological aggravation after anesthesia with sevoflurane in a patient with xeroderma pigmentosum: a case report

    OpenAIRE

    Fjouji, Salaheddine; Bensghir, Mustapha; Yafat, Bahija; Bouhabba, Najib; Boutayeb, Elhoucine; Azendour, Hicham; Kamili, Nordine Drissi

    2013-01-01

    Introduction Xeroderma pigmentosum is a rare autosomal recessive disease that causes changes in skin pigmentation, precancerous lesions and neurological abnormalities. It is a defect in the nucleotide excision repair mechanism. It has been reported that volatile anesthetics has a possible genotoxic side effect and deranged nucleotide excision repair in cells obtained from a patient with xeroderma pigmentosum. We report an unusual case of postoperative neurological aggravation in a patient wit...

  8. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis

    OpenAIRE

    Bellido, Miriam; Lugo, Laura; Roman-Blas, Jorge A; Castañeda, Santos; Caeiro, Jose R; Dapia, Sonia; Calvo, Emilio; Largo, Raquel; Herrero-Beaumont, Gabriel

    2010-01-01

    Introduction Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model. Methods OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabb...

  9. Does International Mobility of High-Skilled Workers Aggravate Between-Country Inequality ?

    OpenAIRE

    Grossmann, Volker; Stadelmann, David

    2010-01-01

    This paper analyzes the interaction of international migration of high-skilled labor and relative wage income between source and destination economies of expatriates. We develop an overlapping-generations model with increasing returns which suggests that international integration of the market for skilled labor aggravates between-country inequality by harming those which are source economies to begin with while benefiting host economies. The result is robust to allowing governments to optimal...

  10. Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Cavalcanti Correia

    2012-12-01

    Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.

  11. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

    OpenAIRE

    Hathaway, Catherine K.; Chang, Albert S.; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J.; Bagnell, C. Robert; Jennette, J. Charles; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    About one-third of patients with type 1 diabetes mellitus develop nephropathy, which often progresses to end-stage renal diseases. The present study demonstrates that below-normal Elmo1 expression in mice ameliorates the albuminuria and glomerular histological changes resulting from long-standing type 1 diabetes, whereas above-normal Elmo1 expression makes both worse. Increasing Elmo1 expression leads to aggravation of oxidative stress markers and enhances the expression of fibrogenic genes. ...

  12. A homozygous nonsense mutation in the {beta}3 chain gene of laminin 5 (LAMB3) in herlitz junctional epidermolysis bullosa

    Energy Technology Data Exchange (ETDEWEB)

    Pulkkinen, L.; Christiano, A.M.; Uitto, J. [Thomas Jefferson Univ., Phildelphia, PA (United States)] [and others

    1994-11-15

    Herlitz junctional epidermolysis bullosa (H-JEB) is a severe autosomal recessive disorder characterized by blister formation within the dermal-epidermal basement membrane. Based on immunofluorescence analysis recognizing laminin 5 epitopes (previously known as nicein/kalinin), the genes for this lamina lucida protein have been proposed as candidate genes in H-JEB. Amplification of mRNA by RT-PCR, followed by direct nucleotide sequencing, revealed a homozygous C-to T transition resulting in a premature termination codon (CGA{r_arrow}TGA) on both alleles. This mutation was verified at the genomic DNA level, and both parents were shown to be heterozygous carriers of the same mutation. This is the first description of a mutation in the laminin {beta}3 chain gene (LAMB3) of laminin 5 in an H-JEB patient. 15 refs., 2 figs.

  13. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation.

    Science.gov (United States)

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V; Cines, Douglas B; Takada, Yoshikazu

    2006-03-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity receptors for the uPA kringle. We found that uPA binds specifically to integrin alpha v beta 3 on CHO cells depleted of uPAR. The binding of uPA to alpha v beta 3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner. The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist. We studied whether the binding of uPA to integrin alpha v beta 3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and alpha v beta 3-dependent manner. Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling. PMID:16525582

  14. Viola Playing May Be a Strong Aggravating Factor for Temporomandibular Disorder

    Directory of Open Access Journals (Sweden)

    Mahmut Alpayci

    2014-12-01

    Full Text Available Temporomandibular disorder (TMD is the general term used to describe the symptoms originated from temporomandibular joint region. The most common symptom of the disorder is pain during mandibular movement. Etiology of TMD is multifactorial. Several factors such as trauma, occlusal discrepancies, stress, parafunctions, hypermobility, and heredity can make one more vulnerable to this disorder. It has been reported that viola playing might be a predisposing factor for TMD. In this article, we present a 24 year old male patient suffering from TMD symptoms exacerbated by viola playing and emphasize that viola playing may be a powerful aggravating factor for TMD.

  15. Cloning of the {beta}3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa

    Energy Technology Data Exchange (ETDEWEB)

    Pulkkinen, L.; Christiano, A.M.; Uitto, J. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1995-01-01

    Laminin 5 consists of three polypeptides, {alpha}3, {beta}3, and {gamma}2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMB3 gene. Characterization of five overlapping {lambda} phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 hp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon-intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. 33 refs., 3 figs., 2 tabs.

  16. Detection of sequence variants in the gene encoding the beta 3 chain of laminin 5 (LAMB3).

    Science.gov (United States)

    Pulkkinen, L; McGrath, J A; Christiano, A M; Uitto, J

    1995-01-01

    Laminin 5, a candidate gene/protein system for mutations in the junctional forms of epidermolysis bullosa (JEB), consists of three polypeptides encoded by the LAMA3, LAMB3, and LAMC2 genes. In this study, primer pairs for the amplification of the complete cDNA as well as 22 exons of the LAMB3 gene encoding the entire beta 3 chain of laminin 5, were established. The primers for amplification of individual exons from genomic DNA were placed at least 50 bp away from the exon-intron borders in the flanking intronic sequences. For amplification of cDNA generated by RT-PCR, eight primer pairs covering overlapping segments of mRNA were used. The amplified sequences were used to study sequence variations of the LAMB3 gene in patients with JEB and unrelated individuals using heteroduplex analysis. Nine out of 13 JEB patients examined showed heteroduplexes in at least one of the PCR products, indicating the existence of two variable alleles in their DNA. Sequence analyses revealed putative pathogenetic mutations in seven of the JEB patients, while four of the heteroduplexes resulted from polymorphisms, reflecting a single basepair substitution. The results demonstrate that this method is useful in the detection of JEB mutations, as well as polymorphisms in the LAMB3 gene. PMID:7550237

  17. Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa.

    Science.gov (United States)

    Pulkkinen, L; Gerecke, D R; Christiano, A M; Wagman, D W; Burgeson, R E; Uitto, J

    1995-01-01

    Laminin 5 consists of three polypeptides, alpha 3, beta 3, and gamma 2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon-intron organization of the human LAMB3 gene. Characterization of five overlapping lambda phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 bp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon-intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes. PMID:7774918

  18. Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

    DEFF Research Database (Denmark)

    Cha, Joo Hwan; Zou, Mu-Fa; Adkins, Erika M; Rasmussen, Søren G F; Loland, Claus Juul; Schoenenberger, Bernhard; Gether, Ulrik; Newman, Amy Hauck

    2005-01-01

    Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane, using an ethylamino lin...

  19. Inversion in the lactose region of Escherichia coli K-12: inversion termini map within IS3 elements alpha 3 beta 3 and beta 5 alpha 5.

    OpenAIRE

    Savić, D J; Romac, S P; Ehrlich, S D

    1983-01-01

    In this work, the previously described inversion in the lactose region of the Escherichia coli K-12 chromosome (D. J. Savić, J. Bacteriol. 140:311-319, 1979) is analyzed in greater detail. The results presented indicate that the inversion most likely occurred by a homologous recombination between alpha 3 beta 3 and beta 5 alpha 5 IS3 elements.

  20. Consumption of Mercury-contaminated Rice Induces Oxidative Stress and Free Radical Aggravation in Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-LING JI; GUI-WEN JIN; JIN-PING CHENG; WEN-HUA WANG; JING LU; LI-YA QU

    2007-01-01

    Objective To study the oxidative stress induced by consumption of mercury-contaminated rice in rats, and to assess the possible public health risk of mercury contamination in Wanshan mining area. Methods Sprague Dawley rats were fed the mercury-contaminated rice produced from Wanshan area for 90 days. The antioxidant status and the free radicals in rat serum were evaluated. Results High mercury accumulation in organs of rats fed the mercury-contaminated rice confirmed the server pollution of mercury in Wanshan mining area. The intensity of electron spin resonance (ESR) signal increased by 87.38% in rats fed the rice from Wanshan compared with that in the control rats fed the rice from Shanghai, suggesting that chronic dietary consumption of rice from mercury mining area could induce an aggravation of free radicals. Feeding the mercury-contaminated rice was associated with significant decreases in the antioxidant enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentration of serum nitric oxide (NO), but it had no effect on serum nitric oxide synthase (NOS) activity. Feeding the mercury-contaminated rice raised the level of serum malonyldialdehyde (MDA), indicating the occurrence of oxidative stress. Conclusion The long-term dietary consumption of mercury-contaminated rice induces the aggravation of free radicals and exerts oxidative stress.

  1. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.

    Science.gov (United States)

    Nozako, Masanori; Koyama, Takashi; Nagano, Chifumi; Sato, Makoto; Matsumoto, Satoshi; Mitani, Kiminobu; Yasufuku, Reiko; Kohashi, Masayuki; Yoshikawa, Tomohiro

    2015-01-01

    Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD) on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment. PMID:26606054

  2. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.

    Directory of Open Access Journals (Sweden)

    Masanori Nozako

    Full Text Available Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment.

  3. Early atherosclerosis aggravates renal microvascular loss and fibrosis in swine renal artery stenosis.

    Science.gov (United States)

    Sun, Dong; Eirin, Alfonso; Ebrahimi, Behzad; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

    2016-04-01

    Renal function in patients with atherosclerosis and renal artery stenosis (ARAS) deteriorates more frequently than in nonatherosclerotic RAS. We hypothesized that ARAS aggravates stenotic-kidney micro vascular loss compared to RAS. Domestic pigs were randomized to normal, RAS, and ARAS (RAS fed a high-cholesterol diet) groups (n = 7 each). Ten weeks later stenotic-kidney oxygenation, renal blood flow, and glomerular filtration rate (GFR) were evaluated in vivo, and micro vascular density by micro-computed tomography. Blood pressure in both RAS and ARAS was elevated; and stenotic-kidney renal blood flow and GFR similarly decreased. RAS decreased the density of small-size cortical microvessels (sized microvessels (200-300 μm). Cortical hypoxia and interstitial fibrosis increased in both RAS and ARAS but correlated inversely with micro vascular density only in RAS. Atherosclerosis aggravates loss of stenotic-kidney microvessels, yet additional determinants likely contribute to cortical hypoxia and fibrosis in swine ARAS. PMID:26879682

  4. Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling.

    Science.gov (United States)

    Park, Ji-Won; Lee, In-Chul; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Ko, Je-Won; Kim, Jong-Choon; Oh, Sei-Ryang; Shin, In-Sik; Ahn, Kyung-Seop

    2016-05-01

    Copper oxide nanoparticles (CuONPs), metal oxide nanoparticles were used in multiple applications including wood preservation, antimicrobial textiles, catalysts for carbon monoxide oxidation and heat transfer fluid in machines. We investigated the effects of CuONPs on the respiratory system in Balb/c mice. In addition, to investigate the effects of CuONPs on asthma development, we used a murine model of ovalbumin (OVA)-induced asthma. CuONPs markedly increased airway hyper-responsiveness (AHR), inflammatory cell counts, proinflammatory cytokines and reactive oxygen species (ROS). CuONPs induced airway inflammation and mucus secretion with increases in phosphorylation of the MAPKs (Erk, JNK and p38). In the OVA-induced asthma model, CuONPs aggravated the increased AHR, inflammatory cell count, proinflammatory cytokines, ROS and immunoglobulin E induced by OVA exposure. In addition, CuONPs markedly increased inflammatory cell infiltration into the lung and mucus secretions, and MAPK phosphorylation was elevated compared to OVA-induced asthmatic mice. Taken together, CuONPs exhibited toxicity on the respiratory system, which was associated with the MAPK phosphorylation. In addition, CuONPs exposure aggravated the development of asthma. We conclude that CuONPs exposure has a potential toxicity in humans with respiratory disease. PMID:26472121

  5. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

    International Nuclear Information System (INIS)

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  6. Proteasome β5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia.

    Science.gov (United States)

    Kirschner, Felicia; Reppe, Katrin; Andresen, Nadine; Witzenrath, Martin; Ebstein, Frédéric; Kloetzel, Peter-Michael

    2016-01-01

    Immunoproteasomes, harboring the active site subunits β5i/LMP7, β1i/LMP2, and β2i/MECL1 exert protective, regulatory or modulating functions during infection-induced immune responses. Immunoproteasomes are constitutively expressed in hematopoietic derived cells, constituting the first line of defense against invading pathogens. To clarify the impact of immunoproteasomes on the innate immune response against Streptococcus pneumoniae, we characterized the progression of disease and analyzed the systemic immune response in β5i/LMP7-/- mice. Our data show that β5i/LMP7 deficiency, which affected the subunit composition of proteasomes in murine macrophages and liver, was accompanied by reduced transcription of genes encoding immune modulating molecules such as pentraxins, ficolins, and collectins. The diminished opsonin expression suggested an impaired humoral immune response against invading pneumococci resulting in an aggravated systemic dissemination of S. pneumoniae in β5i/LMP7-/- mice. The impaired bacterial elimination in β5i/LMP7-/- mice was accompanied by an aggravated course of pneumonia with early mortality as a consequence of critical illness during the late phase of disease. In summary our results highlight an unsuspected role for immuno-subunits in modulating the innate immune response to extracellular bacterial infections. PMID:27100179

  7. Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

    Science.gov (United States)

    Li, Guanggang; Cao, Yinghua; Sun, Yue; Xu, Ruxiang; Zheng, Zhendong; Song, Haihan

    2016-09-01

    Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs. PMID:27179778

  8. [The Trp64Arg polymorphism of beta3-adrenoreceptor gene study in persons with overweight and obesity].

    Science.gov (United States)

    Baturin, A K; Pogozheva, A V; Sorokina, E Iu; Makurina, O N; Tutel'ian, V A

    2012-01-01

    The development of obesity is determined by lifestyle and genetic mechanisms. In particular, the polymorphisms in the adrenergic receptor genes (ADRB) have been extensively studied for association with obesity-related phenotypes. ADRB3 is an obvious candidate gene given its involvement in the regulation of lipolysis and thermogenesis. ADRB3 Trp64Arg polymorphism, a missense mutation in the first transmembrane domain of the R3-adrenergic receptor is associated with visceral obesity and insulin resistance in the Pima Indian, French, and Finnish populations. The recent meta-analysis that combined data of 6582 individuals from Japanese populations showed significant association the Arg64 allele with increased BMI. There are tested the polymorphisms in the beta3-Adrenoreceptor (ADRB3) gene in associated with body mass index (BMI), fat mass and biochemical parameters.We have been examined 91 persons from Moscow region with BMI >25 kg/m2. The Trp64Arg polymorphism of ADRB3 genes were genotyped with the use of an allelic discrimination assay. The TaqMan-based real-time PCR method was applied. There have been estimated of anthropometric and biochemicalparameters. The frequencies of the Trp64Trp and Trp64Arggenotypes of ADRB3 gene were 82% and 12%, respectively, the frequencies of mutant allele was 6%. Trp64Arg genotypes of ADRB3 compared to Trp64Trp genotypes had significantly higher body fat percentage (respectively 48,6 +/- 0,96% and 43,8 +/- 1,72%, pADRB3 gene polymorphisms can be used for the personalization of diet in persons with obesity. PMID:22774474

  9. Is Behavioral Regulation in Children With ADHD Aggravated by Comorbid Anxiety Disorder?

    DEFF Research Database (Denmark)

    Sørensen, Lin; Plessen, Kerstin J; Nicholas, Jude;

    2010-01-01

    Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were...... compared to BRIEF reports in a group of children with a "pure" ADHD (n = 23), a "pure" anxiety (n = 24) and a group without any diagnosis (n = 104) in a 2 (ADHD vs. no ADHD) x 2 (anxiety vs. no anxiety) design. Results: The children with ADHD and anxiety disorder scored significantly higher on the Inhibit...... children is aggravated by comorbid anxiety. (J. of Att. Dis. 2010; XX(X) 1-XX)....

  10. Formation of structures in nonlinear media and nonequilibrium thermodynamics of aggravation regimes

    International Nuclear Information System (INIS)

    In a medium, the description of which includes quasilinear transport equations (the thermal conductivity, conductivity and viscosity coefficients depend on temperature, density and magnetic field), the effect of nonlinear bulk heat sources, under specific conditions, generates strongly nonequilibrium processes, the so-called regimes with aggravation. They can cause heat localization and magnetic field phenomena on certain space scales or in certain sections of the mass in a compressible medium. This results in different spatial distribution of the quantities indicated, i.e., development of different types of structures in the medium. The work, on the basis of consideration of the quasilinear thermal conductivity equation with nonlinear bulk heat sources, found the characteristics of the strongly nonequilibrium thermodynamics which cause such a complication of organization of the medium. 88 references

  11. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

    OpenAIRE

    Roulet Agnès; Armand Lucie; Dagouassat Maylis; Rogerieux Françoise; Simon-Deckers Angélique; Belade Esther; Van Nhieu Jeanne; Lanone Sophie; Pairon Jean-Claude; Lacroix Ghislaine; Boczkowski Jorge

    2012-01-01

    Abstract Background Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. Methods On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, t...

  12. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    Science.gov (United States)

    HSU, YA-LING; HSIEH, CHIA-JUNG; TSAI, EING-MEI; HUNG, JEN-YU; CHANG, WEI-AN; HOU, MING-FENG; KUO, PO-LIN

    2016-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID:26893687

  13. Calreticulin Translocation Aggravates Endoplasmic Reticulum Stress-associated Apoptosis during Cardiomyocyte Hypoxia/Reoxygenation

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Xu; Xiu-Hua Liu

    2015-01-01

    Background:Calreticulin (CRT) is major Ca2+-binding chaperone mainly resident in the endoplasmic reticulum (ER) lumen.Recently,it has been shown that non-ER CRT regulates a wide array of cellular responses.We previously found that CRT was up-regulated during hypoxia/reoxygenation (H/R) and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress (ERS)-associated apoptosis during H/R injury in neonatal rat cardiomyocytes.Methods:Apoptosis rate and lactate dehydrogenase (LDH) leakage in culture medium were measured as indices of cell injury.Immunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT.Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules.Results:Compared with control,H/R increased apoptosis rate and LDH activity.The ER became condensed and bubbled,and CRT translocated to the nucleus.Western blotting showed up-regulation of CRT,Nrf2,activating transcription factor 4 (ATF4),CHOP and caspase-12 expression after H/R.Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis,LDH leakage,ER disorder,CRT nuclear translocation and the expression of ERS-associated molecules.However,administration of the ERS inhibitor,taurine,or CRT siRNA alleviated cell injury,ER disorder,and inhibited ERS-associated apoptosis.Conclusions:Our results indicated that during H/R stress,CRT translocation increases cell apoptosis and LDH leakage,aggravates ER disorder,up-regulates expression of nuclear transcription factors,Nrf2 and ATF4,and activates ERS-associated apoptosis.

  14. Obesity does not aggravate vitrification injury in mouse embryos: a prospective study

    Directory of Open Access Journals (Sweden)

    Ma Wenhong

    2012-08-01

    Full Text Available Abstract Background Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively. Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing. Methods Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group or a high-fat diet (obese group for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification. Results In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, Pvs.9.3%, Pvs. 93.1%, P Conclusions This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.

  15. Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis.

    Directory of Open Access Journals (Sweden)

    Keisuke Mishiro

    Full Text Available Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO in streptozotocin (STZ -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells. Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP-9 activity, but not reactive oxygen species production. Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption. A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.

  16. Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene

    DEFF Research Database (Denmark)

    Højlund, K; Christiansen, C; Bjørnsbo, K S;

    2006-01-01

    secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X......AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin......-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild...

  17. Noninvasive visualization and quantification of tumor {alpha}{sub V{beta}3} integrin expression using a novel positron emission tomography probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Zhao-Hui [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Furukawa, Takako, E-mail: tfuru@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Galibert, Mathieu; Boturyn, Didier [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Coll, Jean-Luc [INSERM U823, Institut Albert Bonniot and Universite Joseph Fourier, 38706 La Tronche Cedex, Grenoble (France); Fukumura, Toshimitsu; Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Dumy, Pascal [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)

    2011-05-15

    Introduction: The {alpha}{sub V{beta}3} integrin is a well-known transmembrane receptor involved in tumor invasion, angiogenesis and metastasis. Our aim was to evaluate a novel positron emission tomography (PET) probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}, for noninvasive visualization and quantification of {alpha}{sub V{beta}3} integrin expression. Methods: RAFT-c(-RGDfK-){sub 4}, a tetrameric cyclic Arg-Gly-Asp (RGD)-based peptide, was conjugated with a bifunctional chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam), radiolabeled with the positron emitter {sup 64}Cu and evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies, and PET imaging. The following cell lines, human embryonic kidney HEK293({beta}{sub 1}) [{alpha}{sub V{beta}3}-negative] and HEK293({beta}{sub 3}) [{alpha}{sub V{beta}3}-overexpressing] and human glioblastoma U87MG [naturally expressing {alpha}{sub V{beta}3}], together with their subcutaneous xenografts in athymic nude mice, were used for the present study. The expression levels of {alpha}{sub V{beta}3} on these cell lines and tumor xenografts were analyzed by flow cytometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography, respectively. Results: {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} demonstrated the in vitro and in vivo specificity for the {alpha}{sub V{beta}3} integrin and displayed rapid blood clearance, predominantly renal excretion and low uptake in nontumor tissues. Tumor uptake of {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} (3 h postinjection) in HEK293({beta}{sub 3}) (high levels of {alpha}{sub V{beta}3}), U87MG (moderate levels of {alpha}{sub V{beta}3}) and HEK293({beta}{sub 1}) (undetectable levels of {alpha}{sub V{beta}3}) tumors was 9.35%{+-}1.19%, 3.46%{+-}0.45% and 1.18%{+-}0.30% injected dose per gram, respectively, with a strong and positive correlation with the tumor {alpha}{sub V{beta}3} expression levels

  18. 77 FR 24415 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Science.gov (United States)

    2012-04-24

    ... $650, the ordinary maximum of $25,000, and the aggravated maximum CMP of $100,000). See 73 FR 79698...-adjusted $550. 69 FR 30591 (May 28, 2004) and 69 FR 62817 (Oct. 28, 2004). (In 2004, FRA had determined, by... should be increased to $650. 73 FR 79698 (Dec. 30, 2008). In 2009, FRA also published a...

  19. Aggravation of Risk and Precautionary Measures in Non-Life Insurance: A Tricky Scope for the Insurer?

    Directory of Open Access Journals (Sweden)

    Olavi-Jüri Luik

    2015-12-01

    Full Text Available Aggravation of risk and failure to take precautionary measures are focal issues in non-life insurance in terms of potential partial or full release of the insurer from the duty to perform. Not infrequently, it is difficult to draw a line between the aggravation of risk on the one hand, and non-compliance with precautionary measures on the other, since a particular action by a policyholder may present both situations. At the same time, the legal remedies available to the insurer regarding these two situations are different in scope. The aggravation of risk and non-compliance with precautionary measures are precisely the bases on which insurers actually reduce indemnity or refuse to compensate for damages. This article explores the differences between insurance laws in the Baltic states—specifically, the Estonian Law of Obligations Act, the Latvian Insurance Contract Law and Lithuanian rules contained in the Civil Code and Insurance Law. The article explores the differences between the Baltic states’ insurance laws and the Principles of European Insurance Contract Law (PEICL with regard to a policyholder’s duty in relation to aggravation of risk and precautionary measures, as the rights and obligations of policyholders do change where the optional instrument is applied. The article also includes comparisons to German, Finnish and Russian insurance law.

  20. Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation.

    Science.gov (United States)

    Bissay, Véronique; Keymolen, Kathelijn; Lissens, Willy; Laureys, Guy; Schmedding, Eric; De Keyser, Jacques

    2011-08-01

    We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia. These families represent a distinct phenotype within the spectrum of sodium channel myotonia. PMID:21664816

  1. Effect of lysozyme chloride on betel quid chewing aggravated gastric oxidative stress and hemorrhagic ulcer in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Road Hung

    2005-01-01

    AIM: To evaluate the protective effect of lysozyme chloride on betel quid chewing (BQC) aggravated gastric oxidative stress and hemorrhagic ulcer in rats with diabetes mellitus (DM).METHODS: Male Wistar rats were challenged intravenously with streptozotocin (65 mg/kg) to induce DM. Rats were fed with regular pellet food or BQC-containing diets. After 90 d, rats were deprived of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or simulated gastric juice. Rats were killed and gastric specimens were harvested.RESULTS: An enhancement of various gastric ulcerogenic parameters, including acid back-diffusion, mucosal lipid peroxide generation, as well as decreased glutathione levels and mucus content, were observed in DM rats. After feeding DM rats with BQC, an exacerbation of these ulcerogenic parameters was achieved. Gastric juice caused a further aggravation of these ulcerogenic parameters. Daily intragastric lysozyme chloride dose-dependently inhibited exacerbation of various ulcerogenic parameters in those BQC-fed DM rats.CONCLUSION: (1) Gastric juice could aggravate both DM and BQC-fed DM rat hemorrhagic ulcer; (2) BQC exacerbated gastric hemorrhagic ulcer in DM rats via enhancing oxidative stress and reducing defensive factors; (3) lysozyme chloride effectively protected BQC aggravated gastric damage in DM rats.

  2. 多疣壁虎tubulin beta 3基因克隆和多克隆抗体制备%Molecular cloning of tubulin beta 3 (TUBB3) in Gekkojaponicus and preparation of its polyclonal antibody

    Institute of Scientific and Technical Information of China (English)

    李静; 秦勇; 顾云; 刘炎; 刘梅

    2012-01-01

    The tubulin beta III (TUBB3) gene encodes a class III member of the beta tubulin protein family that is primarily expressed in neurons and is considered to play a critical role in proper axon guidance and maintenance. This protein is generally used as a specific marker of neurons in the central nervous system. We obtained the full length cDNA sequence of TUBB3 by using the RACE method based on the EST fragment from the brain and spinal cord cDNA library of Gekko japonicus. We further investigated the multi-tissue expression pattern by RT-PCR and identified one transcript of TUBB3 about 1.8 kb in the central nervous system of Gekko japonicus by Northern blotting. The completed cDNA of gecko TUBB3 is 1790 bp with an open reading frame of 1350 bp, encoding a 450 amino-acid protein. The recombinant plasmid of pET-32a-TUBB3 was constructed and induced to express His-tagged TUBB3 protein in prokaryotic BL21 cells. The purified TUBB3 protein was then used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65 536 determined by ELISA. The result of western blotting showed that the TUBB3 antibody could specifically recognize the recombinant TUBB3 protein and endogenous TUBB3 protein. Our findings provide the tools to further understand the TUBB3 gene and investigate the regeneration of the central nervous system in Gekko japonicas.%Tubulin beta 3 (TUBB3)是特异表达于神经元的微管蛋白tubulin beta家族成员,被认为在维持轴突正常状态起着重要作用,是神经元特异的标志蛋白.该研究旨在获得多疣壁虎TUBB3全长cDNA序列并制备其多克隆抗体,为进一步研究多疣壁虎断尾再生提供基因和抗体工具.根据多疣壁虎中枢神经组织cDNA文库中TUBB3的EST片段序列,采用RACE-PCR方法,获得了全长cDNA,序列全长1790 bp,编码450个氨基酸,与其他物种TUBB3蛋白高度同源;RT-PCR方法和Northern blotting检测了TUBB3组织表达谱及其转录本的大

  3. DNase I aggravates islet β-cell apoptosis in type 2 diabetes

    Science.gov (United States)

    ZHU, BIN; ZHANG, LEI; ZHANG, YUE-YING; WANG, LEI; LI, XIN-GANG; LIU, TENG; FU, YU-KE; ZHENG, YAN-FEI; LI, PING; ZHAO, ZHI-GANG

    2016-01-01

    Deoxyribonuclease I (DNase I) is an endonuclease responsible for the destruction of chromatin during apoptosis. However, its role in diabetes remains unclear. The aim of the current study was to investigate the role of DNase I combined with high glucose levels in β-cell apoptosis. Human samples were collected and the DNase I activity was examined. High glucose-cultured INS-1 cells were transfected with DNase I small interfering RNA (siRNA) and the cell apoptosis was examined by western blotting and flow cytometry. Cell viability was analyzed by the Cell Counting Kit-8 assay. Cell apoptosis resulting from 50 mU/μl DNase I was also observed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling stain and western blotting. Compared with healthy controls, the serum DNase I activity of patients with diabetes was significantly increased (Pdiabetes, and high glucose combined with increased DNase I is suggested to aggravate β-cell apoptosis. PMID:27082840

  4. Organic molecules showing the characteristics of localised corrosion aggravation and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Tan Yongjun, E-mail: yj.tan@curtin.edu.a [Department of Chemistry, Curtin University, GPO Box U1987, Perth (Australia); Mocerino, Mauro; Paterson, Tristan [Department of Chemistry, Curtin University, GPO Box U1987, Perth (Australia)

    2011-05-15

    Research highlights: {yields} Novel experiment for the discovery of localised corrosion inhibitors. {yields} New method of identifying inhibitors promoting random distribution of anodic currents. {yields} Discovery of resorcinarene acid as an effective localised corrosion inhibitor. - Abstract: The behaviour of imidazoline and an acid functionalised resorcinarene as steel corrosion inhibitors in carbon dioxide (CO{sub 2})-saturated brine solutions has been studied using an electrochemically integrated multi-electrode array namely the wire beam electrode (WBE). Both imidazoline and resorcinarene acid provided excellent inhibition to general CO{sub 2} corrosion; however imidazoline was found to aggravate localised corrosion by creating a small number of major anodes that focused on a small area of the WBE surface, leading to highly concentrated anodic dissolution. The resorcinarene acid showed distinctively different behaviour by generating a large number of minor anodes randomly distributing over the WBE surface, leading to insignificant general anodic dissolution. These results indicate that resorcinarene acid provided effective localised corrosion inhibition by promoting a random distribution of insignificant anodic currents.

  5. Dietary fructose aggravates the pathobiology of traumatic brain injury by influencing energy homeostasis and plasticity.

    Science.gov (United States)

    Agrawal, Rahul; Noble, Emily; Vergnes, Laurent; Ying, Zhe; Reue, Karen; Gomez-Pinilla, Fernando

    2016-05-01

    Fructose consumption has been on the rise for the last two decades and is starting to be recognized as being responsible for metabolic diseases. Metabolic disorders pose a particular threat for brain conditions characterized by energy dysfunction, such as traumatic brain injury. Traumatic brain injury patients experience sudden abnormalities in the control of brain metabolism and cognitive function, which may worsen the prospect of brain plasticity and function. The mechanisms involved are poorly understood. Here we report that fructose consumption disrupts hippocampal energy homeostasis as evidenced by a decline in functional mitochondria bioenergetics (oxygen consumption rate and cytochrome C oxidase activity) and an aggravation of the effects of traumatic brain injury on molecular systems engaged in cell energy homeostasis (sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1alpha) and synaptic plasticity (brain-derived neurotrophic factor, tropomyosin receptor kinase B, cyclic adenosine monophosphate response element binding, synaptophysin signaling). Fructose also worsened the effects of traumatic brain injury on spatial memory, which disruption was associated with a decrease in hippocampal insulin receptor signaling. Additionally, fructose consumption and traumatic brain injury promoted plasma membrane lipid peroxidation, measured by elevated protein and phenotypic expression of 4-hydroxynonenal. These data imply that high fructose consumption exacerbates the pathology of brain trauma by further disrupting energy metabolism and brain plasticity, highlighting the impact of diet on the resilience to neurological disorders. PMID:26661172

  6. Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats.

    Science.gov (United States)

    Chen, Xin; Zhang, Ke-Li; Yang, Shu-Yuan; Dong, Jing-Fei; Zhang, Jian-Ning

    2009-02-11

    Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI. PMID:19236166

  7. Efficacy of enzyme replacement therapy in an aggravated mouse model of metachromatic leukodystrophy declines with age.

    Science.gov (United States)

    Matthes, Frank; Stroobants, Stijn; Gerlach, Debora; Wohlenberg, Claudia; Wessig, Carsten; Fogh, Jens; Gieselmann, Volkmar; Eckhardt, Matthias; D'Hooge, Rudi; Matzner, Ulrich

    2012-06-01

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of arylsulfatase A (ASA). Previous studies in ASA-knockout mice suggested enzyme replacement therapy (ERT) to be a promising treatment option. The mild phenotype of ASA-knockout mice did, however, not allow to examine therapeutic responses of the severe neurological symptoms that dominate MLD. We, therefore, generated an aggravated MLD mouse model displaying progressive demyelination and reduced nerve conduction velocity (NCV) and treated it by weekly intravenous injections of 20 mg/kg recombinant human ASA for 16 weeks. To analyze the stage-dependent therapeutic effects, ERT was initiated in a presymptomatic, early and progressed disease stage, at age 4, 8 and 12 months, respectively. Brain sulfatide storage, NCV and behavioral alterations were improved only in early, but not in late, treated mice showing a clear age-dependent efficacy of treatment. Hematopoietic stem cell transplantation (HSCT) for late-onset variants is the only therapeutic option for MLD to date. ERT resembles a part of the HSCT rationale, which is based on ASA supply by donor cells. Beyond ERT, our results, therefore, corroborate the clinical observation that HSCT is only effective when performed in early stages of disease. PMID:22388935

  8. 147 Mitigating and Aggravating Circumstances. Their Impact on Judicial Individualization of Punishment

    Directory of Open Access Journals (Sweden)

    Cosmin Peonaşu

    2015-08-01

    Full Text Available For an act to fall under criminal law it is sufficient for it to meet the minimum conditions to achieve constitutive content of the offense. However, committing a criminal act takes place, in most cases, in a complex set of variables specific to each case, variables that, without characterizing the act as an offense or the perpetrator's person as subject of that offence, helps determining, on one hand, the social danger of the committed crime and, on the other hand, knowing the offender as an individual and its social dangerousness. Mitigating and aggravating circumstances are such variables and they have a specific impact on criminal responsibility of the perpetrator. These circumstances have a major influence on judicial individualization of punishment because their effect is preset by the Law and acts separately on the length or amount of punishment. This study aims both students and practitioners or academics and highlights on one hand, the legislative solutions of the new Criminal Code and on the other hand, the differences between the old and the new Criminal Code.

  9. GSN antibody pretreatment aggravates radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation therapy. Gelsolin (GSN) is a widespread, multifunctional regulator of cellular structure and metabolism. In this work, the roles of GSN in radiation-induced lung injury in Balb/c mice were studied. The GSN levels in plasma reduced progressively in 72 hours after irradiation, and then increased gradually. GSN contents in the bronchoalveolar lavage (BAL) fluid increased after thoracic irradiation, whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased again. Mice were intravenously injected with 50 μg GSN antibody 0.5 hour before 20 Gy of thoracic irradiation. GSN antibody pretreatment increased lung inflammation, protein concentration in the BAL fluid and leukocytes infiltration in the irradiated mice. The activities of superoxidase dismutase (SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups, whereas the levels of malondialdehyde (MDA) increased. These results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis. (authors)

  10. IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.

    Directory of Open Access Journals (Sweden)

    Abukar Ali

    Full Text Available Interleukin-1 receptor antagonist (IL-1Ra is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus septic arthritis and sepsis in mice.NMRI mice were treated with anakinra (IL-1Ra daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.

  11. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  12. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

    Science.gov (United States)

    Zhang, Ji; Qiao, Congzhen; Chang, Lin; Guo, Yanhong; Fan, Yanbo; Villacorta, Luis; Chen, Y Eugene; Zhang, Jifeng

    2016-01-01

    Fatty acid binding protein 4 (FABP4) is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG) mice using α myosin-heavy chain (α-MHC) promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC) procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway. PMID:27294862

  13. Strenuous exercise aggravates MDMA-induced skeletal muscle damage in mice

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the influence of ecstasy (MDMA) administration on body temperature and soleus muscle histology in exercised and non-exercised mice. Charles-River mice were distributed into four groups: Control (C), exercise (EX), MDMA treated (M), and M + EX. The treated animals received an i.p. injection (10 mg/kg) of MDMA (saline for C and EX), and the exercise consisted of a 90 min level run at a velocity of 900 m/h, immediately after the MDMA or saline administration. Body temperature was recorded every 30 min via subcutaneous implanted transponder. Animals were sacrificed 1.5, 25.5, and 49.5 h after i.p. injection and the soleus muscles were removed and processed for light and electron microscopy. The MDMA-treated animals showed a significant increase in body temperature (similar in M and M + EX groups), reaching the peak 90 min after i.p. administration; their temperature remained higher than control for more than 5 h. The EX group evidenced a similar and parallel, yet lower temperature increase during exercise and recovery. Morphological signs of damage were rarely encountered in the EX group; they were more pronounced in M group and even aggravated in M + EX group. In conclusion, MDMA and exercise per se increased body temperature but in conjunction did not have a cumulated effect. However, ecstasy and concomitant physical activity might severely accumulate with regard to skeletal muscle toxicity and may lead to rhabdomyolysis

  14. [Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis].

    Science.gov (United States)

    Albot, G; Geraudias, P; Kind, M

    1975-02-14

    The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of "metacritical aggravation" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct. PMID:169583

  15. Nimesulide aggravates redox imbalance and calcium dependent mitochondrial permeability transition leading to dysfunction in vitro

    International Nuclear Information System (INIS)

    Nimesulide (selective cyclooxygenase-2 inhibitor) is a nonsteroidal anti-inflammatory drug for the symptomatic treatment of painful conditions like osteoarthritis, spondilitis and primary dysmenorrhoea. Nimesulide induced liver damage is a serious side effect of this otherwise popular drug. The mechanism involved in nimesulide induced hepatotoxicity is still not fully elucidated. However, both mitochondrial dysfunction and oxidative stress have been implicated in contributing to liver injury in susceptible patients. Mitochondria besides being the primary source of energy, act as a hub of signals responsible for initiating cell death, irrespective of the pathway, i.e. apoptosis or necrosis. The present study was aimed to explore the role of compounding stress, i.e. Ca2+ overload and GSH depletion in nimesulide induced mitochondrial toxicity and dysfunction. Our study showed that, nimesulide (100 μM) treatment resulted into rapid depletion of GSH (60%) in isolated rat liver mitochondria and significant Ca2+ dependent MPT changed. Enhanced ROS generation (DCF fluorescence) was also observed in mitochondria treated with nimesulide. An important finding was that the concentration at which nimesulide oxidized reduced pyridine nucleotides (autofluorescence of NAD(P)H), it affected mitochondrial electron flow (MTT activity decreased by 75%) and enhanced mitochondrial depolarization significantly as assessed by Rhodamine 123 fluorescent probe. Therefore, nimesulide was found to aggravate redox imbalance and affect Ca2+ dependent mitochondrial membrane permeability transition leading to dysfunction and ultimately cell death.

  16. The beta-adrenoceptors mediating relaxation of rat oesophageal muscularis mucosae are predominantly of the beta 3-, but also of the beta 2-subtype.

    OpenAIRE

    de Boer, R. E.; Brouwer, F.; Zaagsma, J

    1993-01-01

    1. beta-Adrenoceptor-mediated relaxation of rat oesophageal smooth muscle was investigated by studying the effects of beta 1- and beta 2-selective antagonists on the relaxation induced by (-)-isoprenaline, the beta 2-selective agonists fenoterol and clenbuterol and the beta 3-agonist, BRL 37344. 2. The highly beta 1-selective antagonist CGP 20721A did not antagonize (-)-isoprenaline- or BRL 37344-induced relaxations in concentrations up to 10 microM. Only at 100 microM of CGP 20712A were clea...

  17. Human-Specific SNP in Obesity Genes, Adrenergic Receptor Beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during Primate Evolution

    OpenAIRE

    Takenaka, Akiko; Nakamura, Shin; Mitsunaga, Fusako; Inoue-Murayama, Miho; Udono, Toshifumi; Suryobroto, Bambang

    2012-01-01

    Adrenergic-receptor beta2 (ADRB2) and beta3 (ADRB3) are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM) in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG) is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and ...

  18. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  19. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

    Directory of Open Access Journals (Sweden)

    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  20. The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

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    Miyauchi Akira

    2011-08-01

    thyrotoxicosis and that it aggravates hyperthyroidism. Psychosomatic therapeutic approaches including antipsychiatric drugs and/or psychotherapy appears to be useful for improving the prognosis of hyperthyroidism.

  1. High Potassium Aggravates the Oxidative Stress Inducedy by Magnesium Deficiency in Rice Leaves

    Institute of Scientific and Technical Information of China (English)

    DING Yu-Chuan; CHANG Chun-Rong; LUO Wen; WU Yan-Shou; REN Xiao-Li; WANG Ping; XU Guo-Hua

    2008-01-01

    Magnesium (Mg) deficiency in plant affects photosynthesis and many other metabolic processes.Rice (Oryza sativa L.cv.'Wuyunjing 7') plants were grown in hydroponics culture at three Mg and two potassium (K) levels under greenhouse conditions to examine the induction of oxidative stress and consequent antioxidant responses in rice leaves due to Mg deficiency.At low Mg (0.2 mmol L-1 Mg supply for two weeks after transplanting) and high K (6 mmol L-1) for 21days,the rice plants showed severe Mg deficiency and a significant decreases in the dry matter production. The Mg deficiency in leaves decreased chlorophyll concentrations,photosynthetic activity,and soluble protein,but significantly increased the concentrations of soluble sugars and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD,EC 1.15.1.1),catalase (CAT,EC 1.11.1.6) and peroxidase (POD,EC 1.11.1.7).In addition,Mg concentrations in the leaves and in the shoot biomass were negatively related to the activities of the three antioxidative enzymes and the concentration of MDA in leaves.There were very significant interactive effects between Mg and K supplied in the culture solution on shoot biomass yield,chlorophyll content,photosynthesis rate,the activities of SOD,CAT and POD,and MDA content in the leaves of rice.It is suggested that the high K level in the nutrient solution aggravated the effect of low Mg supply-induced Mg deficiency and created the oxidative damage in rice plants.

  2. Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries.

    Science.gov (United States)

    Voss, Rudi; Quaas, Martin F; Schmidt, Jörn O; Kapaun, Ute

    2015-01-01

    Ocean Acidification (OA) will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size), economic (profits), consumer-related (harvest) and social (employment) indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort) to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination), which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small scale local

  3. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis.

    Science.gov (United States)

    Asdonk, Tobias; Steinmetz, Martin; Krogmann, Alexander; Ströcker, Christine; Lahrmann, Catharina; Motz, Inga; Paul-Krahe, Kathrin; Flender, Anna; Schmitz, Theresa; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2016-09-01

    Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA-5) belongs to the intracellular retinoic acid inducible gene-I like receptors and its activation promotes pro-inflammatory mechanisms. Here, we studied the effect of MDA-5 stimulation in vascular biology. To gain insights into MDA-5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA-5 agonist polyIC (long double-stranded RNA). Human coronary endothelial cell expressed MDA-5 and reacted with receptor up-regulation upon stimulation. Reactive oxygen species formation, apoptosis and the release of pro-inflammatory cytokines was enhanced, whereas migration was significantly reduced in response to MDA-5 stimulation. To test these effects in vivo, wild-type mice were transfected with 32.5 μg polyIC/JetPEI or polyA/JetPEI as control every other day for 7 days. In polyIC-treated wild-type mice, endothelium-dependent vasodilation and re-endothelialization was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticles and circulating endothelial progenitor cells significantly elevated compared to controls. Importantly, these effects could be abrogated by MDA-5 deficiency in vivo. Finally, chronic MDA-5 stimulation in Apolipoprotein E/toll-like receptor 3 (TLR3) double(-) deficient (ApoE(-/-) /TLR3(-/-) ) mice-enhanced atherosclerotic plaque formation. This study demonstrates that MDA-5 stimulation leads to endothelial dysfunction, and has the potential to aggravate atherosclerotic plaque burden in murine atherosclerosis. Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA-5. PMID:27130701

  4. Administration of Mycobacterium leprae rHsp65 aggravates experimental autoimmune uveitis in mice.

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    Eliana B Marengo

    Full Text Available The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+IL-17(+, CD4(+IFN-gamma(+ and CD4(+Foxp3(+ cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+IFN-gamma(+ and CD4(+IL-17(+ T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.

  5. Polymorphism Trp64Arg of beta 3 adrenoreceptor gene: allelic frequencies and influence on insulin resistance in a multicenter study of Castilla-León Polimorfismo TRP64ARG del gen receptor beta 3: frecuencia alélica e influencia en la resistencia a la insulina en un estudio multicéntrico de Castilla y León

    Directory of Open Access Journals (Sweden)

    D. A. de Luis

    2010-04-01

    Full Text Available Background and objective: The genetic variant (Trp64Arg is a missense mutation located within the beta3 adrenoreceptor (Beta3AR. The aim of our study was to investigate the influence of Trp64Arg polymorphism in the Beta3AR gene on insulin resistance in obese patients and the allelic distribution of this polymorphismin a geographic area of Spain. Design: A population of 264 obese patients was analyzed. A bioimpedance, blood pressure, an assessment of nutritional intake, and biochemical parameters were measured. The beta 3 adrenoreceptor gene polymorphism(Trp64Arg was genotyped. Results: Two hundred and twenty six patients (77 males/149 females (85.6% had the genotype Trp64/Trp64 (wild type group with and average age of 41.12 ± 13.1 years and 38 patients (16 males/22 females Trp64/Arg64 (14.4% (mutant type group with an average age of 40.5 ± 12.7 years. High frequencies of Arg64 allele were observed in Salamanca and Valladolid. In the mutant type group, HOMA (3.75 ± 2.77 vs 5.27 ± 5.4; p Introducción y objetivos: La variante genética (Trp64Arg es una mutación localizada en el adrenoreceptor Beta 3 (Beta3AR. El objetivo de nuestro trabajo es evaluar la influencia de el polimorfismo Trp64Arg del gen de Beta3AR sobre la resistencia a la insulina en pacientes obesos, así como la distribución alélica de este polimorfismo en un área geográfica de España. Diseño: Una muestra de 264 pacientes obesos fue analizada. Se realizó una bioimpedancia, evaluación nutricional y análisis bioquímico. Se genotiparon a los pacientes en función delpolimorfismos Tr64Arg del gen adrenoreceptor-beta 3. Resultados: Un total de 227 pacientes (77 varones/149 mujeres (85,6% presentaron el genotipo Trp64/Trp64 (grupo genotipo salvaje, con una media de edad de 41,12 ± 13,1 años y un total de 38 pacientes (16 varones/22 mujeres Trp64/Arg64 (14,4% (grupo genotipo mutante con una edad media de 40,5 ± 12,7 años. Se detectó una alta frecuencia alélica (Arg64

  6. Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

    Directory of Open Access Journals (Sweden)

    Gagnon Stéphane

    2010-11-01

    Full Text Available Abstract Background Among patients with cystic fibrosis (CF, females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa. A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2 plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1 or type 2 (Th2 lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P. aeruginosa by a Th17-mediated mechanism. Results Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508, to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils. Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro. Conclusions Our data show that E2 increases the

  7. Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury

    Institute of Scientific and Technical Information of China (English)

    DAI Chen-yang; DAI Guo-feng; SUN Yu; WANG Yue-lan

    2013-01-01

    Background p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function,but its role has not been explored in alveolar edema induced by ventilation.We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120.We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed,which resulted from the loss of p120.Methods Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor).After the end of stretching for 0,1,2,and 4 hours,the cells were lysed,and p120 expression and c-src activation was determined by Western blotting analysis.In vivo,SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg,PEEP=0,respiratory rate 30-40 betas/min) for 0,1,2,and 4 hour and some were pretreated with pp2,and alveolar edema was calculated.Rerults It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells.These changes could be reversed by inhibition of c-src.We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group.Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.Conclusions Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema.Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

  8. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  9. Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant.

    Science.gov (United States)

    Leipold, Enrico; Hanson-Kahn, Andrea; Frick, Miya; Gong, Ping; Bernstein, Jonathan A; Voigt, Martin; Katona, Istvan; Oliver Goral, R; Altmüller, Janine; Nürnberg, Peter; Weis, Joachim; Hübner, Christian A; Heinemann, Stefan H; Kurth, Ingo

    2015-01-01

    Gain-of-function mutations in the human SCN11A-encoded voltage-gated Na(+) channel NaV1.9 cause severe pain disorders ranging from neuropathic pain to congenital pain insensitivity. However, the entire spectrum of the NaV1.9 diseases has yet to be defined. Applying whole-exome sequencing we here identify a missense change (p.V1184A) in NaV1.9, which leads to cold-aggravated peripheral pain in humans. Electrophysiological analysis reveals that p.V1184A shifts the voltage dependence of channel opening to hyperpolarized potentials thereby conferring gain-of-function characteristics to NaV1.9. Mutated channels diminish the resting membrane potential of mouse primary sensory neurons and cause cold-resistant hyperexcitability of nociceptors, suggesting a mechanistic basis for the temperature dependence of the pain phenotype. On the basis of direct comparison of the mutations linked to either cold-aggravated pain or pain insensitivity, we propose a model in which the physiological consequence of a mutation, that is, augmented versus absent pain, is critically dependent on the type of NaV1.9 hyperactivity. PMID:26645915

  10. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy; Candida Oral como fator agravante da mucosite radioinduzida

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de odontologia

    2011-07-01

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  11. The Vitamine D3 Analogue (1α Hydroxyvitamin D3) Aggravates Carbon Tetrachloride-Induced Hepatotoxicity In Albino Rats

    International Nuclear Information System (INIS)

    Provitamin D, cholecalciferol, undergoes hydroxylation at the 25 and the 1α position in the liver and the kidney, respectively, before it turns into a hormonally active form regulating calcium homeostasis. The main purpose of the present study is to assess the potential of the 1α hydroxyvitamin D3 analogue to aggravate the ability of carbon tetrachloride (CCl4) to cause hepatotoxicity in albino rats. For this purpose, four groups of male albino rats, each of five, were used as follow: control group (G 1) received no treatment, CCl4 treated group (G 2) received CCl4 at a dose of 0.2 ml/100 g body weight in sunflower oil (1/1) v/v ratio two times per week for three weeks subcutaneously, 1α hydroxyvitamin D3 treated group (G 3) received a total dose of 5 ng/g body weight of 1α hydroxyvitamin D3 dissolved in propyl alcohol divided into six doses each given twice weekly for three weeks via the subcutaneous route, and CCl4 + 1α hydroxyvitamin D3 treated group (G 4) received the same dose of CCl4 and 1α hydroxyvitamin D3 concomitantly as previously described. Liver tissues from sacrificed animals were fixed in 10% formalin before sectioning and stained with eosin and hematoxyline then were examined histopathologically. Sera from control and treated animals were separated from blood and examined for ALT, AST, alkaline phosphatase and LDH levels. Serum total protein, albumin, globulin, A/G, bilirubin, creatinine, phosphorous and Ca levels were also monitored. Data from the present study showed that administration of 1α hydroxyvitamin D3 aggravated CCl4-induced hepatotoxicity as evidenced by the exacerbation of the rise in serum ALT, AST, alkaline phosphatase levels. The analogue, however, had no effect on serum liver enzymes in CCl4 untreated rats. Though, CCl4 caused significant impairment of kidney function as shown by the rise in serum creatinine and urea levels which were differentially affected by the analogue. In conclusion, the 1α hydroxyvitamin D3 compound

  12. Drug: D09903 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rmaceutical integrin alphav/beta3 (VNR) label [HSA:3685 3690] [KO:K06487 K06493]; i...D09903 Drug Fluciclatide F 18 (USAN/INN) C75H115FN18O27S3 1813.7351 1816.0134 D09903.gif Diagnostic radiopha

  13. Drug: D09929 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09929 Drug Maraciclatide (USAN/INN) C72H120N20O21S3 1696.8099 1698.0396 D09929.gif Diagnostic radio-pharmac...eutical integrin alphav/beta3 (VNR) imaging agent [HSA:3685 3690] [KO:K06487 K06493

  14. Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2, Beta3 (ADRB3, and PPAR γ2 (PPARG, during primate evolution.

    Directory of Open Access Journals (Sweden)

    Akiko Takenaka

    Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.

  15. Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Chi-Jen Chu; Shou-Dong Lee; Ching-Chin Hsiao; Teh-Fang Wang; Cho-Yu Chan; Fa-Yauh Lee; Full-Young Chang; Yi-Chou Chen; Hui-Chun Huang; Sun-Sang Wang

    2005-01-01

    AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy.Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure.METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by were divided into two groups to receive intraperitoneal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α(TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay.RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S:438±102 vs841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vsN/S: 22±5 vs 10±1 pg/mL, P<0.05)and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S.CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant

  16. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

    Science.gov (United States)

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-04-29

    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain. PMID:27037020

  17. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium.

    Science.gov (United States)

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-01-01

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates. PMID:27264309

  18. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    Science.gov (United States)

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. PMID:26880342

  19. Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

    Directory of Open Access Journals (Sweden)

    Karl L Wögenstein

    Full Text Available Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/- mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

  20. Make-up improves the quality of life of acne patients without aggravating acne eruptions during treatments.

    Science.gov (United States)

    Hayashi, Nobukazu; Imori, Mizuho; Yanagisawa, Midori; Seto, Yoko; Nagata, Osamu; Kawashima, Makoto

    2005-01-01

    Boehncke et al. suggested that decorative cosmetics can improve the quality of life (QOL) of skin diseases. But dermatologists sometimes discourage female acne patients from applying make-up since decorative cosmetics are considered one of the aggravating factors for acne eruptions. The purpose of this study is to assess whether make-up application interferes with acne treatments and how QOL changes when the make-up items are designed for acne patients and used in order to disguise acne eruptions. Eighteen female acne patients were trained by a make-up artist and advised to apply acne-designed basic and decorative cosmetics for 2 to 4 weeks while their acne was appropriately treated. The acne-severity and QOL of patients were assessed before and after the study. The results revealed that the number of acne eruptions decreased even though patients were applying make-up. The QOL scores of Skindex-16, GHQ30 and anxiety state index greatly improved. Our results suggest that dermatologists should encourage acne patients to utilize appropriate make-up to improve their QOL. PMID:16048760

  1. Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

    Directory of Open Access Journals (Sweden)

    Wujing Dai

    2016-01-01

    Full Text Available CD4+ T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+ T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+ T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs. Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

  2. Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages.

    Science.gov (United States)

    Marchini, Timoteo; Wolf, Dennis; Michel, Nathaly Anto; Mauler, Maximilian; Dufner, Bianca; Hoppe, Natalie; Beckert, Jessica; Jäckel, Markus; Magnani, Natalia; Duerschmied, Daniel; Tasat, Deborah; Alvarez, Silvia; Reinöhl, Jochen; von Zur Muhlen, Constantin; Idzko, Marco; Bode, Christoph; Hilgendorf, Ingo; Evelson, Pablo; Zirlik, Andreas

    2016-07-01

    Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased the levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease. PMID:27240856

  3. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

    Directory of Open Access Journals (Sweden)

    Yen Chia-Hung

    2012-07-01

    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  4. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    Science.gov (United States)

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  5. Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice

    Institute of Scientific and Technical Information of China (English)

    SONG Jun-min; WANG Rong; LIU Hong-xiang; LI Yuan; ZENG Yu-jian; ZHOU Zong-guang; LIU Hai-yi; XU Bing; WANG Ling; ZHOU Bin

    2008-01-01

    Background In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).Methods Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-a) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-KB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.Results Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-α concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-a concentrations.Conclusions The results suggest that extracellular HspTO might induce systemic inflammatory response syndrome (SIRS)-Iike response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

  6. Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

    Directory of Open Access Journals (Sweden)

    Yamamoto Y

    2013-03-01

    Full Text Available Yumiko Yamamoto,1 Yoshitake Kato,2 Hitoshi Tabuchi,2 Atsuki Fukushima11Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan; 2Department of Ophthalmology, Tsukazaki Hospital, Hyogo, JapanAbstract: We report a case of cytomegalovirus (CMV retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy.Keywords: cytomegalovirus, retinitis, uveitis, immunocompromised, immunocompetent, triamcinolone acetonide, diabetes, ganciclovir, valganciclovir

  7. Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment.

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    Analia E Garcia

    Full Text Available Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

  8. Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Noda, M.; Yasuda, M.; Kitagawa, M. (Toyama Medical and Pharmaceutical Univ. (Japan))

    1991-03-01

    Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. We examined 23 autopsy cases of itai-itai disease and 18 cases of sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe anemia and renal tubular injuries. Undecalcified sections of iliac bone were stained with Aluminon reagent, and ammonium salt of aurintricarboxylic acid, and Prussian blue reagent in all cases of itai-itai disease. These two reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of iron at mineralization fronts in itai-itai disease. Five patients showed evidence of hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion iron overload. Renal calculi and calcified aortic walls were also stained with Prussian blue reagent in several patients. Neither ferritin nor transferrin were visualized at mineralization fronts in itai-itai disease by immunohistochemical staining. These results suggest that iron is bound to calcium or to calcium phosphate by a physicochemical reaction. A marked osteomalacia was observed in 10 cases of itai-itai disease by histomorphometry. Regression analyses of data from cases of itai-itai disease suggested that an Aluminon-positive metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone iron is another possible aggravating factor for osteopathy in itai-itai disease, and a synergistic effect between iron and Cd on mineralization is proposed.

  9. Accreditation not Aggravation

    Science.gov (United States)

    Moss, Cath; Archer, Judith

    2014-01-01

    This paper describes an action research project that investigated a range of activities to improve learners' mathematical communication skills. It also gives details of a subsequent case study that illustrates how technology can provide a means of overcoming some of the difficulties learners and tutors face in communicating about numeracy, while…

  10. Genetic predisposition to essential hypertension in a Mongolian population Detecting the C825T polymorphism of the G-protein beta 3 subunit gene

    Institute of Scientific and Technical Information of China (English)

    Chunyu Zhang; Shigang Zhao; Guangming Niu; Rile Hu; Zhiguang Wang; Mingfang Jiang; Rile Hu

    2007-01-01

    BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful for prevention to develop researches on the genetics of various diseases including hypertension in Mongolian population.OBJECTIVE: To analyze the association between C825T polymorphisms of G-protein beta 3 subunit gene (GNB3), the important candidate gene of various disease of cardiovascular system, and Mongolian patients with essential hypertension.DESIGN: A comparative observation.SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College;Wulate Houqi Red Cross Society.PARTICIPANTS: Totally 267 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia. The patients were screened based on the diagnostic standard of hypertension set by WHO in 1999, and the enrolled subjects were divided into two groups according to the level of blood pressure: ① Normal blood pressure group (n =124): 64 males and 60 females, systolic blood pressure (SBP) < 140 mm Hg (1 mm Hg=0.133 kPa), diastolic blood pressure (DBP) <90 mm Hg; ② Essential hypertension group (n =143): 71 males and 72 females, including 60 patients with simple high SBP (SBP ranged 145 to 195 mm Hg, whereas DBP < 90 mm Hg).METHODS: Peripheral venous blood (5 mL) was drawn from all the subjects, the genome DNA was extracted, and the polymorphisms of the GNB3 C825T genotype were detected with the Sequenom system.Polymerase chain reaction (PCR) experiment and SNP detection were performed in Beijing Huada gene laboratory. Then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio (OR) and 95% confidence interval (CI)were calculated.MAIN OUTCOME MEASURES: The

  11. Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

    Directory of Open Access Journals (Sweden)

    Persson Carl GA

    2005-08-01

    eosinophils progressed into the pro-inflammatory cellular fate of secondary necrosis this may also explain the aggravated inflammation. Our data indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in vivo may cause severe disease exacerbation due to direct cytolysis and secondary necrosis of eosinophils.

  12. The Trp64Arg mutation of the beta3 adrenergic receptor gene has no effect on obesity phenotypes in the Québec Family Study and Swedish Obese Subjects cohorts.

    OpenAIRE

    Gagnon, J; Mauriège, P; S Roy; Sjöström, D; Chagnon, Y. C.; Dionne, F.T.; Oppert, J.M.; Pérusse, L.; Sjöström, L.; Bouchard, C

    1996-01-01

    The beta adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the beta3 adrenergic receptor (ADRB3) gene was involved in obesity and insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Québec Family Study (QFS) a...

  13. Vascular Endothelial Growth Factor-Receptor 1 Inhibition Aggravates Diabetic Nephropathy through eNOS Signaling Pathway in db/db Mice

    OpenAIRE

    Keun Suk Yang; Ji Hee Lim; Tae Woo Kim; Min Young Kim; Yaeni Kim; Sungjin Chung; Seok Joon Shin; Beom Soon Choi; Hyung Wook Kim; Yong-Soo Kim; Yoon Sik Chang; Hye Won Kim; Cheol Whee Park

    2014-01-01

    The manipulation of vascular endothelial growth factor (VEGF)-receptors (VEGFRs) in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progre...

  14. Enhanced formation of secondary air pollutants and aggravation of urban smog due to crop residue burning emissions in North India

    Science.gov (United States)

    Sarkar, Chinmoy; Kumar, Vinod; Sinha, Vinayak

    2013-04-01

    Biomass burning causes intense perturbations to regional atmospheric chemistry and air quality and is a significant global source of reactive pollutants to the atmosphere (Andreae and Merlet, 2001). In November 2012, large areas in North India including New Delhi experienced several weeks of aggravated smog and poor air quality due to the impact of crop residue burning, which is a biannual post harvest activity that occurs during Oct-Nov and April-May every year in the agricultural belts of North western India. In-situ high temporal resolution (1 measurement every minute) measurements of a suite of volatile organic compounds measured using proton transfer reaction mass spectrometry (PTR-MS) such as acetonitrile (biomass burning tracer) and aromatic hydrocarbons were performed simultaneously with carbon monoxide, nitrogen oxides, ozone and aerosol mass concentrations (PM 2.5 and PM 10) at a suburban site (30.667°N, 76.729°E and 310 m asl), impacted by air masses that had passed over the burning fields less than 72 hours ago. By using data from the same season but before the post harvest crop residue burning activity had commenced, we were able to quantify enhancements in ambient levels of the measured species due to the crop residue burning activity. When air masses influenced by the fire emissions reached the measurement site, peak values of about 8 ppbV acetonitrile, 4 ppmV CO, 100 ppbV NOx , 30 ppbV toluene and 15 ppbV benzene were observed which represented a factor of 2-5 increase over their ambient levels in the non-fire influenced period. Emission ratios of aromatic hydrocarbons/CO also showed a marked increase. Non fire event (N.F. E.) influenced and fire event (F.E.) influenced air masses had the following emission ratio enhancements: benzene/CO (N.F.E = 3; F.E. = 5), toluene/CO (N.F.E = 4; F.E. = 8.7) and sum of C8 aromatics/CO (N.F.E = 4; F.E. = 7.3) and sum of C9 aromatics/CO (N.F.E = 2.6; F.E. = 3.4). The OH reactivity of air masses which has strong

  15. Carboxylated multi-walled carbon nanotubes aggravated biochemical and subcellular damages in leaves of broad bean (Vicia faba L.) seedlings under combined stress of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chengrun, E-mail: chengrunwang@163.com [School of Life Science, Huainan Normal University, Huainan 232001 (China); Liu, Haitao; Chen, Jinyun [School of Life Science, Huainan Normal University, Huainan 232001 (China); Tian, Yuan [Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, MI 48824 (United States); Shi, Jian; Li, Dongdong; Guo, Chen; Ma, Qingping [School of Life Science, Huainan Normal University, Huainan 232001 (China)

    2014-06-01

    Highlights: • MWCNTs-COOH disturb mineral elements and cause oxidative damages in the leaves. • Cd and Pb combination result in reduction of mineral elements and enrichment of Na, involving in toxicity mechanisms. • MWCNTs-COOH facilitate Cd and Pb uptake, and aggravate biochemical and subcellular damages. - Abstract: Increasing industrialization of multi-walled carbon nanotubes (MWCNTs) would inevitably lead to their release into the environment and combination with heavy metals. However, studies concerning the combined effects of MWCNTs and heavy metals on agricultural crops are limited. Herein, effects and mechanisms of carboxylated MWCNTs (MWCNTs-COOH) (2.5, 5 and 10 mg/L) and their combination with 20 μM Pb and 5 μM Cd (shortened as Pb + Cd) on Vicia faba L. seedlings were investigated. The results showed that the MWCNTs-COOH disturbed the imbalance of nutrient elements, and caused oxidative stress and damages in the leaves. Additionally, the combination of MWCNTs-COOH with Pb + Cd resulted in enrichment of Pb and Cd, and deterioration of oxidative damages compared with the treatments of MWCNTs-COOH or Pb + Cd alone in the leaves. As the results, the concentrations of MWCNTs-COOH not only caused oxidative stress, but also exacerbated the biochemical and subcellular damages due to the treatment of Pb + Cd in the leaves. It also suggests that persistent release of MWCNTs-COOH into the environment may cause phytotoxicity and aggravate ecological risks due to combination of heavy metals.

  16. Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, G.; Brown, A.; Szabo, S.

    1987-03-01

    Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer.

  17. Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat

    International Nuclear Information System (INIS)

    Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer

  18. Effects of Kanlijian (坎离煎) on Exercise Tolerance, Quality of Life, and Frequency of Heart Failure Aggravation in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    JIANG Mei-xian; RUAN Xiao-fen; XU Yan

    2006-01-01

    Objective: To observe the effects of conventional therapy combined with Kanlijian (坎离煎,KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure(CHF). Methods: Sixty. CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2: 1 into the KLJ group (n=39) and the control group(n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed. Results: ( 1 ) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group. Conclusion: The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function

  19. Fentanyl-droperidol supplementation of rapid sequence induction in the presence of severe pregnancy-induced and pregnancy-aggravated hypertension.

    Science.gov (United States)

    Lawes, E G; Downing, J W; Duncan, P W; Bland, B; Lavies, N; Gane, G A

    1987-11-01

    Twenty-six patients manifesting severe pregnancy-induced (PIH) or pregnancy-aggravated (PAH) hypertension who presented for emergency Caesarean section under general anaesthesia were studied. All patients came from a previously identified high risk group--namely greater than 25 yr, multiparous and with diastolic arterial pressures sustained at greater than 120 mm Hg. Our standard accelerated induction technique for the management of severely hypertensive mothers was modified to include the use of fentanyl and droperidol before induction. This modification of the induction sequence produced a clinically significant amelioration of the reflex sympathetic hypertensive response to laryngoscopy and intubation in most mothers receiving antihypertensive therapy, without apparent deleterious effect in the immediate postoperative period to those neonates unaffected by intrauterine asphyxia. PMID:3689612

  20. Aggravation of atopic dermatitis in breast-fed infants by tree nut-related foods and fermented foods in breast milk.

    Science.gov (United States)

    Uenishi, Toshiaki; Sugiura, Hisashi; Tanaka, Toshihiro; Uehara, Masami

    2011-02-01

    Ninety-two exclusively breast-fed Japanese infants with atopic dermatitis were studied to see whether tree nut-related foods (chocolate and coffee) and fermented foods (cheese, yogurt, bread, soy sauce, miso soup and fermented soy beans) eaten by their mothers affected their skin condition. Of the 92 infants, 67 (73%) showed improvement of skin lesions when their mothers avoided these foods and showed aggravation of skin lesions when these foods were reintroduced. The predominant offending foods were chocolate, yogurt, soy sauce and miso soup. A long-term maternal exclusion of the trigger foods brought about progressive improvement of skin lesions in the majority of the infants. These findings suggest that tree nut-related foods and fermented foods are important offending foods of atopic dermatitis in breast-fed infants. PMID:21269309

  1. Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase.

    Science.gov (United States)

    Fang, H; Liu, A; Dahmen, U; Dirsch, O

    2013-01-01

    The anti-malaria drug chloroquine is well known as autophagy inhibitor. Chloroquine has also been used as anti-inflammatory drugs to treat inflammatory diseases. We hypothesized that chloroquine could have a dual effect in liver ischemia/reperfusion (I/R) injury: chloroquine on the one hand could protect the liver against I/R injury via inhibition of inflammatory response, but on the other hand could aggravate liver I/R injury through inhibition of autophagy. Rats (n=6 per group) were pre-treated with chloroquine (60 mg/kg, i.p.) 1 h before warm ischemia, and they were continuously subjected to a daily chloroquine injection for up to 2 days. Rats were killed 0.5, 6, 24 and 48 h after reperfusion. At the early phase (i.e., 0-6 h after reperfusion), chloroquine treatment ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines and fewer histopathologic changes. In contrast, chloroquine worsened liver injury at the late phase of reperfusion (i.e., 24-48 h after reperfusion). The mechanism of protective action of chloroquine appeared to involve its ability to modulate mitogen-activated protein kinase activation, reduce high-mobility group box 1 release and inflammatory cytokines production, whereas chloroquine worsened liver injury via inhibition of autophagy and induction of hepatic apoptosis at the late phase. In conclusion, chloroquine prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury. This dual role of chloroquine should be considered when using chloroquine as an inhibitor of inflammation or autophagy in I/R injury. PMID:23807223

  2. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida

    2015-07-01

    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  3. Human Cytomegalovirus-Encoded miR-US25-1 Aggravates the Oxidised Low Density Lipoprotein-Induced Apoptosis of Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jianmin Fan

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV infection is linked to the development and severity of the cardiovascular disease atherosclerosis; however, there is little known about the promotion of atherosclerosis. miR-US25-1 is one of HCMV-encoded miRNAs and targets cellular genes that are essential for virus growth to control the life cycle of the virus and host cells. The prominent regulation on cell cycle genes of the miR-US25-1 attracts us to explore its role in the atherosclerosis promotion. It was indicated that miR-US25-1 level was upregulated in subjects or in endothelial cells with HCMV infection; and the miR-US25-1 downregulated the expression of BRCC 3 by targeting the 5′ UTR of BRCC 3. And a miR-US25-1 mimics transfection could reduce the EAhy926 cell viability but did not induce apoptosis in EAhy926 cells. And what is more, miR-US25-1 mimicis transfection deteriorated the ox-LDL-induced apoptosis and aggravated the upregulation of apoptosis-associated molecules by oxidised low density lipoprotein (ox-LDL in EAhy926 cells. And we have also confirmed the deregulation of BRCC 3 expression by miR-US25-1 by targeting the 5′ UTR of it. Given the vital role of BRCC 3 in DNA damage repairing, we speculated that the targeting inhibition of BRCC 3 by miR-US25-1 may contribute to the aggravation of ox-LDL-promoted apoptosis of endothelial EAhy926 cells.

  4. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    Science.gov (United States)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  5. In vitro and in vivo pharmacological characterization of ethyl-4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino]-phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640), a new potent and selective human beta3-adrenoceptor agonist for the treatment of preterm labor.

    OpenAIRE

    Croci, Tiziano; Cecchi, Roberto; Marini, Pietro; Rouget, Céline; Viviani, Nunzia; Germain, Guy; Guagnini, Fabio; Fradin, Yvon; Descamps, Laurence; Pascal, Marc; Advenier, Charles; Breuiller-Fouché, Michelle; Leroy, Marie-Josèphe; Bardou, Marc

    2007-01-01

    Ethyl-4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl)amino] phenoxy]propyl) amino]cyclohexyl]benzoate hydrochloride (SAR150640) was characterized as a new potent and selective beta(3)-adrenoceptor agonist for the treatment of preterm labor. SAR150640 and its major metabolite, the corresponding acid 4-[trans-4-[((2S)-2-hydroxy-3-[4-hydroxy-3[(methylsulfonyl) amino] phenoxy]propyl)amino]cyclohexyl]benzoic acid (SSR500400), showed high affinity for beta(3)-adrenoceptors (K(i) = 73 an...

  6. High-resolution mapping of the [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett, D.; Wagstaff, J.; Woolf, E. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)); Glatt, K. (Children' s Hospital, Boston, MA (United States)); Kirkness, E.J. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States))Lalande, M. (Children' s Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Inst., Boston, MA (United States))

    1993-06-01

    The [gamma]-aminobutyric acid (GABA[sub A]) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABA[sub A] receptor [beta]3 subunit gene (GABRB3) and [alpha]5 subunit gene (GABRA5) in chromosome 15q11-q13, the authors have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. The authors have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints -- in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion -- are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region. 64 refs., 6 figs., 2 tabs.

  7. Differential cytokine modulation of the genes LAMA3, LAMB3, and LAMC2, encoding the constitutive polypeptides, alpha 3, beta 3, and gamma 2, of human laminin 5 in epidermal keratinocytes.

    Science.gov (United States)

    Korang, K; Christiano, A M; Uitto, J; Mauviel, A

    1995-07-24

    Laminin 5, an anchoring filament protein previously known as nicein/kalinin/epiligrin, consists of three polypeptide chains, alpha 3, beta 3, and gamma 2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. The expression of laminin 5 was detected by Northern hybridization with specific cDNA probes in various epidermal keratinocyte cultures, whereas no expression of any of the three genes could be detected in foreskin fibroblast cultures. Transforming growth factor-beta (TGF-beta) enhanced LAMA3, LAMB3, and LAMC2 gene expression in human epidermal keratinocytes, as well as in HaCaT and Balb/K cells in culture, although the extent of enhancement was greater for LAMA3 and LAMC2 genes than for LAMB3. Interestingly, tumor necrosis factor-alpha, (TNF-alpha) alone did not alter the expression of LAMB3 and LAMC2 genes in human epidermal keratinocytes, whereas it inhibited the expression of LAMA3. These results suggest that the expression of the three genes encoding the laminin 5 subunits is not coordinately regulated by the cytokines tested. PMID:7635220

  8. Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta-3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program.

    Science.gov (United States)

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Takahashi, Kaoru; Kuzuya, Hideshi

    2016-05-01

    The beta-3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6-month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non-carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high-density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients. PMID:27330719

  9. Vascular endothelial growth factor-receptor 1 inhibition aggravates diabetic nephropathy through eNOS signaling pathway in db/db mice.

    Directory of Open Access Journals (Sweden)

    Keun Suk Yang

    Full Text Available The manipulation of vascular endothelial growth factor (VEGF-receptors (VEGFRs in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progression of diabetic nephropathy in db/db mice. While diabetes suppressed VEGFR1, it did increase VEGFR2 expressions in the glomerulus. Db/db mice with VEGFR1 inhibition showed more prominent features with respect to, albuminuria, mesangial matrix expansion, inflammatory cell infiltration and greater numbers of apoptotic cells in the glomerulus, and oxidative stress than that of control db/db mice. All these changes were related to the suppression of diabetes-induced increases in PI3K activity and Akt phosphorylation as well as the aggravation of endothelial dysfunction associated with the inactivation of FoxO3a and eNOS-NOx. In cultured human glomerular endothelial cells (HGECs, high-glucose media with VEGFR1 inhibition induced more apoptotic cells and oxidative stress than did high-glucose media alone, which were associated with the suppression of PI3K-Akt phosphorylation, independently of the activation of AMP-activated protein kinase, and inactivation of FoxO3a and eNOS-NOx pathway. In addition, transfection with VEGFR1 siRNA in HGECs also suppressed PI3K-Akt-eNOS signaling. In conclusion, the specific blockade of VEGFR1 with GNQWFI caused severe renal injury related to profound suppression of the PI3K-Akt, FoxO3a and eNOS-NOx pathway, giving rise to the oxidative stress-induced apoptosis of glomerular cells in type 2 diabetic nephropathy.

  10. VNN1, a potential biomarker for pancreatic cancer-associated new-onset diabetes, aggravates paraneoplastic islet dysfunction by increasing oxidative stress.

    Science.gov (United States)

    Kang, Muxing; Qin, Wenjie; Buya, Miranbieke; Dong, Xin; Zheng, Wen; Lu, Wenjie; Chen, Jian; Guo, Qingqu; Wu, Yulian

    2016-04-10

    In our previous clinical microarray analysis, we were the first to report on Vanin-1 (VNN1) as a novel clinically derived biomarker of pancreatic cancer-associated new-onset diabetes (PCAND). The functional mechanisms of VNN1 in the pathogenesis of PCAND, however, are not completely understood. In the present study, we further extend our previous clinical study to include laboratory research. The functions and mechanisms of neoplastic overexpressed VNN1 in PCAND have been explored using a co-culture model. Furthermore, the serum concentrations and discrimination power of downstream molecules of VNN1 were tested in a PCAND cohort. Pancreatic ductal adenocarcinoma (PDA) overexpressed VNN1 further aggravates paraneoplastic islet dysfunction; decreases in GSH/PPAR-γ concentrations and increases in ROS/cysteamine might be primary cause of this effect. Clinical serum analyses revealed that the expression profiles of these molecules were aberrant in the PCAND group. Our results further demonstrated that PCAND is a type of paraneoplastic diabetes. As the only clinically derived biomarker for PCAND screening available today, the biological role of VNN1 in triggering oxidative stress within the pancreatic microenvironment is important. The molecules downstream of VNN1 are also potential biomarkers for PCAND screening. PMID:26845448

  11. The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture

    Directory of Open Access Journals (Sweden)

    Li Gan

    2015-01-01

    Full Text Available Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as well as the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. After immediate surgery, the above variables were further increased. The serum mtDNA levels were significantly related with the serum cytokine (TNF-α and IL-10 levels and pulmonary histological score. In order to identify the meaning of mtDNA release following hip fracture, the elderly rats received injections with mtDNA. After treatment, the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. These results demonstrated that the immediate surgery increased the mtDNA release that could aggravate systemic inflammatory response and lung injury induced by elderly hip fracture; serum mtDNA might serve as a potential biomarker of systemic inflammatory response and lung injury following elderly hip fracture.

  12. Are drought occurrence and severity aggravating? A study on SPI drought class transitions using log-linear models and ANOVA-like inference

    Directory of Open Access Journals (Sweden)

    E. E. Moreira

    2012-08-01

    Full Text Available Long time series (95 to 135 yr of the 12-month time scale Standardized Precipitation Index (SPI relative to 10 locations across Portugal were studied with the aim of investigating if drought frequency and severity are changing through time. Considering four drought severity classes, time series of drought class transitions were computed and later divided into several sub-periods according to the length of SPI time series. Drought class transitions were calculated to form a 2-dimensional contingency table for each sub-period, which refer to the number of transitions among drought severity classes. Two-dimensional log-linear models were fitted to these contingency tables and an ANOVA-like inference was then performed in order to investigate differences relative to drought class transitions among those sub-periods, which were considered as treatments of only one factor. The application of ANOVA-like inference to these data allowed to compare the sub-periods in terms of probabilities of transition between drought classes, which were used to detect a possible trend in droughts frequency and severity. Results for a number of locations show some similarity between alternate sub-periods and differences between consecutive ones regarding the persistency of severe/extreme and sometimes moderate droughts. In global terms, results do not support the assumption of a trend for progressive aggravation of drought occurrence during the last century, but rather suggest the existence of long duration cycles.

  13. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia [v1; ref status: indexed, http://f1000r.es/1tf

    OpenAIRE

    Adlette Inati; Grace Akouri; Abbas, Hussein A.

    2013-01-01

    Oral mucositis is a debilitating manifestation in children undergoing chemotherapy and radiotherapy. Children with mucositis should be properly managed in order to prevent further exacerbation and adverse complications. We hereby present the first report of a severe chemotherapy-induced mucositis, plausibly aggravated by improper dental hygiene leading to shedding of the ventral part of the tongue in a child with pre-B acute lymphoblastic leukemia (ALL). The patient steadily and gradually rec...

  14. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Science.gov (United States)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Bhadja, Poonam; Yao, Xiu-Qiong; Ouyang, Jian-Ming

    2016-01-01

    Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H2O2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H2O2-injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone

  15. Are droughts occurrence and severity aggravating? A study on SPI drought class transitions using loglinear models and ANOVA-like inference

    Directory of Open Access Journals (Sweden)

    E. E. Moreira

    2011-12-01

    Full Text Available Long time series (95 to 135 yr of the Standardized Precipitation Index (SPI computed with the 12-month time scale relative to 10 locations across Portugal were studied with the aim of investigating if drought frequency and severity are changing through time. Considering four drought severity classes, time series of drought class transitions were computed and later divided into 4 or 5 sub-periods according to length of time series. Drought class transitions were calculated to form a 2-dimensional contingency table for each period. Two-dimensional loglinear models were fitted to these contingency tables and an ANOVA-like inference was then performed in order to investigate differences relative to drought class transitions among those sub-periods, which were considered as treatments of only one factor. The application of ANOVA-like inference to these data allowed to compare the four or five sub-periods in terms of probabilities of transition between drought classes, which were used to detect a possible trend in time evolution of droughts frequency and severity that could be related to climate change. Results for a number of locations show some similarity between the first, third and fifth period (or the second and the fourth if there were only 4 sub-periods regarding the persistency of severe/extreme and sometimes moderate droughts. In global terms, results do not support the assumption of a trend for progressive aggravation of droughts occurrence during the last century, but rather suggest the existence of long duration cycles.

  16. Does ageing aggravate parkinsonian disability?

    OpenAIRE

    Blin, J; DuBois, B; Bonnet, A M; Vidailhet, M; Brandabur, M; Agid, Y

    1991-01-01

    The influence of age of onset of Parkinson's disease on the severity and the pattern of motor symptoms was investigated by comparing the motor scores with and without levodopa therapy in two groups of patients divided according to age of onset (early less than 50, late greater than 60 years) and matched for disease duration (n = 69 in each group, Study I). The baseline score, that is, the motor disability of patients when off levodopa, was similar in the early- and late- onset groups. In cont...

  17. Constitution of pseudobinary hypoeutectic beta-NiAl + alpha-V alloys

    Science.gov (United States)

    Cotton, J. D.; Kaufman, M. J.; Noebe, R. D.

    1991-01-01

    The formation of pseudobinary eutectics between NiAl (beta) and V (alpha) at high temperatures was investigated as a possible way of improving the ductility and toughness of the alloy. It is found that a pseudobinary eutectic, characterized by a large beta+alpha field, is formed in the Ni-Al-V ternary system below about 1370 C. The high-temperature solubility of V in beta is about 14 percent, decreasing markedly with decreasing temperature and increasing Al content above 50 at. pct Al. The pseudobinary hypoeutectic exibits crack resistance under indentation loading.

  18. Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    Full Text Available Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

  19. Targeting of Alpha-V Integrins Reduces Malignancy of Bladder Carcinoma

    Science.gov (United States)

    van der Horst, Geertje; Bos, Lieke; van der Mark, Maaike; Cheung, Henry; Heckmann, Bertrand; Clément-Lacroix, Philippe; Lorenzon, Giocondo; Pelger, Rob C. M.; Bevers, Rob F. M.; van der Pluijm, Gabri

    2014-01-01

    Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy invitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical invivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer. PMID:25247809

  20. Is alpha-V2O5 a cathode material for Mg insertion batteries?

    Science.gov (United States)

    Sa, Niya; Wang, Hao; Proffit, Danielle L.; Lipson, Albert L.; Key, Baris; Liu, Miao; Feng, Zhenxing; Fister, Timothy T.; Ren, Yang; Sun, Cheng-Jun; Vaughey, John T.; Fenter, Paul A.; Persson, Kristin A.; Burrell, Anthony K.

    2016-08-01

    When designing a high energy density battery, one of the critical features is a high voltage, high capacity cathode material. In the development of Mg batteries, oxide cathodes that can reversibly intercalate Mg, while at the same time being compatible with an electrolyte that can deposit Mg reversibly are rare. Herein, we report the compatibility of Mg anodes with α-V2O5 by employing magnesium bis(trifluoromethane sulfonyl)imide in diglyme electrolytes at very low water levels. Electrolytes that contain a high water level do not reversibly deposit Mg, but interestingly these electrolytes appear to enable much higher capacities for an α-V2O5 cathode. Solid state NMR indicates that the major source of the higher capacity in high water content electrolytes originates from reversible proton insertion. In contrast, we found that lowering the water level of the magnesium bis(trifluoromethane sulfonyl)imide in diglyme electrolyte is critical to achieve reversible Mg deposition and direct evidence for reversible Mg intercalation is shown. Findings we report here elucidate the role of proton intercalation in water-containing electrolytes and clarify numerous conflicting reports of Mg insertion into α-V2O5.

  1. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-08-14

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

  2. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    International Nuclear Information System (INIS)

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33 is

  3. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Directory of Open Access Journals (Sweden)

    Gan QZ

    2016-06-01

    , and cell death rate increased.Conclusion: Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation. Keywords: nano-calcium oxalate crystals, cell injury, crystal adhesion, kidney stones

  4. Synthesis of 25-hydroxyvitamin D sub 3 3. beta. -3 prime -(N-(4-azido-2-nitrophenyl)amino)propyl ether, a second-generation photoaffinity analogue of 25-hydroxyvitamin D sub 3 : Photoaffinity labeling of rat serum vitamin D binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Ray, R.; Holick, M.F. (Boston Univ. School of Medicine, MA (USA)); Bouillon, R.; Van Baelen, H. (Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Gasthuisberg, Leuven (Belgium))

    1991-05-14

    Vulnerability of 25-hydroxy-(26,27-{sup 3}H)vitamin D{sub 3} 3{beta}-N-(4-azido-2-nitrophenyl)glycinate, a photoaffinity analogue of 25-hydroxyvitamin D{sub 3} (25-OH-D{sub 3}) toward standard conditions of carboxymethylationin promoted the authors to synthesize 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitrophenyl)amino)propyl ether (25-ANE), a hydrolytically stable photoaffinity analogue of 25-OH-D{sub 3}, and 25-hydroxyvitamin D{sub 3} 3{beta}-3{prime}-(N-(4-azido-2-nitro-(3,5-{sup 3}H)phenyl)amino)propyl ether ({sup 3}H-25-ANE), the radiolabeled counterpart of 25-ANE competes for the 25-OH-D{sub 3} binding site in rat serum vitamin D binding protein (rDBP). On the other hand, UV exposure of a sample of purified rat DBP (rDBP), preincubated in the dark with {sup 3}H-25-ANE, covalently labeled the protein. However, very little covalent labeling was observed in the absence of UV light or in the presence of a large excess of 25-OH-D{sub 3}. These results provide strong evidence for the covalent labeling of the 25-OH-D{sub 3} binding site in rDPB by {sup 3}H-25-ANE.

  5. Research on Strategy of Foreign Trade Enterprises in Guangxi Based on the Aggravation of European Debt Crisis%欧债危机加剧下广西外贸企业对策探讨

    Institute of Scientific and Technical Information of China (English)

    林赵华

    2012-01-01

      The global economic, financial and trade situations deteriorate sharply with the European debt crisis erupting, spreading and upgrading. China's foreign trade is impacted tremendously and the development of foreign trade enterprises in Guangxi will inevitably be affected. In the paper, the aggravation of the European debt crisis is described. Its adverse effects on the development of foreign trade enterprises in Guangxi are analyzed through several aspects of the transmission mechanism in external demand, exchange rate fluctuations, exchange risk and trade frictions. And the development strategies coping with aggravation of the European debt crisis are proposed.%  欧债危机的爆发、蔓延和加剧,使全球经济、金融、贸易形势急剧恶化,我国外贸经济遭受巨大冲击,广西外贸企业的发展也不可避免地受到影响。文章就欧债危机加剧的态势,通过其外部需求、汇率变动、汇兑风险和贸易摩擦等几方面的传导机制,分析了欧债危机对广西对外贸易发展的不利影响,并相应地提出了外贸企业应对欧债危机日益加剧的策略。

  6. Beta-3 adrenoceptors as new therapeutic targets for cardiovascular pathologies.

    OpenAIRE

    Gauthier, Chantal; Rozec, Bertrand; Manoury, Boris; Balligand, Jean-Luc

    2011-01-01

    Catecholamines play a key role in the regulation of cardiovascular function, classically through ß(1/2)-adrenoreceptors (AR) activation. After ß(3)-AR cloning in the late 1980s, convincing evidence for ß(3)-AR expression and function in cardiovascular tissues recently initiated a reexamination of their involvement in the pathophysiology of cardiovascular diseases. Their upregulation in diseased cardiovascular tissues and resistance to desensitization suggest they may be attractive therapeutic...

  7. Asthma aggravation, combustion, and stagnant air

    OpenAIRE

    Norris, G; Larson, T; Koenig, J.; Claiborn, C.; Sheppard, L; D. Finn

    2000-01-01

    BACKGROUND—The relationship between current concentrations of ambient air pollution and adverse health effects is controversial. We report a meteorological index of air stagnation that is associated with daily visits to the emergency department for asthma in two urban areas.
METHODS—Data on daily values of a stagnation persistence index and visits to the emergency department for asthma were collected for approximately two years in Spokane, Washington, USA and for 15months...

  8. Renalase deficiency aggravates ischemic myocardial damage.

    Science.gov (United States)

    Wu, Yanling; Xu, Jianchao; Velazquez, Heino; Wang, Peili; Li, Guoyong; Liu, Dinggang; Sampaio-Maia, Benedita; Quelhas-Santos, Janete; Russell, Kerry; Russell, Raymond; Flavell, Richard A; Pestana, Manuel; Giordano, Frank; Desir, Gary V

    2011-04-01

    Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD. PMID:21178975

  9. Hyperbaric oxygen therapy aggravates liver reperfusion injury in rats Oxigenoterapia hiperbárica agrava lesão de reperfusão hepática em ratos

    Directory of Open Access Journals (Sweden)

    Cristiano Xavier Lima

    2008-08-01

    Full Text Available PURPOSE: To evaluate the effects of hyperbaric oxygen (HO therapy in the protection against liver ischemia/reperfusion injury. METHODS: Thirty-two male Wistar rats were divided into four groups of eight animals each: group A - laparotomy and liver manipulation, group B - liver ischemia and reperfusion, group C - HO pretreatment for 60 min followed by liver ischemia and reperfusion, and group D - pretreatment with ambient air at 2.5 absolute atmospheres for 60 min followed by liver ischemia and reperfusion. Plasma was assayed for aspartate aminotransferase (AST, alanine aminotransferase (ALT and lactate dehydrogenase (LDH. Intra-arterial blood pressure was monitored continuously. Myeloperoxidase activity in the liver and lung was assessed 30 min after reperfusion. RESULTS: Plasma AST, ALT and LDH increased after reperfusion in all animals. Plasma ALT values and myeloperoxidase activity in the liver parenchyma were higher in HO-pretreated animals than in groups A, B and D. HO had a negative hemodynamic effect during liver reperfusion. CONCLUSION: Liver preconditioning with hyperbaric oxygen therapy aggravated liver ischemia/reperfusion injury in rats as demonstrated by plasma ALT and liver myeloperoxidase activity.OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (OH como método preventivo da lesão de isquemia e reperfusão (LIR do fígado. MÉTODOS: Trinta e dois ratos machos Wistar foram distribuídos em quatro grupos de oito animais cada: A - laparotomia e manipulação hepática, B - isquemia e reperfusão hepática, C - pré-tratamento com OH por 60 minutos seguido de isquemia e reperfusão hepática e D - pré-tratamento com ar ambiente a 2,5 atmosferas absolutas por 60 minuto e isquemia e reperfusão hepática. Dosagens seriadas de AST, ALT e DHL foram realizadas. A pressão intra arterial foi monitorizada continuamente. O grau de infiltração leucocitária no fígado e pulmões foi inferido pela dosagem de mieloperoxidade

  10. 在中国北方汉族人群中血管紧张素转换酶基因I/D多态与G蛋白beta3亚基基因C825T多态对原发性高血压的联合作用%Combined Action of ACE Gene I/D and GNB3 Gene C825T Polymorphisms on Essential Hypertension in Northern Han Chinese

    Institute of Scientific and Technical Information of China (English)

    黄文涛; 于鸿江; 鲁向锋; 赵维燕; 王月兰; 顾东风; 陈润生

    2007-01-01

    原发性高血压是一种复杂的多基因疾病,被认为是多个变异了的基因遗传交互以及环境因素共同作用的结果.证据表明,血管紧张素转换酶基因和G蛋白beta3亚基基因各自都是重要的原发性高血压的易感基因,并且可能存在共同的通路来导致高血压疾病的发展.为了探索这两个基因在中国北方汉族人群中是否对高血压有影响,挑选血管紧张素转换酶基因I/D多态与G蛋白beta3亚基基因C825T多态,在一个包含502个高血压病例和490个健康对照的样本中做了关联研究.连锁不平衡分析揭示,仅仅在男性中有显著性的非随机性分布,表明血管紧张素转换酶基因与G蛋白beta3亚基基因倾向在男性中造成高血压.调整了的单位点的多变量逐步回归分析展示,在男性显性模型中DD/ID对Ⅱ的比值比达到显著性水平(OR 1.57;95%CI,1.09~2.27;P=0.016).在对性别进行分层后的联合分析中,在男性中经过调整后的比值比具有弱显著性水平:在血管紧张素转换酶基因的DD基因型中,TT对CC的比值比是0.11;95%CI,0.01~0.99;P=0.049;在G蛋白beta3亚基基因的CC+CT基因型中,DD/ID对Ⅱ的比值比是1.52;95%CI,1.01~2.29;P=0.047.结果暗示,血管紧张素转换酶基因或附近的某个基因是具有男性性别倾向的高血压易感侯选基因,同时,在血管紧张素转换酶基因基因的D等位基因和G蛋白beta3亚基基因的825C等位基因之间,可能存在具有上位效应的基因-基因相互作用.%Essential hypertension (EH), a complex polygenic disease, is considered to the result of the genetic interaction of multiple gene alterations in concert with environmental factors. Evidences showed that angiotensin-converting enzyme (ACE) gene and G protein beta3 subunit (GNB3) gene are both important susceptibility genes for EH, and that there exists putative biological connection between the two genes in developing hypertension. To investigate

  11. 高血糖通过抑制线粒体自噬加重大鼠脑缺血/再灌注损伤%Hyperglycemia aggravated cerebral ischemia/reperfusion injury by inhibiting mitophagy

    Institute of Scientific and Technical Information of China (English)

    左玮; 梅丹

    2016-01-01

    Aim Toinvestigatetheroleofhyperglyce-mia in cerebral ischemia/reperfusion(I/R)injury with a middle cerebral artery occlusion(MCAO)rat model anditsmechanism.Methods EightyhealthymaleSD rats were randomly assigned into sham group, I/R group (normoglycemia),hyperglycemic I/R groupⅠ(HG1 )and hyperglycemic I/R groupⅡ(HG2 ).The cerebral I/R model was established by occluding the middle cerebral artery(MCA)in rats.Hyperglycemia was induced by intraperitoneal injection of 50% glu-cose solution.Neurological deficit was determined by Ludmila Belayev test;infarct size and brain edema were measured by TTC staining;mitophagy was ob-served by double immunofluorescent staining and elec-tron microscope.The expressions of autophagy-related proteins(LC3 and Beclin-1 )and apoptosis-related pro-teins(Cyt-C,AIF,caspase-9 and caspase-3 )were ex-aminedbyWesternblotfurtherly.Results Bloodglu-cose level was controlled at 4 mmol·L-1 (normoglyce-mia),10 mmol · L-1 (HG1 ) and 20 mmol · L-1 (HG2)respectively.There were no significant differ-ences between model group and HG1 group in neuro-logical deficit scores,infarct volume and edema size(P>0. 05 ).However,these indications in HG2 group were significantly increased compared with model group (P<0. 05 ).After 3 days of reperfusion,the level of mitophagy was significantly reduced accompanied with increased mitochondria damages in HG 2 group (P <0. 05 ),and the expressions of mitochondrial related ap-optotic proteins(Cyt-C,AIF,caspase-9 and caspase-3 ) were significantly increased accordingly compared to modelgroup.Conclusions Mildhyperglycemiacan not intensify the cerebal ischemic injury.In contrast, severe hyperglycemia significantly aggravates the brain ischemic injury by inhibiting the removal of injured mi-tochondria in a manner of mitophagy,thus amplifying the mitochondrial mediated cascade damage responses.%目的探讨急性高血糖对局灶性脑缺血大鼠神经功能损伤的作用及机制。方

  12. Respiratory training and prompting effective discharging of sputum for COPD patients in acute aggravation period%呼吸训练和促进有效排痰应用于急性加重期慢性阻塞性肺疾病患者的效果观察

    Institute of Scientific and Technical Information of China (English)

    张洪; 邱丽清; 陈丽延

    2008-01-01

    Objective To discuss the influence of respiratory training and prompting effective discharging of sputum for chronic obstructive pulmonary disease (COPD) patients in acute aggravation period. Methods 50 patients were randomized into the intervention group and the control group with 25 cases in each group.The intervention group received respiratory training and prompting effective discharging of sputum while the control was only given routine treatment and nursing.The ratio of first second expiration volume to forced vital capacity, oxygen partial pressure (PaO2),carben dioxide partial pressure (PaCO2) ,blood oxygen saturation (SpO2)and the in-hospital days were compared between the two groups. Results The clinical effect in the intervention group was superior to that of the control group with shorter in-hospital days (P<0.01).Conclusion Better results could be obtained by application of respiratory training and prompting effective discharging of sputum for COPD patients in acute aggravation period.%目的 探讨呼吸训练和促进有效排痰对慢性阻塞性肺疾病(COPD)急性加重期患者康复的影响.方法 将50例患者随机分成干预组和对照组各25例,干预组由护士进行呼吸训练和促进有效排痰,对照组按常规进行治疗护理,比较2组患者第1秒用力呼气容积占用力肺活量百分比、氧分压、二氧化碳分压、血氧饱和度及2组患者住院天数.结果 干预组肺功能各项指标显著优于对照组,P<0.05,住院天数缩短,P<0.01. 结论呼吸训练和促进有效排痰对COPD急性加重期患者康复有较好的效果.

  13. Does Population Ageing Aggravate Income Inequality? Evidence from China 1996 -2009%人口老龄化是否加剧收入不平等?——基于中国(1996~2009)的实证研究

    Institute of Scientific and Technical Information of China (English)

    董志强; 魏下海; 汤灿晴

    2012-01-01

    Since inequality differs cross population groups, changing population age structure may have an effect on overall income inequality. This paper develops an analytical (statistical) model to describe conditions under which population ageing could aggravate income inequality, and show theoretically and empirically that the conditions are true in China. Thus, it is hypothesized that population ageing aggravates inequality in China. With Gini coefficient as measurement of income inequality, and employing provincial level panel data over 1996 -2009, this paper confirms that population ageing (i. e. an increasing aged dependency ratio and a decreasing child dependency ratio) is a positive and significant factor contributing to income inequality. This suggests that inequality studies need to incorporate population ageing, as it conveys different policy implications as compared to other factors.%不同年龄群体内部的收入程度通常存在差异,因而人口年龄结构变迁会影响整个经济的收入不平等程度。文章建立了一个(统计性)分析框架,刻画出老龄化导致收入不平等加剧的条件,并从经济理论和经验证据上说明该条件在中国成立,从而提出假说:中国的老龄化加剧了经济中的收入不平等。运用1996—2009年省级面板数据,以基尼系数衡量收入不平等,从经验上证实老龄化(老年抚养比上升和少儿抚养比下降)对我国收入不平等有显著的正向影响。这一结论表明,研究收入不平等问题时,应注意老龄化这一长期被研究者们忽视的因素,因为它蕴含着与其他因素大不相同的政策含义。

  14. Association between -238 but not -308 polymorphism of Tumor necrosis factor alpha (TNF-alphav and unexplained recurrent spontaneous abortion (URSA in Chinese population

    Directory of Open Access Journals (Sweden)

    Zhou Sirui

    2010-09-01

    Full Text Available Abstract Objectives TNF-alpha is a critical cytokine produced by Th1 cells while altered T helper 1 (Th1-Th2 balance is found crucial for a successful pregnancy. Study Design A cohort of 132 Southern Chinese Han RSA patients and 152 controls constituted the subjects of this study. Two functional polymorphisms -308 and -238 of TNF-alpha were studied by association analysis. Results lack of association was found in TNF-alpha -308 SNP yet a significant difference was discovered in -238 polymorphism. Conclusion This study suggested that TNF-alpha may be a risk factor in Chinese RSA patients. However the ethnic differences may also contribute to the results.

  15. Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil Características agravantes por infestación residencial de Culex quinquefasciatus, en una región del Noreste de Brasil Características agravantes por infestação residencial de Culex quinquefasciatus, em Olinda, PE

    Directory of Open Access Journals (Sweden)

    Juliana Cavalcanti Correia

    2012-12-01

    Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.OBJETIVO: Analizar como las condiciones de saneamiento básico, abastecimiento de agua y habitaciones afectan la densidad de Culex quinquefasciatus MÉTODOS: se monitoreó la población de C. quinquefasciatus en 61 residencias del municipio de Olinda, PE, Brasil, de octubre de 2009 a octubre de

  16. Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene

    NARCIS (Netherlands)

    de Wit, M J; Landsvater, R M; Sinke, R J; Geurts van Kessel, A; Lips, C J; Höppener, J W

    1997-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human pho

  17. Closed headpiece of integrin [alpah]IIb[beta]3 and its complex with an [alpha]IIb[beta]3-specific antagonist that does not induce opening

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jieqing; Zhu, Jianghai; Negri, Ana; Provasi, Davide; Filizola, Marta; Coller, Barry S.; Springer, Timothy A. (Sinai); (Rockefeller); (CH-Boston)

    2011-08-24

    The platelet integrin {alpha}{sub IIb}{beta}{sub 3} is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the {alpha}{sub IIb}{beta}{sub 3} headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the {alpha}{sub IIb}{beta}{sub 3} headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the {alpha}{sub IIb} subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, {alpha}{sub IIb} Y190 and {alpha}{sub aIIb} D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce {alpha}{sub IIb}{beta}{sub 3} to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.

  18. Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Lee, Jiyoung; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Kim, Su Young; Rhyou, Hyo In

    2015-01-01

    We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis. PMID:25684968

  19. Therapy with Minocycline Aggravates Experimental Rabies in Mice▿

    OpenAIRE

    Jackson, Alan C.; Scott, Courtney A.; Owen, James; Weli, Simon C.; Rossiter, John P.

    2007-01-01

    Minocycline is a tetracycline derivative with antiapoptotic and anti-inflammatory properties, and the drug has been shown to have beneficial effects in a variety of models of neurological disorders. The potentially neuroprotective role of minocycline was assessed in experimental in vitro and in vivo models of rabies virus infection. In this study, 5 nM minocycline did not improve the viability of embryonic mouse cortical and hippocampal neurons infected in vitro with the attenuated SAD-D29 st...

  20. Inflammation aggravates disease severity in Marfan syndrome patients.

    Directory of Open Access Journals (Sweden)

    Teodora Radonic

    Full Text Available BACKGROUND: Marfan syndrome (MFS is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-β and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-β and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-β were found especially in MFS patients with aortic root dilatation (124 pg/ml, when compared to MFS patients with normal aorta (10 pg/ml; p = 8×10(-6, 95% CI: 70-159 pg/ml. Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR = 0%, ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC = 1.8; 1.4; 1.5, FDR = 0% and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%. Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02 and increased number of CD8+ T-cells (p = 0.003 in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients.

  1. Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses

    DEFF Research Database (Denmark)

    Nielsen, T G; Djurhuus, C; Pedersen, Erik Morre; Laustsen, J; Hasenkam, J M; Schroeder, Torben Veith

    1996-01-01

    PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced...... the systolic pressure drop from 31% to 48% and had significant impact on all waveform parameters. CONCLUSIONS: Distal arteriovenous fistulas enhance pressure loss across stenoses and affect downstream velocity waveform configuration. The presence of a combined fistula and a stenosis mimics the distal...... 10 cm upstream of a fistula with low outflow resistance. Flow and intraluminal pressure were measured proximal to the stenosis and downstream of the fistula. The waveform parameters peak systolic velocity, end-diastolic velocity, pulsatility index, and pulse rise time were determined from midstream...

  2. Can pregnancy aggravate the course of non-Hodgkin's lymphoma?

    Science.gov (United States)

    Giovannini, M; Saccucci, P; Cannone, D; Damiani, G; Pomini, P

    1989-01-01

    The Authors present three cases of Non-Hodgkin's Lymphoma (NHL) in pregnancy and discuss about problem of diagnosis and management of NHL in this condition. They stress that the diagnosis of NHL in pregnancy is delayed and the clinical progression of lymphoma is probably influenced by hormonal and immunological changes occurring during pregnancy. On the other hand the management of NHL is problematic because radiotherapy is potentially teratogenic. (By editorial staff). PMID:2776787

  3. The proliferation of ballistic missiles: an aggravating factor of crises

    International Nuclear Information System (INIS)

    After a brief recall of the history of the development of ballistic missiles from World War II, the author discusses the various uses of these missiles, on the one hand by major powers, and on the other hand by other countries like Israel, Pakistan and India, and also Egypt and Iraq. He recalls the uses of these missiles during regional conflicts (Scuds by Iraq) and then discusses the issue of proliferation of ballistic missiles. He notices that most of these weapons are present in the arsenal of major powers under the form of intercontinental missiles, intermediate range weapons or theatre weapons. On the Third World side, proliferation concerns short- and medium-range missiles produced from technology transfers or national programmes. Mobile systems are now present in all conflicts (notably Libya, Syria) and are now based on more advanced technologies for propellers as well as for control and guidance systems. In the last part, the author discusses the perspectives associated with these missiles which are a strong offensive weapon, and are also modernised to carry nuclear warheads or multiple warheads. These evolutions could put the western superiority into question again

  4. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Patrizia Pessina

    2015-06-01

    Full Text Available Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD, skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  5. Caffeine treatment aggravates secondary degeneration after spinal cord injury.

    Science.gov (United States)

    Yang, Cheng-Chang; Jou, I-Ming

    2016-03-01

    Spinal cord injury (SCI) often results in some form of paralysis. Recently, SCI therapy has been focused on preventing secondary injury to reduce both neuroinflammation and lesion size so that functional outcome after an SCI may be improved. Previous studies have shown that adenosine receptors (AR) are a major regulator of inflammation after an SCI. The current study was performed to examine the effect of caffeine, a pan-AR blocker, on spontaneous functional recovery after an SCI. Animals were assigned into 3 groups randomly, including sham, PBS and caffeine groups. The rat SCI was generated by an NYU impactor with a 10 g rod dropped from a 25 mm height at thoracic 9 spinal cord level. Caffeine and PBS were injected daily during the experiment period. Hind limb motor function was evaluated by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale at 1 week and 4 weeks after the SCI. Spinal cord segments were collected after final behavior evaluation for morphological analysis. The tissue sparing was evaluated by luxol fast blue staining. Immunofluorescence stain was employed to assess astrocyte activation and neurofilament positioning, while microglia activation was examined by immunohistochemistry stain.The results showed that spontaneous functional recovery was blocked after the animals were subjected caffeine daily. Moreover, caffeine administration increased the demyelination area, promoted astrocyte and microglia activation and decreased the quantity of neurofilaments. These findings suggest that the neurotoxicity effect of caffeine may be associated with the inhibition of neural repair and the promotion of neuroinflammation. PMID:26746340

  6. [Aggravation of snake bite in France and their treatment].

    Science.gov (United States)

    de Haro, Luc

    2003-07-12

    VIPERS AT THE ORIGIN OF ENVENOMING: Out of the 4 species of vipers found in France, only two can be responsible for severe envenoming: the aspic viper (Vipera aspis) and the addetr (Vipera berus). CLINICAL GRADING: Since 1992, a grading table published by the Institut Pasteur in Paris helps to assess the severity of the clinical and biological picture. A grade 2 (extensive oedema +/- accompanied by moderate general signs) or notably a grade 3 (giant oedema + severe general signs + biological signs) implies the administration of an antivenom. ANTIVENOM VIPERFAV: Available on the market since 2000, is administered in intravenous infusion, the only route effective. Tolerance to the treatment is good and clinical improvement is rapid after administration of 1 to 4 infusions of antivenom. When confronted with life-threatening envenoming, there is no strong argument to justify the non-use of an antivenom. VIPERINE ENVENOMING: Among the grass snakes, the viperine snake of Montpellier is the only species that is actually venomous. The fangs are posterior in the buccal cavity of the snake, which does not usually permit it to inject its venom in humans. In exceptional circumstances (finger placed in the throat), envenoming has been observed with, in this case, essentially neurological clinical signs: involvement of the cranial nerves, drowsiness. There is no specific treatment for these extremely rare accidents. PMID:12947747

  7. Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

    OpenAIRE

    Radonic, T.; Witte, P.; Groenink, M.; de Waard, V.; Lutter, R.; van Eijk, M.; Jansen, J.L.M.; Timmermans, J; Kempers, M.J.; Scholte, A. J. H. A.; Hilhorst-Hofstee, Y; Berg, M. P. Den; van Tintelen, J. P.; Pals, G.; Baars, M.J.

    2012-01-01

    BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS pa...

  8. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    DEFF Research Database (Denmark)

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo;

    2013-01-01

    overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow; group 2 (n=15) standard chow and intraperitoneal paricalcitol at 800ng/kg thrice weekly; and group 3 (n=15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were......INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats...... determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. RESULTS: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4mmHg, 95% CI 9.1-37.7) and tended to...

  9. ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Frohlich, Camilla; Nielsen, Christian Kamp;

    2005-01-01

    ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to...

  10. Roles of Beta2- and Beta3-Adrenoceptor Polymorphisms in Hypertension and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Kazuko Masuo

    2010-01-01

    gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

  11. $\\beta$3p- spectroscopy and P-$\\gamma$ width determination in the decay of $^{31}$Ar

    CERN Multimedia

    We propose to perform a detailed study of the $\\beta$-decay of the dripline nucleus $^{31}$Ar. This will allow a detailed study of the $\\beta$-delayed 3p-decay as well as provide important information on the resonances of $^{30}$S and $^{29}$P, in particular the ratio between the P- and $\\gamma$- partial widths relevant for astrophysics.

  12. The electroconvulsive shock can aggravate the cognitive impairment of the depression model rats though up-regulate the hyperphosphorylation of protein tau%电休克通过上调tau蛋白过度磷酸化程度加重抑郁模型大鼠认知障碍

    Institute of Scientific and Technical Information of China (English)

    陈安; 刘鸿章; 刘超

    2016-01-01

    indicate that the electroconvulsive shock reduce the impairment of learning-memory in depressed rats by aggravating the hyperphosphorylation of tau protein and up-regulating the content of glutamate.%目的 观察不同电量和不同时程电休克(ECT)对嗅球切除抑郁模型大鼠海马ECT后认知能力的变化.方法 建立大鼠嗅球切除抑郁模型,采用随机单位组3×3析因设计:将每只大鼠视为1个单位,对每个单位施加2个处理因素,即电流(25、50、75 mA)和时程(3次、6次、9次ECT)的所有组合(共9组,n=6).电休克结束24 h内行Morris水迷宫、高效液相色谱法测谷氨酸(Glu)在海马组织中含量,Western blot法测磷酸化tau蛋白(p-AT8Ser202)、糖原合成酶激酶-3β(GSK-3β1H8)表达.结果 随ECT电流加大,延长逃避潜伏期并缩短空间探索时间,随ECT时程延长,延长逃避潜伏期缩短空间探索时间,75 mA且行9次ECT组逃避潜伏期最长[(100.51±6.64)s]、空间探索时间最短[(10.02±1.20)s].随ECT电流加大,Glu浓度增加,随ECT时程延长,Glu浓度增加,75 mA且行9次ECT组Glu浓度最高[(184.39±20.86)μmol/gprot].随ECT电流加大,目标蛋白表达增加,随ECT时程延长,目标蛋白表达增加,75 mA且行9次ECT组目标蛋白表达最高(p-AT8Ser202:1771.50 ±278.26;GSK-3β1H8:1747.13±162.23).结论 ECT导致海马Glu浓度升高,加剧海马tau蛋白的磷酸化程度,诱发认知障碍.

  13. Alpha V integrin prolongs collagenase production through Jun activation binding protein 1.

    Science.gov (United States)

    Levinson, Howard; Sil, Alok K; Conwell, John E; Hopper, James E; Ehrlich, H Paul

    2004-08-01

    Robust expression of alphav integrin and matrix metalloproteinase 1 (MMP1) plays an important role in cancer metastasis and wound healing. A patient with an abnormal scar that appeared stretched and thinned out was found to have fibroblasts that overexpressed alphav integrin; therefore, a relationship between alphav integrin expression and MMP1 production was sought. A yeast 2 hybrid screen revealed alphav integrin interacts with jun activation binding domain-1 (JAB1). Mesenchymal-derived cells were transfected with the alphav integrin gene and incorporated into collagen lattices. Transfected cells maximally contracted collagen lattices beginning on day 5, whereas control transfected cells did not contract lattices. Late-phase collagen lattice contraction was inhibited by a pan-MMP inhibitor, BB4. Overexpression of alphav correlated with enhanced MMP1 transcription, as determined by a luciferase assay (P production and that this signaling pathway in fibroblasts may lead to abnormal scarring. PMID:15269586

  14. DMPD: Immunoreceptor-like signaling by beta 2 and beta 3 integrins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available or S, Abram CL, Lowell CA, Mocsai A. Trends Cell Biol. 2007 Oct;17(10):493-501. (.png) (.svg) (.html) (.csml..., Lowell CA, Mocsai A. Publication Trends Cell Biol. 2007 Oct;17(10):493-501. Pathway - PNG File (.png) SVG

  15. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium

    OpenAIRE

    1995-01-01

    To protect the body efficiently from infectious organisms, leukocytes circulate as nonadherent cells in the blood and lymph, and migrate as adherent cells into tissues. Circulating leukocytes in the blood have first to adhere to and then to cross the endothelial lining. CD31/PECAM- 1 is an adhesion molecule expressed by vascular endothelial cells, platelets, monocytes, neutrophils, and naive T lymphocytes. It is a transmembrane glycoprotein of the immunoglobulin gene superfamily (IgSF), with ...

  16. PC02 Beta3-adrenoceptor agonist-induced relaxation of human placental arteries is reduced in pregnancy-induced hypertension

    Institute of Scientific and Technical Information of China (English)

    0BARTHEZ; CROUGET; PGUERARD; MJLEROYZAMIA; MBREUILLER-FOUCHE; EJMORCILLO; TCRPCO; PSAGOT; MDUMAS; MBARDOU

    2004-01-01

    AIM: Preeclampsia is one of the leading causes of neonatal and maternal morbidity and mortality. The purpose of this study is to investigate the functionality of β2- and 133-adrenoreceptors(β-ARs) in human placental arteries and to assess the influence of pregnancy-induced hypertension on β-ARs responsiveness.METHODS: We performed in vitro functional and biochemical studies as well as RT-PCR experiments. RESULTS: SR59119

  17. Aldehyde Selective Wacker Oxidations of Phthalimide Protected Allylic Amines : A New Catalytic Route to beta(3)-Amino Acids

    NARCIS (Netherlands)

    Weiner, Barbara; Baeza Garcia, Alejandro; Jerphagnon, Thomas; Feringa, Ben L.

    2009-01-01

    A new method for the synthesis of B-3-amino acids is presented. Phthalimide protected allylic amines are oxidized under Wacker conditions selectively to aldehydes using PdCl2 and CuCl or Pd(MeCN)(2)Cl(NO2) and CuCl2 as complementary catalyst systems. The aldehydes are produced in excellent yields an

  18. Anti-microRNA-378a Enhances Wound Healing Process by Upregulating Integrin Beta-3 and Vimentin

    OpenAIRE

    Li, Haoran; Chang, Leslie; Du, William W.; Gupta, Shaan; Khorshidi, Azam; Sefton, Michael; Yang, Burton B.

    2014-01-01

    Delayed or impaired wound healing is a major public health issue worldwide, especially in patients with diabetes mellitus and vascular atherosclerosis. MicroRNAs have been identified as key regulators of wound healing. Here, we show that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p function) display enhanced wound healing. Expression of vimentin and β3 integrin, two important modulators of wound healing, is markedly elevated in the transgenic mice. MiR-Pirate378a-transf...

  19. Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide

    Science.gov (United States)

    Dijkgraaf, Ingrid; Terry, Samantha; McBride, William J.; Goldenberg, David M.; Laverman, Peter; Franssen, Gerben M.; Oyen, Wim J. G.; Boerman, Otto C.

    2014-01-01

    Integrin αvβ3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine-glycine-aspartatic acid (RGD) peptide and integrin αvβ3, but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of 18F. In this study, the dimeric RGD peptide, E-[c(RGDfK)]2, was conjugated with NODAGA and radiolabeled with 18F in a simple one-pot process with a radiolabeling yield of 20%; the whole process lasting only 45 min. NODAGA-E-[c(RGDfK)]2 labeled with 18F at a specific activity of 1.8 MBq/nmol and a radiochemical purity of 100% could be achieved. Log P value of 18F-labeled NODAGA-E-[c(RGDfK)]2 was −4.26 ± 0.02. In biodistribution studies, 18F-NODAGA-E-[c(RGDfK)]2 cleared rapidly from the blood with 0.03 ± 0.01 %ID/g in the blood at 2 h p.i., mainly via the kidneys and showed good in vivo stability. Tumor uptake of 18F-NODAGA-E-[c(RGDfK)]2 (3.44 ± 0.20 %ID/g, 2 h p.i.) was significantly lower than that of reference compounds 68Ga-labeled NODAGA-E-[c(RGDfK)]2 (6.26 ± 0.76 %ID/g; P <0.001) and 111In-labeled NODAGA-E-[c(RGDfK)]2 (4.99 ± 0.64 %ID/g; P < 0.01). Co-injection of an excess of unlabeled NODAGA-E-[c(RGDfK)]2 along with 18F-NODAGA-E-[c(RGDfK)]2 resulted in significantly reduced radioactivity concentrations in the tumor (0.85 ± 0.13 %ID/g). The αvβ3 integrin-expressing SK-RC-52 tumor could be successfully visualized by microPET with 18F-labeled NODAGA-E-[c(RGDfK)]2. In conclusion, NODAGA-E-[c(RGDfK)]2 could be labeled rapidly with 18F using a direct aqueous, one-pot method and it accumulated specifically in αvβ3 integrin-expressing SK-RC-52 tumors, allowing for visualization by microPET. PMID:23606427

  20. TRP64ARG polymorphism of the beta 3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle.

    OpenAIRE

    Marti, A; Corbalan, M. (M.S.); Martinez-Gonzalez, M.A. (Miguel Angel); Martinez, J. A.

    2002-01-01

    Aim: We performed a case–control study to assess the association between obesity risk and the Trp64Arg polymorphism of the β3-adrenergic receptor gene. Methods: Obese subjects [n = 159; body mass index (BMI) > 30 kg/m2] and controls (n = 154; BMI < 25 kg/m2) were compared using multivariable logistic regression to control for potential confounders. Results: A higher obesity risk (adjusted OR: 2.98; 95% CI: 1.00–8.56; p = 0.05) was associated with the Trp64Arg polymorphism among sedentar...

  1. Surface structures and osteoblast response of hydrothermally produced CaTiO{sub 3} thin film on Ti-13Nb-13Zr alloy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Woo, E-mail: jinwoo@knu.ac.kr [Department of Periodontology, School of Dentistry, Kyungpook National University, 188-1, Samduk 2Ga, Jung-Gu, Daegu 700-412 (Korea, Republic of); Tustusmi, Yusuke [Department of Metals, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental Univeristy, Tokyo 101-0062 (Japan); Lee, Chong Soo; Park, Chan Hee [Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Kim, Youn-Jeong; Jang, Je-Hee [Department of Periodontology, School of Dentistry, Kyungpook National University, 188-1, Samduk 2Ga, Jung-Gu, Daegu 700-412 (Korea, Republic of); Khang, Dongwoo; Im, Yeon-Min [School of Materials Science and Engineering, Gyeongsang National University, Jinju 600-701 (Korea, Republic of); Doi, Hisashi; Nomura, Naoyuki; Hanawa, Takao [Department of Metals, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental Univeristy, Tokyo 101-0062 (Japan)

    2011-06-15

    This study investigated the surface characteristics and in vitro biocompatibility of a titanium (Ti) oxide layer incorporating calcium ions (Ca) obtained by hydrothermal treatment with or without post heat-treatment in the Ti-13Nb-13Zr alloy. The surface characteristics were evaluated by scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, atomic force microscopy and contact angle measurements. In vitro biocompatibility of the Ca-containing surfaces was assessed in comparison with untreated surfaces using a pre-osteoblast cell line. Hydrothermal treatment produced a crystalline CaTiO{sub 3} layer. Post heat-treatment at 400 deg. C for 2 h in air significantly decreased water contact angles in the CaTiO{sub 3} layer (p < 0.001). The Ca-incorporated alloy surfaces displayed markedly increased cell viability and ALP activity compared with untreated surfaces (p < 0.001), and also an upregulated expression of various integrin genes ({alpha}1, {alpha}2, {alpha}5, {alpha}v, {beta}1 and {beta}3) at an early incubation time-point. Post heat-treatment further increased attachment and ALP activity in cells grown on Ca-incorporated Ti-13Nb-13Zr alloy surfaces. The results indicate that the Ca-incorporated oxide layer produced by hydrothermal treatment and a simple post heat-treatment may be effective in improving bone healing in Ti-13Nb-13Zr alloy implants by enhancing the viability and differentiation of osteoblastic cells.

  2. The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis.

    Science.gov (United States)

    Shih, Shou-Ching; Zukauskas, Andrew; Li, Dan; Liu, Guanmei; Ang, Lay-Hong; Nagy, Janice A; Brown, Lawrence F; Dvorak, Harold F

    2009-04-15

    Transmembrane-4-L-six-family-1 (TM4SF1) was originally described as a cancer cell protein. Here, we show that it is highly expressed in the vascular endothelium of human cancers and in a banded pattern in the filopodia of cultured endothelial cells (EC). TM4SF1 knockdown prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and rendered EC senescent. Integrin-alpha5 and integrin-beta1 subunits gave a similar staining pattern and interacted constitutively with TM4SF1, whereas integrin subunits often associated with angiogenesis (alphaV, beta3, beta5) interacted with TM4SF1 only after vascular endothelial growth factor (VEGF)-A or thrombin stimulation. TM4SF1 knockdown substantially inhibited maturation of VEGF-A(164)-induced angiogenesis. Thus, TM4SF1 is a key regulator of EC function in vitro and of pathologic angiogenesis in vivo and is potentially an attractive target for antiangiogenesis therapy. PMID:19351819

  3. MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions.

    Science.gov (United States)

    Bazaa, Amine; Pasquier, Eddy; Defilles, Céline; Limam, Ines; Kessentini-Zouari, Raoudha; Kallech-Ziri, Olfa; El Battari, Assou; Braguer, Diane; El Ayeb, Mohamed; Marrakchi, Naziha; Luis, José

    2010-01-01

    Integrins are essential protagonists of the complex multi-step process of angiogenesis that has now become a major target for the development of anticancer therapies. We recently reported and characterized that MVL-PLA2, a novel phospholipase A2 from Macrovipera lebetina venom, exhibited anti-integrin activity. In this study, we show that MVL-PLA2 also displays potent anti-angiogenic properties. This phospholipase A2 inhibited adhesion and migration of human microvascular-endothelial cells (HMEC-1) in a dose-dependent manner without being cytotoxic. Using Matrigel and chick chorioallantoic membrane assays, we demonstrated that MVL-PLA2, as well as its catalytically inactivated form, significantly inhibited angiogenesis both in vitro and in vivo. We have also found that the actin cytoskeleton and the distribution of alphav beta3 integrin, a critical regulator of angiogenesis and a major component of focal adhesions, were disturbed after MVL-PLA2 treatment. In order to further investigate the mechanism of action of this protein on endothelial cells, we analyzed the dynamic instability behavior of microtubules in living endothelial cells. Interestingly, we showed that MVL-PLA2 significantly increased microtubule dynamicity in HMEC-1 cells by 40%. We propose that the enhancement of microtubule dynamics may explain the alterations in the formation of focal adhesions, leading to inhibition of cell adhesion and migration. PMID:20405031

  4. Crystal structure of schistatin, a disintegrin homodimer from saw-scaled viper (Echis carinatus) at 2.5 A resolution.

    Science.gov (United States)

    Bilgrami, Sameeta; Tomar, Shailly; Yadav, Savita; Kaur, Punit; Kumar, Janesh; Jabeen, Talat; Sharma, Sujata; Singh, Tej P

    2004-08-13

    This is the first structure of a biological homodimer of disintegrin. Disintegrins are a class of small (4-14 kDa) proteins that bind to transmembrane integrins selectively. The present molecule is the first homodimer that has been isolated from the venom of Echis carinatus. The monomeric chain contains 64 amino acid residues. The three-dimensional structure of schistatin has been determined by the multiple isomorphous replacement method. It has been refined to an R-factor of 0.190 using all the data to 2.5 A resolution. The two subunits of the disintegrin homodimer are related by a 2-fold crystallographic symmetry. Thus, the crystallographic asymmetric unit contains a monomer of disintegrin. The monomer folds into an up-down topology with three sets of antiparallel beta-strands. The structure is well ordered with four intramolecular disulfide bonds. the two monomers are firmly linked to each other through two intermolecular disulfide bridges at their N termini together with several other interactions. This structure has corrected the error in the disulfide bond pattern of the two intermolecular disulfide bridges that was reported earlier using chemical methods. Unique sequence and structural features of the schistatin monomers suggest that they have the ability to bind well with both alphaIIb beta3 and alphav beta3 integrins. The N termini anchored two chains of the dimer diverge away at their C termini exposing the Arg-Gly-Asp motif into opposite directions thus enhancing their binding efficiency to integrins. This is one of the unique features of the present disintegrin homodimer and seems to be responsible for the clustering of integrin molecules. The homodimer binds to integrins apparently with a higher affinity than the monomers and also plays a role in the signaling pathway. PMID:15317139

  5. No aggravation of the course of experimental glomerulonephritis in spontaneously hypertensive rats.

    OpenAIRE

    Stein, H. D.; Sterzel, R. B.; Hunt, J D; Pabst, R; Kashgarian, M.

    1986-01-01

    Functional and morphologic glomerular alterations induced by antiglomerular basement membrane (anti-GBM) nephritis were investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto controls (WKY) for assessment of the role of systemic hypertension in immunologically mediated renal injury. Over a 6-week period serial measurements of systolic blood pressure (BP), serum creatinine (SCreat), creatinine clearance (CCreat), and urinary albumin excretion (UAlbV) were obtained ...

  6. Shift work aggravates metabolic syndrome development among early-middle-aged males with elevated ALT

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Tun-Jen Hsiao; Pau-Chung Chen

    2009-01-01

    AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle- aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfilling MetS criteria at screening were enrolled. Age, MetScomponents,liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to daynight rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components at follow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a significant risk for MetS development (odds ratio, 2.7; 95% confidence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middleaged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.

  7. Storm surges-An option for Hamburg, Germany, to mitigate expected future aggravation of risk

    International Nuclear Information System (INIS)

    Summary: Rising sea level together with regionally increased storm activity, caused by elevated and increasing levels of greenhouse gases in the atmosphere will in many parts of the world increase the risk of storm surges significantly. Reducing the emissions of greenhouse gases into the atmosphere may mitigate the increasing risks somewhat, but the major task for regional and local stakeholders will be to prepare for appropriate adaptation. In most cases, possible strategies include intensification of coastal defense measures, in particular strengthening dykes, and adaptation to intermittent flooding. In case of Hamburg and the tidal Elbe river a third option seems to be available, which aims at mitigating storm surge risks by applying estuary engineering constructions. This option is sketched in this paper. The option has the potential to significantly reduce the expected future increases of local surge heights

  8. Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats.

    Science.gov (United States)

    Incerpi, Erika K; Oliveira, Luiz M; Pereira, Elisângela M; Soncini, Roseli

    2015-06-01

    The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty-five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2 O2 ) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC. PMID:25664386

  9. If high folic acid aggravates vitamin B12 deficiency what should be done about it?

    Science.gov (United States)

    Johnson, Mary Ann

    2007-10-01

    The most common cause of vitamin B12 deficiency in older people is malabsorption of food-bound vitamin B12. Thus, it is suggested that the recommended daily allowance of 2.4 microg/d be met primarily with crystalline vitamin B12, which is believed to be well absorbed in individuals who have food-bound malabsorption. There is concern that high intakes of folic acid from fortified food and dietary supplements might mask the macrocytic anemia of vitamin B12 deficiency, thereby eliminating an important diagnostic sign. One recent study indicates that high serum folate levels during vitamin B12 deficiency exacerbate (rather than mask) anemia and worsen cognitive symptoms. Another study suggests that once vitamin B12 deficiency is established in subjects with food-bound malabsorption, 40 microg/d to 80 microg/d of oral crystalline vitamin B12 for 30 d does not reverse the biochemical signs of deficiency. Together, these studies provide further evidence that public health strategies are needed to improve vitamin B12 status in order to decrease the risk of deficiency and any potentially adverse interactions with folic acid. PMID:17972439

  10. Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension

    OpenAIRE

    Wang, Youping; Wang, Donna H.

    2009-01-01

    To test the hypothesis that deletion of the transient receptor potential vanilloid type 1 (TRPV1) channel exaggerates hypertension-induced renal inflammatory response, wild-type (WT) or TRPV1-null mutant (TRPV1−/−) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 wk. Mean arterial pressure (MAP) determined by radiotelemetry increased in DOCA-salt-treated WT or TRPV1−/− mice, whereas there was no difference in MAP between two strains at the base...

  11. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease.

    Directory of Open Access Journals (Sweden)

    Elena Nobili

    Full Text Available BACKGROUND: Cysteinyl-leukotrienes (cys-LT are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe(-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2 in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from Apoe(-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C(4 synthase (LTC(4S and CysLT1 expression in the myocardium of Apoe(-/- mice. Acute bouts of hypoxia further induced LTC(4S expression, increased LTC(4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe(-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC(4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

  12. Multiple Discriminations – between a Contravention Per Se and an Aggravating Circumstances

    Directory of Open Access Journals (Sweden)

    Cristian Jura

    2011-05-01

    Full Text Available There are some references on multiple discrimination like in the Recital 14 of the Racial Equality Directive, 2000/43/EC: „In implementing the principle of equal treatment irrespective of racial or ethnic origin, the Community should, in accordance with Article 3(2 of the EC Treaty, aim to eliminate inequalities, and to promote equality between men and women, especially since women are often the victims of multiple discrimination”. Even in this case there is no legal definition of multiple discriminations.In 2008, so after 8 years, in the Explanatory Memorandum of the Proposal for a Council Directive on implementing the principle of equal treatment between persons irrespective of religion or belief, disability, age or sexual orientation there is a reference regarding multiple discrimination in the sense that „Attention was also drawn to the need to tackle multiple discrimination, for example by defining it as discrimination and by providing effective remedies. These issues go beyond the scope of this Directive but nothing prevents Member States taking action in these areas.”

  13. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    International Nuclear Information System (INIS)

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function

  14. Maturity aggravates sepsis-associated skeletal muscle catabolism in growing pigs

    Science.gov (United States)

    Synthesis and accretion of muscle protein is elevated in neonates and decreases with development. During sepsis, muscle protein synthesis is reduced, but the effect of development on the metabolic response to sepsis in skeletal muscle is not well understood. Fasted 7- and 26-d-old pigs were infused ...

  15. Imperfect vaccine aggravates the long-standing dilemma of voluntary vaccination.

    Directory of Open Access Journals (Sweden)

    Bin Wu

    Full Text Available Achieving widespread population immunity by voluntary vaccination poses a major challenge for public health administration and practice. The situation is complicated even more by imperfect vaccines. How the vaccine efficacy affects individuals' vaccination behavior has yet to be fully answered. To address this issue, we combine a simple yet effective game theoretic model of vaccination behavior with an epidemiological process. Our analysis shows that, in a population of self-interested individuals, there exists an overshooting of vaccine uptake levels as the effectiveness of vaccination increases. Moreover, when the basic reproductive number, R0, exceeds a certain threshold, all individuals opt for vaccination for an intermediate region of vaccine efficacy. We further show that increasing effectiveness of vaccination always increases the number of effectively vaccinated individuals and therefore attenuates the epidemic strain. The results suggest that 'number is traded for efficiency': although increases in vaccination effectiveness lead to uptake drops due to free-riding effects, the impact of the epidemic can be better mitigated.

  16. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard; Castiglioni, Laura; Kastrup, Jens; Wetterholm, Anders; Tremoli, Elena; Hansson, Göran K; Sironi, Luigi; Haeggström, Jesper Z; Gabrielsen, Anders

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and...

  17. 75 FR 43840 - Inflation Adjustment of the Ordinary Maximum and Aggravated Maximum Civil Monetary Penalties for...

    Science.gov (United States)

    2010-07-27

    ... civil monetary penalties per the Inflation Act. See 74 FR 68701 (December 29, 2009). FRA's maximum and... materials violation was $275. 69 FR 30590, May 28, 2004. To implement these SAFETEA-LU amendments to the maximum and minimum penalties, FRA issued a final rule that was published on December 26, 2006, 71...

  18. Is Behavioral Regulation in Children With ADHD Aggravated by Comorbid Anxiety Disorder?

    DEFF Research Database (Denmark)

    Sørensen, Lin; Plessen, Kerstin J; Nicholas, Jude;

    2010-01-01

    Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were...... scale than children within the other three groups. Main effects of diagnosis appeared in ADHD children on the Inhibit, Emotional Control, and Working Memory scales, and on the Shift and Emotional Control scales in anxious children. Conclusion: The results indicate that a behavioral dysregulation in ADHD...... compared to BRIEF reports in a group of children with a "pure" ADHD (n = 23), a "pure" anxiety (n = 24) and a group without any diagnosis (n = 104) in a 2 (ADHD vs. no ADHD) x 2 (anxiety vs. no anxiety) design. Results: The children with ADHD and anxiety disorder scored significantly higher on the Inhibit...

  19. Is Behavioral Regulation in Children with ADHD Aggravated by Comorbid Anxiety Disorder?

    Science.gov (United States)

    Sorensen, Lin; Plessen, Kerstin J.; Nicholas, Jude; Lundervold, Astri J.

    2011-01-01

    Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were compared to BRIEF reports in a group of children…

  20. Centrally administered ouabain aggravates rapid-eye-movement-sleep-related bradyarrhythmias in freely moving rats.

    OpenAIRE

    Sato, T.; Seto, K.

    1993-01-01

    1. The effects of continuous infusions of ouabain on bradyarrhythmias (cardiac pauses for 0.5 s or longer) during sleep were examined in freely moving Wistar-Kyoto rats. 2. In a control group (n = 7), saline was infused into both the lateral ventricle and the femoral vein. In an intracerebroventricular (i.c.v.) ouabain group (n = 7), ouabain was infused centrally, such that each rat received three stepped doses of 1, 10, and 100 ng kg-1 h-1 for 3 days at each dose, while saline was infused sy...

  1. EVE-TEASING AND ITS AGGRAVATED FORM, SEXUAL HARRASMENT OF WORKING WOMEN IN INDIA

    OpenAIRE

    OMDUTT

    2013-01-01

    Sexual harassment and eve-teasing are treated as low priority offences. The term eve-teasing is itself revealing in its indulgent overtones. It seeks to trivialise a very serious issue. We find women being insulted almost everyday, everywhere and every time. It is almost a torture for a woman to walk along on the road. Section 354 IPC deals with acts that outrage the modesty of a woman and punishes perpetration of this crime with fine and imprisonment but even small girls of tends age are vic...

  2. Acetylcholinesterase (AChE inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    Directory of Open Access Journals (Sweden)

    Shin-Ichi Yokota

    2014-01-01

    Full Text Available Although fasting induces hepatic triglyceride (TG accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1 and liver-fatty acid binding-protein (L-FABP. Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

  3. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver.

    Science.gov (United States)

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  4. [Use of topical non-steroidal anti-inflammatory drugs in aggravated and decompensated arthroses].

    Science.gov (United States)

    Chlud, K

    1999-01-01

    Pain in osteoarthritis of the big weight bearing joints is either derived from periarticular ligaments, tendons, fascias, muscles, bursae--periarthropathy as sign of decompensation or from the reactive synovitis with or without effusion. NSAIDs (ibuprofen, diclofenac, indometacin, some salicylates, etofenamate and piroxicam) have demonstrated relevant advantages of the percutaneous route over the systemic one in soft tissue rheumatism. NSAIDs, mentioned above, locally administered as cream, gel or spray, quickly penetrate through the corneal layer of the skin and the site of application, reach highly effective concentrations in subcutis, fascias, tendons, ligaments and muscles, less in joint-capsule and -fluid indicating direct penetration. The blood levels of topical NSAIDs are extremely low with no systemic side effects, especially no gastric toxicity; however, local skin irritation is observed (1 to 2%). In contrast to this, systemic (oral) NSAIDs lead primarily via high blood levels to a lower concentration--only one tenth--in periarticular soft tissues with a high incidence of side effects. In conclusion the percutaneous application of certain NSAIDs has become a well established therapeutic regimen in painful osteoarthritis and in all other inflammatory degenerative and posttraumatic alterations of soft tissue structure. PMID:10637963

  5. TNF-Like Weak Inducer of Apoptosis Aggravates Left Ventricular Dysfunction after Myocardial Infarction in Mice

    Directory of Open Access Journals (Sweden)

    Kai-Uwe Jarr

    2014-01-01

    Full Text Available Background. TNF-like weak inducer of apoptosis (TWEAK has recently been shown to be potentially involved in adverse cardiac remodeling. However, neither the exact role of TWEAK itself nor of its receptor Fn14 in this setting is known. Aim of the Study. To analyze the effects of sTWEAK on myocardial function and gene expression in response to experimental myocardial infarction in mice. Results. TWEAK directly suppressed the expression of PGC-1α and genes of oxidative phosphorylation (OXPHOS in cardiomyocytes. Systemic sTWEAK application after MI resulted in reduced left ventricular function and increased mortality without changes in interstitial fibrosis or infarct size. Molecular analysis revealed decreased phosphorylation of PI3K/Akt and ERK1/2 pathways associated with reduced expression of PGC-1α and PPARα. Likewise, expression of OXPHOS genes such as atp5O, cycs, cox5b, and ndufb5 was also reduced. Fn14 -/- mice showed significantly improved left ventricular function and PGC-1α levels after MI compared to their respective WT littermates (Fn14 +/+. Finally, inhibition of intrinsic TWEAK with anti-TWEAK antibodies resulted in improved left ventricular function and survival. Conclusions. TWEAK exerted maladaptive effects in mice after myocardial infarction most likely via direct effects on cardiomyocytes. Analysis of the potential mechanisms revealed that TWEAK reduced metabolic adaptations to increased cardiac workload by inhibition of PGC-1α.

  6. Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

    NARCIS (Netherlands)

    Smeding, Lonneke; Kuiper, Jan Willem; Plotz, Frans B.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan

    2013-01-01

    Background: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo

  7. Chronic unpredictable mild stress combined with a high-fat diets aggravates atherosclerosis in rats

    OpenAIRE

    Wang, Shuling; Xiaoling, Gao; Pingting, Li; Shuqiang, Liu; Yuaner, Zeng

    2014-01-01

    Background Depression and high-fat diet are both known as independent risk factors for atherosclerosis and other cardiovascular diseases, suggesting the interaction of psychological and physiological factors in the development of these diseases. The liver is a crucial organ that facilitate lipid metabolism especially in reverse cholesterol transport (RCT), while according to the theory of Traditional Chinese Medicine, depression as a kind of psychological stress has an influence on hepatic fu...

  8. Deficiency of Glycine N-Methyltransferase Aggravates Atherosclerosis in Apolipoprotein E–Null Mice

    OpenAIRE

    Chen, Chien-Yu; Ching, Li-Chieh; Liao, Yi-Jen; Yu, Yuan-Bin; Tsou, Chia-Yuan; Shyue, Song-Kun; Chen, Yi-Ming Arthur; Lee, Tzong-Shyuan

    2012-01-01

    The mechanism underlying the dysregulation of cholesterol metabolism and inflammation in atherogenesis is not understood fully. Glycine N-methyltransferase (GNMT) has been implicated in hepatic lipid metabolism and the pathogenesis of liver diseases. However, little is known about the significance of GNMT in atherosclerosis. We showed the predominant expression of GNMT in foamy macrophages of mouse atherosclerotic aortas. Genetic deletion of GNMT exacerbated the hyperlipidemia, inflammation a...

  9. Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings

    DEFF Research Database (Denmark)

    Brushoj, C.; Holmich, P.; Nielsen, M.B.;

    2008-01-01

    %)), but other synovial covered structures including the fat pad of Hoffa (12 patients (40%)), the medial plica and the joint line (12 patients (40%)) were also involved. Only eight patients (27%) experienced pain on the patellofemoral compression test. Only discrete changes was detected on MRI...

  10. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling

    DEFF Research Database (Denmark)

    Caesar, Robert; Tremaroli, Valentina; Kovatcheva-Datchary, Petia;

    2015-01-01

    Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased......-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation...... in lard-fed mice. These results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids....

  11. Capital Sentencing: The Effect of Adding Aggravators to Death Penalty Statutes in Pennsylvania

    OpenAIRE

    Sandra Schultz Newman; Eric Rayz; Scott Eric Friedman

    2004-01-01

    The birthplace of the American republic—the Commonwealth of Pennsylvania—has historically been at the forefront of the capital punishment legislation in the United States. It was the first colony in the Union to abolish the death penalty for all crimes with the exception of murder. It was the first to set forth a statutory distinction between different degrees of criminal homicide, confining imposition of capital punishment to the most chilling form of this crime—“will...

  12. Capital Sentencing: The Effect of Adding Aggravators to Death Penalty Statutes in Pennsylvania

    Directory of Open Access Journals (Sweden)

    Sandra Schultz Newman

    2004-04-01

    Full Text Available The birthplace of the American republic—the Commonwealth of Pennsylvania—has historically been at the forefront of the capital punishment legislation in the United States. It was the first colony in the Union to abolish the death penalty for all crimes with the exception of murder. It was the first to set forth a statutory distinction between different degrees of criminal homicide, confining imposition of capital punishment to the most chilling form of this crime—“willful, deliberate, and premeditated killing.” With this storied history in mind, we have undertaken the task of examining the current state of the death penalty in the Commonwealth. Hence, in Part II of this Article, we set forth a detailed history of the capital sentencing scheme in Pennsylvania. Part III undertakes a statistical study of the imposition of the death penalty in the Commonwealth from 1978 until 1997. In Part IV, we conclude by summing up our general observations.

  13. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.

    Science.gov (United States)

    Suchomelova, L; Lopez-Meraz, M L; Niquet, J; Kubova, H; Wasterlain, C G

    2015-10-01

    This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. PMID:26259902

  14. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    OpenAIRE

    Singh, Baljit

    2011-01-01

    Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-a...

  15. EVE-TEASING AND ITS AGGRAVATED FORM, SEXUAL HARRASMENT OF WORKING WOMEN IN INDIA

    Directory of Open Access Journals (Sweden)

    OMDUTT

    2013-05-01

    Full Text Available Sexual harassment and eve-teasing are treated as low priority offences. The term eve-teasing is itself revealing in its indulgent overtones. It seeks to trivialise a very serious issue. We find women being insulted almost everyday, everywhere and every time. It is almost a torture for a woman to walk along on the road. Section 354 IPC deals with acts that outrage the modesty of a woman and punishes perpetration of this crime with fine and imprisonment but even small girls of tends age are victims of this crime. Recently such a crime was committed on a baby girl barely seven and half months old.Eve-teasing is no longer confined to innocent remarks; sexual harassment of girls at work place is also increasing, Authorities are concerned about the rising incidents of these crime and have tightened the dragnet to catch the culprits. Most of the times as eve-teaser indulges in an obscene behavior when he is in the company of his fellow friends. There presence facilitates his action and give him a sense of security, anonymity and less chance of his being caught. Inspite of these the crime (women cell and different women's organisations are doing well.

  16. Comparison of the Punitive Damage with Compensatory, Symbolic, Indirect and Aggravated Damages

    Directory of Open Access Journals (Sweden)

    Ebrahim Taghizadeh

    2012-04-01

    Full Text Available The punitive damage is a kind of damage that should be compensated by the defendant for his/her conduct in applying damage tinted with insolence and malice to the plaintiff. The origin of this law institution was in Common Law especially in England which has been developed in other countries quickly. Some conditions should be provided for demanding the punitive damage. The conduct specified in the verdict of punitive damage is the behavior tinted with insolence committed by the defendant; on the other hand, occurrence of loss is one of the conditions required for demanding the compensation of punitive damage; while in other kinds of damages, the required conditions for claiming the indemnity are different.

  17. Comparison of the Punitive Damage with Compensatory, Symbolic, Indirect and Aggravated Damages

    OpenAIRE

    Ebrahim Taghizadeh

    2012-01-01

    The punitive damage is a kind of damage that should be compensated by the defendant for his/her conduct in applying damage tinted with insolence and malice to the plaintiff. The origin of this law institution was in Common Law especially in England which has been developed in other countries quickly. Some conditions should be provided for demanding the punitive damage. The conduct specified in the verdict of punitive damage is the behavior tinted with insolence committed by the defendant; on ...

  18. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy.

    Science.gov (United States)

    Hathaway, Catherine K; Chang, Albert S; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J; Bagnell, C Robert; Jennette, J Charles; Smithies, Oliver; Kakoki, Masao

    2016-02-23

    Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease. PMID:26858454

  19. Lower Limb Arteriovenous Communications in Diabetes Mellitus: A Potential Reason for Aggravation of Ischemic Symptoms

    International Nuclear Information System (INIS)

    The aim of this study was to assess the prevalence and to evaluate the clinical associations of arteriovenous communications in patients with diabetes mellitus (DM) and lower limb peripheral arterial ischemia. Peripheral arteriography of DM patients from an eight-year period (1993-2000) was evaluated retrospectively by two observers. The presence of arteriovenous communications, defined as occurring without evidence of a preceding precipitating event, and the distribution and severity of the vascular disease were evaluated. The type (non-insulin-dependent DM or insulin-dependent DM) and the duration of the DM, the presenting symptoms, and the presence of a peripheral neuropathy were documented by a review of the clinical records. A total of 348 arteriography studies in 285 DM patients were evaluated (duration of DM: median, 16 years; range, 7-42 years); an arteriovenous communication was present in 14/285 patients (4.9%), 9 male and 5 female (median age, 71 years; range, 17-84 years). Symptoms were those of a peripheral leg ulcer (n = 11), claudication (n = 3), and gangrene (n = 1), with symptoms ipsilateral to the side of the arteriovenous communication in 13/14 patients. The sites of the arteriovenous communications were infra popliteal (n = 7), popliteal (n = 3), superficial femoral artery (n = 3), and common femoral artery (n = 1). Features of a peripheral neuropathy were found in 12/14 and ipsilateral to the side of the communication in 11/12. Arteriovenous communications in the peripheral femoral arterial system of patients with DM is an uncommon finding. Although not proven in the current study, arteriovenous communications might be associated with more severe symptoms than that attributable to the underlying vascular disease alone

  20. Transgenic Overexpression of ADAM12 Suppresses Muscle Regeneration and Aggravates Dystrophy in Aged mdx Mice

    OpenAIRE

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M.; Schrøder, Henrik Daa

    2007-01-01

    Muscular dystrophies are characterized by insufficient restoration and gradual replacement of the skeletal muscle by fat and connective tissue. ADAM12 has previously been shown to alleviate the pathology of young dystrophin-deficient mdx mice, a model for Duchenne muscular dystrophy. The observed effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, α7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also imp...

  1. Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M;

    2007-01-01

    ADAM12 could be a candidate for nonreplacement gene therapy of Duchenne muscular dystrophy. We therefore evaluated the long-term effect of ADAM12 overexpression in muscle. Surprisingly, we observed loss of skeletal muscle and accelerated fibrosis and adipogenesis in 1-year-old mdx mice transgenically......Muscular dystrophies are characterized by insufficient restoration and gradual replacement of the skeletal muscle by fat and connective tissue. ADAM12 has previously been shown to alleviate the pathology of young dystrophin-deficient mdx mice, a model for Duchenne muscular dystrophy. The observed...... regeneration as a possible factor in development of muscular dystrophy....

  2. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Floot, Ben [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Russell, Nicola S. [Division of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Coppes, Rob P. [Departments of Radiation Oncology and Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Stewart, Fiona A. [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands)

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  3. MicroRNA-24 inhibits serotonin reuptake transporter expression and aggravates irritable bowel syndrome.

    Science.gov (United States)

    Liao, Xiu-Jun; Mao, Wei-Ming; Wang, Qin; Yang, Guan-Gen; Wu, Wen-Jing; Shao, Shu-Xian

    2016-01-01

    Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder. MicroRNAs (miRNAs) have been widely demonstrated to take part in various physiological and pathological processes. In the present study, the role of miR-24 in the pathogenesis of IBS and the potential mechanism in this process were evaluated. Human intestinal mucosa epithelial cells of colon from IBS patients and healthy subjects were collected. An IBS mouse model was established with the induction of trinitro-benzene-sulfonic acid (TNBS). The expression levels of miR-24 and serotonin reuptake transporter (SERT) were analyzed using Real-time PCR and western blot in both human specimen and mice. miR-24 was upregulated in IBS patients and mice intestinal mucosa epithelial cells. Luciferase reporter assay showed that SERT was a potential target gene of miR-24. The treatment of miR-24 inhibitor increased pain threshold and nociceptive threshold levels and reduced MPO activity in proximal colon of IBS mice, and up-regulated the mRNA and protein expression levels of SERT in intestinal mucosa epithelial cells. miR-24 played a role in the pathogenesis of IBS probably through regulating SERT expression. PMID:26631964

  4. The Blunt-Edged Sword: Genetic Explanations of Misbehavior Neither Mitigate Nor Aggravate Punishment

    Science.gov (United States)

    Scurich, Nicholas; Appelbaum, Paul

    2015-01-01

    Links between genetic variants and negatively valenced behaviors have stimulated intense commentary about the implications for responsibility and punishment. Previous research has suggested that behavioral genetic evidence of a predisposition to negative behaviors has modest to no impact on mitigation of punishment, at least for serious crimes. Data are presented on the effect of such evidence in a representative sample of the general population (n=640) asked to consider 3 vignettes describing lesser offenses, dealt with in less-formal adjudicatory settings and in everyday life. Genetic explanations of behavior had no effect on the severity of the punishment selected in any case, in contrast to the egregiousness of the behavior and respondents’ beliefs in free-will. Public views of genetic influences on behavior may be less deterministic and more nuanced than is often thought, or genetic explanations may simply not have the salience for decision makers that is frequently attributed to them. PMID:27239327

  5. Creating Crisis: How California's Teaching Policies Aggravate Racial Inequalities in Public Schools.

    Science.gov (United States)

    Keleher, Terry; Piana, Libero Della; Fata, Manijeh Gonzalez

    This report outlines problems in California's public school teaching force, from training to recruitment to retention. It describes who currently teaches, notes the lack of minority teachers in an increasingly diverse student population, and examines pathways to teaching and barriers to certification. It details the teaching crisis in the state's…

  6. DEVELOPMENT OF CORPORATE SOCIAL RESPONSIBILITY UNDER AGGRAVATION OF THE CONTEMPORARY GLOBAL ISSUES

    Directory of Open Access Journals (Sweden)

    N. Grazhevska

    2015-10-01

    Full Text Available The article deals with the role and importance of corporate social responsibility as an important mechanism for overcoming the crisis of the welfare state and to mitigate the social problems caused by the world globalization processes. The experience of post-socialist countries, the Baltic States and Ukraine in this field is analyzed and barriers to effective implementation of CSR in the national economy are identified. The priority of the state policy to promote socially responsible business behavior in Ukraine is proved.

  7. Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.

    Science.gov (United States)

    Baru, Abdul Mannan; Hartl, Andrea; Lahl, Katharina; Krishnaswamy, Jayendra Kumar; Fehrenbach, Heinz; Yildirim, Ali O; Garn, Holger; Renz, Harald; Behrens, Georg M N; Sparwasser, Tim

    2010-08-01

    Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance. PMID:20544727

  8. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    Science.gov (United States)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  9. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten;

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged with...... dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...... and at termination, also in lipoproteins. Aortic atherosclerosis was evaluated as cholesterol content and area covered by plaque. Plasma cholesterol was not significantly different between the groups at termination (35.7 mmol/L vs. 35.5 mmol/L). A significant increase in LDL was seen (13.1 mmol/L vs...

  10. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    OpenAIRE

    Hsu, Ya-Ling; Hsieh, Chia-Jung; Tsai, Eing-Mei; HUNG, JEN-YU; CHANG, WEI-AN; Hou, Ming-Feng; Kuo, Po-Lin

    2015-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didym...

  11. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten; Lütjohann, Dieter; Mortensen, Alicja

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged with...... dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...

  12. Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

    Science.gov (United States)

    Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

    2016-08-01

    Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity. PMID:27166294

  13. Aggravation of serum Hepatocyte Growth Factor levels during hepato carcinogenesis in Rats

    International Nuclear Information System (INIS)

    Hepatocyte growth factor (HGF) has an essential role during liver development and it plays an important role in the regeneration and repair of injured tissues and acting as a mitogen, motogen and morphogens for a variety of epithelial cells. The role of HGF in carcinogenesis is in straggle and so, the present study aimed to through light through the level of HGF during different steps of carcinogenesis. Forty male rats were given diethylnitrosamine (DEN) in drinking water (100 mg/l) for up to 16 weeks. Eight rats were sacrificed at 8, 12 and 16 weeks. Besides, 8 hepatoma bearing rats were exposed to a single dose gamma irradiation (3 Gy) were sacrificed after 2 weeks from exposure (2 rats died, 36 hrs post irradiation) and 8 hepatoma bearing rats were sacrificed after 4 weeks from receiving a combined antioxidant (N-acetylcysteine and Lmethionine). Serum HGF was assayed by enzyme linked immunosorbent assay (ELISA). Serum HGF level in DEN treated rats and in exposed hepatoma bearing rats was significantly higher than in control rats whereas, serum HGF level after treatment with N acetylcysteine and L-methionine for 4 weeks was significantly decreased than DEN treated rats and concluded that serum HGF may play a role during promotion and progression of hepatocellular carcinoma (HCC) and during treatment

  14. Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette;

    2004-01-01

    -gun immunization of BALB/c mice with this construct induced an antigen-specific CD8+ T-cell memory. After intranasal RSV challenge, accelerated CD8+ T-cell responses were observed in pulmonary lymph nodes and virus clearance from the lungs was enhanced. The construct induced weaker CD8+ T-cell responses than those...... elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the beta2m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion......8+ T-cell responses were not induced. Thus, in addition to specific CD8+ T cell-mediated immunopathology, gene-gun DNA vaccination causes non-specific enhancement of RSV disease without affecting virus clearance....

  15. ADMINISTRATIVE-POLITICAL GOVERNANCE IN RUSSIA IN CONDITIONS OF SOCIAL TENSION AGGRAVATION: BACKGROUND OF CONFLICT STATE

    Directory of Open Access Journals (Sweden)

    N. N. Yurchenko

    2015-01-01

    Full Text Available The article is devoted to problems of administrative and political governance in Russia in the context of social unrest. The analysis of the situation prevailing in contemporary Russian society and the factors contributing to increased social tensions. It is noted that in the current environment, the organization of the system of administrative and political governance is a key factor in the reduction of tension in the social ecology. In the process of administrative and political management of social conflict is important to consider the stage of its formation and development. The parameters of variability, the variability of political behavior in complex space is a multi-ethnic society are fixed on the basis of monitoring ethno-social interactions, as well as methods of event analysis and cognitive mapping. For sustainable development of the Russian state, there is a need for timely anticipation and prevention of dangerous trends in the growth of social tension that, in turn, indicates the need for continuous improvement of all activities of public authorities, including supervision and management. These circumstances require leadership fundamentally new approaches to the administrative and political management, based on advanced, forward-looking information, allowing you to move from reactive management to proactive government and regional regulation, in a timely manner recognizing potential threats.

  16. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    DEFF Research Database (Denmark)

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L;

    2014-01-01

    pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti...

  17. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    OpenAIRE

    Shin-Ichi Yokota; Kaai Nakamura; Midori Ando; Hiroyasu Kamei; Fumihiko Hakuno; Shin-Ichiro Takahashi; Shigenobu Shibata

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepa...

  18. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats

    Czech Academy of Sciences Publication Activity Database

    Suchomelová, L.; Lopes-Meraz, M. L.; Niquet, J.; Kubová, Hana; Wasterlain, C. G.

    2015-01-01

    Roč. 305, Oct 1 (2015), s. 209-224. ISSN 0306-4522 R&D Projects: GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) ME08045; GA MŠk(CZ) LC554 Institutional support: RVO:67985823 Keywords : neuronal injury * temperature * immature brain * lithium/pilocarpine model * EEG monitoring Subject RIV: FH - Neurology Impact factor: 3.357, year: 2014

  19. Chemotherapy of WAP-T mouse mammary carcinomas aggravates tumor phenotype and enhances tumor cell dissemination.

    Science.gov (United States)

    Jannasch, Katharina; Wegwitz, Florian; Lenfert, Eva; Maenz, Claudia; Deppert, Wolfgang; Alves, Frauke

    2015-07-01

    In this study, the effects of the standard chemotherapy, cyclophosphamide/adriamycin/5-fluorouracil (CAF) on tumor growth, dissemination and recurrence after orthotopic implantation of murine G-2 cells were analyzed in the syngeneic immunocompetent whey acidic protein-T mouse model (Wegwitz et al., PLoS One 2010; 5:e12103; Schulze-Garg et al., Oncogene 2000; 19:1028-37). Single-dose CAF treatment reduced tumor size significantly, but was not able to eradicate all tumor cells, as recurrent tumor growth was observed 4 weeks after CAF treatment. Nine days after CAF treatment, residual tumors showed features of regressive alterations and were composed of mesenchymal-like tumor cells, infiltrating immune cells and some tumor-associated fibroblasts with an intense deposition of collagen. Recurrent tumors were characterized by coagulative necrosis and less tumor cell differentiation compared with untreated tumors, suggesting a more aggressive tumor phenotype. In support, tumor cell dissemination was strongly enhanced in mice that had developed recurrent tumors in comparison with untreated controls, although only few disseminated tumor cells could be detected in various organs 9 days after CAF application. In vitro experiments revealed that CAF treatment of G-2 cells eliminates the vast majority of epithelial tumor cells, whereas tumor cells with a mesenchymal phenotype survive. These results together with the in vivo findings suggest that tumor cells that underwent epithelial-mesenchymal transition and/or exhibit stem-cell-like properties are difficult to eliminate using one round of CAF chemotherapy. The model system described here provides a valuable tool for the characterization of the effects of chemotherapeutic regimens on recurrent tumor growth and on tumor cell dissemination, thereby enabling the development and preclinical evaluation of novel therapeutic strategies to target mammary carcinomas. PMID:25449528

  20. Poverty Alleviation or Aggravation? The Impacts of Community Forestry Policies in Nepal

    OpenAIRE

    Dhakal, Bhubaneswor; Bigsby, Hugh R.; Cullen, Ross

    2006-01-01

    This research studies the effects on income and employment when externally imposed policies constrain use of common forest resources. Using a mixed-integer linear programming model, the study examines the impacts of conservation-oriented community forest policies in Nepal on three household income groups. The results show that current community forest policies, which direct forest use towards environment conservation and timber production, cause large reductions in employment and income of th...

  1. Autophagy activation aggravates neuronal injury in the hippocampus of vascular dementia rats

    OpenAIRE

    Liu, Bin; Tang, Jing; Zhang, Jinxia; Li, Shiying; Yuan, Min; Wang, Ruimin

    2014-01-01

    It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuronal injury in a rat model of vascular dementia. In model rats, hippocampal CA1 neurons were severely damaged, and expression of the autophagy-related proteins beclin-1, cathepsin B and microtubule-associated protein 1 light chain 3 was elevated compared with that in sham-operated animals. These responses were...

  2. Does rapid urbanization aggravate health disparities? Reflections on the epidemiological transition in Pune, India

    Directory of Open Access Journals (Sweden)

    Mareike Kroll

    2014-09-01

    Full Text Available Background: Rapid urbanization in low- and middle-income countries reinforces risk and epidemiological transition in urban societies, which are characterized by high socioeconomic gradients. Limited availability of disaggregated morbidity data in these settings impedes research on epidemiological profiles of different population subgroups. Objective: The study aimed to analyze the epidemiological transition in the emerging megacity of Pune with respect to changing morbidity and mortality patterns, also taking into consideration health disparities among different socioeconomic groups. Design: A mixed-methods approach was used, comprising secondary analysis of mortality data, a survey among 900 households in six neighborhoods with different socioeconomic profiles, 46 in-depth interviews with laypeople, and expert interviews with 37 health care providers and 22 other health care workers. Results: The mortality data account for an epidemiological transition with an increasing number of deaths due to non-communicable diseases (NCDs in Pune. The share of deaths due to infectious and parasitic diseases remained nearly constant, though the cause of deaths changed considerably within this group. The survey data and expert interviews indicated a slightly higher prevalence of diabetes and hypertension among higher socioeconomic groups, but a higher incidence and more frequent complications and comorbidities in lower socioeconomic groups. Although the self-reported morbidity for malaria, gastroenteritis, and tuberculosis did not show a socioeconomic pattern, experts estimated the prevalence in lower socioeconomic groups to be higher, though all groups in Pune would be affected. Conclusions: The rising burden of NCDs among all socioeconomic groups and the concurrent persistence of communicable diseases pose a major challenge for public health. Improvement of urban health requires a stronger focus on health promotion and disease prevention for all socioeconomic groups with a holistic understanding of urban health. In order to derive evidence-based solutions and interventions, routine surveillance data become indispensable.

  3. MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function.

    Science.gov (United States)

    Brauer, R; Tureckova, J; Kanchev, I; Khoylou, M; Skarda, J; Prochazka, J; Spoutil, F; Beck, I M; Zbodakova, O; Kasparek, P; Korinek, V; Chalupsky, K; Karhu, T; Herzig, K-H; Hajduch, M; Gregor, M; Sedlacek, R

    2016-07-01

    Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis. PMID:26555704

  4. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation

    OpenAIRE

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P.; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V.; Cines, Douglas B.; Takada, Yoshikazu

    2006-01-01

    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity recep...

  5. Staphylococcal superantigen-like 5 activates platelets and supports platelet adhesion under flow conditions, which involves glycoprotein Ib alpha and alpha(IIb)beta(3)

    NARCIS (Netherlands)

    De Haas, C. J. C.; Weeterings, C.; Vughs, M. M.; De Groot, P. G.; Van Strijp, J. A.; Lisman, T.

    2009-01-01

    Objectives: Staphylococcal superantigen-like 5 (SSL5) is an exoprotein secreted by Staphylococcus aureus that has been shown to inhibit neutrophil rolling over activated endothelial cells via a direct interaction with P-selectin glycoprotein ligand 1 (PSGL-1). Methods and Results: When purified reco

  6. Integrin beta3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

    DEFF Research Database (Denmark)

    Tofteng, Charlotte L; Bach-Mortensen, Pernille; Bojesen, Stig E;

    2007-01-01

    .02), respectively. Multifactorial adjusted Cox regression revealed a hazard ratio of 2.0 (95% confidence interval: 1.1-3.5) for hip fracture in homozygotes versus noncarriers. After stratification by sex, equivalent hazard ratios were 2.0 (1.0-4.1) in women and 2.0 (0.8-5.0) in men. In the 2193 postmenopausal women......, hazard ratio for hip fracture in homozygotes versus noncarriers after additional adjustment for age at menopause and use of hormone replacement therapy was 2.6 (1.2-5.3). Hazard ratio for hip fracture in heterozygotes versus noncarriers did not differ from 1.0. CONCLUSIONS: Individuals homozygous...

  7. Association of the beta3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: studies of 7605 middle-aged white people

    DEFF Research Database (Denmark)

    Gjesing, A. P.; Andersen, G; Borch-Johnsen, K; Jørgensen, T; Hansen, T; Pedersen, Oluf

    2008-01-01

    cases and 6049 controls) and type 2 diabetes (1373 cases and 4742 controls) and quantitative trait analyses among 5822 individuals. Furthermore, the association of Trp64Arg with type 2 diabetes was examined in a meta-analysis. RESULTS: The Trp64Arg polymorphism was not associated with obesity. However...... does not confer an increased risk of obesity among Danes. Yet, in the present study of 7605 Danes the variant is associated with type 2 diabetes and quantitative traits related to type 2 diabetes....

  8. Trp64Arg Polymorphism in Beta3-Adrenergic Receptor Gene Is Associated with Decreased Fat Oxidation Both in Resting and Aerobic Exercise in the Japanese Male

    OpenAIRE

    Emiko Morita; Hiroshi Taniguchi; Motoyoshi Sakaue

    2009-01-01

    The purpose of our study was to investigate whether the Trp64Arg polymorphism in β3-AR gene and the −3826A/G polymorphism in the UCP1 gene were associated with the reduction in energy expenditure and fat oxidation both in resting and aerobic exercise in Japanese. Eighty-six nonobese young healthy Japanese were recruited. Energy expenditure was measured using indirect calorimetry. The subjects performed an aerobic exercise program at 60% of their maximal heart rate for 30 min...

  9. Trp64Arg Polymorphism in Beta3-Adrenergic Receptor Gene Is Associated with Decreased Fat Oxidation Both in Resting and Aerobic Exercise in the Japanese Male

    Directory of Open Access Journals (Sweden)

    Emiko Morita

    2009-01-01

    Full Text Available The purpose of our study was to investigate whether the Trp64Arg polymorphism in β3-AR gene and the −3826A/G polymorphism in the UCP1 gene were associated with the reduction in energy expenditure and fat oxidation both in resting and aerobic exercise in Japanese. Eighty-six nonobese young healthy Japanese were recruited. Energy expenditure was measured using indirect calorimetry. The subjects performed an aerobic exercise program at 60% of their maximal heart rate for 30 minutes. The level of fat oxidation at rest and aerobic exercise of the male subjects with Trp/Arg of the β3-AR gene was significantly lower than that of the Trp/Trp genotype. No difference in FO0-30 was observed in the female subjects. There was no association between UCP-1 polymorphism and energy expenditure during aerobic exercise. It was revealed that the Trp64Arg polymorphism in β3-AR gene is associated with reduction of fat oxidation both in resting and aerobic exercise in healthy, young Japanese males.

  10. Association of beta3-adrenergic receptor (ADRB3) Trp64Arg gene polymorphism with obesity and metabolic syndrome in the Balinese: a pilot study

    OpenAIRE

    Trimarsanto Hidayat; Oktavianthi Sukma; Suastika Ketut; Saraswati Made R; Malik Safarina G; Sudoyo Herawati

    2011-01-01

    Abstract Background Prevalence of obesity is increasing all over the world. ADRB3 Trp64Arg gene polymorphism was proposed to be associated with obesity, although inconsistent findings and differences of the Arg64 allele frequency among various ethnics were reported. Westernization was reported to increase the prevalence of obesity in developing world. In this study we determined the prevalence of obesity and metabolic syndrome among urban and rural Balinese, and studied the association of ADR...

  11. Association of beta3-adrenergic receptor (ADRB3 Trp64Arg gene polymorphism with obesity and metabolic syndrome in the Balinese: a pilot study

    Directory of Open Access Journals (Sweden)

    Trimarsanto Hidayat

    2011-05-01

    Full Text Available Abstract Background Prevalence of obesity is increasing all over the world. ADRB3 Trp64Arg gene polymorphism was proposed to be associated with obesity, although inconsistent findings and differences of the Arg64 allele frequency among various ethnics were reported. Westernization was reported to increase the prevalence of obesity in developing world. In this study we determined the prevalence of obesity and metabolic syndrome among urban and rural Balinese, and studied the association of ADRB3 Trp64Arg polymorphism with obesity and MetS. Findings A total of 528 Balinese (urban 282, rural 246 were recruited. Body mass index (BMI and waist circumference (WC were determined; high-density lipoprotein cholesterol (HDL-C, triglyceride (TG, systolic and diastolic blood pressure (SBP and DBP, and fasting plasma glucose (FPG were measured using standard procedures. BMI and WC classifications were based on WHO classifications for Asian. Metabolic syndrome (MetS was defined as described in the Joint Interim Statement. Chi-square test was employed to test the association between the ADRB3 Trp64Arg genotype and disease traits. Urban have higher BMI (p = 2.8 × 10-13, WC ( p -16, TG (p = 0.0028, DBP (p = 1.8 × 10-5, and lower HDL-C (p = 0.0376 when compared to rural. Abdominal obesity and MetS prevalence were significantly higher in urban as compared to rural (both p p = 0.041 for BMI and p = 0.012 for WC, and consequently higher abdominal obesity prevalence (p = 0.007. Comparison between male and female, as well as urban and rural, showed different prevalence of MetS co-morbidities. Abdominal obesity and hypertriglyceridaemia were consistently appeared in all groups, suggesting to play a role as determinant of MetS in both urban and rural. Conclusions Prevalence of obesity and MetS in urban were two times higher when compared to rural. Abdominal obesity and hypertriglyceridaemia appears to be the key determinant of MetS in both urban and rural Balinese. Our results indicated an association of the ADRB3 Trp64Arg gene polymorphism with obesity in the rural female.

  12. A dominant negative mutant of rab5 inhibits infection of cells by foot-and-mouth disease virus; implications for virus entry

    DEFF Research Database (Denmark)

    Johns, Helen; Berryman, Stephen; Monaghan, Paul;

    2009-01-01

    Foot-and-mouth disease virus (FMDV) can use a number of different integrins (alphavβ1, alphavβ3, alphavβ6, and alphavβ8) as receptors to initiate infection. Infection mediated by alphavβ6 is known to occur by clathrin-mediated endocytosis and is dependent on the acidic pH within endosomes....... On internalization, virus is detected rapidly in early endosomes (EE) and subsequently in perinuclear recycling endosomes (PNRE), but not in late endosomal compartments. Due to the extreme sensitivity of FMDV to acidic pH, it is thought that EE can provide a pH low enough for infection to occur; however, definitive...... proof that infection takes place from within these compartments is still lacking. Here we have investigated the intracellular transport steps required for FMDV infection of IBRS-2 cells, which express vβ8 as their FMDV receptor. These experiments confirmed that FMDV infection mediated by alphavβ8...

  13. Deficiency of the Complement Component 3 but Not Factor B Aggravates Staphylococcus aureus Septic Arthritis in Mice.

    Science.gov (United States)

    Na, Manli; Jarneborn, Anders; Ali, Abukar; Welin, Amanda; Magnusson, Malin; Stokowska, Anna; Pekna, Marcela; Jin, Tao

    2016-04-01

    The complement system plays an essential role in the innate immune response and protection against bacterial infections. However, detailed knowledge regarding the role of complement in Staphylococcus aureus septic arthritis is still largely missing. In this study, we elucidated the roles of selected complement proteins in S. aureus septic arthritis. Mice lacking the complement component 3 (C3(-/-)), complement factor B (fB(-/-)), and receptor for C3-derived anaphylatoxin C3a (C3aR(-/-)) and wild-type (WT) control mice were intravenously or intra-articularly inoculated with S. aureus strain Newman. The clinical course of septic arthritis, as well as histopathological and radiological changes in joints, was assessed. After intravenous inoculation, arthritis severity and frequency were significantly higher in C3(-/-)mice than in WT controls, whereas fB(-/-)mice displayed intermediate arthritis severity and frequency. This was in accordance with both histopathological and radiological findings. C3, but not fB, deficiency was associated with greater weight loss, more frequent kidney abscesses, and higher bacterial burden in kidneys. S. aureus opsonized with C3(-/-)sera displayed decreased uptake by mouse peritoneal macrophages compared with bacteria opsonized with WT or fB(-/-)sera. C3aR deficiency had no effect on the course of hematogenous S. aureus septic arthritis. We conclude that C3 deficiency increases susceptibility to hematogenous S. aureus septic arthritis and impairs host bacterial clearance, conceivably due to diminished opsonization and phagocytosis of S. aureus. PMID:26787717

  14. Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease

    Science.gov (United States)

    Wei, Zhen; Chen, Xiao-Chun; Song, Yue; Pan, Xiao-Dong; Dai, Xiao-Man; Zhang, Jing; Cui, Xiao-Li; Wu, Xi-Lin; Zhu, Yuan-Gui

    2016-01-01

    Background: Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods: The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1–42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results: In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1–42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population. PMID:27453234

  15. 77 FR 26703 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Science.gov (United States)

    2012-05-07

    ... authority. See 77 FR 24416. In preparing that final ] rule for publication, three errors were made as... 24, 2012. See 77 FR 24416. FRA failed to account for an October 31, 2011 amendment to 49 CFR part 228... removed and reserved Sec. 228.21. See 76 FR 67073, 67087-88. In preparing the April 24, 2012, final...

  16. Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway

    OpenAIRE

    Faisal, Mohammad; Saquib, Quaiser; Alatar, Abdulrahman A.; Al-Khedhairy, Abdulaziz A.; Ahmed, Mukhtar; Ansari, Sabiha M.; Alwathnani, Hend A.; Dwivedi, Sourabh; Musarrat, Javed; Praveen, Shelly

    2016-01-01

    Background Despite manifold benefits of nanoparticles (NPs), less information on the risks of NPs to human health and environment has been studied. Cobalt oxide nanoparticles (Co3O4-NPs) have been reported to cause toxicity in several organisms. In this study, we have investigated the role of Co3O4-NPs in inducing phytotoxicity, cellular DNA damage and apoptosis in eggplant (Solanum melongena L. cv. Violetta lunga 2). To the best of our knowledge, this is the first report on Co3O4-NPs showing...

  17. 1950 MHz radiofrequency electromagnetic fields do not aggravate memory deficits in 5xFAD mice.

    Science.gov (United States)

    Son, Yeonghoon; Jeong, Ye Ji; Kwon, Jong Hwa; Choi, Hyung-Do; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil; Lee, Hae-June

    2016-09-01

    The increased use of mobile phones has generated public concern about the impact of radiofrequency electromagnetic fields (RF-EMF) on health. In the present study, we investigated whether RF-EMFs induce molecular changes in amyloid precursor protein (APP) processing and amyloid beta (Aβ)-related memory impairment in the 5xFAD mouse, which is a widely used amyloid animal model. The 5xFAD mice at the age of 1.5 months were assigned to two groups (RF-EMF- and sham-exposed groups, eight mice per group). The RF-EMF group was placed in a reverberation chamber and exposed to 1950 MHz electromagnetic fields for 3 months (SAR 5 W/kg, 2 h/day, 5 days/week). The Y-maze, Morris water maze, and novel object recognition memory test were used to evaluate spatial and non-spatial memory following 3-month RF-EMF exposure. Furthermore, Aβ deposition and APP and carboxyl-terminal fragment β (CTFβ) levels were evaluated in the hippocampus and cortex of 5xFAD mice, and plasma levels of Aβ peptides were also investigated. In behavioral tests, mice that were exposed to RF-EMF for 3 months did not exhibit differences in spatial and non-spatial memory compared to the sham-exposed group, and no apparent change was evident in locomotor activity. Consistent with behavioral data, RF-EMF did not alter APP and CTFβ levels or Aβ deposition in the brains of the 5xFAD mice. These findings indicate that 3-month RF-EMF exposure did not affect Aβ-related memory impairment or Aβ accumulation in the 5xFAD Alzheimer's disease model. Bioelectromagnetics. 37:391-399, 2016. © 2016 The Authors Bioelectromagnetics published by Wiley Periodicals, Inc. on behalf of Bioelectromagnetics Society. PMID:27434853

  18. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity

    Science.gov (United States)

    He, Lan; Kim, Teayoun; Long, Qinqiang; Liu, Jian; Wang, Peiyong; Zhou, Yiqun; Ding, Yishu; Prasain, Jeevan; Wood, Philip A.; Yang, Qinglin

    2012-01-01

    Background Carnitine palmitoyltransferase 1(CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT-1 activity by specific CPT-1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby posting concerns on the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 in order to evaluate it as a safe and effective therapeutic approach. Methods and Results Heterozygous CPT1b knockout mice (CPT1b+/−) were subjected to transverse aorta constriction (TAC)-induced pressure-overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by two weeks of transverse aorta constriction (TAC), CPT1b+/− mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b+/− mice exhibited exacerbated cardiac hypertrophy and remodeling compared with that in wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b+/− than in controlled mice. Moreover, the CPT1b+/− heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocytes apoptosis. Conclusions We conclude that CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be applied in the clinical use of CPT-1 inhibitors. PMID:22932257

  19. Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Larsen, Fin Stolze;

    2011-01-01

    whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA......Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These...... rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two...

  20. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    OpenAIRE

    Yue, Yongping; Wasala, Nalinda B.; Bostick, Brian; Duan, Dongsheng

    2016-01-01

    Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin...

  1. Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Torsten Schröder

    2016-04-01

    Conclusions: We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial dysfunction. However, a second hit, such as dietary stress, was required to cause hepatic steatosis and inflammation. This study suggests a causative role of hepatic mitochondrial dysfunction in the development of experimental NASH.

  2. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhen Shi; Chun-Zhen Zhao; Bing Zhao; Xiao-Liang Zheng; San-Hua Fang; Yun-Bi Lu; Wei-Ping Zhang; Zhong Chen; Er-Qing Wei

    2012-01-01

    Objective To determine whether aquaporin-4 (AQP4) regulates acute lesions,delayed lesions,and the associated microglial activation after cryoinjury to the brain.Methods Brain cryoinjury was applied to AQP4 knockout (KO)and wild-type mice.At 24 h and on days 7 and 14 after cryoinjury,lesion volume,neuronal loss,and densities of microglia and astrocytes were determined,and their changes were compared between AQP4 KO and wild-type mice.Results Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury,but worsened on days 7 and 14,compared to those in wild-type mice.Besides,microglial density increased more,and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice.Conclusion AQP4 deficiency ameliorates acute lesions,but worsens delayed lesions,perhaps due to the microgliosis in the late phase.

  3. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Yue, Yongping; Wasala, Nalinda B; Bostick, Brian; Duan, Dongsheng

    2016-01-01

    Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index) became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity. PMID:27419194

  4. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    Science.gov (United States)

    Yue, Yongping; Wasala, Nalinda B; Bostick, Brian; Duan, Dongsheng

    2016-01-01

    Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index) became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity. PMID:27419194

  5. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    OpenAIRE

    Lu Zhou; Hyoung-Won Koh; Ui-Jin Bae; Byung-Hyun Park

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R in...

  6. Increased cardiac index due to terbutaline treatment aggravates capillary-alveolar macromolecular leakage in oleic acid lung injury in dogs

    OpenAIRE

    Briot, Raphael; Bayat, Sam; Anglade, Daniel; Martiel, Jean-Louis; Grimbert, Francis

    2009-01-01

    Introduction We assessed the in vivo effects of terbutaline, a beta2-agonist assumed to reduce microvascular permeability in acute lung injury. Methods We used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung injured dogs. BAL was performed in a closed lung sampling site, using a bronchoscope fitted with an infl...

  7. Investigation of Aggravating Psychosocial Factors on Health and Predictability of Smoking and Alcohol Use in Post Adolescent Students.

    Science.gov (United States)

    Barmpagianni, Effrosyni; Travlos, Antonios; Kalokairinou, Athina; Sachlas, Athanasios; Zyga, Sofia

    2013-04-18

    Purpose of this study is to explore those factors which affect the health of students in postadolescent age, focusing on smoking and alcohol use, especially in regard to ways of predicting adoption of this behavior and its frequency to detect future users of tobacco and alcohol use but also high-risk groups, i.e. those people who are led to abuses. On the basis of the research part is the Theory of Planned Behaviour, the axes of which are to be investigated. Specifically, the factors evaluated, except for population parameters, behavioral attitudes, i.e. attitudes towards the behavior of tobacco use and alcohol regulations subjective perceptions and perceptions of control, perceived behavioral control and self-efficacy. Intention is explored to continue or start using tobacco and alcohol in the future and evaluate the behavior. The sample consisted of 138 students of postadolescent age, 18-25 years of both sexes, all of the University of Peloponnese and the Technological Educational Institute of Kalamata, Department of Sparta, Greece. The results of a series of statistical analysis, via SPSS 21.0 statistical program revealed the predictive power of perceived behavioral control and subjective norms to the intention of interpreting 64% of the variance of the latter, of the attitudes toward alcohol in relation to intention that interpret 69% of the variance, of the normative beliefs toward smoking with 69% range of interpretation to the dependent variable, of the perceived behavioral control of smoking with 72% and of the attitudes toward smoking with 77% of interpretation. The results demonstrate the significance and application in universities and technological educational institutes appropriate primary preventive interventions for students nonusers of tobacco and alcohol and appropriate programs of secondary and tertiary prevention in heavy users of tobacco and alcohol use and high-risk individual. PMID:26973900

  8. Farmer Resettlements and Water Energy Stresses Arising From Aggravating Drought Conditions in Mahaweli River Watershed, Sri Lanka

    Science.gov (United States)

    Thabrew, L.

    2012-12-01

    Climate change is expected to cause significant changes in water quantity and water quality in river basins throughout the world, with particularly significant impacts in developing regions. Climate change effects are often exacerbated by other simultaneous activities in developing countries, such as population growth, reliance on subsistence agriculture, and expanding provision of electricity. Each of these activities requires access to readily-available freshwater. For example, population growth requires more water for irrigation as food production needs increase. Additionally, water is needed for generating electricity in hydropower facilities as well as other facilities, which require water to run steam turbines or to cool facilities. As such, many developing countries face the real and immediate need to anticipate and adapt to climatic stresses on water resources in both the agricultural and residential sectors. Water withdrawal in both of these sectors is largely driven by individual behaviors, such as electricity use in the home and irrigation practices on farmland, aggregated at the household, community, and regional level. Our ongoing project in Sri Lanka focuses on understanding aforementioned issues in coupled natural and human systems in the Mahaweli River Watershed (MWR) to inform decision-makers to streamline policies and strategies for effective adaptation to worsening drought conditions. MWR produces more than 60% of the rice demand and nearly 40% of the energy requirement of the country. Although irrigation is currently the sector that withdraws the most water, with government plans for resettling farmer communities and developing new urban centers in the region by 2030, electricity production is expected to compete for water against irrigation in the future. Thus, understanding the water-energy nexus is crucial to planning for conservation and efficiency. Through a pilot survey conducted by our interdisciplinary research team, in five locations in MWR, we collect information on household and farm level water and energy use, demand-side water management practices, and farmers' willingness and capacities to practice them. We use these self-reported pilot data together with water and energy utility company data to model increasing water-energy stresses in the watershed, and its effect on existing water allocation issues related to irrigation and power generation. Drawing upon the preliminary results of this work, this paper presents the emerging water-energy issues and plausible adaptation measures in MWR. This work will pave the way to understand the inherent interconnectivities of water energy stresses in multi-purpose watersheds in the developing world.

  9. UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin

    Science.gov (United States)

    Kim, Eun Ju; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Sungsoo; Kim, Jin Yong; Lee, Dong Hun; Chung, Jin Ho

    2016-01-01

    Ultraviolet (UV) exposure to the human skin reduces triglycerides contents and lipid synthesis in the subcutaneous (SC) fat. Because adiponectin and leptin are the most abundant adipokines from the SC fat, we aim to investigate how they interact with UV exposure and skin aging. The expressions of adiponectin and leptin were significantly decreased in SC fat of sun-exposed forearm skin, in comparison with that of sun-protected buttock skin of the same elderly individuals, indicating that chronic UV exposure decreases both adipokines. Acute UV irradiation also decreased the expressions of adiponectin and leptin in SC fat. The expressions of adiponectin receptor 1/2 and leptin receptor were significantly decreased in the dermis as well as in SC fat. Moreover, while exogenous adiponectin and leptin administration prevented UV- and TNF-α induced matrix metalloproteinase (MMP)-1 expression, they also increased UV- and TNF-α induced reduction of type 1 procollagen production. Silencing of adiponectin, leptin or their receptors led to an increased MMP-1 and a decreased type 1 procollagen expression, which was reversed by treatment with recombinant human adiponectin or leptin. In conclusion, UV exposure decreases the expression of adiponectin and leptin, leading to the exacerbation of photoaging by stimulating MMP-1 expression and inhibiting procollagen synthesis. PMID:27161953

  10. Aggravation of dyspnea in stage I non-small cell lung cancer patients following stereotactic body radiotherapy

    DEFF Research Database (Denmark)

    Paludan, Merete; Traberg Hansen, Anders; Petersen, Jørgen; Grau, Cai; Høyer, Morten

    2006-01-01

    association of dose-volume histogram parameters with changes in dyspnea. The study concerns 28 medically inoperable stage I NSCLC patients that received SBRT at our department between 2000 and 2003. A central dose of 45 Gy/3 fractions was delivered in 5-8 days. WHO toxicity scoring of dyspnea was...

  11. PHARMACOTHERAPY MONITORING AND DEGREE OF SATISFACTION OF A FEMALE USER CARRIER PSYCHOSOCIAL DISORDER AGGRAVATED BY USE PSYCHOACTIVE SUBSTANCE

    Directory of Open Access Journals (Sweden)

    Janaína Sheyla Leite Santos

    2015-04-01

    Full Text Available In Brazil, 23 million people (12% of the population require some mental health care. The bipolar disorders, with a prevalence of 1,5%, shown as a public health problem by representing high risk of mortality. This user group is more likely to produce Drug Related Problems (DRPs and it is this respect the pharmacist shown to be important, with the practice of a qualified pharmaceutical care. This study aims to perform the pharmacotherapeutic monitoring under the pharmaceutical care provided to a user of Psychosocial Care Center II - Eastern city of Teresina, Piauí, and to assess the degree of satisfaction with the service. The monitoring was conducted from September 2012 to June 2013. Every pharmaceutical consultation, we collected data to support pharmaceutical interventions. The Negative Outcomes associated with medication (NOMs and DRPs were classified according to the Third Consensus of Granada. The casual blood glucose and blood pressure were within normal values with the potential for interaction were identified type drug - ethanol. Because of NOM and DRP was obtained 100 % effectiveness, and satisfaction of 89%. Realized the importance of the pharmacist in CAPS II to promote rational use of medicines and guidance on better habits of life, providing a better quality of life for the user.

  12. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J;

    2013-01-01

    Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...... model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without...... PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group (p <0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed...

  13. Aggravation of Chronic Stress Effects on Hippocampal Neurogenesis and Spatial Memory in LPA1 Receptor Knockout Mice

    OpenAIRE

    Castilla-Ortega, Estela; Hoyo-Becerra, Carolina; Pedraza, Carmen; Chun, Jerold; Rodríguez de Fonseca, Fernando; Estivill-Torrús, Guillermo; Santín, Luis J.

    2011-01-01

    Background The lysophosphatidic acid LPA1 receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA1 receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory. Methodology/Principal Findings Male LPA1-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous marker...

  14. Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

    OpenAIRE

    Engel, T.; K.Tanaka; Jimenez-Mateos, E M; Caballero-Caballero, A; Prehn, J. H. M.; HENSHALL, D. C.

    2010-01-01

    The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Ana...

  15. Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells.

    Science.gov (United States)

    Lee, Heon Goo; Hsu, Anny; Goto, Hana; Nizami, Saqib; Lee, Jonathan H; Cadet, Edwin R; Tang, Peter; Shaji, Roya; Chandhanayinyong, Chandhanarat; Kweon, Seok Hyun; Oh, Daniel S; Tawfeek, Hesham; Lee, Francis Y

    2013-03-01

    The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor cells, differential and combined effects of mechanical perturbations and particles on such cell types have not been extensively studied. In this study, macrophages and osteoprogenitor cells were subjected to physiological and superphysiological mechanical stimuli in the presence and absence of Ti particles with the aim of simulating various microenvironments of the host bone-implant junction. Macrophages and osteoprogenitor cells were capable of engulfing Ti particles through actin remodeling and also exhibited changes in mRNA levels of proinflammatory cytokines under certain conditions. In osteoprogenitor cells, superphysiological strain increased proinflammatory gene expression; in macrophages, such mechanical perturbations did not affect gene expression. We confirmed that this phenomenon in osteoprogenitor cells occurred via activation of the ERK1/2 signaling pathway as a result of damage to the cytoplasmic membrane. Furthermore, AZD6244, a clinically relevant inhibitor of the ERK1/2 pathway, mitigated particle-induced inflammatory gene expression in osteoprogenitor cells and macrophages. This study provides evidence of more inflammatory responses under mechanical strains in osteoprogenitor cells than macrophages. Phagocytosis of particles and mechanical perturbation costimulate the ERK1/2 pathway, leading to expression of proinflammatory genes. PMID:23255578

  16. Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells

    OpenAIRE

    Lee, Heon Goo; Hsu, Anny; Goto, Hana; Nizami, Saqib; Lee, Jonathan H.; Cadet, Edwin R.; Tang, Peter; Shaji, Roya; Chandhanayinyong, Chandhanarat; Kweon, Seok Hyun; Oh, Daniel S.; Tawfeek, Hesham; Lee, Francis Y.

    2012-01-01

    The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor ce...

  17. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT, confirming the hepatoprotective effects of Marimastat via the TNF-signaling pathway. CONCLUSIONS/SIGNIFICANCE: Inhibition of MMP and TACE activity with Marimastat during chronic CCl4 administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Since effective inhibition of MMPs accelerates fibrosis progression, MMP inhibitors should be used with caution in patients with chronic liver diseases.

  18. Investigation of aggravating psychosocial factors on health and predictability of smoking and alcohol use in post adolescent students

    Directory of Open Access Journals (Sweden)

    Effrosyni Barmpagianni

    2013-04-01

    Full Text Available Purpose of this study is to explore those factors which affect the health of students in postadolescent age, focusing on smoking and alcohol use, especially in regard to ways of predicting adoption of this behavior and its frequency to detect future users of tobacco and alcohol use but also high-risk groups, i.e. those people who are led to abuses. On the basis of the research part is the Theory of Planned Behaviour, the axes of which are to be investigated. Specifically, the factors evaluated, except for population parameters, behavioral attitudes, i.e. attitudes towards the behavior of tobacco use and alcohol regulations subjective perceptions and perceptions of control, perceived behavioral control and self-efficacy. Intention is explored to continue or start using tobacco and alcohol in the future and evaluate the behavior. The sample consisted of 138 students of postadolescent age, 18-25 years of both sexes, all of the University of Peloponnese and the Technological Educational Institute of Kalamata, Department of Sparta, Greece. The results of a series of statistical analysis, via SPSS 21.0 statistical program revealed the predictive power of perceived behavioral control and subjective norms to the intention of interpreting 64% of the variance of the latter, of the attitudes toward alcohol in relation to intention that interpret 69% of the variance, of the normative beliefs toward smoking with 69% range of interpretation to the dependent variable, of the perceived behavioral control of smoking with 72% and of the attitudes toward smoking with 77% of interpretation. The results demonstrate the significance and application in universities and technological educational institutes appropriate primary preventive interventions for students nonusers of tobacco and alcohol and appropriate programs of secondary and tertiary prevention in heavy users of tobacco and alcohol use and high-risk individual.

  19. Bilateral Vestibulopathy Aggravates Balance and Gait Disturbances in Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis: A Case Report.

    Science.gov (United States)

    van Leeuwen, Roeland B; Smits, Bart W; Rodenburg, Richard J; van Engelen, Baziel G

    2016-09-01

    In patients with a triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), the presenting features are mainly ataxia or ptosis. SANDO patients often have impaired balance and gait, which is not surprising considering the combination of sensory ataxic neuropathy, and additional symptoms like cerebellar ataxia and limb girdle weakness. We describe a SANDO patient who noticed an increasingly impaired balance and gait, without any dizziness. Neurological investigation revealed an external ophthalmeplegia and a cerebellar ataxia; the head impulse test was not reliable because of eye movement disorders. The caloric reflex tests showed lack of responses on both sides, compatible with severe bilateral vestibulopathy. Making the diagnosis of bilateral vestibulopathy in SANDO patients may have implications for the management of the patient, because specific vestibular rehabilitation can improve gaze and postural stability. PMID:27552387

  20. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    Science.gov (United States)

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin/adiponectin ratio, higher visfatin and interleukin-6 levels. The fat containing meals stimulate the long-lasting release of incretins, mainly GIP, parallel to the increase of the markers of low grade inflammation associating obesity in metabolic syndrome. The possibility of use of the postprandial (OLTT) GIP release measurement for the low grade inflammation progress in MS patients is suggested. PMID:27226181

  1. Aggravation of Irradiation Induced Impairment in Protein Metabolism in Albino Rate Subjected to Oral Injection of Kelthane Miticide

    International Nuclear Information System (INIS)

    The combined effect of both whole body gamma radiation exposure and administration of organo chlorine miticide kelthaneon protein metabolism was investigated in male albino rats. Kelthane was orally given at a dose level of 100 mg/kg body weight over a period of seven days. Irradiation process permitted the rats to receive one Gray every other day at a weekly cumulative dose of 3 Gy up to a total dose of 15 Gy. The biochemical assays included total proteins, protein fractions, free amino acids (FAAS) and urea level in blood serum as well as protein content and its FAAS in urine . The data revealed significant changes in the protein parameters due to whole body gamma irradiation. These changes were shown to be dose and time dependent which reached their maximum at the end of the experimentation period. The alterations were more pronounced in animal groups exposed to gamma radiation and received keltane pesticide

  2. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

    OpenAIRE

    Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

    2009-01-01

    Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (...

  3. Evaluación de los niveles del factor de crecimiento transformante beta 1 y beta 3 en plasma y líquido peritoneal de caballos con enfermedad abdominal aguda Evaluation of the transforming growth factor beta 1 and beta 3 levels in plasma and peritoneal fluid from horses with acute abdominal disease

    Directory of Open Access Journals (Sweden)

    D Argüelles

    2009-01-01

    Full Text Available Existe información escasa sobre moléculas presentes en el líquido peritoneal de caballos con cólico relacionadas con el desarrollo potencial de adherencias abdominales. Estudios en especies diferentes correlacionan niveles incrementados de las series del factor de crecimiento transformante beta (TGF-ß con la presencia de adherencias abdominales. Los objetivos de este estudio fueron: 1 documentar y comparar los niveles plasmáticos y del líquido peritoneal del TGF-ß1 y TGF-ß3 en caballos con enfermedad abdominal aguda y en caballos normales. 2 correlacionar los niveles de estos péptidos con los hallazgos del hemograma y los resultados citológicos y bioquímicos del líquido peritoneal. Se tomaron muestras de plasma y líquido peritoneal de 104 caballos con cólico (29 cólicos médicos (15 obstructivos simples y 14 inflamatorios y 65 cólicos quirúrgicos, de los cuales 30 padecían problemas isquémicos y 35 de problemas obstructivos simples y de 10 caballos sanos. En cada paciente se realizó un hemograma, análisis citológico de líquido peritoneal y determinación de los niveles plasmáticos y peritoneales de TGF-ß1 y TGF-ß3 mediante ELISA. Los niveles peritoneales de TGF-ß1 fueron estadísticamente más altos en los cólicos quirúrgicos isquémicos y en los cólicos médicos inflamatorios en comparación con los otros tipos de cólicos y con el grupo control. En conclusión, los niveles peritoneales de TGF-ß1 en caballos con crisis abdominal aguda están incrementados como respuesta a la inflamación. Los caballos con lesiones estrangulantes o peritonitis muestran alteración severa en niveles peritoneales de TGF-ß1.There is few information about the molecules present in the peritoneal fluid of horses with colic that are related to the potential development of abdominal adhesions. Studies carried out in different species correlate high levels of transforming growth factor beta (TGF-ß series with the presence of abdominal adhesions. The aims of this study were: 1 to document and compare the plasma and peritoneal fluid levels of TGF-ß1 and TGF-ß3 in horses with acute abdominal disease and normal horses, 2 to correlate the levels of these peptides with the hemogram values and the cytological and biochemical peritoneal fluid findings. Plasma and peritoneal fluid samples from 104 horses were obtained: 29 were medical colics (15 were obstructive simple colic and 14 were inflammatory colic, 65 underwent abdominal surgery (30 horses suffered from ischemic problems and 35 from non ischemic problems, and 10 were controls. A hemogram was performed and peritoneal fluid cytology and TGF-ß1 and TGF-ß3 plasma and peritoneal fluid levels were determined by ELISA. The TGF-ß1 peritoneal fluid levels were statistically (P < 0.05 higher in ischemic colics and inflammatory colics compared with controls and other type of surgical or medical colics. In conclusion, the levels of peritoneal fluid TGF-ß1 are elevated in horses with acute abdominal disease in response to inflammation. The horses with strangulating lesions and peritonitis show greater alterations of TGF-ß1 levels.

  4. Etomidate blocks LTP and impairs learning but does not enhance tonic inhibition in mice carrying the N265M point mutation in the beta3 subunit of the GABA(A) receptor.

    Science.gov (United States)

    Zarnowska, E D; Rodgers, F C; Oh, I; Rau, V; Lor, C; Laha, K T; Jurd, R; Rudolph, U; Eger, E I; Pearce, R A

    2015-06-01

    Enhancement of tonic inhibition mediated by extrasynaptic α5-subunit containing GABAA receptors (GABAARs) has been proposed as the mechanism by which a variety of anesthetics, including the general anesthetic etomidate, impair learning and memory. Since α5 subunits preferentially partner with β3 subunits, we tested the hypothesis that etomidate acts through β3-subunit containing GABAARs to enhance tonic inhibition, block LTP, and impair memory. We measured the effects of etomidate in wild type mice and in mice carrying a point mutation in the GABAAR β3-subunit (β3-N265M) that renders these receptors insensitive to etomidate. Etomidate enhanced tonic inhibition in CA1 pyramidal cells of the hippocampus in wild type but not in mutant mice, demonstrating that tonic inhibition is mediated by β3-subunit containing GABAARs. However, despite its inability to enhance tonic inhibition, etomidate did block LTP in brain slices from mutant mice as well as in those from wild type mice. Etomidate also impaired fear conditioning to context, with no differences between genotypes. In studies of recombinant receptors expressed in HEK293 cells, α5β1γ2L GABAARs were insensitive to amnestic concentrations of etomidate (1 μM and below), whereas α5β2γ2L and α5β3γ2L GABAARs were enhanced. We conclude that etomidate enhances tonic inhibition in pyramidal cells through its action on α5β3-containing GABAA receptors, but blocks LTP and impairs learning by other means - most likely by modulating α5β2-containing GABAA receptors. The critical anesthetic targets underlying amnesia might include other forms of inhibition imposed on pyramidal neurons (e.g. slow phasic inhibition), or inhibitory processes on non-pyramidal cells (e.g. interneurons). PMID:25680234

  5. Changes and effects of helper T cells and their effector molecules on disease aggravation in patients with chronic hepatitis B. MO Ruidong

    Institute of Scientific and Technical Information of China (English)

    莫瑞东

    2014-01-01

    Objective To investigate the role of helper T cell(Th)1,Th17 and Th22 and their effector molecules including interferon-gamma,interleukin(IL)-17 and IL-22in active phase of chronic hepatitis B(CHB)and acuteon-chronic liver failure(ACLF).Methods Forty-five CHB patients and 38 ACLF patients at Ruijin Hospital of Shanghai Jiaotong University School of Medicine were included,and 26 healthy controls(HC)were also enrolled.Fresh heparinized peripheral blood was obtained

  6. Les pénalités de pauvreté en France : comment le marché aggrave la situation des populations pauvres

    OpenAIRE

    Frédéric Dalsace; Charles-Edouard Vincent; Jacques Berger; François Dalens

    2012-01-01

    S’appuyant sur une étude du Boston Consulting Group  effectuée à la demande de l’Action Tank « Entreprise et Pauvreté », cet article permet d'expliquer et de quantifier   ce que l’on appelle les pénalités de pauvreté en France. Les populations pauvres, comme dans les pays émergents - mais pour des raisons profondément différentes, payent plus cher que les autres ménages, les mêmes biens et services,  par unité de consommation. L’objectif ultime est de favoriser le développement de solutions ...

  7. Mobilité des populations sahéliennes durant la sécheresse aggravée de 1984

    OpenAIRE

    RETAILLE Denis

    2014-01-01

    LE DEPARTEMENT DE ZINDER AU NIGER SUD DU DÉPARTEMENT DE ZINDER. RELIEF. PLUVIOMÉTRIE 1985 MOBILITÉ CONJONCTURELLE Les mouvements massifs enregistrés pendant l’année 1984 sont très immédiatement des mouvements de secours. Les pasteurs et éleveurs ont entamé une transhumance exceptionnelle dès le mois d’août après avoir déstocké en mai-juin, à une période inhabituelle de l’année. Les départs des paysans ont été plus tardifs, septembre, après la Pâque musulmane. Pour eux, l’exode est le résult...

  8. TNF-α Inhibits FoxO1 by Upregulating miR-705 to Aggravate Oxidative Damage in Bone Marrow-Derived Mesenchymal Stem Cells during Osteoporosis.

    Science.gov (United States)

    Liao, Li; Su, Xiaoxia; Yang, Xiaohong; Hu, Chenghu; Li, Bei; Lv, Yajie; Shuai, Yi; Jing, Huan; Deng, Zhihong; Jin, Yan

    2016-04-01

    Decline of antioxidant defense after estrogen deficiency leads to oxidative damage in bone marrow-derived mesenchymal stem cells (BMMSCs), resulting a defect of bone formation in osteoporosis. Forkhead box O1 (FoxO1) protein is crucial for defending physiological oxidative damage in bone. But whether FoxO1 is involved in the oxidative damage during osteoporosis is largely unknown. In this study, we found that FoxO1 protein accumulation was decreased in BMMSCs of ovariectomized mice. The decrease of FoxO1 resulted in the suppression of manganese superoxide dismutase (Sod2) and catalase (Cat) expression and accumulation of reactive oxygen species (ROS), inhibiting the osteogenic differentiation of BMMSCs. The decline of FoxO1 protein was caused by tumor necrosis factor-alpha (TNF-α) accumulated after estrogen deficiency. Mechanistically, TNF-α activated NF-κB pathway to promote microRNA-705 expression, which function as a repressor of FoxO1 through post-transcriptional regulation. Inhibition of NF-κB pathway or knockdown of miR-705 largely prevented the decline of FoxO1-mediated antioxidant defense caused by TNF-α and ameliorated the oxidative damage in osteoporotic BMMSCs. Moreover, the accumulated ROS further activated NF-κB pathway with TNF-α, which formed a feed-forward loop to persistently inhibiting FoxO1 protein accumulation in BMMSCs. In conclusion, our study revealed that the decline of FoxO1 is an important etiology factor of osteoporosis and unclosed a novel mechanism of FoxO1 regulation by TNF-α. These findings suggested a close correlation between inflammation and oxidative stress in stem cell dysfunction during degenerative bone diseases. Stem Cells 2016;34:1054-1067. PMID:26700816

  9. Disruption of Notch signaling aggravates irradiation-induced bone marrow injury, which is ameliorated by a soluble Dll1 ligand through Csf2rb2 upregulation

    Science.gov (United States)

    Chen, Juan-Juan; Gao, Xiao-Tong; Yang, Lan; Fu, Wei; Liang, Liang; Li, Jun-Chang; Hu, Bin; Sun, Zhi-Jian; Huang, Si-Yong; Zhang, Yi-Zhe; Liang, Ying-Min; Qin, Hong-Yan; Han, Hua

    2016-01-01

    Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice. Activation of Notch signaling with the endothelial cell (EC)-targeted soluble Dll1 Notch ligand mD1R promoted BM recovery after irradiation. mD1R treatment resulted in a significant increase in myeloid progenitors and monocytes in the BM, spleen and peripheral blood after irradiation. mD1R also enhanced hematopoiesis in mice treated with cyclophosphamide, a chemotherapeutic drug that induces BM suppression. Mechanistically, mD1R increased the proliferation and reduced the apoptosis of myeloid cells in the BM after irradiation. The β chain cytokine receptor Csf2rb2 was identified as a downstream molecule of Notch signaling in hematopoietic cells. mD1R improved hematopoietic recovery through up-regulation of the hematopoietic expression of Csf2rb2. Our findings reveal the role of Notch signaling in irradiation- and drug-induced BM suppression and establish a new potential therapy of BM- and myelo-suppression induced by radiotherapy and chemotherapy. PMID:27188577

  10. ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis[S

    OpenAIRE

    Wang王耀勇, Yaoyong,; Sawashita澤下仁子, Jinko,; Qian钱金泽, Jinze,; Zhang张蓓茹, Beiru,; Fu付笑影, Xiaoying,; Tian田耕, Geng,; Chen陈磊, Lei,; Mori森 政之, Masayuki,; Higuchi樋口京一, Keiichi,

    2011-01-01

    Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. ApoA-II has multiple physiological functions and can form senile amyloid fibrils (AApoAII) in mice. Most circulating apoA-II is present in lipoprotein A-I/A-II. To study the influence of apoA-I on apoA-II and AApoAII amyloidosis, apoA-I-deficient (C57BL/6J.Apoa1−/−) mice were used. Apoa1−/− mice showed the expected significant reduction in total cholesterol (TC), HDL cholesterol (HDL...

  11. Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study

    DEFF Research Database (Denmark)

    Eriksson, J.W.; Jansson, P.A.; Carlberg, B.;

    2008-01-01

    . Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg......Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution...

  12. MAP4K4 deficiency in CD4(+) T cells aggravates lung damage induced by ozone-oxidized black carbon particles.

    Science.gov (United States)

    Jin, Ming; Chu, Hongqian; Li, Yuan; Tao, Xi; Cheng, Zhiyuan; Pan, Yao; Meng, Qinghe; Li, Leilei; Hou, Xiaohong; Chen, Yueyue; Huang, Hongpeng; Jia, Guang; Shang, Jing; Zhu, Tong; Shang, Lanqin; Hao, Weidong; Wei, Xuetao

    2016-09-01

    As the main composition of combustion, black carbon (BC) is becoming more and more noticeable at home and abroad. Ozone-oxidized black carbon (oBC) was produced through aging of ozone, one of the near-surface pollutants, to black carbon. And oBC was found to be more oxidation and cell toxicity when compared with BC. Besides, as a key cell of immunity, whether CD4(+) T cell would involve in lung inflammation induced by particular matter is still unclear. This study aims to observe the effect of oBC on lung damage in mice and discuss how the functional MAP4K4 defect CD4(+) T cells (conditional knockout of MAP4K4) presents its role in this process. In our study, MAP4K4 deletion in CD4(+) T cells (MAP4K4 cKO) could increase cell number of macrophages, lymphocytes and neutrophils in bronchoalveolar lavage fluid (BALF) exposed to oBC. MAP4K4 deletion in CD4(+) T cell also affected CD4(+) T cell differentiation in mediastinal lymph nodes after oBC stimulation. The number of CD4(+) IL17(+) T cell increased obviously. The levels of IL-6 mRNA of lung in MAP4K4 cKO mice was higher than that in wild type mice after exposed to oBC, while the level of IL-6 in BALF had the same trend. Histological examination showed that MAP4K4 deletion in CD4(+) T cells affected lung inflammation induced by oBC. Results indicated that MAP4K4 cKO in CD4(+) T cells upgraded the level of inflammation in lung when exposed to oBC, which may be connected to the CD4(+) T cell differentiation and JNK, ERK and P38 pathways. PMID:27504712

  13. Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

    Directory of Open Access Journals (Sweden)

    Babar E.

    2002-01-01

    Full Text Available The interactions between the median raphe nucleus (MRN serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 µg/side produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

  14. Les pénalités de pauvreté en France : comment le marché aggrave la situation des populations pauvres

    Directory of Open Access Journals (Sweden)

    Frédéric Dalsace

    2012-01-01

    Full Text Available S’appuyant sur une étude du Boston Consulting Group  effectuée à la demande de l’Action Tank « Entreprise et Pauvreté », cet article permet d'expliquer et de quantifier   ce que l’on appelle les pénalités de pauvreté en France. Les populations pauvres, comme dans les pays émergents - mais pour des raisons profondément différentes, payent plus cher que les autres ménages, les mêmes biens et services,  par unité de consommation. L’objectif ultime est de favoriser le développement de solutions pour lutter contre ce phénomène ; des expérimentations actuellement menées par des entreprises françaises représentent un espoir dans la lutte contre ces pénalités de pauvreté.

  15. Impaired removal of Vβ8(+) lymphocytes aggravates colitis in mice deficient for B cell lymphoma-2-interacting mediator of cell death (Bim)

    OpenAIRE

    Leucht, K; Caj, M; Fried, M; Rogler, G; Hausmann, M.

    2013-01-01

    We investigated the role of B cell lymphoma (BCL)-2-interacting mediator of cell death (Bim) for lymphocyte homeostasis in intestinal mucosa. Lymphocytes lacking Bim are refractory to apoptosis. Chronic colitis was induced in Bim-deficient mice (Bim(-/-) ) with dextran sulphate sodium (DSS). Weight loss and colonoscopic score were increased significantly in Bim(-/-) mice compared to wild-type mice. As Bim is induced for the killing of autoreactive cells we determined the role of Bim in the re...

  16. Mycoplasma hyorhinis is a potential pathogen of porcine respiratory disease complex that aggravates pneumonia caused by porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Lee, Jung-Ah; Oh, Yu-Ri; Hwang, Min-A; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Sang-Won

    2016-09-01

    The porcine respiratory disease complex (PRDC) caused by numerous bacterial and viral agents has a great impact on pig industry worldwide. Although Mycoplasma hyorhinis (Mhr) has been frequently isolated from lung lesions from pigs with PRDC, the pathological importance of Mhr may have been underestimated. In this study, 383 serum samples obtained from seven herds with a history of PRDC were tested for specific antibodies to Mhr, Mycoplasma hyopneumoniae (Mhp), and porcine reproductive and respiratory syndrome virus (PRRSV). Seropositive rates of PRRSV were significantly correlated with those of Mhr (correlation coefficient, 0.862; P-value, 0.013), but not with those of Mhp (correlation coefficient, -0.555; P-value, 0.196). In vivo experiments demonstrated that pigs co-infected with Mhr and PRRSV induced more severe lung lesions than pigs infected with Mhr or PRRSV alone. These findings suggest that Mhr is closely associated with pneumonia caused by PRRSV and provide important information on Mhr pathogenesis within PRDC. Therefore, effective PRDC control strategies should also consider the potential impact of Mhr in the pathogenesis of PRDC. PMID:27436444

  17. The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture

    OpenAIRE

    Li Gan; Jianfeng Zhong; Ruhui Zhang; Tiansheng Sun; Qi Li; Xiaobin Chen; Jianzheng Zhang

    2015-01-01

    Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as ...

  18. Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

    NARCIS (Netherlands)

    Laskewitz, Anke J.; van Dijk, Theo H.; Grefhorst, Aldo; van Lierop, Marie-Jose; Schreurs, Marijke; Bloks, Vincent W.; Reijngoud, Dirk-Jan; Dokter, Wim H.; Kuipers, Folkert; Groen, Albert K.

    2012-01-01

    Synthetic glucocorticoids such as prednisolone have potent antiinflammatory actions. Unfortunately, these drugs induce severe adverse effects in patients, many of which resemble features of the metabolic syndrome, such as insulin resistance. In this study, we investigated whether adverse effects of

  19. Sleep restriction reduces the survival time and aggravates the neurological dysfunction and memory impairments in an animal model of cerebral hypoperfusion.

    Science.gov (United States)

    Kim, Lenise Jihe; Coelho, Fernando Morgadinho; Araujo, Paula; Tedesco, Roberto Carlos; Souza, Rodrigo Barbosa; Tufik, Sergio; Andersen, Monica Levy

    2016-08-01

    Cerebral blood flow is associated with the cerebrovascular prognosis. Sleep restriction (SR) may be a limiting factor of the prognosis after a cerebrovascular event, impairing the neurological recovery. We aimed to investigate the effects of SR on mortality rate and on behavioral and histological parameters of animals submitted to permanent cerebral hypoperfusion. Sixty male Wistar rats were distributed in 4 groups, according to the protocol of common carotid artery occlusion (CCAO) and SR: nSR+nCCAO, SR+nCCAO, nSR+CCAO, and SR+CCAO. The groups SR+nCCAO and SR+CCAO were submitted to SR during 10 days. The cerebral hypoperfusion was induced by the permanent CCAO. Neurological function and memory were assessed over 14 days of cerebral hypoperfusion. Analysis of neuropathological alterations were performed in the CA1 region of hippocampus. The mortality rate was 40% in the nSR+CCAO and SR+CCAO groups. SR significantly reduced the survival time of animals submitted to CCAO. After 7 and 14 days of cerebral hypoperfusion, 11% and 33% of the nSR+CCAO and SR+CCAO animals showed severe neurological dysfunction, respectively. A significant association between a high frequency of memory impairments with the group SR+CCAO was observed. The neuropathological alterations in CA1 region of hippocampus were similar among the groups. SR potentiates the negative effects of cerebral hypoperfusion conditions, suggesting that SR could be a factor associated with a worse prognosis after a cerebrovascular event. PMID:27174002

  20. Aggravation and decreased risk in the insurance contract in Cuba: does a case of judicial review before the occurrence of unforeseen events?

    Directory of Open Access Journals (Sweden)

    Raúl José Vega Cardona

    2016-06-01

    Full Text Available In every contract people as parties may call upon the court to review the agreed legal business when benefits become excessively burdensome for one of the contractors under the occurrence of unforeseeable, extraordinary, inevitable and totally unrelated to the will of these. But some civil codes deny the possibility of application of this theory to certain contractual types, amongst these random contracts, and particularly insurance. In this sense a sector of the doctrine has also supported this approach based on the analysis that would be improper to speak of unpredictability in a contractual type that is configured exactly the presence of unpredictable elements that will determine the outcome of the contract. But to deny this possibility would be to go against good was as a general principle of law, that the seat is particularly relevant contracts. Given this imperative, this article elaborates on the theory that allows to apply for judicial review of randomized contracts, especially the insurance contract from historical analysis – doctrinal and legislative theory of foresight and their relation to the alloy as characteristic feature of these contract types.

  1. Ferrous sulfate, but not iron polymaltose complex, aggravates local and systemic inflammation and oxidative stress in dextran sodium sulfate-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2015-05-01

    Full Text Available Jorge E Toblli, Gabriel Cao, Margarita Angerosa Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Background and aims: Iron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats.Methods: Animals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed.Results: Body weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment.Conclusion: Iron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease. Keywords: preclinical, oral iron treatment, tolerability, colonic tissue erosion, inflammatory bowel disease

  2. Extracorporeal membrane oxygenation as a bridge to liver transplantation for acute respiratory distress syndrome-induced life-threatening hypoxaemia aggravated by hepatopulmonary syndrome

    OpenAIRE

    Monsel, Antoine; Mal, Hervé; Brisson, Hélène; Luo, Rubin; Eyraud, Daniel; Vézinet, Corinne; Do, Chung Hi; Lu, Qin; Vaillant, Jean-Christophe; Hannoun, Laurent; Houssel, Pauline; Durand, François; Rouby, Jean-Jacques

    2011-01-01

    Introduction Combined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease. Methods The case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described. Results A 51-year-old man with a five-year ...

  3. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation.

    Science.gov (United States)

    Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

    2015-08-14

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm(2) fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C-C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. PMID:26047701

  4. Downregulation of CD99 and upregulation of human leukocyte antigen class II promote tumor aggravation and poor survival in patients with osteosarcomas

    OpenAIRE

    Zhou Q; Xu J; Zhao J; Zhang S; Pan W

    2014-01-01

    Quan Zhou,* Jin Xu,* Jiali Zhao, Shaoxian Zhang, Wei PanDepartment of Orthopaedics, the second Hospital of Huai'an city Affiliated to Xuzhou Medical College and the second Hospital of Huai'an city, Huai'an, People's Republic of China *These authors contributed equally to this workBackground: CD99 is involved in the intracellular transport of human leukocyte antigen class II (HLA-II) protein. The aim of this study was to clarify the clinical value of CD99 and HL...

  5. NCBI nr-aa BLAST: CBRC-SARA-01-1597 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-1597 sp|Q9XT57|ADRB3_CAPHI Beta-3 adrenergic receptor (Beta-3 adrenoceptor) (Beta-3 adreno...receptor) gb|AAD26148.1|AF109929_1 beta 3 adrenergic receptor; beta3-adrenoceptor [Capra hircus] Q9XT57 1e-140 75% ...

  6. Fatal Neurological Respiratory Insufficiency Is Common Among Viral Encephalitides

    OpenAIRE

    Wang, Hong; Siddharthan, Venkatraman; Kesler, Kyle K.; Jeffery O Hall; Motter, Neil E.; Julander, Justin G.; John D Morrey

    2013-01-01

    Background.  Neurological respiratory insufficiency strongly correlates with mortality among rodents infected with West Nile virus (WNV), which suggests that this is a primary mechanism of death in rodents and possibly fatal West Nile neurological disease in human patients. Methods.  To explore the possibility that neurological respiratory insufficiency is a broad mechanism of death in cases of viral encephalitis, plethysmography was evaluated in mice infected with 3 flaviviruses and 2 alphav...

  7. Evaluation of cardiac blood blow, metabolism and sympathetic nerve function in patients with cardiac failure using PET and SPECT. Prognostic diagnosis based on the analysis of aggravating factors of the disease

    International Nuclear Information System (INIS)

    Focusing on the failure of energy metabolism, which is assumed to be attributed to the cardiac muscle disorder of a patient with cardiac failure, the characteristics and diagnostic significance of the metabolic disorders of cadiac muscles were investigated in those patients. The diagnostic efficacy of β-methyl iodophenyl pentadecanoic acid (BMIPP) which is a imaging agent for lipid metabolism in the cardiac muscle was assessed in the clinical states of cardiac failure due to pulmonary hypertension. Even if there was a considerable increase in the mean pulmonary arterial pressure (mPAP), the initial accumulation of BMIPP linearly increased, similarly to the increase in the accumulation of MIBI, a blood flow agent. The initial accumulation of BMIPP was thought to reflect a thicken cardiac muscle and/or increased blood flow. Also, its washing-out rate was suggested to be usable as an clinical indicator to estimate the loading of ventricular pressure. (M.N.)

  8. Throbbing tinnitus in aberrant internal carotid artery aggravated by elevation of the jugular bulb. A case report; Pulsierender Tinnitus bei aberranter Arteria carotis interna in Kombination mit Hochstand des Bulbus venae jugularis. Kasuistik

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, T. [Inst. fuer Roentgendiagnostik, Klinikum der Technischen Univ. Muenchen (Germany); Kirsten, R. [Inst. fuer Roentgendiagnostik, Klinikum der Technischen Univ. Muenchen (Germany); Kau, R.J. [Hals-Nasen-Ohrenklinik und Poliklinik, Klinikum der Technischen Univ. Muenchen (Germany)

    1995-04-01

    Vascular anomalies in the middle ear are rarely observed. They cause no symptoms in the majority of cases, although some may be associated with tinnitus. The false diagnosis of glomus tumour may lead to considerable problems, if surgery is performed. It is therefore necessary that precise pre-operative data are obtained, preferably based on contrast-enhanced computerized tomography. Subsequent 2D and 3D image reconstructions provide further vascular findings regarding the topographic and anatomic factors involved and eliminate the need for invasive angiography of the carotid artery or retrograde jugular venography to make a firm diagnosis. (orig.) [Deutsch] Gefaessanomalien im Mittelohr sind selten. Meist sind sie asymptomatisch, koennen aber assoziiert sein mit Tinnitus. Die Fehldiagnose eines Glomustumors kann im Rahmen einer Operation zu gravierenden Problemen fuehren. Eine exakte praeoperative Abklaerung ist deshalb notwendig und sollte als Computertomographie mit Kontrastmittelgabe durchgefuehrt werden. Die anschliessende 2D- und 3D-Bildwiedergabe klaert die topographisch-anatomischen Gefaessbeziehungen und erlaubt somit die Diagnosestellung ohne die frueher durchgefuehrte invasive Carotisangiographie oder retrograde Jugularisvenographie. (orig.)

  9. Evaluation of cardiac blood blow, metabolism and sympathetic nerve function in patients with cardiac failure using PET and SPECT. Prognostic diagnosis based on the analysis of aggravating factors of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Yoshio; Shimozu, Junko; Yasumura, Yoshio; Nagatani, Kenzo; Miyatake, Kunio [National Cardiovascular Center, Suita, Osaka (Japan)

    1998-02-01

    Focusing on the failure of energy metabolism, which is assumed to be attributed to the cardiac muscle disorder of a patient with cardiac failure, the characteristics and diagnostic significance of the metabolic disorders of cadiac muscles were investigated in those patients. The diagnostic efficacy of {beta}-methyl iodophenyl pentadecanoic acid (BMIPP) which is a imaging agent for lipid metabolism in the cardiac muscle was assessed in the clinical states of cardiac failure due to pulmonary hypertension. Even if there was a considerable increase in the mean pulmonary arterial pressure (mPAP), the initial accumulation of BMIPP linearly increased, similarly to the increase in the accumulation of MIBI, a blood flow agent. The initial accumulation of BMIPP was thought to reflect a thicken cardiac muscle and/or increased blood flow. Also, its washing-out rate was suggested to be usable as an clinical indicator to estimate the loading of ventricular pressure. (M.N.)

  10. Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions

    NARCIS (Netherlands)

    Szalowska, Ewa; Pronk, T.E.; Peijnenburg, A.A.C.M.

    2015-01-01

    Background: The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to

  11. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors.

    Science.gov (United States)

    Bilbao, R; Reay, D P; Hughes, T; Biermann, V; Volpers, C; Goldberg, L; Bergelson, J; Kochanek, S; Clemens, P R

    2003-10-01

    High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle. PMID:12960972

  12. Application of pressure perturbation calorimetry to lipid bilayers.

    OpenAIRE

    Heerklotz, Heiko; Seelig, Joachim

    2002-01-01

    Pressure perturbation calorimetry (PPC) is a new method that measures the heat consumed or released by a sample after a sudden pressure jump. The heat change can be used to derive the thermal volume expansion coefficient, alpha(V), as a function of temperature and, in the case of phase transitions, the volume change, DeltaV, occurring at the phase transition. Here we present the first report on the application of PPC to determine these quantities for lipid bilayers. We measure the volume chan...

  13. PET imaging of alphavbeta integrin expression in tumours with Ga-labelled mono-, di- and tetrameric RGD peptides

    NARCIS (Netherlands)

    Dijkgraaf, I.; Yim, C.B.; Franssen, G.M.; Schuit, R.C.; Luurtsema, G.; Liu, S.; Oyen, W.J.G.; Boerman, O.C.

    2011-01-01

    PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared wi

  14. Synthesis and biological evaluation of potent alphavbeta3-integrin receptor antagonists.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Kruijtzer, J.A.; Frielink, C.; Soede, A.C.; Hilbers, H.W.; Oyen, W.J.G.; Corstens, F.H.M.; Liskamp, R.M.; Boerman, O.C.

    2006-01-01

    INTRODUCTION: alpha(v)beta(3) Integrin is expressed in sprouting endothelial cells in growing tumors, whereas it is absent in quiescent blood vessels. In addition, various tumor cell types express alpha(v)beta(3) integrin. alpha(v)beta(3) Integrin, a transmembrane heterodimeric protein, binds to the

  15. Rétraction: plagiat aggravé dans l'article Aspergillose broncho-pulmonaire allergique lors d'un asthme réfractaire: à propos d'un cas clinique. Khalid Lahmadi, Hind El Youssi, Jawad Rochdi, BoughrineNawal, Er-Rami Mohammed. The Pan African Medical Journal. 2015;20:350. (doi:10.11604/pamj.2015.20.350.6572)

    OpenAIRE

    ,

    2015-01-01

    Cet article retracte l'article "Aspergillose broncho-pulmonaire allergique lors d'un asthme réfractaire: à propos d'un cas clinique. Khalid Lahmadi, Hind El Youssi, Jawad Rochdi, BoughrineNawal, Er-Rami Mohammed. The Pan African Medical Journal. 2015;20:350. (doi:10.11604/pamj.2015.20.350.6572)"

  16. Rétraction: plagiat aggravé dans l'article Aspergillose broncho-pulmonaire allergique lors d'un asthme réfractaire: à propos d'un cas clinique. Khalid Lahmadi, Hind El Youssi, Jawad Rochdi, BoughrineNawal, Er-Rami Mohammed. The Pan African Medical Journal. 2015;20:350. (doi:10.11604/pamj.2015.20.350.6572)

    Science.gov (United States)

    2015-01-01

    Cet article retracte l'article "Aspergillose broncho-pulmonaire allergique lors d'un asthme réfractaire: à propos d'un cas clinique. Khalid Lahmadi, Hind El Youssi, Jawad Rochdi, BoughrineNawal, Er-Rami Mohammed. The Pan African Medical Journal. 2015;20:350. (doi:10.11604/pamj.2015.20.350.6572)" PMID:26401219

  17. Can Institutional Investors Aggravate the Effect of Stock Markets on Physical Economic?--- Based on the Perspective of the Effect of Investor Sentiment on Corporate Investment%机构投资者是股票市场影响实体经济的助推器吗?--基于投资者情绪对公司资本投资的视角

    Institute of Scientific and Technical Information of China (English)

    花贵如; 刘志远; 郑凯

    2015-01-01

    Inefficient capital markets affect the corporate physical investment.Which role can institutional investors play?Does it affect the relationships between investor sentiment and corporate investment?From the perspective of behavioral corporate finance,this paper theoretically analyzes and empirically studies the questions.It is found that in the listed compa-nies holding institutional investor,investor sentiment has a significant effect on corporate investment.Institutional investors do play an adjustment role through the intermediate channel of managerial optimism.The results can help to identify the roles of institutional investors in China’s capital market which is important to make policy about institutional investor,and to under-stand the information handed by institutional investor and evade the “expert trap”in the decision-making process.%“资本市场并非有效”,股票市场上投资者情绪对公司的实体投资行为具有重大影响。被监管层寄予厚望的机构投资者从中扮演了什么角色?上述重大影响的助推器抑或制衡器,深层的作用机理又是什么?运用行为公司金融理论,研究发现,公司资本投资决策倾向于遵循机构投资者的“专家意见”,机构投资者是投资者情绪影响公司资本投资的“助推器”,“管理者信心”是上述助推功能得以发挥的重要渠道。上述研究发现有助于从微观企业的视角,有效识别机构投资者在股票市场影响实体经济中的角色,为监管层在“后金融危机时代”制定和执行有关机构投资者的政策提供依据;也有益于公司管理层科学理解机构投资者传递的信息,合理规避决策过程中的“专家陷阱”。

  18. Social disruption stress exacerbates alpha-galactosylceramide-induced hepatitis in mice

    OpenAIRE

    Sonoda, J.; Chida, Y; Sudo, N.; Kubo, C

    2005-01-01

    Objective: Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag+ T cell-dependent a-galactosylceramide (alpha-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation,...

  19. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    Science.gov (United States)

    Dellambra, E; Vailly, J; Pellegrini, G; Bondanza, S; Golisano, O; Macchia, C; Zambruno, G; Meneguzzi, G; De Luca, M

    1998-06-10

    Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses. PMID:9650620

  20. Yeast Interacting Proteins Database: YBR288C, YGR261C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YBR288C APM3 Mu3-like subunit of the clathrin associated protein complex (AP-3); functions in tr ... as prey (0) YGR261C APL6 Beta3-like subunit of the yeast ... AP-3 complex; functions in transport of alkaline p ... me APL6 Prey description Beta3-like subunit of the yeast ... AP-3 complex; functions in transport of alkaline p ...

  1. Erythroblastic Islands: Specialized Mircoenvironmental Niches forErythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Chasis, Joel Anne

    2006-01-06

    This review focuses on current understanding of molecular mechanisms operating within erythroblastic islands including cell-cell adhesion, regulatory feedback, and central macrophage function. RECENT FINDINGS: Erythroblasts express a variety of adhesion molecules and recently two interactions have been identified that appear to be critical for island integrity. Erythroblast macrophage protein, expressed on erythroblasts and macrophages, mediates cell-cell attachments via homophilic binding. Erythroblast intercellular adhesion molecule-4 links erythroblasts to macrophages through interaction with macrophage alphav integrin. In intercellular adhesion molecule-4 knockout mice, erythroblastic islands are markedly reduced, whereas the erythroblast macrophage protein null phenotype is severely anemic and embryonic lethal. Retinoblastoma tumor suppressor (Rb) protein stimulates macrophage differentiation by counteracting inhibition of Id2 on PU.1, a transcription factor that is a crucial regulator of macrophage differentiation. Rb-deficient macrophages do not bind Rb null erythroblasts and the Rb null phenotype is anemic and embryonic lethal. Lastly, extruded nuclei rapidly expose phosphatidylserine on their surface, providing a recognition signal similar to apoptotic cells. SUMMARY: Although understanding of molecular mechanisms operating within islands is at an early stage, tantalizing evidence suggests that erythroblastic islands are specialized niches where intercellular interactions in concert with cytokines play critical roles in regulating erythropoiesis.

  2. Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses.

    Science.gov (United States)

    Maree, Francois F; Blignaut, Belinda; de Beer, Tjaart A P; Visser, Nico; Rieder, Elizabeth A

    2010-10-01

    Foot-and-mouth disease virus (FMDV) infects host cells by adhering to the alpha(V) subgroup of the integrin family of cellular receptors in a Arg-Gly-Asp (RGD) dependent manner. FMD viruses, propagated in non-host cell cultures are reported to acquire the ability to enter cells via alternative cell surface molecules. Sequencing analysis of SAT1 and SAT2 cell culture-adapted variants showed acquisition of positively charged amino acid residues within surface-exposed loops of the outer capsid structural proteins. The fixation of positively charged residues at position 110-112 in the beta F-beta G loop of VP1 of SAT1 isolates is thought to correlate with the acquisition of the ability to utilise alternative glycosaminoglycan (GAG) molecules for cell entry. Similarly, two SAT2 viruses that adapted readily to BHK-21 cells accumulated positively charged residues at positions 83 and 85 of the beta D-beta E loop of VP1. Both regions surround the fivefold axis of the virion. Recombinant viruses containing positively charged residues at position 110 and 112 of VP1 were able to infect CHO-K1 cells (that expresses GAG) and demonstrated increased infectivity in BHK-21 cells. Therefore, recombinant SAT viruses engineered to express substitutions that induce GAG-binding could be exploited in the rational design of vaccine seed stocks with improved growth properties in cell cultures. PMID:20637812

  3. Digital Rectal Exam (DRE)

    Science.gov (United States)

    ... tell your health care team if you have hemorrhoids or anal fissures, as the DRE may aggravate ... from the rectum afterward, particularly if you have hemorrhoids or anal fissures. Tell your doctor if you ...

  4. Radiation therapy in complex treatment for stage III breast cancer with reconstructive plastic surgery

    International Nuclear Information System (INIS)

    Post-operative radiation therapy in patients with stage III breast cancer on the third month after reconstructive plastic surgery allows to eliminate scar deformities of the organ and does not aggravate the treatment results when compared with mastectomized patients.

  5. The Optimal Dentition of the Periodontitis Patient

    DEFF Research Database (Denmark)

    Melsen, Birte; Laursen, Morten Godtfredsen

    2014-01-01

    This article focuses on the evolution of orthodontic treatment possibilities developed for degenerating dentitions in adult patients. Indications for such therapy comprise dentition suffering from an aggravation of a malocclusion, horizontal loss of periodontal tissue support, elongation and...

  6. 12 CFR Appendix J to Part 334 - Interagency Guidelines on Identity Theft Detection, Prevention, and Mitigation

    Science.gov (United States)

    2010-01-01

    ... aggravating factors that may heighten the risk of identity theft, such as a data security incident that... verification set forth in the Customer Identification Program rules implementing 31 U.S.C. 5318(l)(31 CFR...

  7. 38 CFR 3.12 - Character of discharge.

    Science.gov (United States)

    2010-07-01

    ... was otherwise honest, faithful and meritorious. (5) Homosexual acts involving aggravating circumstances or other factors affecting the performance of duty. Examples of homosexual acts involving..., homosexual prostitution, homosexual acts or conduct accompanied by assault or coercion, and homosexual...

  8. 综合康复治疗贝尔面瘫瘫32例%Treatment of Bell facial paralysis by comprehensive rehabilitation therapy

    Institute of Scientific and Technical Information of China (English)

    徐纪香

    2002-01-01

    Background:Bell facial paralysis is characterized by acutely peripheral facial paralysis.Simple approaches can aggravate symptoms and induce permanent facial paralysis.Optimal therapy time may be missed.Comprehensive therapy is effective in treating the condition.

  9. Nutrition in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Marco Silva

    2015-11-01

    The large majority of patients with grade I/II hepatic encephalopathy can tolerate a regular diet. Protein restriction can aggravate malnutrition and is not recommended, except in cases of hepatic encephalopathy unresponsive to optimized therapy.

  10. The Mind-Body Connection - How to Fight Stress and Ward Off Illness

    Science.gov (United States)

    ... aggravate existing health problems. It can worsen angina, disturb heart rhythm, raise blood pressure, and lead to ... stress response, she says. If starting an exercise program seems too hard, then go slowly, she advises. " ...

  11. Alleviation of Severe Restless Legs Syndrome (RLS) Symptoms by Cigarette Smoking

    OpenAIRE

    Oksenberg, Arie

    2010-01-01

    Cigarette smoking is in general considered an aggravating factor for restless legs syndrome (RLS). The author presents a case in which cigarette smoking has produced for many years a consistent and effective alleviation of RLS symptoms.

  12. Food Chromium Contents, Chromium Dietary Intakes And Related Biological Variables In French Free-Living Elderly

    Science.gov (United States)

    Chromium (Cr III), an essential trace element, functions in potentiating insulin sensitivity, regulating glucose homeostasis, improving lipid profile, and maintaining lean body mass. Glucose intolerance and chromium deficiency increase with age, and could be aggravating factors of the metabolic synd...

  13. 20 CFR 10.5 - What definitions apply to these regulations?

    Science.gov (United States)

    2010-04-01

    ... employee at the time of his or her death, or living apart for reasonable cause or because of the deceased employee's desertion. (dd) Temporary aggravation of a pre-existing condition means that factors...

  14. Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt

    DEFF Research Database (Denmark)

    Trebicka, Jonel; Krag, Aleksander; Gansweid, Stefan; Appenrodt, Beate; Schiedermaier, Peter; Sauerbruch, Tilman; Spengler, Ulrich

    2011-01-01

    In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor α (TNFα...

  15. Iron and erythropoiesis-stimulating agents in anaemia

    Directory of Open Access Journals (Sweden)

    Thomas Rath

    2010-01-01

    Full Text Available Anaemia is a frequent and clinically relevant problem in patients with malignancy and may be aggravated in patients receiving chemotherapy. Blood transfusions, iron supplementation, and erythropoiesis-stimulating agents (ESAs are established treatment options for anaemic patients.

  16. Intramedullary neuroepithelial cyst of the spinal cord

    OpenAIRE

    Vanwyck, R; Vliegen, A S

    2011-01-01

    Background: A 32-year-old woman presented with low back ache aggravating after several sessions of osteopathy and increasing radiating pain to the right flank. There was no trauma in the medical history and neurological examination was unremarkable.

  17. Heavy metal accumulation in a flow restricted, tropical estuary

    Digital Repository Service at National Institute of Oceanography (India)

    Balachandran, K.K.; Laluraj, C.M.; Nair, M.; Joseph, T.; Sheeba, P.; Venugopal, P.

    the region among the impacted estuaries in the world. Accumulation of metals in this estuarine system is aggravated by the weak flushing. These pressures are deemed inevitable with growth initiated in the harbour and associated with mega city development...

  18. The underinvestment problem under conglomeration

    Directory of Open Access Journals (Sweden)

    Jacques A. Schnabel

    2015-12-01

    Full Text Available This theoretical paper explores whether the underinvestment problem is aggravated or ameliorated by the formation of a pure conglomerate. It establishes that the answer depends critically on the volatility of corporate assets. If volatility is low, conglomeration ameliorates the underinvestment problem, whereas if volatility is high, conglomeration aggravates the underinvestment problem. These analytical results are then invoked as a potential explanation for the ambiguous conclusions of empirical studies that delve into the existence of a conglomerate discount.

  19. Psoriasis triggered by bupropion in a patient with major depression

    OpenAIRE

    Akpınar, Abdullah; Ceyhan, Murat Ali; Yaman, Ayşe Rümeysa

    2013-01-01

    Despite extensive use of antidepressants in patients with psoriasis, there have been very few case reports of antidepressant-related psoriasis. In this case, a patient with major depression who was treated with varies types of antidepressants including fluoxetine, reboxetine, bupropion, and venlafaxine, and in who pre-existing psoriatic lesions were aggravated after bupropion treatment. Clinicians should be aware of the influence of bupropion to aggravate pre-existing psoriasis.

  20. Hair removal in hirsute women with normal testosterone levels: a randomized controlled trial of long-pulsed diode laser vs. intense pulsed light

    DEFF Research Database (Denmark)

    Haak, C S; Jensen, Pernille Nymann; Pedersen, A T; Clausen, H V; Feldt Rasmussen, U; Rasmussen, Åse Krogh; Main, K; Haedersdal, M

    2010-01-01

    Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels.......Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels....

  1. Virtual reality and musculoskeletal pain:manipulating sensory cues to improve motor performance during walking

    OpenAIRE

    Powell, Wendy; Simmonds, Maureen J.

    2014-01-01

    Musculoskeletal pain (MSP) is the most expensive nonmalignant health problem and the most common reason for activity limitation. Treatment approaches to improve movement without aggravating pain are urgently needed. Virtual reality (VR) can decrease acute pain, as well as influence movement speed. It is not clear whether VR can improve movement speed in individuals with MSP without aggravating pain. This study investigated the extent to which different audio and optic flow cues in a VR enviro...

  2. Potential Risk Factors of Persistent Low Back Pain Developing from Mild Low Back Pain in Urban Japanese Workers

    OpenAIRE

    Ko Matsudaira; Hiroaki Konishi; Kota Miyoshi; Tatsuya Isomura; Kyoko Inuzuka

    2014-01-01

    STUDY DESIGN: Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study in urban settings were used for this analysis. OBJECTIVE: To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain. SUMMARY OF BACKGROUND DATA: Although psychosocial factors are strongly indicated as yellow flags of low back pain (LBP) leading to disability, the association between aggravated LB...

  3. Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100 % O2

    OpenAIRE

    Wagner, Katja; Gröger, Michael; McCook, Oscar; Scheuerle, Angelika; Asfar, Pierre; Stahl, Bettina; Huber-Lang, Markus; Ignatius, Anita; Jung, Birgit; Duechs, Matthias; Möller, Peter; Georgieff, Michael; Calzia, Enrico; Radermacher, Peter; Wagner, Florian

    2015-01-01

    Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperox...

  4. Complete obstruction of right side lymphatic of lower limb%右下肢淋巴管完全性阻塞案

    Institute of Scientific and Technical Information of China (English)

    尚军; 孟苏华

    2010-01-01

    @@ A patient, female, aged 65 years, paid her visit on 18thJanuary, 2008.She complained of edema, soreness and heaviness of right side of lower limb for 9 years,aggravated for half a year.The right side of lumbus and lower limb were injured in an accident 9 years ago.Although the function was basically recovered after treatment, edema appeared at right side of lower limb, aggravated day by day, and difficulty of walking with heavy sensation occurred.

  5. Launching a novel preclinical infrastructure: comparative oncology trials consortium directed therapeutic targeting of TNFalpha to cancer vasculature.

    Directory of Open Access Journals (Sweden)

    Melissa C Paoloni

    Full Text Available BACKGROUND: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC. The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. METHODOLOGY/PRINCIPAL FINDINGS: Through this established infrastructure, the first trial of the COTC (COTC001 evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF to alphaV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24 determined an optimal safe dose (5x10(12 transducing units intravenous of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%, stable disease in six (43%, and disease progression in six (43% via Response Evaluation Criteria in Solid Tumors (RECIST. CONCLUSIONS/SIGNIFICANCE: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies.

  6. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    Science.gov (United States)

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  7. КЛИНИКО-ЭЛЕКТРОЭНЦЕФАЛОГРАФИЧЕСКИЙ АНАЛИЗ ТЕРАПИИ АСТЕНИЧЕСКИХ РАССТРОЙСТВ НООТРОПАМИ И ИХ КОМБИНАЦИЕЙ С ИММУНОМОДУЛЯТОРОМ

    OpenAIRE

    Бочкарев, В.; Файзуллоев, А.; Куликова, Т.

    2009-01-01

    The article presents the results of investigation of basic EEG-rhythms (delta, theta, alpha, beta-1, beta-2 and beta-3) during a course of medication with nootropic drugs (Phenotropil or Nooklerin) and their combination with an immune modulator Galavit in patients with asthenic disorders within frames of neurasthenia (F48.0) and organic asthenic disorder (F06.6). Similar changes have been found in beta-2 and beta-3 rhythms in the course of purely nootropic and combined medication: they became...

  8. Binding of Actinomyces naeslundii to glycosphingolipids.

    OpenAIRE

    Brennan, M J; Joralmon, R A; Cisar, J O; Sandberg, A L

    1987-01-01

    The type 2 fimbrial lectin of Actinomyces naeslundii WVU45 mediated the binding of this bacterium to glycosphingolipids chromatographed on thin-layer silica gel plates. Radioiodinated bacteria attached to GM1, GD1b, and globoside. After chromatograms were treated with sialidase, the bacteria also bound to GD1a and GT1b. The actinomyces lectin apparently recognized the Gal beta 3GalNAc termini of these gangliosides and the GalNAc beta 3Gal terminus of globoside, suggesting that glycolipids con...

  9. Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Jacobsen, Nicklas Raun;

    2016-01-01

    Free palmitic acid (PA) is a potential pro-atherogenic stimulus that may aggravate particle-mediated cardiovascular health effects. We hypothesized that the presence of PA can aggravate oxidative stress and endothelial activation induced by multi-walled carbon nanotube (MWCNT) exposure in vitro. We...... investigated the interaction between direct exposure to MWCNTs and PA on THP-1 monocyte adhesion to human umbilical vein endothelial cells (HUVECs), as well as on indirect exposure in an alveolar-endothelial co-culture model with A549 cells and THP-1-derived macrophages exposed in inserts and the effect...... monocultures. Both effects were found to be independent of the presence of PA. MWCNT exposure significantly increased THP-1 monocyte adhesion to HUVECs, and co-exposure to PA aggravated the NM400-mediated adhesion but decreased the NM402-mediated adhesion. For the co-cultures, the exposure of A549 cells did...

  10. Acute Calcific Bursitis After Ultrasound-Guided Percutaneous Barbotage of Rotator Cuff Calcific Tendinopathy: A Case Report.

    Science.gov (United States)

    Kang, Bo-Sung; Lee, Seung Hak; Cho, Yung; Chung, Sun Gun

    2016-08-01

    Ultrasound-guided percutaneous barbotage is an effective treatment for rotator cuff calcific tendinopathy, providing rapid and substantial pain relief. We present the case of a 49-year-old woman with aggravated pain early after ultrasound-guided barbotage of a large calcific deposit in the supraspinatus tendon. Subsequent examination revealed a thick calcification spreading along the subacromial-subdeltoid bursa space, suggesting acute calcific bursitis complicated by barbotage. Additional barbotage alleviated her pain completely. Therefore, a high index of suspicion for acute calcific bursitis is required in patients with unresolved or aggravated pain after barbotage. Repeated barbotage could be effective for this condition. PMID:26902864

  11. Restructuring the Homicide Offences to Tackle Violence, Discrimination and Drugs in a Modern Society

    OpenAIRE

    Elliott, C.; de Than, C.

    2009-01-01

    This article argues that the current law on homicide fails to satisfy the goal of “fair labelling” leading to an indirect risk of discrimination against vulnerable members of our society who are not being consistently recognized as the victims of a fatal crime. The case is put forward for two new rungs in the homicide ladder of “aggravated murder” and “aggravated manslaughter”, along with statutory offences which directly cater for the victims of drug homicides and domestic abuse leading to a...

  12. [Psychiatric complications of cannabis use].

    Science.gov (United States)

    Coscas, Sarah; Benyamina, Amine; Reynaud, Michel; Karila, Laurent

    2013-12-01

    Cannabis is the most widely used illicit substance, especially among young people. Cannabis use is extremely commonplace and frequently comorbid with psychiatric disorders that raise questions about the etiology. The use of cannabis is an aggravating factor of all psychiatric disorders. Psychiatric complications are related to the age of onset, duration of exposure and individual risk factors of the individual (mental and social health). The panic attack is the most common complication. The link with psychosis is narrow that leads to increased prevention for vulnerable populations. Cannabis is also an indicator of increased depressive vulnerability and an aggravating factor for bipolar disorder. PMID:24579344

  13. The frequency of dietary references in homeopathic consultations.

    Science.gov (United States)

    Filho, Rubens Dolce

    2011-07-01

    A retrospective quantitative study on dietary references found in medical records of 2753 patients attending consultations from 10/1/1994 to 5/31/2007 was conducted. The symptoms found in the rubrics relating to food and drink aggravation and amelioration, aversion and craving of homeopathic repertories reflect diets at different places and times and do not correspond fully, to contemporary gastronomy. Desires for sweet and spicy foods were statistically more frequent, revealing the prevailing taste for such food among the studied population. Food cravings should be carefully analyzed before considering them as indications for choosing homeopathic therapy, they are less significant than aversions, aggravations and ameliorations. PMID:21784331

  14. Renal tubular acidosis presenting as respiratory paralysis: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Kalita J

    2010-01-01

    Full Text Available Respiratory paralysis due to renal tubular acidosis (RTA is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L and hyperchloremic (110 meq/l acidosis (pH 7.1. She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

  15. Reflections on the society’s reaction towards rape victims in Delhi City

    OpenAIRE

    Hetu Vibha

    2014-01-01

    In general, most people display stronger beliefs in ‘aggravated rape‘ or ‘real rape‘; including victims of such rape cases who often identify themselves as ‘rape victims’ than the victims of ‘simple rape’, where none of the aggravating circumstances are present. Despite myths to the contrary these ‘simple rape’ cases in fact make up the majority of cases. This article considers the implications of ‘real rape‘ and demonstrates how notions about what a ‘typic...

  16. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.G.; Liskamp, R.M.; Corstens, F.H.M.; Boerman, O.C.

    2007-01-01

    INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study,

  17. A new triterpenoid, madhunolic acid, from the seeds of Madhuca latifolia.

    Science.gov (United States)

    Siddiqui, B S; Khan, S; Kardar, M N; Perwaiz, S

    2007-01-01

    A new triterpenoid, madhunolic acid, along with the three known constituents stigmasterol, 4-hydroxymethyl benzoate, and hydroquinone were isolated from the fruit seeds of Madhuca latifolia. The structure of the new compound was elucidated as 2beta,3beta,23-trihydroxyurs-5,12,20-trien-28-oic acid (1) on the basis of spectral data and chemical evidence. PMID:17566924

  18. The glucagon-like peptide 2 receptor is expressed in enteric neurons and not in the epithelium of the intestine

    DEFF Research Database (Denmark)

    Pedersen, Jens; B. Pedersen, Nis; Brix, Sophie W.;

    2015-01-01

    alone, (2) mucosa with lamina propria and epithelium, (3) the external muscle coat including myenteric plexus, (4) a compartment enriched for the myenteric plexus and (5) intestine without epithelium. Expression of Glp2r; chromogranin A; tubulin, beta 3; actin, gamma 2, smooth muscle, enteric and glial...

  19. Converging signals synergistically activate the LAMC2 promoter and lead to accumulation of the laminin gamma 2 chain in human colon carcinoma cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Kirkeby, Lene T; Brorsson, Marianne M; Dabelsteen, Sally; Troelsen, Jesper T; Bordoy, Randi; Fenger, Kirsten; Larsson, Lars-Inge; Simon-Assmann, Patricia

    The trimeric extracellular matrix molecule laminin-5 and its constituent chains (alpha 3, beta 3, gamma 2) are normally not detectable intracellularly in intestinal epithelial cells but the laminin gamma 2 chain can be detected in cancer cells at the invasive front of a subset of colon carcinomas...

  20. Light baryon masses with dynamical twisted mass fermions

    CERN Document Server

    Alexandrou, C; Blossier, B; Brinet, M; Carbonell, J; Dimopoulos, P; Drach, V; Farchioni, F; Frezzotti, R; Guichon, P; Herdoiza, G; Jansen, K; Korzec, T; Koutsou, G; Liu, Z; Michael, C; Pène, O; Shindler, A; Urbach, C; Wenger, U

    2008-01-01

    We present results on the mass of the nucleon and the Delta using two dynamical degenerate twisted mass quarks. The evaluation is performed at four quark masses corresponding to a pion mass in the range of about 300-600 MeV on lattices of 2.1-2.7 fm. We check for cut-off effects by evaluating these baryon masses on lattices of spatial size 2.1 fm at beta=3.9 and beta=4.05 and on a lattice of 2.4 fm at beta=3.8. The values we find are compatible within our statistical errors. Lattice results are extrapolated to the physical limit using continuum chiral perturbation theory. Performing a combined fit to our lattice data at beta=3.9 and beta=4.05 we find a nucleon mass of 964\\pm 28 (stat.) \\pm 8 (syst.) MeV. The nucleon mass at the physical point provides an independent determination of the lattice spacing. Using heavy baryon chiral perturbation theory at O(p^3) we find a_{\\beta=3.9}=0.0890\\pm 0.0039(stat.) \\pm 0.0014(syst.) fm, and a_{\\beta=4.05}= 0.0691\\pm 0.0034(stat.) \\pm 0.0010(syst.) fm, in good agreement w...

  1. Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

    DEFF Research Database (Denmark)

    Andersen, G; Overgaard, J; Albrechtsen, Anders;

    2006-01-01

    The 825C>T polymorphism in the gene encoding the G protein beta3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with...

  2. Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Ebert, Bjarke; Klaerke, Dan;

    2009-01-01

    effects on gramicidin channel A appearance rate and lifetime in artificial lipid bilayers. In the present study, the pharmacological action of Triton-X 100 on GABA(A) receptors expressed in Xenopus laevis oocytes was examined. Triton-X 100 inhibited GABA(A) alpha(1)beta(3)gamma(2S) receptor currents in a...

  3. Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy.

    Science.gov (United States)

    Tanaka, Miyabi; Olsen, Richard W; Medina, Marco T; Schwartz, Emily; Alonso, Maria Elisa; Duron, Reyna M; Castro-Ortega, Ramon; Martinez-Juarez, Iris E; Pascual-Castroviejo, Ignacio; Machado-Salas, Jesus; Silva, Rene; Bailey, Julia N; Bai, Dongsheng; Ochoa, Adriana; Jara-Prado, Aurelio; Pineda, Gregorio; Macdonald, Robert L; Delgado-Escueta, Antonio V

    2008-06-01

    Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents. PMID:18514161

  4. Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report

    OpenAIRE

    Kudo, Chieko; Wakabayashi, Hiroshi; Shimoe, Masayuki; Kobayashi, Hiroya; Ito, Takashi; Ohkawa, Toshinori; Isoshima-Nakamura, Arisa; Mineshiba, Junji; Yoshioka, Norie; Nawachi, Kumiko; Maeda, Hiroshi; Matsuo,Toshihiko; Makino,Hirofumi; Takashiba, Shogo

    2014-01-01

    Key Clinical Message We report a case of Behçet's disease which was aggravated by psychological stress and oral infection. The control of oral infection under medical and dental collaboration is important for providing Behçet's disease patients with the optimal medical care and for facilitating the relief of the primary disease.

  5. The role of fungi in allergic diseases

    OpenAIRE

    Żukiewicz-Sobczak, Wioletta A.

    2013-01-01

    Allergic diseases such as allergic rhinitis, pharyngitis, laryngitis, asthma, airborne dermatitis, or allergic conjunctivitis, can be caused or aggravated by components of bioaerosol from natural environment or from indoor environment in enclosed spaces, workplaces and homes. The main components of bioaerosol are fungi and their metabolites, which are common in the environment.

  6. [State of the autonomic nervous system after induced abortion in the lst trimester].

    Science.gov (United States)

    Bakuleva, L P; Gatina, G A; Kuz'mina, T I; Solov'eva, A D

    1990-04-01

    The autonomic nervous system has been examined in 271 patients with a history of first-trimester induced abortion. It was ascertained that induced abortion affected the autonomic nervous system, thus impairing adaptive potentials and entailing the onset or aggravation of preexisting autonomic vascular dystonia. PMID:2378404

  7. 32 CFR 901.11 - Children of deceased or disabled veterans and children of military or civilian personnel in a...

    Science.gov (United States)

    2010-07-01

    .... Appointments authorized in this category are limited to 65 cadets at the Academy at any one time. (a) The child... disease aggravated by active service. (b) The child of a parent who is in “missing status” is eligible if... parent and adopted children whose adoption proceedings were initiated before the 15th birthday....

  8. Striga hermonthica parasitism in maize in response to N and P fertilisers

    NARCIS (Netherlands)

    Jamil, M.; Kanampiu, F.K.; Karaya, H.; Charnikova, T.; Bouwmeester, H.J.

    2012-01-01

    Parasitism by the parasitic weed, Striga hermonthica (Striga), constitutes a major biological constraint to maize production in sub-Sahara Africa. Nutrient deficiency is known to aggravate Striga infestation and in a number of plant species it was recently shown that this may be due to increased sec

  9. The Tip of the Iceberg: Teacher Distrust of Administrators.

    Science.gov (United States)

    Rothstein, Stanley W.

    1980-01-01

    The ambivalent attitudes of prospective administrators is the tip of the iceberg, hiding resentments which have been aggravated by teachers' militancy and administrators' obtuseness. To get teachers to understand and cope with these feelings, as they study educational administration, is an important challenge for professional schools of education.…

  10. An Ever-Rebounding Crisis

    OpenAIRE

    Jean-Paul Guichard; Antoine Brunet

    2009-01-01

    The current crisis is spreading from the rich countries to those which surround them respectively, countries wherein its degree of gravity is even greater; in turn, that effect sets off a yet stronger backwash in those countries in the Centre, which further aggravates the situation. This reaction is particularly true of the relations between Western and Eastern Europe.

  11. Restricted Liberty, Parental Choice and Homeschooling

    Science.gov (United States)

    Merry, Michael S.; Karsten, Sjoerd

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequality, worsens societal conflict and works against…

  12. Restricted liberty, parental choice and homeschooling

    NARCIS (Netherlands)

    M.S. Merry; S. Karsten

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequalit

  13. Who Gets up or Gets out?——A joint circular to urge textile industry to be restructured and upgraded

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ten governmental organizations recently issued a joint circular (No.762-2006, State Development & Reform Commission) to guide Chinese textile growth in the next five years (2006-2010). The circular, seriously taken as guideline policy, is given out amid aggravating factors for resources, environment, trade disputes, structural problems and other challenging issues that Chinese textile industry is supposed to address in the

  14. Portrayal of Muslims in the media: “24” and the ‘Othering’ process

    OpenAIRE

    Abu Sadat Nurullah

    2010-01-01

    The Hollywood media in general depict the image of Muslims and Arabs in a negative way. Drawing from Edward Said's understanding of Orientalism, the current study critically analyzes the television serial "24", which portrays stereotypical images of Arabs and Muslims, and aggravates the 'othering process'.

  15. Portrayal of Muslims in the media: “24” and the ‘Othering’ process

    Directory of Open Access Journals (Sweden)

    Abu Sadat Nurullah

    2010-04-01

    Full Text Available The Hollywood media in general depict the image of Muslims and Arabs in a negative way. Drawing from Edward Said's understanding of Orientalism, the current study critically analyzes the television serial "24", which portrays stereotypical images of Arabs and Muslims, and aggravates the 'othering process'.

  16. 76 FR 17421 - Request for Information on Conditions Relating to Cancer To Consider for the World Trade Center...

    Science.gov (United States)

    2011-03-29

    ... established by the James Zadroga 9/11 Health and Compensation Act (Pub. L. 111-347). In accordance with... terrorist attacks, is substantially likely to be a significant factor in aggravating, contributing to, or... to the dust cloud, gases and vapors on 9/11/01 and those living and working in the affected area;...

  17. Effect of meals with varying glycemic index on blood glucose response in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Maulik S. Nayak

    2016-08-01

    Conclusions: It was concluded in the study that Plasma Glucose shows a positive response to high GI foods and this may aggravate the hyperglycemia already present in Type 2 DM. Low GI diets may be helpful in reducing risks related to Type 2 DM. [Int J Res Med Sci 2016; 4(8.000: 3444-3448

  18. 42 CFR 38.3 - Assistance; procedures, limitations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Assistance; procedures, limitations. 38.3 Section 38.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND... problem which was caused or aggravated by the major disaster or its aftermath. (2) Disaster workers...

  19. Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model.

    NARCIS (Netherlands)

    Halteren, H.K. van; Bongaerts, G.P.A.; Verhagen, C.A.H.H.V.M.; Kamm, Y.J.L.; Willems, J.L.; Grutters, G.J.; Koopman, J.P.; Wagener, D.J.T.

    2004-01-01

    BACKGROUND: Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact

  20. Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: The Netherlands cohort study on diet and cancer

    NARCIS (Netherlands)

    Engeland, M. van; Weijenberg, M.P.; Roemen, G.M.J.M.; Brink, M.; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Baylin, S.B.; Goeij, A.F.P.M. de; Herman, J.G.

    2003-01-01

    Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aherrant DNA methylation is associated with low dietary folate intake, which is aggravated by high

  1. Disrupting Traditions: Swimming against the Current of Adolescent Bullying

    Science.gov (United States)

    Khasnabis, Debi; Upton, Kevin

    2013-01-01

    Advances in technology have aggravated the generations-old problem of bullying in schools. In this article, the authors attend to the impact of social media on bullying and advocate an approach to teaching anti-bullying that incorporates a project-based learning approach for young adolescents. Process drama as a model of learning and the use of…

  2. Complementary Therapy in Polycystic Ovary Syndrome

    OpenAIRE

    Aquino, Carmen Imma; Nori, Stefania Lucia

    2014-01-01

    Polycystic Ovary Syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10 % of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality of life are also common. This review highlights the mechanisms an...

  3. No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux

    NARCIS (Netherlands)

    Boeree, MJ; Peters, FTM; Postma, DS; Kleibeuker, JH

    1998-01-01

    Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway hyperresponsiveness through vagally-mediated pathways. We wanted to determine whether elimination of acid reflux could improve symptoms in s

  4. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection.

    NARCIS (Netherlands)

    Poll, M.C. van de; Derikx, J.P.M.; Buurman, W.A.; Peters, W.H.M.; Roelofs, H.M.J.; Wigmore, S.J.; Dejong, C.H.

    2007-01-01

    BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injur

  5. Menopause versus aging: The predictor of obesity and metabolic aberrations among menopausal women of Karnataka, South India

    Directory of Open Access Journals (Sweden)

    Shruti Dasgupta

    2012-01-01

    Conclusions: Menopausal transition brings about anomalies in total body composition characterized by an increased body fat mass and central adiposity. This creates a compatible atmosphere for abnormal metabolism and aggravated cardio metabolic risk factors. Thus, menopausal status and associated obesity is the major predictor of metabolic aberrations over age in menopausal women.

  6. Ulnarisneuropati hos fjerkræslagteriarbejder

    DEFF Research Database (Denmark)

    Svendsen, Susanne Wulff; Juhl, Anne

    2008-01-01

    -25 kg with flexion of the elbow, pronation of the forearm, and ulnar deviation of the wrist. A nerve conduction study indicated ulnar neuropathy just distal to the elbow. Surgery at this level alleviated the symptoms, but shortly after his return to work, he changed jobs because of aggravation...

  7. Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature.

    NARCIS (Netherlands)

    Halbertsma, F.J.; Vaneker, M.; Scheffer, G.J.; Hoeven, J.G. van der

    2005-01-01

    BACKGROUND: Mechanical ventilation is known to induce and aggravate lung injury. One of the underlying mechanisms is biotrauma, an inflammatory response in which cytokines play a crucial role. OBJECTIVE: To review the literature on the role of cytokines in ventilator-induced lung injury (VILI) and m

  8. A Pilot Study of Cognitive-Behavioral Therapy of Insomnia in People with Mild Depression

    Science.gov (United States)

    Taylor, Daniel J.; Lichstein, Kenneth L.; Weinstock, Jeremiah; Sanford, Stacy; Temple, Jeff R.

    2007-01-01

    In some cases, insomnia and depression may have a reciprocal relationship, in which each aggravates and maintains the other. To test the hypothesis that reduction of insomnia would result in reduction of depression in patients (N=10) with both disorders, a repeated-measures design was used comparing depression and insomnia levels before and after…

  9. Students' Misperceptions of Violence: Affirming the Need for Better Education.

    Science.gov (United States)

    Mersky, Rebecca A.; Chambliss, Catherine A.

    Despite the fact that both national and regional statistics show that violent crimes (murder, non negligent manslaughter, aggravated assault, robbery, and forcible rape) in the U.S. have been declining in recent years, many believe that violent crime rates have been steadily escalating. Exaggerated media portrayals of violence, including both news…

  10. Statistical Bits and Pieces: Juvenile Arrests of Persons under Age 18 Reported by State and Types of Crime.

    Science.gov (United States)

    Journal of At-Risk Issues, 2000

    2000-01-01

    This table reports on juvenile arrests in 1998 by state and type of crime (violent crime, property crime, drug abuse, and alcohol violation). The violent crime index includes the offenses of murder and non-negligent manslaughter, forcible rape, robbery, and aggravated assault. The property crime index includes burglary, larceny-theft, motor…

  11. Understanding the Writing Habits of Tomorrow's Students: Technology and College Readiness

    Science.gov (United States)

    Relles, Stefani R.; Tierney, William G.

    2013-01-01

    This article reports on a study analyzing the digital skills of 91 low-income students enrolled in writing remediation. Findings suggest that technological demands widen the equity dimensions of the college preparation gap by aggravating the academic challenges remedial writers already face. Suggestions to support the compound literacy needs of…

  12. Vulnerability of Brazilian Megacities to Climate Change: The São Paulo Metropolitan Region

    OpenAIRE

    Carlos Afonso Nobre; Andrea Ferraz Young; Paulo Hilário Nascimento Saldiva; José Antônio Marengo Orsini; Antonio Donato Nobre; Agostinho Tadashi Ogura; Osório Thomaz; Guillermo Oswaldo Obregón Párraga; Gustavo Costa M. da Silva; Maria Valverde; André Carvalho Silveira; Grasiela de Oliveira Rodrigues

    2012-01-01

    A major concern of contemporary society in relation to future climate projections relates to possible changes in the frequencies and intensities of extreme weather events. Megacities such as São Paulo have numerous social and environmental problems associated with patterns of development and transformation of space, which have been aggravated by increases in temperature and intensification of extreme weather events. (?)

  13. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction

    NARCIS (Netherlands)

    Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Dijkstra, Gerard; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M. J.

    2011-01-01

    Objective: Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins (HS

  14. Foreword

    Directory of Open Access Journals (Sweden)

    Mmaphaka Tau

    2009-04-01

    Full Text Available The conditions prevailing in the world, where fast growing populations are coupled with rapidly expanding urbanization and a general increase in poverty levels, are greatly aggravating the disaster risks and vulnerabilities of a large part of the world’s populations.

  15. Is Psychopathology the Key to Understanding Why Some Children Become Aggressive When They Are Exposed to Violent Television Programming?

    Science.gov (United States)

    Grimes, Tom; Bergen, Lori; Nichols, Kathie; Vernberg, Eric; Fonagy, Peter

    2004-01-01

    Children with diagnosed psychopathologies may experience aggravation of those illnesses with their exposure to media violence. Children with the most common, often undiagnosed, form of psychopathology--Disruptive Behavior Disorders (DBDs)--manifested changes in heart rate, heart vagal heart tone and other psychophysiological reactions to media…

  16. P41

    Directory of Open Access Journals (Sweden)

    M. Kruchinina

    2015-11-01

    Conclusion: Identified microcirculatory disturbances probably aggravate the course of CC and, therefore, require additional therapeutic effects. Differences in Er and BS parameters associated with the stage of CC, give hope for the development of new diagnostic methods at the early stages of the disease.

  17. Treating an HIV/AIDS Patient's PTSD and Medication Nonadherence with Cognitive-Behavioral Therapy: A Principle-Based Approach

    Science.gov (United States)

    Chernoff, Robert A.

    2007-01-01

    HIV/AIDS patients with medication adherence problems are vulnerable to developing drug resistance, immune system degradation, and opportunistic infections. Poor adherence to antiretroviral medication regimens can be aggravated by psychiatric problems, including depression and posttraumatic stress disorder. This article presents the case study of a…

  18. 38 CFR 9.9 - Conversion privilege.

    Science.gov (United States)

    2010-07-01

    ... LIFE INSURANCE AND VETERANS' GROUP LIFE INSURANCE § 9.9 Conversion privilege. (a) With respect to a... disability incurred or aggravated during such a period of duty. (b) The individual policy of life insurance... loss due to such excess mortality among the reinsurers and converters....

  19. 12 CFR Appendix J to Part 717 - Interagency Guidelines on Identity Theft Detection, Prevention, and Mitigation

    Science.gov (United States)

    2010-01-01

    ... should consider aggravating factors that may heighten the risk of identity theft, such as a data security... Identification Program rules implementing 31 U.S.C. 5318(l) (31 CFR 103.121); and (b) Authenticating members....C. 5318(g) and 12 CFR 748.1(c); (b) Implementing any requirements under 15 U.S.C....

  20. Communication Design Education: Could Nine Reflections Be Sufficient?

    Science.gov (United States)

    van der Waarde, Karel; Vroombout, Maurits

    2012-01-01

    Situation: Graphic design education is subject to substantial changes. Changes in professional practice and higher education aggravate insecurities about the contents and structure of courses, assessment criteria, relations between practice, research and theory and teaching methods. Assumption: Graphic design education (visual communication design…

  1. Hair removal in hirsute women with normal testosterone levels: a randomized controlled trial of long-pulsed diode laser vs. intense pulsed light

    DEFF Research Database (Denmark)

    Haak, C S; Jensen, Pernille Nymann; Pedersen, A T;

    2010-01-01

    Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels....

  2. Impact of Oral Iron Challenges on Circulating Non-Transferrin-Bound Iron in Healthy Guatemalan Males

    NARCIS (Netherlands)

    Schuemann, Klaus; Kroll, Sylvia; Romero-Abal, Maria-Eugenia; Georgiou, Niki A.; Marx, Jo J. M.; Weiss, Guenter; Solomons, Noel W.

    2012-01-01

    Introduction:Oral iron as a supplement has been associated with adverse health consequences, especially in the context of young children with active malaria. A potential aggravating role of non-transferrin-bound iron (NTBI) has been proposed. Material and Methods: NTBI responses in both a fasting an

  3. Psychosomatic factors in pruritus

    OpenAIRE

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidis...

  4. Violent Girls or Relabeled Status Offenders?: An Alternative Interpretation of the Data

    Science.gov (United States)

    Feld, Barry C.

    2009-01-01

    Policy makers and juvenile justice officials express alarm over the rise in arrests of girls for simple and aggravated assault. Others see this perceived increase as an artifact of decreased public tolerance for violence, changes in parental attitudes or law enforcement policies, or heightened surveillance of domestic violence, which…

  5. Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression

    NARCIS (Netherlands)

    Burkhardt, J.; Blume, M.; Petit-Teixeira, E.; Teixeira, V.H.; Steiner, A.; Quente, E.; Wolfram, G.; Scholz, M.; Pierlot, C.; Migliorini, P.; Bombardieri, S.; Balsa, A.; Westhovens, R.; Barrera, P.; Radstake, T.R.D.J.; Alves, H.; Bardin, T.; Prum, B.; Emmrich, F.; Cornelis, F.; Ahnert, P.; Kirsten, H.

    2014-01-01

    In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, IT

  6. The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin

    DEFF Research Database (Denmark)

    Rasmussen, Andreas Rosén; Viby, Niels-Erik; Hare, Kristine Juul;

    2010-01-01

    Erlotinib, an epidermal-growth-factor receptor inhibitor, belongs to a new generation of targeted cancer therapeutics. Gastrointestinal side-effects are common and have been markedly aggravated when erlotinib is combined with cytostatics. We examined the effects of erlotinib alone and combined wi...

  7. An Analysis of China's Fertilizer Policies: Impacts on the Industry, Food Security, and the Environment

    NARCIS (Netherlands)

    Li, Y.X.; Zhang, W.F.; Ma, L.; Huang, G.Q.; Oenema, O.; Zhang, F.S.; Dou, Z.X.

    2013-01-01

    China has made remarkable strides in recent decades to grow enough food to feed 20% of the world's population with only 9% of the world's arable land. Meanwhile, the nation is experiencing exacerbated air and water pollution problems. Agricultural growth and the pollution aggravation are closely lin

  8. Regulation and function of innate and adaptive interleukin-17-producing cells

    OpenAIRE

    Hirota, Keiji; Ahlfors, Helena; Duarte, João H.; Stockinger, Brigitta

    2012-01-01

    IL-17-mediated immunity is key for mucosal host defence against a range of pathogens, but can also elicit or aggravate autoimmune and cardiovascular disease, as well as affect tumour formation. The regulation and function of such versatile cells is discussed here.

  9. Bangladesh : Climate Change and Sustainable Development

    OpenAIRE

    World Bank

    2000-01-01

    The study examines Bangladesh's extreme vulnerability to climate change, whose low-lying topography, and funnel-shaped coast, further exposes the land to cyclones, and tidal surges, resulting in seasonal floods. These factors, and the large population base, widespread poverty, aggravated by the lack of strong institutional development, makes the country particularly vulnerable to climate v...

  10. Effect of local weather on butterfly flight behaviour, movement, and colonization: significance for dispersal under climate change

    NARCIS (Netherlands)

    Cormont, A.; Malinowska, A.H.; Kostenko, O.; Radchuk, V.; Hemerik, L.; Wallis de Vries, M.F.; Verboom, J.

    2011-01-01

    Recent climate change is recognized as a main cause of shifts in geographical distributions of species. The impacts of climate change may be aggravated by habitat fragmentation, causing regional or large scale extinctions. However, we propose that climate change also may diminish the effects of frag

  11. ПЕРИФЕРИЧЕСКАЯ ВЕГЕТАТИВНАЯ НЕДОСТАТОЧНОСТЬ. КЛИНИЧЕСКИЙ СЛУЧАЙ

    Directory of Open Access Journals (Sweden)

    Л. М. Фархутдинова

    2014-01-01

    Full Text Available The article contains a description of a clinical case of refractory hypotension, developed after surgery for pituitary macroadenoma. Postoperative period was complicated by the development of acute myocardial infarction, connected with aggravation of megakariocyte leukemia. Presented differential diagnosis causes hypotension in a patient with severe comorbidity.

  12. 8 CFR 1003.44 - Special motion to seek section 212(c) relief for aliens who pleaded guilty or nolo contendere to...

    Science.gov (United States)

    2010-01-01

    ... basis of a crime that is an aggravated felony, except as provided in 8 CFR 1212.3(f)(4). (d) Effect of... or removal, and who are eligible to apply for relief under former section 212(c) of the Act and 8 CFR... adjudicated under the standards of this section and 8 CFR 1212.3. This section is not applicable with...

  13. 8 CFR 1.1 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... Immigration Appeals. (t) The term aggravated felony means a crime (or a conspiracy or attempt to commit a... chapter: (a) The terms defined in section 101 of the Immigration and Nationality Act (66 Stat. 163) shall... in this chapter. (b) The term Act means the Immigration and Nationality Act, as amended. (c) The...

  14. Schools and Neighborhoods: Organizational and Environmental Factors Associated with Crime in Secondary Schools

    Science.gov (United States)

    Limbos, Mary Ann P.; Casteel, Carri

    2008-01-01

    Background: While crime and violence in schools are derived primarily from factors external to schools, violent behavior may also be aggravated by factors in the school environment, including the physical environment, its educational and social climate, and its organizational capacity and composition. The objective of this study is to examine the…

  15. I Like the Idea of Choice, and I Want to Tell You Why.

    Science.gov (United States)

    Smith, Geoffrey, P.

    1993-01-01

    Using educational vouchers for private schooling will aggravate the fragmented society that Jonathan Kozol visualizes in the November 1992 issue of "Educational Leadership." However, public schools of choice are desirable because they permit diverse teaching/learning styles, curricular emphases, or organizational structures to coexist within one…

  16. Diogenes in the Tower of Babel: The Generation Gap and the Role of the University.

    Science.gov (United States)

    Woodward, Calvin A.

    1978-01-01

    This article argues that intergenerational communication problems are aggravated by university education, primarily because of the present state of the social sciences, where emphasis on scientific methodology and skepticism teach students that practically nothing can withstand critical scientific review; that, in effect, all established authority…

  17. Activation of pain by sumatriptan

    NARCIS (Netherlands)

    Coulter, David M; Passier, J L M; Clark, David W J; van Puijenbroek, Eugene P

    2003-01-01

    OBJECTIVE: To demonstrate that sumatriptan may induce activation or aggravation of pain at sites of inflammation caused by trauma or disease. METHODS: Case reports from the national pharmaco vigilancecenters of 2 countries, The Netherlands and New Zealand, are presented. These reports come from prog

  18. La politique de l'environnement de l'Union européenne%简析21世纪的欧盟环境政策

    Institute of Scientific and Technical Information of China (English)

    林玲; 毛在丽

    2004-01-01

    Au fur et a mesure de son e1argissement et de l'aggravation de la situation environnementale du monde, l'Union europeennne a modifie la politique vis a vis de 1'environnement en s' appuyant sur une cooperation plus large entre pays europeens et du veste du monde.

  19. 5 CFR 890.1064 - Determining the amounts of penalties and assessments to be imposed on a provider.

    Science.gov (United States)

    2010-01-01

    ... knowledge of the material facts (for example, submitting claims that the provider knew to contain false... carrier's investigations, constitute aggravating circumstances. OPM may consider violations where the provider did not have direct knowledge of the material facts, or in which the provider cooperated with...

  20. Bio-filtration of helminth eggs and coliforms from municipal sewage for agricultural reuse in Peru

    NARCIS (Netherlands)

    Yaya Beas, R.E.

    2016-01-01

    Where fresh water resources are scarce, treated wastewater becomes an attractive alternative for agricultural irrigation. However, the presence of large amounts of pathogens, even in treated wastewater, constraints its productive use, which is aggravated when sanitation and public health are poor. A

  1. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis

    OpenAIRE

    Jose Carlos Pereira Jr.; Marcia Pradella-Hallinan; Hugo de Lins Pessoa

    2010-01-01

    Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregn...

  2. Understanding Farmers: Explaining Soil and Water Conservation in Konso, Wolaita and Wello, Ethiopia

    NARCIS (Netherlands)

    Beshah, T.

    2003-01-01

    Soil erosion by water is an old problem in Ethiopia. The prevalence of mountainous and undulating landscapes, coupled with the expansion of arable farming on steep areas due to population pressure have aggravated the soil erosion problem in the country. Prompted by one of the great famines in the co

  3. 31 CFR 19.860 - What factors may influence the debarring official's decision?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false What factors may influence the... may influence the debarring official's decision? This section lists the mitigating and aggravating... harm or impact that results or may result from the wrongdoing. (b) The frequency of incidents...

  4. Take Not a Musket to Kill a Butterfly

    DEFF Research Database (Denmark)

    Ploug, Thomas; Holm, Søren

    2014-01-01

    Social media applications such as Facebook hold great promise as means of communicable disease control. We argue here that the use of social media in communicable disease control may cause various forms of harm, and that these harms are aggravated by some of the very same features making social m...

  5. Tough New Issues Refocus Health Education

    Science.gov (United States)

    Dessoff, Alan

    2011-01-01

    From dating violence to sexting and social networking, districts are struggling to address a number of sensitive and relatively new health education issues that are aggravated by students' increasing access to computers, cell phones and other digital devices. Through new or revised curricula, administrators are attempting to deal with these and…

  6. Length of stay in asylum centres and mental health in asylum seekers

    DEFF Research Database (Denmark)

    Hallas, Peter; Hansen, Anne R; Staehr, Mia A;

    2007-01-01

    BACKGROUND: The length of stay in asylum centres is generally mentioned as a possible health risk to asylum seekers. Medical staff working with asylum seekers has claimed that long lengths of stay in asylum centres might cause or aggravate mental disorders. We used records from a large, multiethnic...

  7. 32 CFR 553.15 - Persons eligible for burial in Arlington National Cemetery.

    Science.gov (United States)

    2010-07-01

    ...). (3) Distinguished Service Medal. (4) Silver Star. (5) Purple Heart. (e) Persons who have held any of... injury incurred or aggravated in line of duty. (g) The spouse, widow or widower, minor child and, at the discretion of the Secretary of the Army, unmarried adult child of any of the persons listed above. (1)...

  8. 28 CFR 2.20 - Paroling policy guidelines: Statement of general policy.

    Science.gov (United States)

    2010-07-01

    ...) Civil Contempt. See 28 CFR 2.10. Subchapter C—Official Corruption 621Bribery or Extortion (a)Grade as a... aggravated crimes are considered, by definition, at the extreme high end of Category Eight offenses. For... guideline range. (The fact that an offense does not fall under the definition contained herein does not...

  9. From "Brain Drain" to "Brain Bridging": Transnational Higher Education Development and Graduate Employment in China

    Science.gov (United States)

    Mok, Ka Ho; Han, Xiao

    2016-01-01

    In the past few decades, the internationalisation of higher education has become an increasingly popular trend across different parts of the globe. The fierce global competition and the aggravating unemployment rate, coupled with low teaching and research quality revealed by universities in mainland China, have inevitably compelled a growing…

  10. Bioimpedance in Severely Malnourished Children

    DEFF Research Database (Denmark)

    Girma Nigatu, Tsinuel

    Worldwide severe acute malnutrition (SAM) affects millions of children and considerably contributes to under-five mortality, mainly in low-income settings. Among children with SAM, deaths occur largely in those with oedema and during early phase of treatment often aggravated by infection. Treatment...

  11. Meningococcal disease and future drug targets

    DEFF Research Database (Denmark)

    Gammelgaard, L K; Colding, H; Hartzen, S H; Penkowa, M

    2011-01-01

    recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how host immune responses ultimately may aggravate neuropathology and the clinical prognosis. Within this context, particular importance is paid to the endotoxic components that provide potential drug targets...

  12. The clinical aspects of the acute facet syndrome

    DEFF Research Database (Denmark)

    Hestbaek, Lise; Kongsted, Alice; Jensen, Tue Secher;

    2009-01-01

    with pain and decreased range of motion in extension and rotation both standing and sitting. They thought that the pain could be relieved by walking, lying with knees bent, using ice packs and taking non-steroidal anti-inflammatory drugs, and aggravated by prolonged standing or resting. They also stated...

  13. 32 CFR 757.4 - Claims that may be collected.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Claims that may be collected. 757.4 Section 757.4 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS AFFIRMATIVE... aggravating circumstances. (b) For money paid or reimbursed by the government for damage to a rental car...

  14. Armed Conflict: A Model for Understanding and Intervention

    Science.gov (United States)

    Death Studies, 2013

    2013-01-01

    Acts of deadly violence give rise to powerful emotions and trigger pre-programmed responses that often cause affected persons, including leaders, media, armed forces, and the general public, to act in ways that aggravate the situation and feed into cycles of violence. In this article, a model of the cycle of violence is presented that facilitates…

  15. Maths in the Board Room

    Science.gov (United States)

    Johnston, Scott

    2012-01-01

    The author has recently been experimenting with having students work at a set of six blackboards mounted on the walls of a maths teaching space. In this article, he describes this project which he started because he had become impatient with, and aggravated by the usual setup of a maths teaching space. He had started to question why there are…

  16. Dynamic Channel Selection for Cognitive Femtocells

    DEFF Research Database (Denmark)

    Da Costa, Gustavo Wagner Oliveira; Cattoni, Andrea Fabio; Mogensen, Preben;

    2014-01-01

    , but not least, the possibility of having closed-subscriber-groups aggravates the inter-cell interference problems. In order to tackle these issues we consider the implementation of some aspects of cognitive radio technology into femtocells, leading to the concept of cognitive femtocells. This chapter focuses...

  17. Cryptosporidium parvum: infectivity and pathogenicity of the 'porcine' genotype

    DEFF Research Database (Denmark)

    Enemark, Heidi L.; Ahrens, Peter; Bille-Hansen, Vivi; Heegaard, Peter M. H.; Vigre, Håkan; Thamsborg, S.M.; Lind, Peter

    2003-01-01

    mild clinical signs in piglets despite the excretion of high numbers of oocysts. Concomitant infection with rotavirus, however, caused a dramatic aggravation of the clinical signs, and 5 of 6 experimentally infected piglets died. CPP-13 appeared to be adapted to porcine hosts as illustrated by the lack...

  18. HEPA Help

    Science.gov (United States)

    Rathey, Allen

    2006-01-01

    Poor indoor air quality in school facilities can detract from the health and productivity of students, teachers and other employees. Asthma--often triggered or aggravated by dust--is the No. 1 cause of chronic absenteeism in schools. Using vacuum cleaners equipped with high-efficiency particulate air (HEPA) filters to clean education institutions…

  19. Adapting to Climate Variability and Change: Experiences from Cereal-Based Farming in the Central Rift and Kobo Valleys, Ethiopia

    NARCIS (Netherlands)

    Kassie, B.T.; Hengsdijk, H.; Rötter, R.; Kahiluoto, H.; Asseng, S.; Ittersum, van M.K.

    2013-01-01

    Small-holder farmers in Ethiopia are facing several climate related hazards, in particular highly variable rainfall with severe droughts which can have devastating effects on their livelihoods. Projected changes in climate are expected to aggravate the existing challenges. This study examines farmer

  20. Simultaneous administration of vitamin A and DTP vaccine modulates the immune response in a murine cerebral malaria model

    DEFF Research Database (Denmark)

    Hein-Kristensen, L; Jørgensen, M J; Ravn, H;

    2010-01-01

    -tetanus-pertussis (DTP) vaccine may increase mortality from non-targeted diseases. We investigated the non-targeted effect of pretreatment with VAS and DTP vaccine in a murine model of experimental cerebral malaria. Our a priori hypothesis was that VAS/DTP would aggravate the infection. We found that the effect of VAS...

  1. Calcinosis of joints and periarticular tissues associated with vitamin D intoxication.

    Science.gov (United States)

    Butler, R C; Dieppe, P A; Keat, A C

    1985-01-01

    We describe a patient with rheumatoid arthritis and widespread joint and periarticular calcinosis related to self-medication with vitamin D, which was aggravated by oral phosphate therapy prescribed for her hypercalcaemia. Hydroxyapatite was shown in the synovial fluid from affected joints. The role played by tissue injury in the pathogenesis of soft tissue calcification is discussed. Images PMID:4026410

  2. Calcinosis of joints and periarticular tissues associated with vitamin D intoxication.

    OpenAIRE

    Butler, R C; Dieppe, P A; Keat, A C

    1985-01-01

    We describe a patient with rheumatoid arthritis and widespread joint and periarticular calcinosis related to self-medication with vitamin D, which was aggravated by oral phosphate therapy prescribed for her hypercalcaemia. Hydroxyapatite was shown in the synovial fluid from affected joints. The role played by tissue injury in the pathogenesis of soft tissue calcification is discussed.

  3. Application of a wavelet technique for the detection of earthquake signatures in the geomagnetic field

    OpenAIRE

    ALPEROVICH, L; ZHELUDEV, V; Hayakawa, M

    2001-01-01

    We developed an algorithm especially adapted to single-station wavelet detection of geomagnetic events, which precede or accompany the earthquakes. The detection problem in this situation is complicated by a great variability of earthquakes and accompanied phenomena, which aggravates finding characteristic features of the events. Therefore we chose to search for the characteristic features of both "disturbed" intervals (...

  4. Confident and "wrong"? Towards a mindful use of visuals in project portfolio decisions

    DEFF Research Database (Denmark)

    Geraldi, Joana; Arlt, Mario

    , visuals can also aggravate the challenges involved in portfolio decisions. Inspired by Weick and Sufcliffe’s concept of mindfulness, we conducted an experiment with 204 participants to explore how to use visual mindfully in project portfolio context. The results suggest that use of purposeful and familiar...

  5. Macrophages Regulators of Sex Differences in Asthma?

    NARCIS (Netherlands)

    Melgert, Barbro N.; Oriss, Timothy B.; Qi, Zengbiao; Dixon-McCarthy, Barbara; Geerlings, Marie; Hylkema, Machteld N.; Ray, Anuradha

    2010-01-01

    Females are more susceptible to development of asthma than are males. In a mouse model of ovalbumin-induced airway inflammation, with aggravated disease in females compared with males, we studied interactions between immune and resident lung cells during asthma development to elucidate which process

  6. 38 CFR 3.806 - Death gratuity; certification.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death gratuity... ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Special Benefits § 3.806 Death... claim filed with it that: (1) Death resulted from: (i) Disease or injury incurred or aggravated while...

  7. Sensitivity of water scarcity events to ENSO-driven climate variability at the global scale

    NARCIS (Netherlands)

    Veldkamp, T.I.E.; Eisner, S.; Wada, Y.; Aerts, J.C.J.H.; Ward, P.J.

    2015-01-01

    Globally, freshwater shortage is one of the most dangerous risks for society. Changing hydro-climatic and socioeconomic conditions have aggravated water scarcity over the past decades. A wide range of studies show that water scarcity will intensify in the future, as a result of both increased consum

  8. Tabac et maladie parodontale

    OpenAIRE

    Geerts, Sabine

    1996-01-01

    Le tabac est un facteur aggravant la parodontite. Beaucoup d'études cliniques ont été menées et ont souvent montré des résultats contradictoires. Cet article est une revue de littérature sur la relation entre le tabagisme et la parodontite. Peer reviewed

  9. Hydrological modeling and climate change impacts in an agricultural semiarid region. Case study: Guadalupe River basin, Mexico

    DEFF Research Database (Denmark)

    Molina-Navarro, Eugenio; Hallack-Alegría, Michelle; Martínez-Pérez, Silvia;

    2015-01-01

    Abstract In northern Mexico, water resources management has become a challenging task, aggravated by the vulnerability of this region to climate change. The semiarid Guadalupe River Basin is under additional pressure due to wine production and drinking water supply. We have applied the SWAT model...

  10. fMRI neurofeedback facilitates anxiety regulation in females with spider phobia

    NARCIS (Netherlands)

    Zilverstand, Anna; Sorger, Bettina; Sarkheil, Pegah; Goebel, R.

    2015-01-01

    BACKGROUND: Spider phobics show an exaggerated fear response when encountering spiders. This fear response is aggravated by negative and irrational beliefs about the feared object. Cognitive reappraisal can target these beliefs, and therefore has a fear regulating effect. The presented study investi

  11. Central serous chorioretinopathy misdiagnosed as posterior uveitis and the vicious circle of corticosteroid therapy

    Directory of Open Access Journals (Sweden)

    Marina Papadia

    2015-01-01

    Conclusion: CSCR is a rare but not negligible misdiagnosis in posterior uveitis representing approximately 1% of subjects from a collective series of uveitis cases at a referral center. Investigative measures such as FA, ICGA and OCT are crucial for reaching a correct diagnosis and avoiding disease aggravation due to corticosteroid therapy.

  12. Chromium poisoning of LSM/YSZ and LSCF/CGO composite cathodes

    DEFF Research Database (Denmark)

    Bentzen, Janet Jonna; Høgh, Jens Valdemar Thorvald; Barfod, Rasmus;

    2009-01-01

    from 300 to 2,970 h. Both LSM/YSZ and LSCF/CGO cathodes were sensitive to chromium poisoning; LSCF/CGO cathodes to a lesser extent than LSM/YSZ. Humid air aggravated the degradation of the cathode performance. Post-mortem electron microscopic investigations revealed several Cr-containing compounds...

  13. Mesa-height Dependent Quantum Efficiency Characteristics of InGaN Micro-LEDs

    KAUST Repository

    Shen, Chao

    2013-01-01

    The mechanisms of mesa-height dependent efficiency and efficiency droop of blue InGaN/GaN micro-LED is presented. Device with a large etch-depth (> 1.3 µm) shows significant strain relief with aggravated current crowding.

  14. 24 CFR 203.675 - Notice to occupants of pending acquisition.

    Science.gov (United States)

    2010-04-01

    ... illness or injury provisions of § 203.674(a), the occupant shall provide to the HUD Field Office, at the... notify the mortgagor and each head of household who is actually occupying a unit of the property of its... severely aggravating the illness or injury, and a statement by a State-certified physician establishing...

  15. 14 CFR 67.105 - Ear, nose, throat, and equilibrium.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Ear, nose, throat, and equilibrium. 67.105..., nose, throat, and equilibrium. Ear, nose, throat, and equilibrium standards for a first-class airman... internal ear, nose, oral cavity, pharynx, or larynx that— (1) Interferes with, or is aggravated by,...

  16. The influence of tibial component fixation techniques on resorption of supporting bone stock after total knee replacement

    NARCIS (Netherlands)

    Chong, D.Y.; Hansen, U.N.; Venne, R. van der; Verdonschot, N.J.J.; Amis, A.A.

    2011-01-01

    Periprosthetic bone resorption after tibial prosthesis implantation remains a concern for long-term fixation performance. The fixation techniques may inherently aggravate the "stress-shielding" effect of the implant, leading to weakened bone foundation. In this study, two cemented tibial fixation ca

  17. Targeted mass spectrometry analysis of the proteins IGF1, IGF2, IBP2, IBP3 and A2GL by blood protein precipitation

    DEFF Research Database (Denmark)

    Such-Sanmartín, Gerard; Bache, Nicolai; Callesen, Anne K;

    2015-01-01

    aggravated when using fast high-throughput methods, which are necessary for analysis of hundreds and thousands of samples in clinical laboratories. The blood proteins IGF1, IGF2, IBP2, IBP3 and A2GL have been proposed as indirect biomarkers for detection of GH administration and as putative biomarkers for...

  18. Parenting among Low-Income, African American Single Mothers with Preschool-Age Children: Patterns, Predictors, and Developmental Correlates.

    Science.gov (United States)

    McGroder, Sharon M.

    2000-01-01

    Examined dimensions and patterns of parenting among 193 low-income African American single mothers with preschoolers. Identified four parenting patterns (aggravated but nurturant, cognitively stimulating, patient and nurturant, and low nurturance). Found that maternal well-being and sociodemographic characteristics accounted for 93 percent of…

  19. 2 year follow-up of childhood moyamoya after encephalo-arterio-myo-synangiosis (EDAMS): evaluation with acetazolamide brain SPECT (Acz-SPECT) and MR angiography (MRA)

    International Nuclear Information System (INIS)

    Longterm F/U evaluation of cerebrovascular hemodynamic changes after EDAMS is important because childhood moyamoya disease has a progressive nature and EDAMS is an indirect revascularization method. We evaluated cerebro-vascular hemodynamic changes of moyamoya pts during 2 yr after EDAMS with Acz-SPECT and correlated with MRA finding. 23 operated cerebral hemispheres of the 21 childhood moyamoya pts (M/F: 10/11, mean age 8±3 yrs) were evaluated with Acz-SPECT using 99mTc-ECD and MRA within 1 mo before, 1 yr ( 6 ±3 mo) and 2 yr (21 ±7 mo) after EDAMS. 10 pts also underwent frontal encephalo-galeo-synangiosis. Regional cerebral blood flow (rCBF) and cerebrovascular reserve (rCVR) of 8 cortical regions in each hemisphere (2 anterior cerebral artery (ACA), 4 mid-cerebral artery (MCA), and 2 posterior cerebral artery (PCA) territories) were scored as 5 grade scale (0=perfusion defect to 4=normal). Perfusion index (PI) was defined as the sum scores of rCBF and rCVR in each territory. Arterial stenosis and transdural collaterals were also evaluated. The changes of PIs in each territory and the changes of cerebral arterial stenosis with collateral formation at 1 and 2 yr F/U were correlated. Pre-operative stages of moyamoya disease were Suzuki type 1 in 1, 2 in 6, 3 in 7, and 4 in 9 cases. Mean PIs of each territory were summarized in the table. PIs of operated (MCA and ACA) territories were improved in 14, unchanged in 7, and aggravated in 2 cases at 1 yr F/U. PIs of PCA territory were improved in 4, unchanged in 16, and aggravated in 3 cases. At 2 yr F/U, PIs of operated territories were unchanged in 10 and improved in 12 cases including 2 with aggravation and 5 with no change at 1 yr F/U, but newly aggravated in 2 cases. Pis of PCA territory were improved in 5 or unchanged in 15, but further or newly aggravated in 3 cases. The arterial stenosis was progressed in 9 cases (5 MCA, 3 PCA, and/or 3 ACA). In these cases, PIs were aggravated in 3(2 operated and/or 2 PCA

  20. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1

    Directory of Open Access Journals (Sweden)

    R.A. Roela

    2003-08-01

    Full Text Available Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO, an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control, as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells, alpha3 (93.3 ± 7.0%, alpha5 (50.4 ± 12.0% and alpha6 (34.1 ± 4.9% integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0% and fibronectin (40.0 ± 2.0% substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5% while simultaneously reducing alpha5 (24.2 ± 19% and alpha6 (14.3 ± 10.8% expression as well as c-myc mRNA (7-fold, the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells, was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  1. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2012-02-01

    INTRODUCTION: The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. METHODS: MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and beta1-integrin, we examined activation of the beta1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and beta1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. RESULTS: JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the beta1-integrin substrate fibronectin. This was accompanied by reduced protein expression of beta1-integrin and its binding partners alphaV- and alpha5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and beta1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between

  2. Main features and possibilities of the new scale module for calculation of sensitivity and uncertainty by sampling: SAMPLER

    International Nuclear Information System (INIS)

    Due to the importance of calculating sensitivity and uncertainty in the calculation of field engineering, and especially in the nuclear world, it has been decided to present the main features of the new module present in the new version of SCALE 6.2 (currently beta 3 version) called SAMPLER. This module allows the calculation of uncertainty in a wide range of effective sections, neutron parameters, composition and physical parameters. However, the calculation of sensitivity is not present in the beta 3 release. Even so, this module can be helpful for participants of the proposed Benchmark by Expert Group on Uncertainty Analysis in Modelling (UAM-LWR), as well as to analysts in general. (Author)

  3. Main features and possibilities of the new scale module for calculation of sensitivity and uncertainty by sampling: SAMPLER; Principlaes caracteristicas y posibilidades del nuevo modulo de SCALE 6.2 para calculo de sensibilidad e incertidumbre por muestreo: SAMPLER

    Energy Technology Data Exchange (ETDEWEB)

    Mesado, C.; Miro, R.; Barrachina, T.; Verdu, G.

    2014-07-01

    Due to the importance of calculating sensitivity and uncertainty in the calculation of field engineering, and especially in the nuclear world, it has been decided to present the main features of the new module present in the new version of SCALE 6.2 (currently beta 3 version) called SAMPLER. This module allows the calculation of uncertainty in a wide range of effective sections, neutron parameters, composition and physical parameters. However, the calculation of sensitivity is not present in the beta 3 release. Even so, this module can be helpful for participants of the proposed Benchmark by Expert Group on Uncertainty Analysis in Modelling (UAM-LWR), as well as to analysts in general. (Author)

  4. Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate

    Science.gov (United States)

    Fong, J. H.; Ingber, D. E.

    1996-01-01

    We measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.

  5. Phosphorylation of a neuronal-specific beta-tubulin isotype

    International Nuclear Information System (INIS)

    Adult rats were intracraneally injected with [32P] phosphate and brain microtubules isolated. The electrophoretically purified, in vivo phospholabeled, beta-tubulin was digested with the V8-protease and the labeled peptide purified by reversed-phase liquid chromatography. Its amino acid sequence corresponds to the COOH-terminal sequence of a minor neuronal beta 3-tubulin isoform from chicken and human. The phosphorylation site was at serine 444. A synthetic peptide with sequence EMYEDDEEESESQGPK, corresponding to that of the COOH terminus of beta 3-tubulin, was efficiently phosphorylated in vitro by casein kinase II at the same serine 444. The functional meaning of tubulin phosphorylation is still unclear. However, the modification of the protein takes place after microtubule assembly, and phosphorylated tubulin is mainly present in the assembled microtubule protein fraction

  6. Two new ent-kaurane diterpenoids from Albizia mollis (Wall.) Boiv

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Zhong-Quan; Yang, Dan; Liu, Yu-Qing; Hu, Jiang-Miao; Jiang, He-Zhong; Wang, Peng-Cheng; Zhoua, Jun; Zhao, You-Xing, E-mail: yxzhao@mail.kib.ac.c [Chinese Academy of Sciences, Kunming (China). Kunming Institute of Botany. State Key Lab. of Phytochemistry and Plant Resources in West China; Li, Ning [Anhui University, Hefei (China). School of Life Sciences

    2010-07-01

    Two new kaurane diterpenoid, 3{alpha}, 16{beta}, 17-trihydroxy-ent-kaurane 3-O-{beta}-D-glucopyranoside and 2{beta},3{alpha}-dihydroxy-ent-kaur-15-en-17-oic acid 3-O-{beta}-D-glucopyranoside, were isolated from the bark of Albizia mollis (Wall.) Boiv. The structures of two new compounds were elucidated by extensive 1D- and 2D-NMR spectroscopic methods in combination with MS experiments. (author)

  7. Dynamic force spectroscopy to probe adhesion strength of living cells

    OpenAIRE

    Prechtel, K.; Bausch, A. R.; Marchi-Artzner, V.; Kantlehner, M.; Kessler, H; Merkel, R

    2002-01-01

    We studied the mechanical strength of the adhesion of living cells to model membranes. The latter contained a RGD lipopeptide which is a high affinity binding site for a cell adhesion molecule (integrin alpha(V)beta(3)). Cells adhered specifically to the vesicles. We used micropipette aspiration for breaking this adhesion with well defined forces. Systematic variation of the rate of force application revealed pronounced kinetic effects. The dependence of the detachment forces on the loading r...

  8. Cyr61/CCN1 Displays High-Affinity Binding to the Somatomedin B (1-44) Domain of Vitronectin

    Czech Academy of Sciences Publication Activity Database

    Francischetti, I.M.B.; Kotsyfakis, Michalis; Andersen, J. F.; Lukszo, J.

    2010-01-01

    Roč. 5, č. 2 (2010), e9356. E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z60220518 Keywords : PLASMINOGEN-ACTIVATOR INHIBITOR-1 * UROKINASE RECEPTOR * EXTRACELLULAR-MATRIX * CELL-ADHESION * CCN FAMILY * INTEGRIN ALPHA-V-BETA-3 * IXODES-SCAPULARIS * SALIVARY-GLAND * MELANOMA -CELLS * EXPRESSION Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 4.411, year: 2010

  9. Retroviral transfer of a human tyrosine hydroxylase cDNA in various cell lines: regulated release of dopamine in mouse anterior pituitary AtT-20 cells.

    OpenAIRE

    Horellou, P; Guibert, B; Leviel, V; Mallet, J

    1989-01-01

    Little is known about the molecular events mediating neurotransmitter release, a crucial step in synaptic transmission. In this paper, the biosynthesis and release of L-beta-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine were analyzed in three heterologous cell lines after retroviral-mediated gene transfer of tyrosine hydroxylase (EC 1.14.16.2), the rate-limiting enzyme in catecholamine synthesis. A recombinant retrovirus encoding human tyrosine hydroxylase type I as well as neomycin-resist...

  10. Osteocyte: the unrecognized side of bone tissue.

    OpenAIRE

    Rochefort, Gaël,; Pallu, Stéphane; Benhamou, Claude-Laurent

    2010-01-01

    INTRODUCTION: Osteocytes represent 95% of all bone cells. These cells are old osteoblasts that occupy the lacunar space and are surrounded by the bone matrix. They possess cytoplasmic dendrites that form a canalicular network for communication between osteocytes and the bone surface. They express some biomarkers (osteopontin, beta3 integrin, CD44, dentin matrix protein 1, sclerostin, phosphate-regulating gene with homologies to endopeptidases on the X chromosome, matrix extracellular phosphog...

  11. Time-dependent Hartree-Fock Study of Octupole Vibrations in doubly magic nuclei

    OpenAIRE

    Simenel, C; Buete, J.; Vo-Phuoc, K.

    2016-01-01

    Octupole vibrations are studied in some doubly magic nuclei using the time-dependent Hartree-Fock (TDHF) theory with a Skyrme energy density functional. Through the use of the linear response theory, the energies and transition amplitudes of the low-lying vibrational modes for each of the nuclei were determined. Energies were found to be close to experimental results. However, transition amplitudes, quantified by the deformation parameter $\\beta_3$, are underestimated by TDHF. A comparison wi...

  12. Program MASTERCALC: an interactive computer program for radioanalytical computations. Description and operating instructions

    International Nuclear Information System (INIS)

    MASTERCALC is a computer program written to support radioanalytical computations in the Los Alamos Scientific Laboratory (LASL) Environmental Surveillance Group. Included in the program are routines for gross alpha and beta, 3H, gross gamma, 90Sr and alpha spectroscopic determinations. A description of MASTERCALC is presented and its source listing is included. Operating instructions and example computing sessions are given for each type of analysis

  13. A Characteristic Particle Length

    CERN Document Server

    Roberts, Mark D

    2015-01-01

    It is argued that there are characteristic intervals associated with any particle that can be derived without reference to the speed of light $c$. Such intervals are inferred from zeros of wavefunctions which are solutions to the Schr\\"odinger equation. The characteristic length is $\\ell=\\beta^2\\hbar^2/(8Gm^3)$, where $\\beta=3.8\\dots$; this length might lead to observational effects on objects the size of a virus.

  14. ADRB3 adrenergic receptor is a key regulator of human myometrial apoptosis and inflammation during chorioamnionitis.

    OpenAIRE

    Lirussi, Fréderic; Rakotoniaina, Zo; Madani, Siham; Goirand, Françoise; Breuiller-Fouché, Michelle; Leroy, Marie-Josèphe; Sagot, Paul; Morrison, John; Dumas, Monique; Bardou, Marc

    2008-01-01

    The pathophysiology underlying preterm labor triggered by inflammatory conditions such as chorioamnionitis remains largely unclear. It has already been suggested that beta-3 adrenergic (ADRB3) agonists might be of interest in the pharmacological management of preterm labor. Although there is evidence implicating ADRB receptors in the control of inflammation, there are minimal data relating specifically to ADRB3. To explore the cellular consequences of chorioamnionitis and detect apoptosis, we...

  15. Assoziation von Genpolymorphismen mit der Cholelithiasis

    OpenAIRE

    Lauer, Nadine

    2009-01-01

    OBJECTIVES: The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g. Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independ...

  16. Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

    OpenAIRE

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively...

  17. ENG — EDRN Public Portal

    Science.gov (United States)

    ENG, or endoglin, is a cell surface adhesion protein involved the regulation of angiogenesis. ENG is a major glycoprotein of the vascular endothelium and is also a component of the transforming growth factor beta receptor complex. ENG binds to the beta1 and beta3 peptides with high affinity. ENG may also be involved in preeclampsia and several types of cancer. There are several isoforms encoded by transcript variants.

  18. Mechanizmus účinku katecholaminů v termogenezi izolovaných lidských leukocytů

    OpenAIRE

    MIKULKA, Aleš

    2007-01-01

    Effects of {$\\alpha$}1, {$\\alpha$}2, {$\\beta$}3 adrenergic agonists on resting oxygen consumption and effects of {$\\alpha$} and {$\\beta$}2 adrenergic antagonists on noradrenaline stimulated oxygen consumption of the human peripheral blood mononuclear cells (PBMC) were studied using the Clark oxygen electrode. It was found that, the {$\\alpha$}2 agonist increases slightly the resting oxygen consumption in the PBMC while, the {$\\beta$}2 and the {$\\alpha$} antagonists inhibit the noradrenaline st...

  19. Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

    International Nuclear Information System (INIS)

    The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1 2 (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 −/−), TLR4 −/−, and MyD88 −/− mice (on Balb/c background). ASD2-stimulated TLR2 −/− BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4 −/− BMDMs. Protein expression from ASD2-stimulated MyD88 −/− BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO2. - Highlights: • Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. • The aggravating effects of two ASDs on lung eosinophilia were compared. • The ASDs contained different LPS and β-glucan (ASD1 2 (ASD1 > ASD2). • The ASD2 aggravating effects on lung

  20. Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

    Energy Technology Data Exchange (ETDEWEB)

    He, Miao, E-mail: hemiao.cmu@gmail.com [Environment and Chronic Non-communicable Disease Research Center, College of Public Health, China Medical University, 11001 Shenyang (China); Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita (Japan); Ichinose, Takamichi, E-mail: ichinose@oita-nhs.ac.jp [Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita (Japan); Song, Yuan, E-mail: freude@med.uoeh-u.ac.jp [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555 Fukuoka (Japan); Yoshida, Yasuhiro, E-mail: songyuan1107@163.com [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555 Fukuoka (Japan); Arashidani, Keiichi, E-mail: arashi@snow.ocn.ne.jp [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555 Fukuoka (Japan); Yoshida, Seiichi, E-mail: syoshida@oita-nhs.ac.jp [Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita (Japan); Liu, Boying, E-mail: boyingliu321@gmail.com [Environment and Chronic Non-communicable Disease Research Center, College of Public Health, China Medical University, 11001 Shenyang (China); Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201 Oita (Japan); Nishikawa, Masataka, E-mail: mnishi@nies.go.jp [Environmental Chemistry Division, National Institute for Environmental Studies, 305-8506 Tsukuba, Ibaraki (Japan); Takano, Hirohisa, E-mail: htakano@health.env.kyoto-u.ac.jp [Environmental Health Division, Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, Kyoto daigaku-Katsura, Nishikyo-ku, Kyoto 615-8530 (Japan); and others

    2013-11-01

    The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and β-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 < ASD2) and chemokine eotaxin (ASD1 > ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and β-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 −/−), TLR4 −/−, and MyD88 −/− mice (on Balb/c background). ASD2-stimulated TLR2 −/− BMDMs enhanced IL-6, IL-12, TNF-α, MCP-1 and MIP-1α secretion compared with ASD2-stimulated TLR4 −/− BMDMs. Protein expression from ASD2-stimulated MyD88 −/− BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO{sub 2}. - Highlights: • Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. • The aggravating effects of two ASDs on lung eosinophilia were compared. • The ASDs contained different LPS and β-glucan (ASD1