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Sample records for dysfunction bacterial proliferation

  1. Lubricin: a novel means to decrease bacterial adhesion and proliferation.

    Science.gov (United States)

    Aninwene, George E; Abadian, Pegah N; Ravi, Vishnu; Taylor, Erik N; Hall, Douglas M; Mei, Amy; Jay, Gregory D; Goluch, Edgar D; Webster, Thomas J

    2015-02-01

    This study investigated the ability of lubricin (LUB) to prevent bacterial attachment and proliferation on model tissue culture polystyrene surfaces. The findings from this study indicated that LUB was able to reduce the attachment and growth of Staphylococcus aureus on tissue culture polystyrene over the course of 24 h by approximately 13.9% compared to a phosphate buffered saline (PBS)-soaked control. LUB also increased S. aureus lag time (the period of time between the introduction of bacteria to a new environment and their exponential growth) by approximately 27% compared to a PBS-soaked control. This study also indicated that vitronectin (VTN), a protein homologous to LUB, reduced bacterial S. aureus adhesion and growth on tissue culture polystyrene by approximately 11% compared to a PBS-soaked control. VTN also increased the lag time of S. aureus by approximately 43%, compared to a PBS-soaked control. Bovine submaxillary mucin was studied because there are similarities between it and the center mucin-like domain of LUB. Results showed that the reduction of S. aureus and Staphylococcus epidermidis proliferation on mucin coated surfaces was not as substantial as that seen with LUB. In summary, this study provided the first evidence that LUB reduced the initial adhesion and growth of both S. aureus and S. epidermidis on a model surface to suppress biofilm formation. These reductions in initial bacteria adhesion and proliferation can be beneficial for medical implants and, although requiring more study, can lead to drastically improved patient outcomes.

  2. Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.

    Science.gov (United States)

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y Eugene; Pennathur, Subramaniam; Smith, Jonathan D; Liu, George; Zheng, Lemin

    2012-01-01

    Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (-/-) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (-/-) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically. Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically.

  3. Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media▿

    Science.gov (United States)

    Furukawa, Masayuki; Ebmeyer, Jörg; Pak, Kwang; Austin, Darrell A.; Melhus, Åsa; Webster, Nicholas J. G.; Ryan, Allen F.

    2007-01-01

    Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation. PMID:17325051

  4. Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis.

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    Zhang, Yi; Cheng, Yan; Ren, Xingcong; Hori, Tsukasa; Huber-Keener, Kathryn J; Zhang, Li; Yap, Kai Lee; Liu, David; Shantz, Lisa; Qin, Zheng-Hong; Zhang, Suping; Wang, Jianrong; Wang, Hong-Gang; Shih, Ie-Ming; Yang, Jin-Ming

    2012-08-15

    Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We show that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.

  5. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

    Science.gov (United States)

    Gao, Shui-Ping; Sun, He-Fen; Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-12-22

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

  6. Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo.

    Science.gov (United States)

    Kim, In Hwang; Kim, Ik-Jung; Wen, Yancheng; Park, Na-Young; Park, Jinyoung; Lee, Keun-Woo; Koh, Ara; Lee, Ji-Hyun; Koo, Seung-Hoi; Kim, Kun-Soo

    2015-07-24

    We describe a novel insulin-degrading enzyme, SidC, that contributes to the proliferation of the human bacterial pathogen Vibrio vulnificus in a mouse model. SidC is phylogenetically distinct from other known insulin-degrading enzymes and is expressed and secreted specifically during host infection. Purified SidC causes a significant decrease in serum insulin levels and an increase in blood glucose levels in mice. A comparison of mice infected with wild type V. vulnificus or an isogenic sidC-deletion strain showed that wild type bacteria proliferated to higher levels. Additionally, hyperglycemia leads to increased proliferation of V. vulnificus in diabetic mice. Consistent with these observations, the sid operon was up-regulated in response to low glucose levels through binding of the cAMP-receptor protein (CRP) complex to a region upstream of the operon. We conclude that glucose levels are important for the survival of V. vulnificus in the host, and that this pathogen uses SidC to actively manipulate host endocrine signals, making the host environment more favorable for bacterial survival and growth.

  7. Diabetic HDL Is Dysfunctional in Stimulating Endothelial Cell Migration and Proliferation Due to Down Regulation of SR-BI Expression

    Science.gov (United States)

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y. Eugene; Pennathur, Subramaniam; Smith, Jonathan D.; Liu, George; Zheng, Lemin

    2012-01-01

    Background Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. Methodology/Principal Findings We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (−/−) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (−/−) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. Conclusions/Significance Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. PMID:23133640

  8. Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis.

    Science.gov (United States)

    Tauber, Simone C; Stadelmann, Christine; Spreer, Annette; Brück, Wolfgang; Nau, Roland; Gerber, Joachim

    2005-09-01

    Proliferation and differentiation of neural progenitor cells is increased after bacterial meningitis. To identify endogenous factors involved in neurogenesis, expression of brain-derived neurotrophic factor (BDNF), TrkB, nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) was investigated. C57BL/6 mice were infected by intracerebral injection of Streptococcus pneumoniae. Mice were killed 30 hours later or treated with ceftriaxone and killed 4 days after infection. Hippocampal BDNF mRNA levels were increased 2.4-fold 4 days after infection (p = 0.026). Similarly, BDNF protein levels in the hippocampal formation were higher in infected mice than in control animals (p = 0.0003). This was accompanied by an elevated proliferation of dentate granule cells (p = 0.0002). BDNF protein was located predominantly in the hippocampal CA3/4 area and the hilus of the dentate gyrus. The density of dentate granule cells expressing the BDNF receptor TrkB as well as mRNA levels of TrkB in the hippocampal formation were increased 4 days after infection (p = 0.027 and 0.0048, respectively). Conversely, NGF mRNA levels at 30 hours after infection were reduced by approximately 50% (p = 0.004). No significant changes in GDNF expression were observed. In conclusion, increased synthesis of BDNF and TrkB suggests a contribution of this neurotrophic factor to neurogenesis after bacterial meningitis.

  9. Bacterial flagellin triggers cardiac innate immune responses and acute contractile dysfunction.

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    Joelle Rolli

    Full Text Available BACKGROUND: Myocardial contractile failure in septic shock may develop following direct interactions, within the heart itself, between molecular motifs released by pathogens and their specific receptors, notably those belonging to the toll-like receptor (TLR family. Here, we determined the ability of bacterial flagellin, the ligand of mammalian TLR5, to trigger myocardial inflammation and contractile dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: TLR5 expression was determined in H9c2 cardiac myoblasts, in primary rat cardiomyocytes, and in whole heart extracts from rodents and humans. The ability of flagellin to activate pro-inflammatory signaling pathways (NF-kappaB and MAP kinases and the expression of inflammatory cytokines was investigated in H9c2 cells, and, in part, in primary cardiomyocytes, as well as in the mouse myocardium in vivo. The influence of flagellin on left ventricular function was evaluated in mice by a conductance pressure-volume catheter. Cardiomyocytes and intact myocardium disclosed significant TLR5 expression. In vitro, flagellin activated NF-kappaB, MAP kinases, and the transcription of inflammatory genes. In vivo, flagellin induced cardiac activation of NF-kappaB, expression of inflammatory cytokines (TNF alpha, IL-1 beta, IL-6, MIP-2 and MCP-1, and provoked a state of reversible myocardial dysfunction, characterized by cardiac dilation, reduced ejection fraction, and decreased end-systolic elastance. CONCLUSION/SIGNIFICANCE: These results are the first to indicate that flagellin has the ability to trigger cardiac innate immune responses and to acutely depress myocardial contractility.

  10. Surface tailored organobentonite enhances bacterial proliferation and phenanthrene biodegradation under cadmium co-contamination.

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    Mandal, Asit; Biswas, Bhabananda; Sarkar, Binoy; Patra, Ashok K; Naidu, Ravi

    2016-04-15

    Co-contamination of soil and water with polycyclic aromatic hydrocarbon (PAH) and heavy metals makes biodegradation of the former extremely challenging. Modified clay-modulated microbial degradation provides a novel insight in addressing this issue. This study was conducted to evaluate the growth and phenanthrene degradation performance of Mycobacterium gilvum VF1 in the presence of a palmitic acid (PA)-grafted Arquad® 2HT-75-based organobentonite in cadmium (Cd)-phenanthrene co-contaminated water. The PA-grafted organobentonite (ABP) adsorbed a slightly greater quantity of Cd than bentonite at up to 30mgL(-1) metal concentration, but its highly negative surface charge imparted by carboxylic groups indicated the potential of being a significantly superior adsorbent of Cd at higher metal concentrations. In systems co-contained with Cd (5 and 10mgL(-1)), the Arquad® 2HT-75-modified bentonite (AB) and PA-grafted organobentonite (ABP) resulted in a significantly higher (72-78%) degradation of phenanthrene than bentonite (62%) by the bacterium. The growth and proliferation of bacteria were supported by ABP which not only eliminated Cd toxicity through adsorption but also created a congenial microenvironment for bacterial survival. The macromolecules produced during ABP-bacteria interaction could form a stable clay-bacterial cluster by overcoming the electrostatic repulsion among individual components. Findings of this study provide new insights for designing clay modulated PAH bioremediation technologies in mixed-contaminated water and soil.

  11. Surface tailored organobentonite enhances bacterial proliferation and phenanthrene biodegradation under cadmium co-contamination

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Asit [Future Industries Institute (formerly Centre for Environmental Risk Assessment and Remediation), University of South Australia, Mawson Lakes, SA 5095 (Australia); Indian Council of Agricultural Research (ICAR), Indian Institute of Soil Science, Bhopal (India); Biswas, Bhabananda [Future Industries Institute (formerly Centre for Environmental Risk Assessment and Remediation), University of South Australia, Mawson Lakes, SA 5095 (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), ACT Building, University of Newcastle, Callaghan, NSW 2308 (Australia); Sarkar, Binoy, E-mail: binoy.sarkar@unisa.edu.au [Future Industries Institute (formerly Centre for Environmental Risk Assessment and Remediation), University of South Australia, Mawson Lakes, SA 5095 (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), ACT Building, University of Newcastle, Callaghan, NSW 2308 (Australia); Patra, Ashok K. [Indian Council of Agricultural Research (ICAR), Indian Institute of Soil Science, Bhopal (India); Naidu, Ravi, E-mail: ravi.naidu@newcastle.edu.au [Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), ACT Building, University of Newcastle, Callaghan, NSW 2308 (Australia); Global Centre for Environmental Remediation (GCER), Faculty of Science and Information Technology, University of Newcastle, Callaghan, NSW 2308 (Australia)

    2016-04-15

    Co-contamination of soil and water with polycyclic aromatic hydrocarbon (PAH) and heavy metals makes biodegradation of the former extremely challenging. Modified clay-modulated microbial degradation provides a novel insight in addressing this issue. This study was conducted to evaluate the growth and phenanthrene degradation performance of Mycobacterium gilvum VF1 in the presence of a palmitic acid (PA)-grafted Arquad® 2HT-75-based organobentonite in cadmium (Cd)-phenanthrene co-contaminated water. The PA-grafted organobentonite (ABP) adsorbed a slightly greater quantity of Cd than bentonite at up to 30 mg L{sup −1} metal concentration, but its highly negative surface charge imparted by carboxylic groups indicated the potential of being a significantly superior adsorbent of Cd at higher metal concentrations. In systems co-contained with Cd (5 and 10 mg L{sup −1}), the Arquad® 2HT-75-modified bentonite (AB) and PA-grafted organobentonite (ABP) resulted in a significantly higher (72–78%) degradation of phenanthrene than bentonite (62%) by the bacterium. The growth and proliferation of bacteria were supported by ABP which not only eliminated Cd toxicity through adsorption but also created a congenial microenvironment for bacterial survival. The macromolecules produced during ABP–bacteria interaction could form a stable clay-bacterial cluster by overcoming the electrostatic repulsion among individual components. Findings of this study provide new insights for designing clay modulated PAH bioremediation technologies in mixed-contaminated water and soil. - Highlights: • Surface tailored organobentonite synthesised and characterised • Modified clay adsorbs Cd and reduces toxicity to Mycobacterium gilvum. • It creates congenial microenvironment for bacterial survival. • It enhances phenanthrene biodegradation in metal co-contaminated condition.

  12. SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly.

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    Singh, Dipty; Bhattacharya, Anusri; Rai, Ankit; Dhaked, Hemendra Pal Singh; Awasthi, Divya; Ojima, Iwao; Panda, Dulal

    2014-05-13

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials.

  13. Telmisartan protects against microvascular dysfunction during myocardial ischemia/reperfusion injury by activation of peroxisome proliferator-activated receptor gamma

    Science.gov (United States)

    2013-01-01

    Background We investigated the potential of telmisartan to improve microvascular dysfunction induced by myocardial ischemia/reperfusion (I/R) injury by activating the peroxisome proliferator-activated receptor gamma (PPARG) pathway. Methods Forty-eight male rabbits were randomly allocated into sham-operated, I/R, GW9662, telmisartan, telmisartan–GW9662, or candesartan groups. Rabbits were anesthetized, and the left anterior descending coronary artery (LAD) was ligated for 60 minutes. Following reperfusion for 6 hours, angiotensin II content of the heart was determined using radioimmunoassay. Myocardial neutrophil accumulation and microvessel cross-sectional area were examined histologically. Myocardial capillaries were examined with transmission electron microscopy. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the myocardium were measured using enzyme-linked immunosorbent assay. Western blot was utilized for investigating the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and PPARG. Results Angiotensin II concentration was significantly increased in all treatment groups compared with the sham-operated group (P telmisartan, telmisartan-GW9662, and candesartan groups compared with the I/R group (P telmisartan group compared with the telmisartan–GW9662 and candesartan groups. Telmisartan significantly increased PPARG protein expression compared with all other groups (P telmisartan improved microvascular dysfunction during myocardial I/R injury via the PPARG pathway. PMID:23738781

  14. Early Administration of Probiotics Alters Bacterial Colonization and Limits Diet-Induced Gut Dysfunction and Severity of Necrotizing Enterocolitis in Preterm Pigs

    DEFF Research Database (Denmark)

    Siggers, Richard H.; Siggers, Jayda; Boye, Mette

    2008-01-01

    Following preterm birth, bacterial colonization and interal formula feeding predispose neonates to gut dysfunction and necrotizing enterocilitis (NEC), a serious gastrointestinal inflammatory disease. We hypothesized that administration of probiotics would beneficially influence early bacterial...... colonization, thereby reducing the susceptibility to formula-induced gut atrophy, dysfunction, and NEC. Caesarean-delivered preterm pigs were provided total parenteral nutrition (1.5 d) followed by enteral feeding (2d) with porcine colosstrum (COLOS; n= 5), formula (FORM; n = 9), or formula with probiotics...

  15. Peroxisome proliferator-activated receptors modulate cardiac dysfunction in diabetic cardiomyopathy.

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    Lee, T-I; Kao, Y-H; Chen, Y-C; Huang, J-H; Hsiao, F-C; Chen, Y-J

    2013-06-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). Chronic inflammation and derangement of myocardial energy and lipid homeostasis are common features of DM. The transcription factors of peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily, which are important in regulating energy and lipid homeostasis. There are three PPAR isoforms, α, γ, and δ, and their roles have been increasingly recognized to be important in CVD. These three isoforms are expressed in the heart and play pivotal roles in myocardial lipid metabolism, as well as glucose and energy homeostasis, and contribute to extra metabolic roles with effects on inflammation and oxidative stress. Moreover, regulation of PPARs may have significant effects on cardiac electrical activity and arrhythmogenesis. This review describes the roles of PPARs and their agonists in DM cardiomyopathy, inflammation, and cardiac electrophysiology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Early Administration of Probiotics Alters Bacterial Colonization and Limits Diet-Induced Gut Dysfunction and Severity of Necrotizing Enterocolitis in Preterm Pigs

    DEFF Research Database (Denmark)

    Siggers, Richard H.; Siggers, Jayda; Boye, Mette

    2008-01-01

    Following preterm birth, bacterial colonization and interal formula feeding predispose neonates to gut dysfunction and necrotizing enterocilitis (NEC), a serious gastrointestinal inflammatory disease. We hypothesized that administration of probiotics would beneficially influence early bacterial c...... (FORM-P, Bifidobacterium animalis and Lactobacillus: L. acidophilus, L. casei, L. pentosus, L. planterum; (n=13). Clinical NEC scores were reduced (P...

  17. Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation.

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    Houngbédji, Germain Mabèrou; Bouchard, Patrice; Frenette, Jérôme

    2011-03-01

    Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.

  18. Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

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    Portal-Celhay Cynthia

    2012-03-01

    Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

  19. A small volatile bacterial molecule triggers mitochondrial dysfunction in murine skeletal muscle.

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    A Aria Tzika

    Full Text Available Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA, produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS, proton ((1H nuclear magnetic resonance (NMR metabolomics, in vivo (31P NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by (1H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-γ, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo (31P NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance

  20. Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection.

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    Cunha, Luiz G; Assis, Maria-Cristina; Machado, Gloria-Beatriz; Assef, Ana P; Marques, Elizabeth A; Leão, Robson S; Saliba, Alessandra M; Plotkowski, Maria-Cristina

    2010-01-18

    Burkholderia cenocepacia, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of B. cenocepacia from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both in vitro and in vivo assays. B. cenocepacia-infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase. ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the in vivo assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs. B. cenocepacia were shown to exhibit cytotoxic

  1. Animal model of non-bacterial multiple organ dysfunction syndrome in the elderly

    Institute of Scientific and Technical Information of China (English)

    Qinglei ZHU; Shiwen WANG; Jie YANG; Tong YIN; Xiaoshun QIAN; Qiao XUE; Bin XU

    2004-01-01

    Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was 0.Sg/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.

  2. Reduced bacterial growth and increased osteoblast proliferation on titanium with a nanophase TiO2 surface treatment

    Directory of Open Access Journals (Sweden)

    Bhardwaj G

    2017-01-01

    Full Text Available Garima Bhardwaj, Thomas J Webster Department of Chemical Engineering, Northeastern University, Boston, MA, USA Background: The attachment and initial growth of bacteria on an implant surface dictates the progression of infection. Treatment often requires aggressive antibiotic use, which does not always work. To overcome the difficulties faced in systemic and local antibiotic delivery, scientists have forayed into using alternative techniques, which includes implant surface modifications that prevent initial bacterial adhesion, foreign body formation, and may offer a controlled inflammatory response.Objective: The current study focused on using electrophoretic deposition to treat titanium with a nanophase titanium dioxide surface texture to reduce bacterial adhesion and growth. Two distinct nanotopographies were analyzed, Ti-160, an antimicrobial surface designed to greatly reduce bacterial colonization, and Ti-120, an antimicrobial surface with a topography that upregulates osteoblast activity while reducing bacterial colonization; the number following Ti in the nomenclature represents the atomic force microscopy root-mean-square roughness value in nanometers.Results: There was a 95.6% reduction in Staphylococcus aureus (gram-positive bacteria for the Ti-160-treated surfaces compared to the untreated titanium alloy controls. There was a 90.2% reduction in Pseudomonas aeruginosa (gram-negative bacteria on Ti-160-treated surfaces compared to controls. For ampicillin-resistant Escherichia coli, there was an 81.1% reduction on the Ti-160-treated surfaces compared to controls. Similarly for surfaces treated with Ti-120, there was an 86.8% reduction in S. aureus, an 82.1% reduction in P. aeruginosa, and a 48.6% reduction in ampicillin-resistant E. coli. The Ti-120 also displayed a 120.7% increase at day 3 and a 168.7% increase at day 5 of osteoblast proliferation over standard titanium alloy control surfaces.Conclusion: Compared to untreated surfaces

  3. Nanogrooves and keratin nanofibers on titanium surfaces aimed at driving gingival fibroblasts alignment and proliferation without increasing bacterial adhesion.

    Science.gov (United States)

    Ferraris, S; Truffa Giachet, F; Miola, M; Bertone, E; Varesano, A; Vineis, C; Cochis, A; Sorrentino, R; Rimondini, L; Spriano, S

    2017-07-01

    Periimplantitis and epithelial downgrowth are nowadays the main conditions associated to transmucosal dental implants. Gingival fibroblasts can play an important role in periimplantitis because they are the promoters of the inflammatory process and eventual tissue homeostasis and destruction. Moreover, the related inflammatory state is commonly driven also to counteract bacteria implants colonization. In the present research, a new technology based on mechanically produced nanogrooves (0.1-0.2μm) and keratin nanofibers deposited by electrospinning has been proposed in order to obtain titanium surfaces able to drive gingival fibroblasts alignment and proliferation without increasing bacterial adhesion. The prepared surfaces have been characterized for their morphology (FESEM), chemical composition (FTIR, XPS), surface charge (zeta potential) and wettability (contact angle). Afterwards, their performances in terms of cells (human primary gingival fibroblasts) and bacteria (Staphylococcus aureus) adhesion were compared to mirror-like polished titanium surfaces. Results revealed that gingival fibroblasts viability was not negatively affected by the applied surface roughness or by keratin nanofibers. On the opposite, cells adhesion and spread were strongly influenced by surface roughness revealing a significant cell orientation along the produced nanogrooves. However, the keratin influence was clearly predominant with respect to surface topography, thus leading to increased cells proliferation on the surfaces with nanofibers, disregarding the presence of the surfaces grooves. Moreover, nor nanogrooves nor keratin nanofibers increase bacterial biofilm adhesion in comparison with mirror polished surfaces. Thus, the present research represents a promising innovative strategy and technology for a surface modification finalized to match the main requirements for transmucosal dental implants. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.

    Science.gov (United States)

    Cui, Jixin; Yao, Qing; Li, Shan; Ding, Xiaojun; Lu, Qiuhe; Mao, Haibin; Liu, Liping; Zheng, Ning; Chen, She; Shao, Feng

    2010-09-03

    A family of bacterial effectors including Cif homolog from Burkholderia pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a functionally important papain-like hydrolytic fold. We show here that CHBP was a potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a deamidase that specifically and efficiently deamidated Gln40 in ubiquitin and ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the activity of neddylated Cullin-RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations of substrate-contacting residues in Cif abolished or attenuated EPEC-induced cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.

  5. Fluoroquinolone-macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

    Institute of Scientific and Technical Information of China (English)

    Vittorio Magri; Emanuele Montanari; Vi(s)nja (S)kerk; Alemka Markoti(c); Emanuela Marras; Antonella Restelli; Kurt G Naber; Gianpaolo Perletti

    2011-01-01

    We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category Ⅱ chronic bacterial prostatitis (CBP).The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg,thrice-weekly) with a once-daily 500-or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort,respectively).Combined administration of azithromycin (1500 mg week-1) with ciprofloxacin at the rate of 750 mg day-1 for 4 weeks rather than at 500 mg day-1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%.A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups.Ejaculatory pain,haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups,but the latter subsided more promptly in the Cipro-750 cohort.In total,59 Cipro-750 patients showed mild-to-severn erectile dysfunction (ED) at baseline,while 22 patients had no ED on microbiological eradication and throughout the follow-up period.In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation,including pain,voiding disturbances and sexual dysfunction.A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks.Our results are open to further prospective validation.

  6. Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

    Science.gov (United States)

    Magri, Vittorio; Montanari, Emanuele; Škerk, Višnja; Markotić, Alemka; Marras, Emanuela; Restelli, Antonella; Naber, Kurt G; Perletti, Gianpaolo

    2011-01-01

    We previously demonstrated the safety and efficacy of fluoroquinolone–macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week−1) with ciprofloxacin at the rate of 750 mg day−1 for 4 weeks rather than at 500 mg day−1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone–macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation. PMID:21765442

  7. Multifunctional CuS nanocrystals for inhibiting both osteosarcoma proliferation and bacterial infection by photothermal therapy

    Science.gov (United States)

    Hu, Xiaoming; Li, Lihua; Lu, Yao; Liu, Cong; Lei, Yangqing; Zhang, Chengcheng; Yin, Qingshui; Zhang, Yu

    2017-09-01

    Photothermal therapy (PTT) has attracted great attention in cancer therapy because of high efficiency and low side effect. The semiconductors have been proved to be ideal photothermal agents in the past years. Herein, we synthesized a novel hexahedron structure of polyvinyl pyrrolidone (PVP) coating CuS nanocrystals (NCs) by a facile hydrothermal method. The synthesized CuS NCs (150 nm for average length of edge and 125 nm for length of width) have good biocompatibility due to their PVP coating and strong absorption in the near infrared region. Moreover, the CuS NCs exhibit high photothermal conversion efficiency as well as good antibacterial effect. Notably, the proliferation of osteosarcoma cancer cells can be efficiently inhibited both in vitro and in vivo by the fatal heat with very low concentration of CuS NCs under the near infrared ray at a power density of 0.5 W/cm2. Therefore, the CuS-PVP NCs have great potential to work as an ideal photothermal and antibacterial agent in clinical applications.

  8. Heteroclitic Peptides Increase Proliferation and Reduce Evidence of Human Immunodeficiency Virus-Specific CD8⁺ T Cell Dysfunction.

    Science.gov (United States)

    Adegoke, Adeolu; Gladney, Krista; Gallant, Maureen; Grant, Michael

    2015-10-01

    Human immunodeficiency virus (HIV)-specific CD8(+) T cell dysfunction parallels disease progression; therefore, restoring potent HIV-specific CD8(+) T cell responses is a key therapeutic goal. Certain CD8(+) T cell peptide epitope variants, termed heteroclitic, enhance cytokine production by the HIV-specific CD8(+) T cells of some individuals. In this study, we investigated whether heteroclitic peptides that enhance cytokine production by HIV-specific CD8(+) T cells also reduce functional and phenotypic evidence of HIV-specific CD8(+) T cell exhaustion in those instances. Twenty-four variant peptides of human histocompatibility-linked leukocyte antigen (HLA)-A2-restricted reference HIV peptide epitopes designated as A2-7; Nef 83→91, A2-8; Nef 135→143, A2-Gag; Gag 77→85 and A2-9; Gag 433→440 were synthesized with conservative and semiconservative amino acid substitutions at positions 3, 5, and 7 or 3, 5, and 8 of Gag 433→440. Variants that enhanced interferon-gamma (IFN-γ) and/or interleukin-2 (IL-2) production in enzyme-linked immunospot assays (29 cases overall) were subsequently tested by 7-day in vitro peptide stimulation for their effects on HIV-specific CD8(+) T cell proliferation and programmed death-1 (PD-1) expression. Heteroclitic variants enhanced HIV-specific CD8(+) T cell proliferation by >20% in 13/29 cases tested, reduced PD-1 expression on proliferating cells by 15-50% in 10 cases, and reduced PD-1 expression on proliferating cells by >50% in 3 cases. In five cases, the same heteroclitic peptide increased proliferation by >20% and reduced PD-1 expression by >15%. These data demonstrate that heteroclitic peptides can alter the magnitude and character of HIV-specific CD8(+) cell responses relative to reference peptides and may have a unique immunotherapeutic value in therapeutic vaccines.

  9. Selenium nanoparticles incorporated into titania nanotubes inhibit bacterial growth and macrophage proliferation.

    Science.gov (United States)

    Liu, Wenwen; Golshan, Negar H; Deng, Xuliang; Hickey, Daniel J; Zeimer, Katherine; Li, Hongyi; Webster, Thomas J

    2016-08-25

    Since implants often fail due to infection and uncontrolled inflammatory responses, we designed an in vitro study to investigate the antibacterial and anti-inflammatory properties of titanium dioxide nanotubes (TNTs) incorporated with selenium nanoparticles (SeNPs). Selenium incorporation was achieved by the reaction of sodium selenite (Na2SeO3) with glutathione (GSH) under a vacuum in the presence of TNTs. Two types of bacteria and macrophages were cultured on the samples to determine their respective antibacterial and anti-inflammatory properties. The results showed that the TNT samples incorporating SeNPs (TNT-Se) inhibited the growth of Escherichia coli and Staphylococcus aureus compared to unmodified TNTs, albeit the SeNP concentration still needs to be optimized for maximal effect. At their maximum effect, the TNT-Se samples reduced the density of E. coli by 94.6% and of S. aureus by 89.6% compared to titanium controls. To investigate the underlying mechanism of this effect, the expression of six E. coli genes were tracked using qRT-PCR. Results indicated that SeNPs weakened E. coli membranes (ompA and ompF were down-regulated), decreased the function of adhesion-mediating proteins (csgA and csgG were progressively down-regulated with increasing SeNP content), and induced the production of damaging reactive oxygen species (ahpF was up-regulated). Moreover, TNT-Se samples inhibited the proliferation of macrophages, indicating that they can be used to control the inflammatory response and even prevent chronic inflammation, a condition that often leads to implant failure. In conclusion, we demonstrated that SeNP-TNTs display antibacterial and anti-inflammatory properties that are promising for improving the performance of titanium-based implants for numerous orthopedic and dental applications.

  10. Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation

    Science.gov (United States)

    Kübler, André; Luna, Brian; Larsson, Christer; Ammerman, Nicole C.; Andrade, Bruno B.; Orandle, Marlene; Bock, Kevin W.; Xu, Ziyue; Bagci, Ulas; Molura, Daniel J.; Marshall, John; Burns, Jay; Winglee, Kathryn; Ahidjo, Bintou Ahmadou; Cheung, Laurene S.; Klunk, Mariah; Jain, Sanjay K.; Kumar, Nathella Pavan; Babu, Subash; Sher, Alan; Friedland, Jon S.; Elkington, Paul T. G.; Bishai, William R.

    2014-01-01

    Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1 are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model results in consistent progression of consolidation to human-like cavities (100% by day 28) with resultant bacillary burdens (>107 CFU/g) far greater than those found in matched granulomatous tissue (105 CFU/g). Using a novel, breath-hold computerized tomography scanning and image analysis protocol. We show that cavities develop rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue as estimated by changes in lung density during controlled pulmonary expansion (R2=0.6356, p<0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) is specifically greater in cavitary compared to granulomatous lesions (p<0.01), and that TIMP-3 significantly decreases at the cavity surface. Our findings demonstrate that an MMP-1/TIMP imbalance, is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels,. It also provides a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB; and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV=92.9%; 95%CI 66.1–99.8%, NPV=85.6%; 95%CI 77.0–91.9%). PMID:25186281

  11. Ileocecal valve dysfunction in small intestinal bacterial overgrowth: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Larry S Miller; Anil K Vegesna; Aiswerya Madanam Sampath; Shital Prabhu; Sesha Krishna Kotapati; Kian Makipour

    2012-01-01

    AIM:To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.METHODS:Using a colonoscope,under conscious sedation,the ICV was intubated and the colonoscope was placed within the terminal ileum (TI).A manometry catheter with 4 pressure channels,spaced 1 cm apart,was passed through the biopsy channel of the colonoscope into the TI.The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced.The catheter was placed across the ICV so that at least one pressure port was within the TI,ICV and the cecum respectively.Pressures were continuously measured during air insufflation into the cecum,under direct endoscopic visualization,in 19 volunteers.Air was insufflated to a maximum of 40 mmHg to prevent barotrauma.All subjects underwent lactulose breath testing one month after the colonoscopy.The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation.RESULTS:Nineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope.Initial baseline readings showed no statistical difference in the pressures of the TI and ICV,between subjects with positive lactulose breath tests and normal lactulose breath tests.The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactulose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg,P =0.0011).The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%,P =0.0006).The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal pressures during

  12. Cell proliferation, viability, and in vitro differentiation of equine mesenchymal stem cells seeded on bacterial cellulose hydrogel scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Favi, Pelagie M.; Benson, Roberto S. [Department of Materials Science and Engineering, College of Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Neilsen, Nancy R. [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Hammonds, Ryan L. [Department of Materials Science and Engineering, College of Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Bates, Cassandra C. [Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Stephens, Christopher P. [Department of Surgery, Graduate School of Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Center for Materials Processing, University of Tennessee, Knoxville, TN 37996 (United States); Dhar, Madhu S., E-mail: mdhar@utk.edu [Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

    2013-05-01

    The culture of multipotent mesenchymal stem cells on natural biopolymers holds great promise for treatments of connective tissue disorders such as osteoarthritis. The safety and performance of such therapies relies on the systematic in vitro evaluation of the developed stem cell-biomaterial constructs prior to in vivo implantation. This study evaluates bacterial cellulose (BC), a biocompatible natural polymer, as a scaffold for equine-derived bone marrow mesenchymal stem cells (EqMSCs) for application in bone and cartilage tissue engineering. An equine model was chosen due to similarities in size, load and types of joint injuries suffered by horses and humans. Lyophilized and critical point dried BC hydrogel scaffolds were characterized using scanning electron microscopy (SEM) to confirm nanostructure morphology which demonstrated that critical point drying induces fibre bundling unlike lyophilisation. EqMSCs positively expressed the undifferentiated pluripotent mesenchymal stem cell surface markers CD44 and CD90. The BC scaffolds were shown to be cytocompatible, supporting cellular adhesion and proliferation, and allowed for osteogenic and chondrogenic differentiation of EqMSCs. The cells seeded on the BC hydrogel were shown to be viable and metabolically active. These findings demonstrate that the combination of a BC hydrogel and EqMSCs are promising constructs for musculoskeletal tissue engineering applications. - Highlights: ► Critical point drying induces fibre bundling unlike lyophilisation. ► Cells positively expressed undifferentiated pluripotent stem cell markers. ► BCs were cytocompatible, supported cell adhesion, proliferation and differentiation ► Cells seeded on BC scaffolds were viable and metabolically active. ► Findings demonstrate that BC and EqMSCs are promising tissue engineered constructs.

  13. Fragmented Lactic Acid Bacterial Cells Activate Peroxisome Proliferator-Activated Receptors and Ameliorate Dyslipidemia in Obese Mice.

    Science.gov (United States)

    Nakamura, Futoshi; Ishida, Yu; Sawada, Daisuke; Ashida, Nobuhisa; Sugawara, Tomonori; Sakai, Manami; Goto, Tsuyoshi; Kawada, Teruo; Fujiwara, Shigeru

    2016-03-30

    Recent studies suggest that peroxisome proliferator-activated receptor (PPAR) activation ameliorates metabolic disorders, including dyslipidemia. To identify an effective PPAR agonist, we screened the in vitro PPARα/γ activation ability of organic solvent extracts from food-oriented bacterial strains belonging to 5 genera and 32 species, including lactic acid bacteria, and of these, Lactobacillus amylovorus CP1563 demonstrated the highest PPARα/γ agonist activity. We also found that physical fragmentation of the strain could substitute organic solvent extraction for the expression of CP1563 activity in vitro. For functional food manufacturing, we selected the fragmented CP1563 and conducted subsequent animal experiments. In an obese mouse model, we found that treatment with fragmented CP1563 for 12 weeks decreased the levels of low-density lipoprotein (LDL)-cholesterol and triglyceride in plasma, significantly decreased the atherosclerosis index, and increased the plasma high-density lipoprotein (HDL)-cholesterol level. Thus, we conclude that fragmented CP1563 may be a candidate for the prevention and treatment of dyslipidemia.

  14. Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition

    DEFF Research Database (Denmark)

    Bjørnvad, Charlotte R.; Thymann, Thomas; Deutz, Nicolaas E.

    2008-01-01

    Preterm neonates have an immature gut and metabolism and may benefit from total parenteral nutrition (TPN) before enteral food is introduced. Conversely,delayed enteral feeding may inhibit gut maturation and sensitize to necrotizing enterocolitis (NEC). Intestinal mass and NEC lesions were first...

  15. Activation of peroxisome proliferator-activated receptor-γ coactivator 1α ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury.

    Science.gov (United States)

    Yuan, Yanggang; Huang, Songming; Wang, Wenyan; Wang, Yingying; Zhang, Ping; Zhu, Chunhua; Ding, Guixia; Liu, Bicheng; Yang, Tianxin; Zhang, Aihua

    2012-10-01

    Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity.

  16. Effect of Bacterial Infection on Proliferating Cell Nuclear Antigen Expression after Partial Splenectomy of Rabbits Using Microwave Coagulator

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The purpose of this study was to investigate the proliferating cell nuclear antigen (PCNA) expression of preserved spleen in rabbits when pneumonia diplococcus suspension was administered after partial splenectomy using microwaver coagulator.

  17. Sendai Virus Induces Persistent Olfactory Dysfunction in a Murine Model of PVOD via Effects on Apoptosis, Cell Proliferation, and Response to Odorants.

    Directory of Open Access Journals (Sweden)

    Jun Tian

    Full Text Available Viral infection is a common cause of olfactory dysfunction. The complexities of studying post-viral olfactory loss in humans have impaired further progress in understanding the underlying mechanism. Recently, evidence from clinical studies has implicated Parainfluenza virus 3 as a causal agent. An animal model of post viral olfactory disorders (PVOD would allow better understanding of disease pathogenesis and represent a major advance in the field.To develop a mouse model of PVOD by evaluating the effects of Sendai virus (SeV, the murine counterpart of Parainfluenza virus, on olfactory function and regenerative ability of the olfactory epithelium.C57BL/6 mice (6-8 months old were inoculated intranasally with SeV or ultraviolet (UV-inactivated virus (UV-SeV. On days 3, 10, 15, 30 and 60 post-infection, olfactory epithelium was harvested and analyzed by histopathology and immunohistochemical detection of S-phase nuclei. We also measured apoptosis by TUNEL assay and viral load by real-time PCR. The buried food test (BFT was used to measure olfactory function of mice at day 60. In parallel, cultured murine olfactory sensory neurons (OSNs infected with SeV or UV-SeV were tested for odorant-mixture response by measuring changes in intracellular calcium concentrations indicated by fura-4 AM assay.Mice infected with SeV suffered from olfactory dysfunction, peaking on day 15, with no loss observed with UV-SeV. At 60 days, four out of 12 mice infected with SeV still had not recovered, with continued normal function in controls. Viral copies of SeV persisted in both the olfactory epithelium (OE and the olfactory bulb (OB for at least 60 days. At day 10 and after, both unit length labeling index (ULLI of apoptosis and ULLI of proliferation in the SeV group was markedly less than the UV-SeV group. In primary cultured OSNs infected by SeV, the percentage of cells responding to mixed odors was markedly lower in the SeV group compared to UV-SeV (P = 0.007.We

  18. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  19. Antigen-specific bacterial vaccine combined with anti-PD-L1 rescues dysfunctional endogenous T cells to reject long-established cancer.

    Science.gov (United States)

    Binder, David C; Engels, Boris; Arina, Ainhoa; Yu, Ping; Slauch, James M; Fu, Yang-Xin; Karrison, Theodore; Burnette, Byron; Idel, Christian; Zhao, Ming; Hoffman, Robert M; Munn, David H; Rowley, Donald A; Schreiber, Hans

    2013-08-01

    Immunogenic tumors grow progressively even when heavily infiltrated by CD8(+) T cells. We investigated how to rescue CD8(+) T cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1(+) tumor-specific CD8(+) T cells that were dysfunctional. Treatment with αPD-L1 and αCTLA-4 blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using Salmonella Typhimurium A1-R to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8(+) T cell response: proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1 blocking antibody enhanced the expansion of tumor-specific CD8(+) T cells and resulted in 80% tumor rejection. Collectively, these data demonstrate a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8(+) T cells and eradicate advanced immunogenic tumors.

  20. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Istvan eCzikora

    2014-07-01

    Full Text Available Rationale. Antibiotic treatment of patients infected with G- or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS and pneumolysin (PLY in their lungs. Growth Hormone-releasing Hormone (GHRH agonist JI-34 protects human lung microvascular cells (HL-MVEC, expressing splice variant 1 (SV-1 of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated PKA depletion.Methods. Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye incorporation. Cytokine generation in broncho-alveolar lavage fluid was measured by multiplex analysis. PKA and PKC-alpha activity were assessed by Western blotting. Results. GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-alpha activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions. GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-alpha-induced pathway in the presence of PLY, the former of which dominates the latter.

  1. Differential effects of β-catenin and NF-κB interplay in the regulation of cell proliferation, inflammation and tumorigenesis in response to bacterial infection.

    Directory of Open Access Journals (Sweden)

    Parthasarathy Chandrakesan

    Full Text Available Both β-catenin and NF-κB have been implicated in our laboratory as candidate factors in driving proliferation in an in vivo model of Citrobacter rodentium (CR-induced colonic crypt hyper-proliferation and hyperplasia. Herein, we test the hypothesis that β-catenin and not necessarily NF-κB regulates colonic crypt hyperplasia or tumorigenesis in response to CR infection. When C57Bl/6 wild type (WT mice were infected with CR, sequential increases in proliferation at days 9 and 12 plateaued off at day 19 and paralleled increases in NF-κB signaling. In Tlr4(-/- (KO mice, a sequential but sustained proliferation which tapered off only marginally at day 19, was associated with TLR4-dependent and independent increases in NF-κB signaling. Similarly, increases in either activated or total β-catenin in the colonic crypts of WT mice as early as day 3 post-infection coincided with cyclinD1 and c-myc expression and associated crypt hyperplasia. In KO mice, a delayed kinetics associated predominantly with increases in non-phosphorylated (active β-catenin coincided with increases in cyclinD1, c-myc and crypt hyperplasia. Interestingly, PKCζ-catalyzed Ser-9 phosphorylation and inactivation of GSK-3β and not loss of wild type APC protein accounted for β-catenin accumulation and nuclear translocation in either strain. In vitro studies with Wnt2b and Wnt5a further validated the interplay between the Wnt/β-catenin and NF-κB pathways, respectively. When WT or KO mice were treated with nanoparticle-encapsulated siRNA to β-catenin (si-β-Cat, almost complete loss of nuclear β-catenin coincided with concomitant decreases in CD44 and crypt hyperplasia without defects in NF-κB signaling. si-β-Cat treatment to Apc(Min/+ mice attenuated CR-induced increases in β-catenin and CD44 that halted the growth of mutated crypts without affecting NF-κB signaling. The predominant β-catenin-induced crypt proliferation was further validated in a Castaneus strain (B6

  2. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    Science.gov (United States)

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans.

  3. Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose

    Science.gov (United States)

    Zhang, Ming; Dong, Chunsheng; Xiong, Sidong

    2017-01-01

    Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development. PMID:28224119

  4. Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism

    DEFF Research Database (Denmark)

    Frigerio, F; Brun, T; Bartley, C

    2009-01-01

    and investigated key metabolic pathways and genes responsible for metabolism-secretion coupling during a culture period of 3 days in the presence of 0.4 mmol/l oleate. RESULTS: In INS-1E cells, the secretory dysfunction primarily induced by oleate was aggravated by silencing of PPARalpha. Conversely, PPARalpha....../INTERPRETATION: PPARalpha protected INS-1E beta cells from oleate-induced dysfunction, promoting both preservation of glucose metabolic pathways and fatty acid turnover.......AIMS/HYPOTHESIS: Pancreatic beta cells chronically exposed to fatty acids may lose specific functions and even undergo apoptosis. Generally, lipotoxicity is triggered by saturated fatty acids, whereas unsaturated fatty acids induce lipodysfunction, the latter being characterised by elevated basal...

  5. Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages.

    Science.gov (United States)

    Hensel, M; Shea, J E; Waterman, S R; Mundy, R; Nikolaus, T; Banks, G; Vazquez-Torres, A; Gleeson, C; Fang, F C; Holden, D W

    1998-10-01

    The type III secretion system of Salmonella pathogenicity island 2 (SPI-2) is required for systemic infection of this pathogen in mice. Cloning and sequencing of a central region of SPI-2 revealed the presence of genes encoding putative chaperones and effector proteins of the secretion system. The predicted products of the sseB, sseC and sseD genes display weak but significant similarity to amino acid sequences of EspA, EspD and EspB, which are secreted by the type III secretion system encoded by the locus of enterocyte effacement of enteropathogenic Escherichia coli. The transcriptional activity of an sseA::luc fusion gene was shown to be dependent on ssrA, which is required for the expression of genes encoding components of the secretion system apparatus. Strains carrying nonpolar mutations in sseA, sseB or sseC were severely attenuated in virulence, strains carrying mutations in sseF or sseG were weakly attenuated, and a strain with a mutation in sseE had no detectable virulence defect. These phenotypes were reflected in the ability of mutant strains to grow within a variety of macrophage cell types: strains carrying mutations in sseA, sseB or sseC failed to accumulate, whereas the growth rates of strains carrying mutations in sseE, sseF or sseG were only modestly reduced. These data suggest that, in vivo, one of the functions of the SPI-2 secretion system is to enable intracellular bacterial proliferation.

  6. Hypothalamic dysfunction

    Science.gov (United States)

    ... common causes of hypothalamic dysfunction are surgery, traumatic brain injury, tumors, and radiation. Other causes include: Anorexia nervosa or bulimia Bleeding Genetic disorders that cause iron ...

  7. Tigecycline inhibits proliferation of Acanthamoeba castellanii.

    Science.gov (United States)

    Jha, Bijay Kumar; Seo, Incheol; Kong, Hyun-Hee; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki

    2015-03-01

    Acanthamoeba is an opportunistic protozoan parasite responsible for different diseases in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Tigecycline, a third-generation tetracycline antibiotic, has potential activity to treat most of the antibiotic resistant bacterial infections. The effects of tigecycline in eukaryotic cells as well as parasites are less well studied. In the present study, we tested the effects of tigecycline on trophozoites of Acanthamoeba castellanii. The inhibitory effect of tigecycline on Acanthamoeba was determined by resazurin reduction and trypan blue exclusion assays. We found that tigecycline significantly inhibited the growth of Acanthamoeba (46.4 % inhibition at the concentration of 100 μM) without affecting cell viability and induction of encystation, whereas other tetracycline groups of antibiotics such as tetracycline and doxycycline showed no inhibitory effects. Furthermore, tigecycline decreased cellular adenosine triphosphate (ATP) level by 26 % than the control and increased mitochondrial mass, suggesting mitochondrial dysfunction in tigecycline-treated cells. These findings suggest that mitochondrial dysfunction with decreased ATP production might play an important mechanism of tigecycline in suppression of Acanthamoeba proliferation.

  8. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    Michelle L Boland

    2013-12-01

    Full Text Available A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability and other more conventional aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the sigificance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis and spatial dynamics and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knockon effects for cell proliferation and growth. Scientifically, there is also scope for defining what mitochondria dysfunction is and here we address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

  9. Erectile dysfunction.

    Science.gov (United States)

    Wylie, Kevan

    2008-01-01

    Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.

  10. Erectile dysfunction

    African Journals Online (AJOL)

    that increase blood flow to the penis. The blood ... The pressure of the blood in the chambers makes the ... What are the risk factors for erectile dysfunction? The most .... losing excessive weight and increasing physical activity, may improve the ...

  11. Oral Dysfunction

    OpenAIRE

    鈴木, 規子; スズキ, ノリコ; Noriko, SUZUKI

    2004-01-01

    The major oral functions can be categorized as mastication, swallowing, speech and respiratory functions. Dysfunction of these results in dysphagia, speech disorders and abnormal respiration (such as Sleep Apnea). These functions relate to dentistry in the occurrence of : (1) oral preparatory and oral phases, (2) articulation disorders and velopharyngeal incompetence (VPI), and (3) mouth breathing, respiratory and blowing disorders. These disorders are related to oral and maxillofacial diseas...

  12. Bacterial Vaginosis

    Science.gov (United States)

    ... Form Controls Cancel Submit Search the CDC Bacterial Vaginosis (BV) Note: Javascript is disabled or is not ... STD on Facebook Sexually Transmitted Diseases (STDs) Bacterial Vaginosis – CDC Fact Sheet Language: English (US) Españ ...

  13. Bacterial Vaginosis

    Science.gov (United States)

    ... Issues > Conditions > Sexually Transmitted > Bacterial Vaginosis Health Issues Listen Español Text Size Email Print Share Bacterial Vaginosis Page Content Bacterial vaginosis (BV) is the most common vaginal infection in sexually active teenaged girls . It appears to be caused by ...

  14. Posterior Tibial Tendon Dysfunction

    Science.gov (United States)

    .org Posterior Tibial Tendon Dysfunction Page ( 1 ) Posterior tibial tendon dysfunction is one of the most common problems of the foot and ankle. It occurs when the posterior tibial tendon becomes inflamed or torn. As a result, the ...

  15. Female Sexual Dysfunction

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Female Sexual Dysfunction February 2012 Download PDFs English Espanol Editors ... Resources Mayo Clinic Cleveland Clinic What is female sexual dysfunction (FSD)? Many women have a low sex ...

  16. Bacterial Sialidase

    Science.gov (United States)

    2004-01-01

    Data shows that elevated sialidase in bacterial vaginosis patients correlates to premature births in women. Bacterial sialidase also plays a significant role in the unusual colonization of Pseudomonas aeruginosa in cystic fibrosis patients. Crystals of Salmonella sialidase have been reproduced and are used for studying the inhibitor-enzyme complexes. These inhibitors may also be used to inhibit a trans-sialidase of Trypanosome cruzi, a very similar enzyme to bacterial sialidase, therefore preventing T. cruzi infection, the causitive agent of Chagas' disease. The Center for Macromolecular Crystallography suggests that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases.

  17. Liver Cirrhosis and Intestinal Bacterial Translocation

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Intestinal defense system including microbial barrier, immunologic barrier, mechanical barrier, chemical barrier, plays an important role in the maintenance of intestinal function. Under normal circumstances, the intestinal barrier can prevent intestinal bacteria through the intestinal wall from spreading to the body. Severe infection, trauma, shock, cirrhosis, malnutrition, immune suppression conditions, intestinal bacteria and endotoxin translocation, can lead to multiple organ dysfunction. The intestinal microlfora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microlfora may lead to microbial translocation, deifned as the passage of viable microorganisms or bacterial products from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. In patients with cirrhosis, primary and intestinal lfora imbalance, intestinal bacterial overgrowth, intestinal mucosal barrier dysfunction, endotoxemia is associated with weakened immunity.

  18. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

  19. Bacterial gastroenteritis

    Science.gov (United States)

    ... most common types of bacterial gastroenteritis in a couple of days. The goal is to make you feel better and avoid dehydration. Drinking enough fluids and learning what to eat will help ease symptoms. You ...

  20. Bacterial vaginosis

    National Research Council Canada - National Science Library

    Islam, Aliya; Safdar, Anjum; Malik, Ayesha

    2009-01-01

    To estimate the frequency of bacterial vaginosis in women with preterm labour. Descriptive cross sectional study carried out in department of Obstetrics and Gynaecology, Military Hospital and Army Medical College Laboratory, Rawalpindi...

  1. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

    Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

  2. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management.

  3. Female Sexual Dysfunction

    Science.gov (United States)

    ... to be comfortable with your sexuality, improve your self-esteem and accept your body. Try practicing these healthy ... mayoclinic.org/diseases-conditions/female-sexual-dysfunction/basics/definition/CON-20027721 . Mayo Clinic Footer Legal Conditions and ...

  4. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  5. Basal ganglia dysfunction

    Science.gov (United States)

    ... ganglia dysfunction. They include: Dystonia (muscle tone problems) Huntington disease (disorder in which nerve cells in certain parts ... ed. Philadelphia, PA: Elsevier Mosby; 2013:chap 20. Review Date 5/30/2016 Updated by: Amit M. ...

  6. [Beyond immunopathogenesis. Insulin resistance and "epidermal dysfunction"].

    Science.gov (United States)

    Boehncke, W-H; Boehncke, S; Buerger, C

    2012-03-01

    Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize "epidermal dysfunction", thus complementing the immunomodulatory strategies of today's biologics.

  7. Sexual Dysfunction in Women

    OpenAIRE

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life.

  8. Effect of Vibration on Bacterial Growth and Antibiotic Resistance

    Science.gov (United States)

    Juergensmeyer, Elizabeth A.; Juergensmeyer, Margaret A.

    2004-01-01

    The purpose of this research grant was to provide a fundamental, systematic investigation of the effects of oscillatory acceleration on bacterial proliferation and their responses to antibiotics in a liquid medium.

  9. Bacterial Ecology

    DEFF Research Database (Denmark)

    Fenchel, Tom

    2011-01-01

    Bacterial ecology is concerned with the interactions between bacteria and their biological and nonbiological environments and with the role of bacteria in biogeochemical element cycling. Many fundamental properties of bacteria are consequences of their small size. Thus, they can efficiently exploit...

  10. Bacterial lipases

    NARCIS (Netherlands)

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    1994-01-01

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, mea

  11. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    tract to the microbial flocs in waste water treatment facilities. Microbial biofilms may however also cause a wide range of industrial and medical problems, and have been implicated in a wide range of persistent infectious diseases, including implantassociated microbial infections. Bacterial adhesion...... is the first committing step in biofilm formation, and has therefore been intensely scrutinized. Much however, still remains elusive. Bacterial adhesion is a highly complex process, which is influenced by a variety of factors. In this thesis, a range of physico-chemical, molecular and environmental parameters......, which influence the transition from a planktonic lifestyle to a sessile lifestyle, have been studied. Protein conditioning film formation was found to influence bacterial adhesion and subsequent biofilm formation considerable, and an aqueous extract of fish muscle tissue was shown to significantly...

  12. Spontaneous bacterial peritonitis

    Institute of Scientific and Technical Information of China (English)

    Anastasios Koulaouzidis; Shivaram Bhat; Athar A Saeed

    2009-01-01

    Since its initial description in 1964, research has transformed spontaneous bacterial peritonitis (SBP) from a feared disease (with reported mortality of 90%) to a treatable complication of decompensated cirrhosis,albeit with steady prevalence and a high recurrence rate. Bacterial translocation, the key mechanism in the pathogenesis of SBP, is only possible because of the concurrent failure of defensive mechanisms in cirrhosis.Variants of SBP should be treated. Leucocyte esterase reagent strips have managed to shorten the 'tap-toshot' time, while future studies should look into their combined use with ascitic fluid pH. Third generation cephalosporins are the antibiotic of choice because they have a number of advantages. Renal dysfunction has been shown to be an independent predictor of mortality in patients with SBP. Albumin is felt to reduce the risk of renal impairment by improving effective intravascular volume, and by helping to bind proinflammatory molecules. Following a single episode of SBP, patients should have long-term antibiotic prophylaxis and be considered for liver transplantation.

  13. Voiding dysfunction - A review

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2005-01-01

    Full Text Available In a child who is toilet trained the sudden onset of daytime wetting with frequency or urgency is alarming to the parents. Initially this subject was subdivided into a number of descriptive clinical conditions which led to a lot of confusion in recognition and management. Subsequently, the term elimination dysfunction was coined by Stephen Koff to emphasise the association between recurrent urinary infection, wetting, constipation and bladder overactivity. From a urodynamic point of view, in voiding dysfunction, there is either detrusor overactivity during bladder filling or dyssynergic action between the detrusor and the external sphincter during voiding. Identifying a given condition as a ′filling phase dysfunction′ or ′voiding phase dysfunction′ helps to provide appropriate therapy. Objective clinical criteria should be used to define voiding dysfunction. These include bladder wall thickening, large capacity bladder and infrequent voiding, bladder trabeculation and spinning top deformity of the urethra and a clinically demonstrated Vincent′s curtsy. The recognition and treatment of constipation is central to the adequate treatment of voiding dysfunction. Transcutaneous electric nerve stimuation for the treatment of detrusor overactivity, biofeedback with uroflow EMG to correct dyssynergic voiding, and behavioral therapy all serve to correct voiding dysfunction in its early stages. In established neurogenic bladder disease the use of Botulinum Toxin A injections into the detrusor or the external sphincter may help in restoring continence especially in those refractory to drug therapy. However in those children in whom the upper tracts are threatened, augmentation of the bladder may still be needed.

  14. Neurogenic voiding dysfunction.

    Science.gov (United States)

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  15. Biology of Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Anil Kumar Mysore Nagaraj

    2009-05-01

    Full Text Available Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic difficulties more often than not coexist, suggesting an integration of phases. Sexual dysfunction can result from a wide variety of psychological and physiological causes including derangements in the levels of sex hormones and neurotrensmitters. This review deals with the biology of different phases of sexual function as well as implications of hormones and neurotransmitters in sexual dysfunction

  16. [Bacterial vaginosis].

    Science.gov (United States)

    Romero Herrero, Daniel; Andreu Domingo, Antonia

    2016-07-01

    Bacterial vaginosis (BV) is the main cause of vaginal dysbacteriosis in the women during the reproductive age. It is an entity in which many studies have focused for years and which is still open for discussion topics. This is due to the diversity of microorganisms that cause it and therefore, its difficult treatment. Bacterial vaginosis is probably the result of vaginal colonization by complex bacterial communities, many of them non-cultivable and with interdependent metabolism where anaerobic populations most likely play an important role in its pathogenesis. The main symptoms are an increase of vaginal discharge and the unpleasant smell of it. It can lead to serious consequences for women, such as an increased risk of contracting sexually transmitted infections including human immunodeficiency virus and upper genital tract and pregnancy complications. Gram stain is the gold standard for microbiological diagnosis of BV, but can also be diagnosed using the Amsel clinical criteria. It should not be considered a sexually transmitted disease but it is highly related to sex. Recurrence is the main problem of medical treatment. Apart from BV, there are other dysbacteriosis less characterized like aerobic vaginitis of which further studies are coming slowly but are achieving more attention and consensus among specialists.

  17. Bacterial cell biology outside the streetlight.

    Science.gov (United States)

    Bulgheresi, Silvia

    2016-09-01

    As much as vertical transmission of microbial symbionts requires their deep integration into the host reproductive and developmental biology, symbiotic lifestyle might profoundly affect bacterial growth and proliferation. This review describes the reproductive oddities displayed by bacteria associated - more or less intimately - with multicellular eukaryotes.

  18. Bacterial proteases: targets for diagnostics and therapy

    NARCIS (Netherlands)

    Kaman, W.E.; Hays, J.P.; Endtz, H.P.; Bikker, F.J.

    2014-01-01

    Proteases are essential for the proliferation and growth of bacteria, and are also known to contribute to bacterial virulence. This makes them interesting candidates as diagnostic and therapeutic targets for infectious diseases. In this review, the authors discuss the most recent developments and po

  19. Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

    Directory of Open Access Journals (Sweden)

    Mehri Salari

    2016-01-01

    Full Text Available Currently, gastrointestinal (GI dysfunctions in Parkinson's disease (PD are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed.

  20. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Wiese, Signe Skovgaard; Halgreen, Hanne

    2016-01-01

    Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased st...

  1. Female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Wåhlin-Jacobsen, Sarah

    2016-01-01

    Female sexual dysfunction (FSD) is a controversial condition, which has prompted much debate regarding its aetiology, components, and even its existence. Our inability to work together as clinicians, psychologists, patients, and advocates hinders our understanding of FSD, and we will only improve...

  2. Shared Parenting Dysfunction.

    Science.gov (United States)

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  3. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol...

  4. What Is a Dysfunctional School?

    Science.gov (United States)

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  5. Lesson Nine Sinus node dysfunction

    Institute of Scientific and Technical Information of China (English)

    鲁端; 吴文烈

    2004-01-01

    @@ Sinus node dysfunction most often is found in the elderly as an isolated phenomenon. Although interruption of the blood supply to the sinus node may produce dysfunction, the correlation between obstruction of the sinus node artery and clinical evidence of sinus node dysfunction is poor.

  6. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    tract to the microbial flocs in waste water treatment facilities. Microbial biofilms may however also cause a wide range of industrial and medical problems, and have been implicated in a wide range of persistent infectious diseases, including implantassociated microbial infections. Bacterial adhesion...... in the formation of highly complex sessile communities, referred to as biofilms. Such microbial communities are often highly dynamic and heterogeneous in nature. Microbial biofilms are of great importance in a wide range of natural processes and industrial settings, from the commensal flora of the gastrointestinal...

  7. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome

    Directory of Open Access Journals (Sweden)

    Hadi AR Hadi

    2005-10-01

    Full Text Available Hadi AR Hadi, Cornelia S Carr, Jassim Al SuwaidiDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital – Hamad Medical Corporation, Doha, State of QatarAbstract: Endothelial dysfunction is a well established response to cardiovascular risk factors and precedes the development of atherosclerosis. Endothelial dysfunction is involved in lesion formation by the promotion of both the early and late mechanisms of atherosclerosis including up-regulation of adhesion molecules, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, platelet activation, cytokine elaboration, and vascular smooth muscle cell proliferation and migration. Endothelial dysfunction is a term that covers diminished production/availability of nitric oxide and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. Also, when cardiovascular risk factors are treated the endothelial dysfunction is reversed and it is an independent predictor of cardiac events. We review the literature concerning endothelial dysfunction in regard to its pathogenesis, treatment, and outcome.Keywords: endothelial dysfunction, coronary atherosclerosis, coronary artery disease

  8. The cone dysfunction syndromes

    Science.gov (United States)

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  9. Dysfunctional Uterine Bleeding

    OpenAIRE

    1987-01-01

    Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding that results from an ovarian endocrinopathy. It may be associated with ovulatory and anovulatory cycles. The diagnosis of DUB depends on a thorough history and physical examination to exclude organic disorders. In older women, endometrial biopsy should be done before starting therapy. The treatment depends on an understanding of the menstrual cycle. In less urgent cases, anovulatory cycles are managed using progester...

  10. Biology of Sexual Dysfunction

    OpenAIRE

    MN, Anil Kumar; Pai, NB; Rao, S; Rao, TSS; Goyal, N.

    2009-01-01

    Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic di...

  11. Male Gender Role Dysfunction

    OpenAIRE

    Daig, Isolde

    2010-01-01

    Background: Men have a higher alcohol and cigarette consumption than women, they use more drugs, they have twice as high a suicide rate and only a minority of men attend on preventive medical checkups. Hypotheses: The central questions of the present study pertained to the identification of dysfunctional aspects of a male self concept and the possible correlations with risk behaviour of men in different age stages. One possible explanation for this high risk behaviour may be higher mascul...

  12. Thyroid dysfunction and subfertility.

    Science.gov (United States)

    Cho, Moon Kyoung

    2015-12-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women.

  13. Bacterial hydrodynamics

    CERN Document Server

    Lauga, Eric

    2015-01-01

    Bacteria predate plants and animals by billions of years. Today, they are the world's smallest cells yet they represent the bulk of the world's biomass, and the main reservoir of nutrients for higher organisms. Most bacteria can move on their own, and the majority of motile bacteria are able to swim in viscous fluids using slender helical appendages called flagella. Low-Reynolds-number hydrodynamics is at the heart of the ability of flagella to generate propulsion at the micron scale. In fact, fluid dynamic forces impact many aspects of bacteriology, ranging from the ability of cells to reorient and search their surroundings to their interactions within mechanically and chemically-complex environments. Using hydrodynamics as an organizing framework, we review the biomechanics of bacterial motility and look ahead to future challenges.

  14. The nuclear proliferation; La proliferation nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Gere, F. [Ecole Polytechnique, 91 - Palaiseau (France)

    1995-04-01

    In this book is detailed the beginning of nuclear military power, with the first bomb of Hiroshima, the different ways of getting uranium 235 and plutonium 239, and how the first countries (Usa, Ussr, China, United kingdom, France) got nuclear weapons. Then the most important part is reviewed with the details of non-proliferation treaty and the creation of IAEA to promote civilian nuclear power in the world and to control the use of plutonium and uranium in nuclear power plants. The cases of countries who reached the atom mastery, such Israel, South Africa, Pakistan, Iraq, North Korea, Argentina, Brazil, Iran, Algeria, Taiwan and the reasons which they wanted nuclear weapon for or why they gave up, are exposed.

  15. Sexual dysfunction with antihypertensive drugs.

    Science.gov (United States)

    Prisant, L M; Carr, A A; Bottini, P B; Solursh, D S; Solursh, L P

    1994-04-11

    The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

  16. The bacterial microbiota in inflammatory lung diseases.

    Science.gov (United States)

    Huffnagle, Gary B; Dickson, Robert P

    2015-08-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920s, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined.

  17. The Bacterial Microbiota in Inflammatory Lung Diseases

    Science.gov (United States)

    Huffnagle, Gary B.; Dickson, Robert P.

    2016-01-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920's, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined. PMID:26122174

  18. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    1 Editorials on Faliero’s Parliamentary Address... Parliamentary Address dence-building measures it would promote in the region to realise the objective of non-proliferation. New Delhi Rejects U.S...takes about 250 tonnes of used at Manuguru in the face of advice from juniors that heavy water to run each nuclear reactor. But during the all but a

  19. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers , books, and periodicals. Items...COMMERCE 8NATIONAL TECHNICAL INFORMATION SERVICE ’TIC Q.,’U ’ SPRINGFIELD, VA. 22161 PROLIFERATION ISSUES JPRS-TND-92-023 CONTENTS 16 July 1992 [This...Experts To Tour Azerbaijan ........................................................................................ 12 To Conduct Biochemical Analysis

  20. Battling Nuclear Proliferation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    As the North Korean and Iranian nuclear issues develop and efforts to resolve them continue, global attention to anti-nuclear proliferation and the work of the International Atomic Energy Agency (IAEA) has become even more intense. Pang Sen, Chairman of

  1. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    competence in handling delicate and agricultral projects, medical research, sterilizing issues. tools, and digging oilfields. Electricity Minister Engineer ...CONTENTS 21 October 1992 [This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear...be built by shipping plutonium through the Strait of Malacca, For- the year 2006 to meet the soaring electricity demand, eign Ministry officials said

  2. The Nightmare of Proliferation

    Institute of Scientific and Technical Information of China (English)

    PANG SEN; ZHOU WENYI

    2010-01-01

    @@ The year 2010 unfolded with conflicting developments in the arena of nuclear non-proliferation. Positive news foreshadowed the resumption of the once "dead" six-party talks regarding hostilities on the Korean Peninsula. On the other hand, the Iranian nuclear issue took a downward turn.

  3. Pregnancy Complications: Bacterial Vaginosis

    Science.gov (United States)

    ... Complications & Loss > Pregnancy complications > Bacterial vaginosis and pregnancy Bacterial vaginosis and pregnancy E-mail to a friend Please ... this page It's been added to your dashboard . Bacterial vaginosis (also called BV or vaginitis) is an infection ...

  4. Pregnancy Complications: Bacterial Vaginosis

    Science.gov (United States)

    ... Loss > Pregnancy complications > Bacterial vaginosis and pregnancy Bacterial vaginosis and pregnancy E-mail to a friend Please ... page It's been added to your dashboard . Bacterial vaginosis (also called BV or vaginitis) is an infection ...

  5. Bacterial vaginosis -- aftercare

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000687.htm Bacterial vaginosis - aftercare To use the sharing features on this ... back after you use the bathroom. Preventing Bacterial Vaginosis You can help prevent bacterial vaginosis by: Not ...

  6. Bacterial pericarditis (image)

    Science.gov (United States)

    Bacterial pericarditis is an inflammation of the pericardium, the sac-like covering of the heart, caused by a bacterial infection. The bacterial infection causes inflammation and swelling of the pericardium. Pain ...

  7. Diabetic bladder dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guiming Liu; Firouz Daneshgari

    2014-01-01

    Objective To review studies on diabetic bladder dysfunction (DBD),a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were "diabetes" and "bladder dysfunction" or "cystopathy".Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular

  8. Mitochondrial dysfunction in autism.

    Science.gov (United States)

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  9. Depression and erectile dysfunction.

    Science.gov (United States)

    Makhlouf, Antoine; Kparker, Ashay; Niederberger, Craig S

    2007-11-01

    Depression and erectile dysfunction (ED) clearly are associated. Although urologists and psychiatrists have long recognized that antidepressant medications affect erectile function negatively, the interplay between the two conditions remains underappreciated. Psychiatrists may be reluctant to question a patient in detail about ED, and urologists seldom perform a formal assessment of the presence of depression in patients who have ED. This article gives a quick overview of the relationship between these two conditions and provides the clinician with the knowledge required to effectively manage ED with comorbid depression.

  10. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  11. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

  12. Proliferation in cycle

    Energy Technology Data Exchange (ETDEWEB)

    Piao Yunsong [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: yspiao@gucas.ac.cn

    2009-06-15

    In the contracting phase with w{approx_equal}0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w{approx_equal}0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

  13. JPRS Report, Proliferation Issues

    Science.gov (United States)

    2016-03-24

    TECHNICAL INFORMATION SERVICE SPRINGFIELD, VA 22161 PROLIFERATION ISSUES JPRS-TND-93-011 CONTENTS 23 April 1993 [This report contains foreign media ...likely after the U.N. Security [Text] Pyongyang, April 17 (KCNA)-Mass media of the Council adopts its first resolution against Pyongyang United States...his interview to the ARGUMENTY I FAKTY upon the path of confrontation and violence . We do not weekly President Leonid Kravchuk dismissed reports want

  14. Electronic mail dysfunction: a reality check.

    Science.gov (United States)

    Case, C J

    1999-01-01

    Computer-mediated communication systems, including electronic mail, are systems that businesses employ to improve efficiency, effectiveness, and communication within the organization. As use of these systems proliferate, it is crucial that the communication systems have a positive, rather than negative impact, on the organization. Negative behavior could include flaming and personal use of the electronic mail system. Much of prior research has examined the use of electronic mail in academic settings. Results indicate that flaming and personal use have a relative high incidence. However, is electronic mail dysfunction a consistent reality for both academia and the business world? This case study empirically examines the role of electronic messaging in business firms. Specifically, this research investigates the usage of inter-organizational electronic messaging in intermediate-size firms. Electronic mail messages were analyzed in a three-site case study. Results indicate that dysfunctional electronic mail uses such as personal use and flaming have minimal incidence in a business environment. Implications relate to organizational professionalism and the use of students as electronic mail research subjects.

  15. Progressive posterior cortical dysfunction

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

  16. Cycling and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Ina Šibli

    2015-01-01

    Full Text Available Abstract: For many years medical studies have implicated bicycle riding is causing erectile dysfunction (ED in association with higher perineal pressure. This review focuses upon epidemiological studies assesing the impact of cycling on ED, pathogenesis of ED in cyclists  as well as on research considering changes of perineal pressure, hemodynamics, and nerve conduction when cycling. Investigestors were also interested in different saddle sizes, materials and geometry and also in the impact of saddle and riders position on changes to the perineum. Research on female cyclists is very limited but indicates similar genitourinary disorders as in male cyclists. We also review  research on preventative and therapeutic options regarding bicycle riding and ED.

  17. Dysfunctional anger and sexual violence.

    Science.gov (United States)

    Ahmed, A G

    2014-06-01

    Sexual offenses with or without aggression attract attention from the popular media and the scientific community. Empirical research suggests a relationship between anger and sexual violence. This article describes the key themes of dysfunctional anger and sexual violence, and how dysfunctional anger relates to sexual fantasies, sexual offending, and sexual recidivism. The implications of the findings for clinical practice and future research are discussed.

  18. Defining sphincter of oddi dysfunction

    DEFF Research Database (Denmark)

    Funch-Jensen, P

    1996-01-01

    Sphincter of Oddi (SO) dysmotility may give rise to pain. The golden standard for the demonstration of SO dysfunction is endoscopic manometry. A number of abnormalities are observed in patients with postcholecystectomy pain and in patients with idiopathic recurrent pancreatitis. Criteria for defi...... for defining SO dysfunction and the possible mechanisms for the precipitation of pain are discussed....

  19. Bladder Dysfunction and Vesicoureteral Reflux

    Directory of Open Access Journals (Sweden)

    Ulla Sillén

    2008-01-01

    Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

  20. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Andersen, J L

    2014-01-01

    implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...... dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented...

  1. Bacterial translocation and cardiovascular complications of cirrhosis. Authors' response to letter

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2008-01-01

    dysfunction have been somewhat unpredictable.3-5 In two conditions, however, a direct relationship between bacterial infection and increased mortality have been proved, namely infections in relation to bleeding from oesophageal varices and spontaneous bacterial peritonitis.6-8 In both of these complications...

  2. JPRS Report: Proliferation Issues

    Science.gov (United States)

    2016-03-24

    Industry (MITI) plans to hold a seminar on arms export control as early as this fall in an Asian country. The countries include Indonesia, Malaysia ...NPT BK1703072393 Kuala Lumpur BERNAMA in English 0604 GMT 17 Mar 93 [Text] Kuala Lumpur, March 17 (OANA/ BERNAMA)— Malaysia Wednesday, expressed ...JPRS-TND-93-009 29 March 1993 !■■■■! FOREIGN BROADCAST INFORMATION SERVICE JPRS Report— Proliferation Issues Sapsevsd tea ßubSa t©l©ɛ

  3. Initiatives for proliferation prevention

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy`s (DOE`s) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway.

  4. Evaluation of anti-bacterial and wound healing activity of the fruits of ...

    African Journals Online (AJOL)

    Evaluation of anti-bacterial and wound healing activity of the fruits of ... the functional roles of the fruits of Amorpha fruticosa L. during wound healing progress. ... fibroblasts proliferation and migration, leading to promotion of wound healing.

  5. Citrobacter rodentium mouse model of bacterial infection.

    Science.gov (United States)

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete.

  6. [Female sexual dysfunction].

    Science.gov (United States)

    Luria, Mijal

    2009-09-01

    Female sexual problems are common, frequently overlooked and have a significant impact on the lives of women. Research in the last decade has brought to the understanding and recognition of a number of standpoints, mainly the broad range of normative function. In 2003, the American Urological Association Foundation convened an international committee of experts in the field of women's sexuality, to reconsider the existing definitions of women's sexual dysfunction. Based on the circular response cycle developed by Basson, the group emphasized motivations that might move a woman from being sexually "neutral" to making a decision to be sexual with her partner, as a normative alternative to the need for spontaneous sexual desire as the trigger for sexual behavior. Etiology may stem from medical as well as psychological factors, thus assessment must include a complete evaluation. Treatment includes psycho-education, improvement of interpersonal communication, cognitive behavioral treatment and elucidation and treatment of medical problems, if necessary. Several pharmacological treatments are under investigation, with modest results and uncertainties about their long term safety. This review presents the female sexual response as it is understood today and the current diagnostic and therapeutic understandings and directions.

  7. [Hypothalamic dysfunction in obesity].

    Science.gov (United States)

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  8. [Thyroid dysfunction during pregnancy].

    Science.gov (United States)

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Multiple organ dysfunction syndrome.

    Science.gov (United States)

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%. © 2013 Published by Mosby, Inc.

  10. Markers of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Kelvin P Davies

    2008-01-01

    Full Text Available With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED, the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients.

  11. DIASTOLIC DYSFUNCTION: A REVIEW

    Directory of Open Access Journals (Sweden)

    Rajat

    2016-01-01

    Full Text Available INTRODUCTION Diastolic heart failure is an underestimated pathology. Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. Symptomatic treatment focuses on the reduction in pulmonary congestion and the improvement in LV filling. Specific treatment is actually lacking, but encouraging data are emerging concerning the use of renin–angiotensin–aldosterone axis blockers, nitric oxide donors, or, very recently, new agents specifically targeting actin–myosin cross-bridges. It is generally considered to have a somewhat better prognosis than systolic HF, but frequency of hospitalizations is comparable in systolic and diastolic HF. 1 Despite the recognition of its importance, definition and diagnostic criteria of diastolic dysfunction and diastolic HF remain controversial. AIMS AND OBJECTIVES This review focus of definition, diagnosis and management of diastolic heart failure with it prognosis. MATERIAL AND METHODS We have studied various guidelines, articles, reviews using given keywords, along with our experience in management of diastolic heart failure in 2015. The articles and the references were reviewed keeping in mind about the simplified management offered to the patient.

  12. Psychoanalysis: a dysfunctional family?

    Science.gov (United States)

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  13. Endothelial dysfunction: EDCF revisited

    Institute of Scientific and Technical Information of China (English)

    PAUL M Vanhoutte

    2008-01-01

    Endothelial cells can initiate contraction (constriction) of the vascular smooth muscle cells that surround them. Such endothelium-dependent, acute increases in contractile tone can be due to the withdrawal of the production of nitric oxide, to the production of vasoconstrictor peptides (angiotensin Ⅱ, endothelin-1), to the formation of oxygen-derived free radicals(superoxide anions) and/or the release of vasoconstrictor metabolites of arachidonic acid. The latter have been termed endothelium-derived contracting factor (EDCF) as they can contribute to moment-to-moment changes in contractile activity of the underlying vascular smooth muscle cells. To judge from animal experiments, EDCF-mediated responses are exacerbated when the production of nitric oxide is impaired as well as by aging, spontaneous hypertension and diabetes. To judge from human studies, they contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive patients. Since EDCF causes vasoconstriction by activation of the TP-receptors on the vascular smooth muscle cells, selective antagonists at these receptors prevent endothelium-dependent contractions, and curtail the endothelial dysfunction in hypertension and diabetes.

  14. [Characteristics of postpartum thyroid dysfunction].

    Science.gov (United States)

    Argatska, A; Nonchev, B; Obretsova, M; Pehlivanov, B

    2015-01-01

    The risk factors and mechanisms for the development of postpartum thyroid dysfunction have been widely discussed. However data on patients suffered spontaneous or induced abortion during early pregnancy are scarce. To reveal the characteristics of thyroid dysfunction in women after an abortion in the first trimester of pregnancy. A total of 28 women (18 euthyroid, 10 with thyroid dysfunction), mean age 30.46 ± 1.01 years following abortion in the first trimester have been included in the study. Thyroid-stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), thyreoglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb) were measured and ultrasound assessment of the thyroid was performed 3 and 9 months after the interruption of pregnancy. Hypothyroidism was found in 6 of the women with thyroid dysfunction and thyrotoxicosis--in 4. Clinical features of thyroid dysfunction were observed in 3 patients while in the remaining 7 cases, diagnosis was made on the basis of hormonal levels. Positive titers of thyroid autoantibodies were detected in the majority of the cases with functional disordes. In 6 patients thyroid dysfunction was transient and in 4 hormonal abnormalities persisted on by the 9th month after the abortion. The comparative analysis showed that the volume of the thyroid gland and the degree of hypoehogenicity were significantly higher in patients with thyroid dysfunction compared to euthyroid women. Thyroid dysfunction after abortion in the first trimester is mainly of autoimmune pathogenesis and its characteristics do not differ from those of postpartum thyroiditis. In the majority of patients these disorders are subclinical and may remain unrecognized. A close active follow up of patients at increased risk of functional thyroid disorders after an abortion is required in order to prevent morbidity and identify the cases developing permanent thyroid dysfunction.

  15. Uncertainties in Nuclear Proliferation Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chul Min; Yim, Man-Sung; Park, Hyeon Seok [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2015-05-15

    There have been various efforts in the research community to understand the determinants of nuclear proliferation and develop quantitative tools to predict nuclear proliferation events. Such systematic approaches have shown the possibility to provide warning for the international community to prevent nuclear proliferation activities. However, there are still large debates for the robustness of the actual effect of determinants and projection results. Some studies have shown that several factors can cause uncertainties in previous quantitative nuclear proliferation modeling works. This paper analyzes the uncertainties in the past approaches and suggests future works in the view of proliferation history, analysis methods, and variable selection. The research community still lacks the knowledge for the source of uncertainty in current models. Fundamental problems in modeling will remain even other advanced modeling method is developed. Before starting to develop fancy model based on the time dependent proliferation determinants' hypothesis, using graph theory, etc., it is important to analyze the uncertainty of current model to solve the fundamental problems of nuclear proliferation modeling. The uncertainty from different proliferation history coding is small. Serious problems are from limited analysis methods and correlation among the variables. Problems in regression analysis and survival analysis cause huge uncertainties when using the same dataset, which decreases the robustness of the result. Inaccurate variables for nuclear proliferation also increase the uncertainty. To overcome these problems, further quantitative research should focus on analyzing the knowledge suggested on the qualitative nuclear proliferation studies.

  16. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  17. Sacroiliac joint dysfunction in athletes.

    Science.gov (United States)

    Brolinson, P Gunnar; Kozar, Albert J; Cibor, Greg

    2003-02-01

    The sacroiliac (SI) joint is a common source of low back pain in the general population. Because it is the link between the lower extremities and the spine, it sustains even higher loads during athletic activity, predisposing athletes to a greater probability of joint dysfunction and pain. The diagnosis and treatment of SI joint dysfunction remains controversial, due to complex anatomy and biomechanics, and a lack of universally accepted nomenclature and terminology, consistently reliable clinical tests and imaging studies, and consistently effective treatments. This article clarifies these issues by presenting a model of SI joint anatomy and function, a systematic approach to the diagnosis of dysfunction, and a comprehensive treatment plan.

  18. Strapping for temporomandibular joint dysfunction

    Directory of Open Access Journals (Sweden)

    Babu Abraham

    2008-01-01

    Full Text Available Temporomandibular joint dysfunction (TMJD is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  19. Strapping for temporomandibular joint dysfunction.

    Science.gov (United States)

    Babu, Abraham Samuel; John, Sandhya Mary; Unni, Amith

    2008-01-01

    Temporomandibular joint dysfunction (TMJD) is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  20. Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2013-03-01

    Full Text Available Invasion of the central nervous system (CNS by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

  1. Antibody-engineered nanoparticles selectively inhibit mesenchymal cells isolated from patients with chronic lung allograft dysfunction.

    Science.gov (United States)

    Cova, Emanuela; Colombo, Miriam; Inghilleri, Simona; Morosini, Monica; Miserere, Simona; Peñaranda-Avila, Jesus; Santini, Benedetta; Piloni, Davide; Magni, Sara; Gramatica, Furio; Prosperi, Davide; Meloni, Federica

    2015-01-01

    Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction.

  2. Full-length PGC-1α salvages the phenotype of a mouse model of human neuropathy through mitochondrial proliferation.

    Science.gov (United States)

    Rona-Voros, Krisztina; Eschbach, Judith; Vernay, Aurélia; Wiesner, Diana; Schwalenstocker, Birgit; Geniquet, Pauline; Mousson De Camaret, Bénédicte; Echaniz-Laguna, Andoni; Loeffler, Jean-Philippe; Ludolph, Albert C; Weydt, Patrick; Dupuis, Luc

    2013-12-20

    Increased mitochondrial mass, commonly termed mitochondrial proliferation, is frequently observed in many human diseases directly or indirectly involving mitochondrial dysfunction. Mitochondrial proliferation is thought to counterbalance a compromised energy metabolism, yet it might also be detrimental through alterations of mitochondrial regulatory functions such as apoptosis, calcium metabolism or oxidative stress. Here, we show that prominent mitochondrial proliferation occurs in Cramping mice, a model of hereditary neuropathy caused by a mutation in the dynein heavy chain gene Dync1h1. The mitochondrial proliferation correlates with post-prandial induction of full-length (FL) and N-terminal truncated (NT) isoforms of the transcriptional co-activator PGC-1α. The selective knock-out of FL-PGC-1α isoform, preserving expression and function of NT-PGC-1α, led to a complete reversal of mitochondrial proliferation. Moreover, FL-PGC-1α ablation potently exacerbated the mitochondrial dysfunction and led to severe weight loss. Finally, FL-PGC-1α ablation triggered pronounced locomotor dysfunction, tremors and inability to rear in Cramping mice. In summary, endogenous FL-PGC-1α activates mitochondrial proliferation and salvages neurological and metabolic health upon disease. NT-PGC-1α cannot fulfil this protective action. Activation of this endogenous salvage pathway might thus be a valuable therapeutic target for diseases involving mitochondrial dysfunction.

  3. Cognitive dysfunction in spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Helio Afonso Ghizoni Teive

    Full Text Available Abstract Spinocerebellar ataxias (SCAs comprise a heterogeneous group of complex neurodegenerative diseases, characterized by the presence of progressive cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs, extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. Objective: To verify the presence of cognitive dysfunction among the main types of SCA described in the literature. Methods: the review was conducted using the search system of the PUBMED and OMIM databases. Results: Cognitive dysfunction occurs in a considerable proportion of SCA, particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA. Mental retardation is a specific clinical feature of SCA 13. Conclusions: The role of the cerebellum in cognitive functions has been observed in different types of SCAs which can manifest varying degrees of cognitive dysfunction, dementia and mental retardation.

  4. Executive Dysfunction in Geriatric Depression

    National Research Council Canada - National Science Library

    Lockwood, Kathryn A; Alexopoulos, George S; van Gorp, Wilfred G

    2002-01-01

    OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD...

  5. Thyroid dysfunction and pregnancy outcomes

    Science.gov (United States)

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  6. Thyroid dysfunction and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Sima Nazarpour

    2015-07-01

    Full Text Available Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective, case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly

  7. Sirolimus-associated proteinuria and renal dysfunction.

    Science.gov (United States)

    Rangan, Gopala K

    2006-01-01

    Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.

  8. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  9. Endothelial dysfunction in morbid obesity.

    Science.gov (United States)

    Mauricio, Maria Dolores; Aldasoro, Martin; Ortega, Joaquin; Vila, José María

    2013-01-01

    Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

  10. Epidemiology and care of female sexual dysfunction

    OpenAIRE

    McCool, Megan Elizabeth

    2017-01-01

    Sexual dysfunction can have a negative impact on the well-being of an individual. For women, sexual dysfunction encompasses sexual interest / arousal disorder, female orgasmic disorder and genitopelvic pain / penetration disorder. Although sexual dysfunction has been identified as a significant public health problem, research on sexual dysfunction has primarily focused on men rather than women. Comprehensive epidemiological data on female sexual dysfunction and information on current levels o...

  11. Nest Material Shapes Eggs Bacterial Environment.

    Directory of Open Access Journals (Sweden)

    Cristina Ruiz-Castellano

    geographically environmental variation associated with risk of bacterial proliferation determining the strength of such effects. Because of costs associated to nest building, birds should adjust nest building effort to expected bacterial environments during incubation, a prediction that should be further explored.

  12. Obesity and pelvic floor dysfunction.

    Science.gov (United States)

    Ramalingam, Kalaivani; Monga, Ash

    2015-05-01

    Obesity is associated with a high prevalence of pelvic floor disorders. Patients with obesity present with a range of urinary, bowel and sexual dysfunction problems as well as uterovaginal prolapse. Urinary incontinence, faecal incontinence and sexual dysfunction are more prevalent in patients with obesity. Uterovaginal prolapse is also more common than in the non-obese population. Weight loss by surgical and non-surgical methods plays a major role in the improvement of these symptoms in such patients. The treatment of symptoms leads to an improvement in their quality of life. However, surgical treatment of these symptoms may be accompanied by an increased risk of complications in obese patients. A better understanding of the mechanism of obesity-associated pelvic floor dysfunction is essential.

  13. Mitochondrial Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    P. C. Keane

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

  14. Vocal cord dysfunction in children.

    Science.gov (United States)

    Noyes, Blakeslee E; Kemp, James S

    2007-06-01

    Vocal cord dysfunction is characterised by paradoxical vocal cord adduction that occurs during inspiration, resulting in symptoms of dyspnoea, wheeze, chest or throat tightness and cough. Although the condition is well described in children and adults, confusion with asthma often triggers the use of an aggressive treatment regimen directed against asthma. The laryngoscopic demonstration of vocal cord adduction during inspiration has been considered the gold standard for the diagnosis of vocal cord dysfunction, but historical factors and pulmonary function findings may provide adequate clues to the correct diagnosis. Speech therapy, and in some cases psychological counselling, is often beneficial in this disorder. The natural course and prognosis of vocal cord dysfunction are still not well described in adults or children.

  15. Sexual dysfunctions in psoriatic patients

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2015-04-01

    Full Text Available Psoriasis is a chronic, immune-mediated disorder with a worldwide occurrence characterized by well-defined infiltrated erythematous papules and plaques, covered by silvery white or yellowish scales. It is a physically, socially and emotionally invalidating disorder that affects 1-2% of the population. Sexual health is an important part of general health and sexual dysfunctions can negatively affect self-esteem, confidence, interpersonal relationships and the quality of life. Dermatology Life Quality Index (DLQI, Psoriasis Disability Index (PDI and the Impact of Psoriasis on Quality of Life (IPSO questionnaire are all questionnaires used to assess the quality of life of patients with psoriasis and each has one question regarding sexual dysfunction. Several scales were also designed to particularly assess sexual satisfaction in men and women. The aim of this paper is to perform an overview of the existing studies on sexual dysfunction in psoriatic patients.

  16. Autophagy-independent senescence and genome instability driven by targeted telomere dysfunction.

    Science.gov (United States)

    Mar, Florie A; Debnath, Jayanta; Stohr, Bradley A

    2015-01-01

    Telomere dysfunction plays a complex role in tumorigenesis. While dysfunctional telomeres can block the proliferation of incipient cancer clones by inducing replicative senescence, fusion of dysfunctional telomeres can drive genome instability and oncogenic genomic rearrangements. Therefore, it is important to define the regulatory pathways that guide these opposing effects. Recent work has shown that the autophagy pathway regulates both senescence and genome instability in various contexts. Here, we apply models of acute telomere dysfunction to determine whether autophagy modulates the resulting genome instability and senescence responses. While telomere dysfunction rapidly induces autophagic flux in human fibroblast cell lines, inhibition of the autophagy pathway does not have a significant impact upon the transition to senescence, in contrast to what has previously been reported for oncogene-induced senescence. Our results suggest that this difference may be explained by disparities in the development of the senescence-associated secretory phenotype. We also show that chromosome fusions induced by telomere dysfunction are comparable in autophagy-proficient and autophagy-deficient cells. Altogether, our results highlight the complexity of the senescence-autophagy interface and indicate that autophagy induction is unlikely to play a significant role in telomere dysfunction-driven senescence and chromosome fusions.

  17. Insulin and glucagon regulate pancreatic α-cell proliferation.

    Directory of Open Access Journals (Sweden)

    Zhuo Liu

    Full Text Available Type 2 diabetes mellitus (T2DM results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from pancreatic α cells: excessively high circulating levels of glucagon lead to excessive hepatic glucose output. We investigated if α-cell numbers increase in T2DM and what factor (s regulate α-cell turnover. Lepr(db/Lepr(db (db/db mice were used as a T2DM model and αTC1 cells were used to study potential α-cell trophic factors. Here, we demonstrate that in db/db mice α-cell number and plasma glucagon levels increased as diabetes progressed. Insulin treatment (EC50 = 2 nM of α cells significantly increased α-cell proliferation in a concentration-dependent manner compared to non-insulin-treated α cells. Insulin up-regulated α-cell proliferation through the IR/IRS2/AKT/mTOR signaling pathway, and increased insulin-mediated proliferation was prevented by pretreatment with rapamycin, a specific mTOR inhibitor. GcgR antagonism resulted in reduced rates of cell proliferation in αTC1 cells. In addition, blockade of GcgRs in db/db mice improved glucose homeostasis, lessened α-cell proliferation, and increased intra-islet insulin content in β cells in db/db mice. These studies illustrate that pancreatic α-cell proliferation increases as diabetes develops, resulting in elevated plasma glucagon levels, and both insulin and glucagon are trophic factors to α-cells. Our current findings suggest that new therapeutic strategies for the treatment of T2DM may include targeting α cells and glucagon.

  18. Thyroid Dysfunction and its Management

    Directory of Open Access Journals (Sweden)

    Supriya Agnihotri

    2016-09-01

    Full Text Available The focus of the present review article is on thyroid dysfunctions which can be hypo or hyper thyroidism. Along with the ongoing allopathic treatment options, one can go for the alternative therapies or natural cures. Various nutritional supplements including iodine, botanicals like guggul and many more play an effective role in the management of thyroid dysfunction apart from the pharmaceuticals like synthetic T3 and T4 hormones and procaine thyroid. Along with these, homeopathy and yoga are equally important. The discussion suggests and emphasizes the importance of improving the lifestyle and nutritional diet; and further providing spiritual support along with natural thyroid medication.

  19. Does stress induce bowel dysfunction?

    Science.gov (United States)

    Chang, Yu-Ming; El-Zaatari, Mohamad; Kao, John Y

    2014-08-01

    Psychological stress is known to induce somatic symptoms. Classically, many gut physiological responses to stress are mediated by the hypothalamus-pituitary-adrenal axis. There is, however, a growing body of evidence of stress-induced corticotrophin-releasing factor (CRF) release causing bowel dysfunction through multiple pathways, either through the HPA axis, the autonomic nervous systems, or directly on the bowel itself. In addition, recent findings of CRF influencing the composition of gut microbiota lend support for the use of probiotics, antibiotics, and other microbiota-altering agents as potential therapeutic measures in stress-induced bowel dysfunction.

  20. Bacterial infections in cirrhosis: A critical review andpractical guidance

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Bacterial infection is common and accounts for majormorbidity and mortality in cirrhosis. Patients withcirrhosis are immunocompromised and increased susceptibilityto develop spontaneous bacterial infections,hospital-acquired infections, and a variety of infectionsfrom uncommon pathogens. Once infection develops,the excessive response of pro-inflammatory cytokineson a pre-existing hemodynamic dysfunction in cirrhosisfurther predispose the development of serious complicationssuch as shock, acute-on-chronic liver failure, renalfailure, and death. Spontaneous bacterial peritonitisand bacteremia are common in patients with advancedcirrhosis, and are important prognostic landmarks inthe natural history of cirrhosis. Notably, the incidenceof infections from resistant bacteria has increasedsignificantly in healthcare-associated settings. Serumbiomarkers such as procalcitonin may help to improvethe diagnosis of bacterial infection. Preventive measures(e.g. , avoidance, antibiotic prophylaxis, and vaccination),early recognition, and proper management are requiredin order to minimize morbidity and mortality of infectionsin cirrhosis.

  1. Peritonitis - spontaneous bacterial

    Science.gov (United States)

    Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

  2. Cell proliferation in gastrointestinal mucosa.

    OpenAIRE

    Wong, W M; Wright, N A

    1999-01-01

    Gastrointestinal cell proliferation plays an important role in the maintenance of the integrity of the gastrointestinal system. The study of gastrointestinal proliferation kinetics allows a better understanding of the complexity of the system, and also has important implications for the study of gastrointestinal carcinogenesis. Gastrointestinal stem cells are shown to be pluripotential and to give rise to all cell lineages in the epithelium. Carcinogenesis in the colon occurs through sequenti...

  3. Sepsis-induced brain dysfunction.

    Science.gov (United States)

    Adam, Nicolas; Kandelman, Stanislas; Mantz, Jean; Chrétien, Fabrice; Sharshar, Tarek

    2013-02-01

    Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

  4. Sweating dysfunction in Parkinson's disease

    NARCIS (Netherlands)

    Swinn, L; Schrag, A; Viswanathan, R; Lees, A; Quinn, N; Bloem, Bastiaan R.

    2003-01-01

    We sought to determine the prevalence and nature of sweating disturbances in patients with Parkinson's disease (PD), and investigated their correlation with other clinical features and with Quality of Life (QoL) measures. A questionnaire on symptoms and consequences of sweating dysfunction was compl

  5. Photobiomodulation on alcohol induced dysfunction

    Science.gov (United States)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  6. Ageing with neurogenic bowel dysfunction

    DEFF Research Database (Denmark)

    Nielsen, S D; Faaborg, Pia Møller; Finnerup, Nanna Brix

    2017-01-01

    The aim of this longitudinal study with postal survey was to describe changes in the patterns of neurogenic bowel dysfunction and bowel management in a population of people with spinal cord injury (SCI) followed for two decades. In 1996, a validated questionnaire on bowel function was sent to the...

  7. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J.E.; Brennan, M.T.; Verdonck- de Leeuw, I.M.; Gibson, R.J.; Eilers, J.G.; Waltimo, T.; Bots, C.P.; Michelet, M.; Sollecito, T.P.; Rouleau, T.S.; Sewnaik, A.; Bensadoun, R.J.; Fliedner, M.C.; Silverman, S.; Spijkervet, F.K.L.

    2012-01-01

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalen

  8. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, Judith E.; Brennan, Mike T.; Leeuw, Irma M. Verdonck-de; Gibson, Rachel J.; Eilers, June G.; Waltimo, Tuomas; Bots, Casper P.; Michelet, Marisol; Sollecito, Thomas P.; Rouleau, Tanya S.; Sewnaik, Aniel; Bensadoun, Rene-Jean; Fliedner, Monica C.; Silverman, Sol; Spijkervet, Fred K. L.

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools,

  9. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  10. Cognitive dysfunction in senior pets.

    Science.gov (United States)

    Crowell-Davis, Sharon L

    2008-02-01

    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  11. Assessing mitochondrial dysfunction in cells.

    Science.gov (United States)

    Brand, Martin D; Nicholls, David G

    2011-04-15

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

  12. Metabolism links bacterial biofilms and colon carcinogenesis.

    Science.gov (United States)

    Johnson, Caroline H; Dejea, Christine M; Edler, David; Hoang, Linh T; Santidrian, Antonio F; Felding, Brunhilde H; Ivanisevic, Julijana; Cho, Kevin; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A; Pardoll, Drew M; White, James R; Patti, Gary J; Sears, Cynthia L; Siuzdak, Gary

    2015-06-02

    Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.

  13. Metabolism links bacterial biofilms and colon carcinogenesis

    Science.gov (United States)

    Johnson, Caroline H.; Dejea, Christine M.; Edler, David; Hoang, Linh T.; Santidrian, Antonio F.; Felding, Brunhilde H.; Cho, Kevin; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A.; Pardoll, Drew M.; White, James R.; Patti, Gary J.; Sears, Cynthia L.; Siuzdak, Gary

    2015-01-01

    SUMMARY Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N1, N12-diacetylspermine in both biofilm positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-diacetylspermine levels to those seen in biofilm negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome, to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. PMID:25959674

  14. Probing bacterial cell biology using image cytometry.

    Science.gov (United States)

    Cass, Julie A; Stylianidou, Stella; Kuwada, Nathan J; Traxler, Beth; Wiggins, Paul A

    2017-03-01

    Advances in automated fluorescence microscopy have made snapshot and time-lapse imaging of bacterial cells commonplace, yet fundamental challenges remain in analysis. The vast quantity of data collected in high-throughput experiments requires a fast and reliable automated method to analyze fluorescence intensity and localization, cell morphology and proliferation as well as other descriptors. Inspired by effective yet tractable methods of population-level analysis using flow cytometry, we have developed a framework and tools for facilitating analogous analyses in image cytometry. These tools can both visualize and gate (generate subpopulations) more than 70 cell descriptors, including cell size, age and fluorescence. The method is well suited to multi-well imaging, analysis of bacterial cultures with high cell density (thousands of cells per frame) and complete cell cycle imaging. We give a brief description of the analysis of four distinct applications to emphasize the broad applicability of the tool.

  15. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach that ...... valuable weapons for preventing pathogen contamination and fighting infectious diseases in the future....

  16. Bacterial diseases affecting apple

    Science.gov (United States)

    Bacterial diseases of plants are usually difficult to control and often require a combination of control measures to successfully manage the disease. There are often stark differences between the means available to control bacterial diseases in annual crops versus a woody tree crop, such as apple. ...

  17. Effect of intestinal function-recovering decoction on treatment of multiple organ dysfunction syndrome in rats

    Institute of Scientific and Technical Information of China (English)

    Shu-Jie Zhao; Dong Zhang; Shi-Ji Wang; Ying Chen; Jin-Feng Han; Yu-Shan Wang

    2013-01-01

    Objective:To analyze the effect of intestinal function-recovering decoction on multiple organ dysfunction syndrome in rats, and to investigate a novel solution to multiple organ dysfunction syndrome.Methods:Multiple organ dysfunction syndrome was induced in60Sprague-Dawley rats by intestinal ischemia-reperfusion combined with cecal ligation and puncture.Then these rats were intragastrically administered physiological saline(groupⅠ,n=20), ampicillin (groupⅡ,n=20) or intestinal function-recovering decoction(groupⅢ,n=20).After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously, bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.Results:Compared with groupI, serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased(all P0.05). The rate of bacterial translocation in the groupsⅡ andⅢ was significantly lower than in the groupⅠ(P0.05). Conclusions:Intestinal function-recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative-antioxidative balance.

  18. Subclinical Thyroid Dysfunction and Fracture Risk

    DEFF Research Database (Denmark)

    Blum, Manuel R; Bauer, Douglas C; Collet, Tinh-Hai

    2015-01-01

    IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLI...

  19. Autonomic dysfunction in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Dümcke, Christine Winkler; Møller, Søren

    2008-01-01

    Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases...

  20. Vimentin in Bacterial Infections

    DEFF Research Database (Denmark)

    Mak, Tim N; Brüggemann, Holger

    2016-01-01

    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate...... filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge...... about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria...

  1. Chronic hypoxia promotes pulmonary artery endothelial cell proliferation through H2O2-induced 5-lipoxygenase.

    Directory of Open Access Journals (Sweden)

    Kristi M Porter

    Full Text Available Pulmonary Hypertension (PH is a progressive disorder characterized by endothelial dysfunction and proliferation. Hypoxia induces PH by increasing vascular remodeling. A potential mediator in hypoxia-induced PH development is arachidonate 5-Lipoxygenase (ALOX5. While ALOX5 metabolites have been shown to promote pulmonary vasoconstriction and endothelial cell proliferation, the contribution of ALOX5 to hypoxia-induced proliferation remains unknown. We hypothesize that hypoxia exposure stimulates HPAEC proliferation by increasing ALOX5 expression and activity. To test this, human pulmonary artery endothelial cells (HPAEC were cultured under normoxic (21% O2 or hypoxic (1% O2 conditions for 24-, 48-, or 72 hours. In a subset of cells, the ALOX5 inhibitor, zileuton, or the 5-lipoxygenase activating protein inhibitor, MK-886, was administered during hypoxia exposure. ALOX5 expression was measured by qRT-PCR and western blot and HPAEC proliferation was assessed. Our results demonstrate that 24 and 48 hours of hypoxia exposure have no effect on HPAEC proliferation or ALOX5 expression. Seventy two hours of hypoxia significantly increases HPAEC ALOX5 expression, hydrogen peroxide (H2O2 release, and HPAEC proliferation. We also demonstrate that targeted ALOX5 gene silencing or inhibition of the ALOX5 pathway by pharmacological blockade attenuates hypoxia-induced HPAEC proliferation. Furthermore, our findings indicate that hypoxia-induced increases in cell proliferation and ALOX5 expression are dependent on H2O2 production, as administration of the antioxidant PEG-catalase blocks these effects and addition of H2O2 to HPAEC promotes proliferation. Overall, these studies indicate that hypoxia exposure induces HPAEC proliferation by activating the ALOX5 pathway via the generation of H2O2.

  2. Acute bacterial sinusitis in children.

    Science.gov (United States)

    DeMuri, Gregory; Wald, Ellen R

    2013-10-01

    On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

  3. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology.

    Science.gov (United States)

    Lemonnier, Marc; Landraud, Luce; Lemichez, Emmanuel

    2007-09-01

    Studies on the interactions of bacterial pathogens with their host have provided an invaluable source of information on the major functions of eukaryotic and prokaryotic cell biology. In addition, this expanding field of research, known as cellular microbiology, has revealed fascinating examples of trans-kingdom functional interplay. Bacterial factors actually exploit eukaryotic cell machineries using refined molecular strategies to promote invasion and proliferation within their host. Here, we review a family of bacterial toxins that modulate their activity in eukaryotic cells by activating Rho GTPases and exploiting the ubiquitin/proteasome machineries. This family, found in human and animal pathogenic Gram-negative bacteria, encompasses the cytotoxic necrotizing factors (CNFs) from Escherichia coli and Yersinia species as well as dermonecrotic toxins from Bordetella species. We survey the genetics, biochemistry, molecular and cellular biology of these bacterial factors from the standpoint of the CNF1 toxin, the paradigm of Rho GTPase-activating toxins produced by urinary tract infections causing pathogenic Escherichia coli. Because it reveals important connections between bacterial invasion and the host inflammatory response, the mode of action of CNF1 and its related Rho GTPase-targetting toxins addresses major issues of basic and medical research and constitutes a privileged experimental model for host-pathogen interaction.

  4. [The influence of bacterial toxins on the carcinogenesis].

    Science.gov (United States)

    Stachowicz, Anna M; Łaniewski, Paweł; Jagusztyn-Krynicka, Elzbieta K

    2010-01-01

    Bacterial infections may constitute an important risk factor of developing cancer disease. Molecular mechanisms by which bacteria contribute to cancer are extremely complex and still remain not fully understood. So far, it is generally accepted that Helicobacter pylori infections are associated with induction of gastric adenocarcinoma and MALT lymphoma. Two H. pylori toxins which modulate many cellular functions are VacA and CagA. So far, CagA is the only one known bacterial oncoprotein. However, many other bacteria produce toxins or effector proteins perturbing host cell homeostasis or/and evoking chronic inflammation. Both processes may be associated with tumour formation. Bacterial toxins which interfere, with various host signal transduction pathways, deregulate processes of cell division, proliferation and differentiation and modulate apoptosis. Some toxins cause even direct DNA damage. This review discuss the potential links between action of bacterial toxins and cancer.

  5. Sexual dysfunctions and psychological disorders associated with type IIIa chronic prostatitis: a clinical survey in China.

    Science.gov (United States)

    Mo, Mu-Qiong; Long, Ling-Li; Xie, Wen-Lin; Chen, Sai; Zhang, Wen-Hui; Luo, Can-Qiao; Deng, Li-Wen

    2014-12-01

    Chronic prostatitis (CP) is a frequent prostate-related complaint, impacts negatively on quality of life and is mostly of unclear etiology. Increasing attention has been paid to the prevalence of sexual dysfunctions in CP patients; however, the impact of specific types of CP and the correlation of sexual dysfunctions with psychological disorders associated with CP are not well understood. Type IIIa CP is characterized by chronic pelvic pain, urination symptoms and white blood cells in expressed prostatic secretion, but free of bacterial infection. A population of 600 type IIIa CP patients were randomly selected and 40 normal man were included as the control group. Queries were conducted by urologists. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function (IIEF-5) and the Symptom Checklist 90-R were used to evaluate the symptoms and severity of prostatitis, erectile dysfunctions and psychological problems, respectively. Scores of ejaculatory pain and premature ejaculation were also collected. Our study revealed that sexual dysfunctions are frequently associated with this specific type of CP. The prevalence of erectile dysfunction, premature ejaculation and ejaculatory pain was 19, 30 and 30 %, respectively. A variety of psychological problems exist among type IIIa CP patients, including depression, anxiety, somatization, obsessive-compulsive and interpersonal sensitivity. In particular, the severity of erectile dysfunctions, but not premature ejaculation and ejaculatory pain, correlated significantly with depression and anxiety. Our data indicate that a moderate level of sexual dysfunctions exists among the type IIIa CP patients, and highlight the association of depression and anxiety with erectile dysfunction in CP patients, suggestting that special attention should be paid to these psychological issues in clinical treatments of the prostatitis symptoms and the associated erectile dysfunctions.

  6. COGNITIVE DYSFUNCTIONS IN DIABETIC POLYNEUROPATHY

    Directory of Open Access Journals (Sweden)

    Mirena Valkova

    2011-12-01

    Full Text Available Introduction: The objective of our study was to examine cognitive status, short – term memory, delayed recall and the retention of visual information in diabetics with polyneuropathy and to establish the impacts of some risk factors on cognitive performance.Contingent and methods: We assessed 47 diabetic patients with polyneuropathy, using the Mini Mental State Examination, 10 words test, the Benton visual retention test and the Hamilton scale.Results: Global cognitive dysfunction, decline in verbal memory and visual retention and tendency for depressive mood were observed. We found statistically significant interaction of ageing, sex, severity of pain, duration and late onset of diabetes mellitus (DM on cognitive functioning. Therapy association on cognition was not found.Conclusions: Our study confirms the hypothesis of global cognitive dysfunction, associated with diabetic polyneuropathy. The interactions of sex and pain severity require further study. We arise a hypothesis of asymmetrical brain injury in diabetics.

  7. Dysfunctional Reward Processing in Depression

    Science.gov (United States)

    Admon, Roee; Pizzagalli, Diego A.

    2015-01-01

    Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression. PMID:26258159

  8. [Sexual dysfunction following pelvic surgery].

    Science.gov (United States)

    Hojo, K

    1997-11-01

    In male, sexual dysfunction was a common complication that occurred after radical pelvic surgery: radical protectomy, radical cysto-, prostatectomy. Upon the recent pelvic neuroanatomical findings and preservation of these nerves, it is now possible to perform successful cancer operation on the rectum, prostate or bladder with preservation of sexual function in the group of early cancer patients. Depending on the location and severity of these nerve injury, this could result in temporary or permanent erectile and ejaculation dysfunction. In female, the total hysterectomy for cervical cancer sacrifices or injuries the faculty of pregnancy or sexual intercourse. The oophorectomies causes a deficiency of female hormones. But recently the numbers of patients with a small or early stages cancer of uterine or ovary are increasing and we have become to be able to save the functions of these organs in many patients well with minimum local excision or partial resection of them.

  9. Neck pain causes respiratory dysfunction.

    Science.gov (United States)

    Kapreli, Eleni; Vourazanis, Evangelos; Strimpakos, Nikolaos

    2008-01-01

    This paper describes a presumptive mechanism for the development of changes in respiratory function due to chronic neck pain. The patient with neck pain presents a number of factors that could constitute a predisposition of leading to a respiratory dysfunction: (a) the decreased strength of deep neck flexors and extensors, (b) the hyperactivity and increased fatigability of superficial neck flexors, (c) the limitation of range of motion, (d) the decrease in proprioception and disturbances in neuromuscular control, (e) the existence of pain and (f) the psychosocial influence of dysfunction. The possible connection of neck pain and respiratory function could have a great impact on various clinical aspects notably patient assessment, rehabilitation and pharmacological prescription.

  10. Drug-induced sexual dysfunction.

    Science.gov (United States)

    Aldridge, S A

    1982-01-01

    Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

  11. Early detection of tubular dysfunction.

    Science.gov (United States)

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  12. Effects of pinacidil on proliferation of cultured rabbit airway smooth muscle cells induced by endothelin-1

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; XIE Wei-ping; QI Xu; ZHANG Xi-long

    2005-01-01

    @@ It has been found that the potassium channel dysfunction of the membrane of airway smooth muscle cells (ASMCs) is closely associated with proliferation of ASMCs.1 Preliminary research has demonstrated that pinacidil, an ATP sensitive potassium channel (KATP) opener, could play a remarkable role in the prevention and treatment of antigen induced bronchial asthma in guinea pigs.2 This study was designed to investigate further the role and molecular mechanism of the proliferation of ASMCs: a chief pathological change of the nonacute phase of bronchial asthmatic episodes.

  13. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  14. Thyroid Dysfunction from Antineoplastic Agents

    Science.gov (United States)

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  15. Thyroid dysfunction from antineoplastic agents.

    Science.gov (United States)

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-02

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.

  16. Myofascial Pain Dysfunction Syndrome (MPDS)

    OpenAIRE

    2010-01-01

    Introduction: Myofascial Pain Dysfunction Syndrome (MPDS) is one of the most important causes of the orofacial pain. The main purpose of this study was to evaluate 40 related variables in this regard. Materials and Methods: Thirty nine patients with MPDS were evaluated in this study. Different factors including age, gender, occupation, marital status, sensitivity of masticatory muscles, maximum opening of the mouth, deviation, deflection, involvement of temporomandibular joint, habit, parafun...

  17. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  18. Hypnotic metaphor and sexual dysfunction.

    Science.gov (United States)

    Gilmore, L G

    1987-01-01

    Although hypnosis can be very effective in alleviating sexual problems, few sex therapists use hypnotic methods. This paper seeks to encourage a greater use of hypnosis among clinicians by presenting: a description of the new hypnosis exemplified in the work of Milton H. Erickson; an explanation of one of Erickson's most important and innovative methods, the use of multiple embedded metaphors; and case histories illustrating the application of hypnotic approaches to sexual dysfunction.

  19. A ROLE OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES M49-16 IN PROMOTING INFECTION AND INHIBITION OF ENDOTHELIAL CELL PROLIFERATION

    Directory of Open Access Journals (Sweden)

    E. A. Starikova

    2016-01-01

    Full Text Available Arginine deiminase is a bacterial enzyme that hydrolyses arginine with citrulline and ammonia formation. In recent years, increasing evidence is reported about in vitro and in vivo anti-angiogenic action of arginine deiminase from Mycoplasma spp. Our studies have shown that arginine deiminase from Streptococcus pyogenes M22 exerts similar effects, i.e., inhibits proliferation and other endothelial cell functions related to angiogenesis. To confirm a leading role of arginine deiminase, as a factor responsible for the anti-proliferative effect, we have constructed an isogenic S. pyogenes M49-16 mutant unable to express arginine deiminase. A comparative analysis of anti-proliferative activity of original S. pyogenes M49-16 strain and its isogenic mutant with arginine deiminase gene deletion (M49-16delAD was performed, using an endothelial EA.hy926 cell line. The bacterial supernatantes obtained by sonication of S. pyogenes M49-16 and M49-16delAD were tested. The ability of S. pyogenes M49-16 and M49-16delAD supernatantes to hydrolyze arginine was assessed. Moreover, we compared effects of the Streptococcus supernatantes upon proliferative activity of endothelial cells and their distribution through the cell cycle phases.Supernatantes from original S. pyogenes 49-16 strain were shown to inhibit endothelial cell proliferation to a significant degree (down to 50% of controls. This effect was due to its arginine hydrolyzing activity, i. e. addition of exogenous arginine to the medium resulted into recovery of the cell proliferation levels. The supernatante from S. pyogenes M49-16delAD showed a lower ability to hydrolyze arginine as compared to the supernatante of original strain. Culturing of endothelial cells supplied with S. pyogenes M49-16delAD supernatantes resulted into reduction of their proliferative activity by 10% of control values. Analysis of the cell cycle distribution was concordant with these results. S. pyogenes M49-16 supernatante

  20. Interfering with bacterial gossip

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael

    2011-01-01

    defense. Antibiotics exhibit a rather limited effect on biofilms. Furthermore, antibiotics have an ‘inherent obsolescence’ because they select for development of resistance. Bacterial infections with origin in bacterial biofilms have become a serious threat in developed countries. Pseudomonas aeruginosa...... that appropriately target bacteria in their relevant habitat with the aim of mitigating their destructive impact on patients. In this review we describe molecular mechanisms involved in “bacterial gossip” (more scientifically referred to as quorum sensing (QS) and c-di-GMP signaling), virulence, biofilm formation......, resistance and QS inhibition as future antimicrobial targets, in particular those that would work to minimize selection pressures for the development of resistant bacteria....

  1. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  2. Endothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases

    OpenAIRE

    Yu-Hsun Kao; Wan-Chun Chiu; Ming-I Hsu; Yi-Jen Chen

    2013-01-01

    Polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age, is characterized by hyperandrogenism and insulin resistance. Women with PCOS have a higher risk for cardiovascular diseases (CVDs) and endothelial dysfunction. The mechanisms underlying these risks are unclear. Human peripheral blood contains circulating endothelial progenitor cells (EPCs) derived from bone marrow that have the ability to proliferate and differentiate into mature endothel...

  3. Blood borne: bacterial components in mother's blood influence fetal development.

    Science.gov (United States)

    Loughran, Allister J; Tuomanen, Elaine I

    2016-01-01

    Bacterial or viral infection of the mother during the course of pregnancy can cross the placenta and actively infect the fetus. However, especially for bacteria, it is more common for mothers to experience an infection that can be treated without overt fetal infection. In this setting, it is less well understood what the risk to fetal development is, particularly in terms of neurological development. This research highlight reviews recent findings indicating that bacterial components generated during infection of the mother can cross the placenta and activate the fetal innate immune system resulting in changes in the course of brain development and subsequent progression to postnatal cognitive disorders. Bacterial cell wall is a ubiquitous bacterial PAMP (pathogen-associated molecular pattern) known to activate inflammation through the stimulation of TLR2. Cell wall is released from bacteria during antibiotic treatment and new work shows that embryos exposed to cell wall from the mother demonstrate anomalous proliferation of neuronal precursor cells in a TLR2 dependent manner. Such proliferation increases the neuronal density of the cortical plate and alters brain architecture. Although there is no fetal death, subsequent cognitive development is significantly impaired. This model system suggests that bacterial infection of the mother and its treatment can impact fetal brain development and requires greater understanding to potentially eliminate a risk factor for cognitive disorders such as autism.

  4. Pyrosequencing analysis of the bacterial community in drinking water wells.

    Science.gov (United States)

    Navarro-Noya, Yendi E; Suárez-Arriaga, Mayra C; Rojas-Valdes, Aketzally; Montoya-Ciriaco, Nina M; Gómez-Acata, Selene; Fernández-Luqueño, Fabián; Dendooven, Luc

    2013-07-01

    Wells used for drinking water often have a large biomass and a high bacterial diversity. Current technologies are not always able to reduce the bacterial population, and the threat of pathogen proliferation in drinking water sources is omnipresent. The environmental conditions that shape the microbial communities in drinking water sources have to be elucidated, so that pathogen proliferation can be foreseen. In this work, the bacterial community in nine water wells of a groundwater aquifer in Northern Mexico were characterized and correlated to environmental characteristics that might control them. Although a large variation was observed between the water samples, temperature and iron concentration were the characteristics that affected the bacterial community structure and composition in groundwater wells. Small increases in the concentration of iron in water modified the bacterial communities and promoted the growth of the iron-oxidizing bacteria Acidovorax. The abundance of the genera Flavobacterium and Duganella was correlated positively with temperature and the Acidobacteria Gp4 and Gp1, and the genus Acidovorax with iron concentrations in the well water. Large percentages of Flavobacterium and Pseudomonas bacteria were found, and this is of special concern as bacteria belonging to both genera are often biofilm developers, where pathogens survival increases.

  5. Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling.

    Science.gov (United States)

    Dossa, Avafia Y; Escobar, Oswaldo; Golden, Jamie; Frey, Mark R; Ford, Henri R; Gayer, Christopher P

    2016-01-15

    Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation.

  6. Symptoms of Nerve Dysfunction After Hip Arthroscopy

    DEFF Research Database (Denmark)

    Dippmann, Christian; Thorborg, Kristian; Kraemer, Otto

    2014-01-01

    PURPOSE: The primary purpose of this study was to analyze the rate, pattern, and severity of symptoms of nerve dysfunction after hip arthroscopy (HA) by reviewing prospectively collected data. The secondary purpose was to study whether symptoms of nerve dysfunction were related to traction time...... year after HA concerning symptoms of nerve dysfunction, possible localization, and erectile dysfunction. Fifty patients participated and returned fully completed questionnaires. Patients reporting symptoms of nerve dysfunction 1 year after HA were re-examined. RESULTS: Twenty-three of 50 patients (46......%) reported symptoms of nerve dysfunction during the first week after HA; this was reduced to 14 patients (28%) after 6 weeks, 11 patients (22%) after 26 weeks, and 9 patients (18%) after 1 year. One patient experienced temporary erectile dysfunction. No difference in traction time between patients...

  7. Autonomic Nervous System Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Zesiewicz, Theresa A.; Baker, Matthew J.; Wahba, Mervat; Hauser, Robert A.

    2003-03-01

    Autonomic nervous system (ANS) dysfunction is common in Parkinson's disease (PD), affects 70% to 80% of patients, and causes significant morbidity and discomfort. Autonomic nervous system dysfunction symptoms in PD include sexual dysfunction, swallowing and gastrointestinal disorders, bowel and bladder abnormalities, sleep disturbances, and derangements of cardiovascular regulation, particularly, orthostatic hypotension. Autonomic nervous system dysfunction in PD may be caused by an underlying degenerative process that affects the autonomic ganglia, brainstem nuclei, and hypothalamic nuclei. Anti-parkinsonian medications can cause or worsen symptoms of ANS dysfunction. The care of a PD patient with ANS dysfunction relies on its recognition and directed treatment, including coordinated care between the neurologist and appropriate subspecialist. Pharmacotherapy may be useful to treat orthostasis, gastrointestinal, urinary, and sexual dysfunction.

  8. Homocysteine inhibits hepatocyte proliferation via endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Xue Yu

    Full Text Available Homocysteine is an independent risk factor for coronary, cerebral, and peripheral vascular diseases. Recent studies have shown that levels of homocysteine are elevated in patients with impaired hepatic function, but the precise role of homocysteine in the development of hepatic dysfunction is unclear. In this study, we examined the effect of homocysteine on hepatocyte proliferation in vitro. Our results demonstrated that homocysteine inhibited hepatocyte proliferation by up-regulating protein levels of p53 as well as mRNA and protein levels of p21(Cip1 in primary cultured hepatocytes. Homocysteine induced cell growth arrest in p53-positive hepatocarcinoma cell line HepG2, but not in p53-null hepatocarcinoma cell line Hep3B. A p53 inhibitor pifithrin-α inhibited the expression of p21(Cip1 and attenuated homocysteine-induced cell growth arrest. Homocysteine induced TRB3 expression via endoplasmic reticulum stress pathway, resulting in Akt dephosphorylation. Knock-down of endogenous TRB3 significantly suppressed the inhibitory effect of homocysteine on cell proliferation and the phosphorylation of Akt. LiCl reversed homocysteine-mediated cell growth arrest by inhibiting TRB3-mediated Akt dephosphorylation. These results demonstrate that both TRB3 and p21(Cip1 are critical molecules in the homocysteine signaling cascade and provide a mechanistic explanation for impairment of liver regeneration in hyperhomocysteinemia.

  9. Novel factors modulating human β-cell proliferation.

    Science.gov (United States)

    Shirakawa, J; Kulkarni, R N

    2016-09-01

    β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.

  10. Bacterial Meningitis in Infants

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-04-01

    Full Text Available A retrospective study of 80 infantile patients (ages 30-365 days; 47 male, 33 female with culture-proven bacterial meningitis seen over a 16 year period (1986-2001 is reported from Taiwan.

  11. Bacterial surface adaptation

    Science.gov (United States)

    Utada, Andrew

    2014-03-01

    Biofilms are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. Parasitic bacterial biofilms can cause lethal infections and biofouling, but commensal bacterial biofilms, such as those found in the gut, can break down otherwise indigestible plant polysaccharides and allow us to enjoy vegetables. The first step in biofilm formation, adaptation to life on a surface, requires a working knowledge of low Reynolds number fluid physics, and the coordination of biochemical signaling, polysaccharide production, and molecular motility motors. These crucial early stages of biofilm formation are at present poorly understood. By adapting methods from soft matter physics, we dissect bacterial social behavior at the single cell level for several prototypical bacterial species, including Pseudomonas aeruginosa and Vibrio cholerae.

  12. Bacterial intermediate filaments

    DEFF Research Database (Denmark)

    Charbon, Godefroid; Cabeen, M.; Jacobs-Wagner, C.

    2009-01-01

    Crescentin, which is the founding member of a rapidly growing family of bacterial cytoskeletal proteins, was previously proposed to resemble eukaryotic intermediate filament (IF) proteins based on structural prediction and in vitro polymerization properties. Here, we demonstrate that crescentin...

  13. Bacterial toxins as immunomodulators.

    Science.gov (United States)

    Donaldson, David S; Williams, Neil A

    2009-01-01

    Bacterial toxins are the causative agent at pathology in a variety of diseases. Although not always the primary target of these toxins, many have been shown to have potent immunomodulatory effects, for example, inducing immune responses to co-administered antigens and suppressing activation of immune cells. These abilities of bacterial toxins can be harnessed and used in a therapeutic manner, such as in vaccination or the treatment of autoimmune diseases. Furthermore, the ability of toxins to gain entry to cells can be used in novel bacterial toxin based immuno-therapies in order to deliver antigens into MHC Class I processing pathways. Whether the immunomodulatory properties of these toxins arose in order to enhance bacterial survival within hosts, to aid spread within the population or is pure serendipity, it is interesting to think that these same toxins potentially hold the key to preventing or treating human disease.

  14. Bacterial Wound Culture

    Science.gov (United States)

    ... and services. Advertising & Sponsorship: Policy | Opportunities Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  15. Dequalinium for bacterial vaginosis.

    Science.gov (United States)

    2017-05-01

    Bacterial vaginosis is an infection characterised by overgrowth of anaerobic bacteria in the vagina with an accompanying loss of lactobacilli, and is thought to be the most common cause of abnormal vaginal discharge in women of child-bearing age.(1) Standard treatment for symptomatic bacterial vaginosis consists of a short course of an oral or topical antibiotic.(2) Dequalinium, a topical antiseptic agent, has been available for many years as a treatment for oral infections.(3) A new formulation, dequalinium 10mg vaginal tablets (Fluomizin-Kora Healthcare), was licensed in the UK in June 2015 for the treatment of bacterial vaginosis.(4) Here, we review evidence for the effectiveness and safety of dequalinium vaginal tablets in the management of bacterial vaginosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    Science.gov (United States)

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  17. Endothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Hsun Kao

    2013-01-01

    Full Text Available Polycystic ovary syndrome (PCOS, the most common endocrine disorder affecting women ofreproductive age, is characterized by hyperandrogenism and insulin resistance. Women withPCOS have a higher risk for cardiovascular diseases (CVDs and endothelial dysfunction. Themechanisms underlying these risks are unclear. Human peripheral blood contains circulatingendothelial progenitor cells (EPCs derived from bone marrow that have the ability to proliferate anddifferentiate into mature endothelial cells, which may contribute to vessel homeostasis and repair.PCOS is associated with insulin resistance, hyperinsulinemia, and dyslipidemia, which may resultin EPC dysfunction. In this review, we summarize the potential mechanisms of EPC dysfunction inPCOS, which possibly result in a higher genesis of CVDs in PCOS-affected subjects.

  18. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing....... These extracellular proteases are activated in complex cascades involving auto-processing and proteolytic maturation. Thus, proteolysis has been adopted by bacterial pathogens at multiple levels to ensure the success of the pathogen in contact with the human host....

  19. [The human gut microbiota: Interactions with the host and dysfunctions].

    Science.gov (United States)

    Lepage, P

    2017-05-12

    The human intestinal microbiota is composed of approximately 100,000 billion microorganisms with the average total number of different commensal bacterial species estimated at over 500 per individual. The human intestinal microbiota can be considered as an organ within another, which co-evolved with its host to achieve a symbiotic relationship leading to physiological homeostasis. The host provides an environment enriched in nutrients and the microbiota provides essential functions. Dysbiosis of the intestinal microbiota (changes in bacterial composition) has been associated with local dysfunctions of the gastrointestinal tract, such as inflammatory bowel disease or irritable bowel syndrome but also with obesity and metabolic diseases. However, a better understanding of the human intestinal ecosystem is still needed to understand the exact role of the microbiota in health and disease. Most intestinal bacteria are anaerobic and therefore, for the large majority, impossible to culture at present. Consequently, their function cannot be inferred from data on their composition. Today, with the help of a metagenomic approach, the bacterial genomic content of an ecosystem and the associated functions can be directly accessed from the environment without culture. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  20. [Diagnosis of bacterial vaginosis].

    Science.gov (United States)

    Djukić, Slobodanka; Ćirković, Ivana; Arsić, Biljana; Garalejić, Eliana

    2013-01-01

    Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  1. Recombiant DNA and cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Stein, G.S.; Stein, J.L.

    1984-01-01

    This book contains 13 chapters. Some of the chapter titles are: Expression of Dihydrofolate Reductase and Thymidylate Synthase Genes in Mammalian Cells; Expression of Histone Genes during the Cell Cycle in Human Cells; Regulation of Nonmuscle Actin Gene Expression during Early Development; and Recombinant DNA Approaches to Studying Control of Cell Proliferation: An Overview.

  2. Nuclear Proliferation Technology Trends Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  3. PMP27 PROMOTES PEROXISOMAL PROLIFERATION

    NARCIS (Netherlands)

    MARSHALL, PA; KRIMKEVICH, YI; LARK, RH; DYER, JM; VEENHUIS, M; GOODMAN, JM; Krimkevich, Yelena I.; Lark, Richard H.; Dyer, John M.; Goodman, Joel M.

    1995-01-01

    Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by olea

  4. Low Proliferation and Differentiation Capacities of Adult Hippocampal Stem Cells Correlate with Memory Dysfunction in Humans

    Science.gov (United States)

    Coras, Roland; Siebzehnrubl, Florian A.; Pauli, Elisabeth; Huttner, Hagen B.; Njunting, Marleisje; Kobow, Katja; Villmann, Carmen; Hahnen, Eric; Neuhuber, Winfried; Weigel, Daniel; Buchfelder, Michael; Stefan, Hermann; Beck, Heinz; Steindler, Dennis A.; Blumcke, Ingmar

    2010-01-01

    The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we…

  5. Proximal tubular dysfunction as an indicator of chronic graft dysfunction

    Directory of Open Access Journals (Sweden)

    N.O.S. Câmara

    2009-03-01

    Full Text Available New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

  6. Drug addiction and sexual dysfunction.

    Science.gov (United States)

    Zaazaa, Adham; Bella, Anthony J; Shamloul, Rany

    2013-09-01

    This article attempts to review the most current and the well-established facts concerning drug addiction and sexual dysfunction. Surprisingly, even though alcohol is prevalent in many societies with many myths surrounding its sexual-enhancing effects, current scientific research cannot provide a solid conclusion on its effect on sexual function. Unfortunately, the same concept applies to tobacco smoking; however, most of the current knowledge tends to support the notion that it, indeed, can negatively affect sexual function. Similar ambiguities also prevail with substances of abuse.

  7. Endothelial dysfunction in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hadi AR Hadi

    2008-01-01

    Full Text Available Hadi AR Hadi, Jassim Al SuwaidiDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital – Hamad Medical Corporation, Doha, State of Qatar; Department of Cardioscience, Sheikh Khalifa Medical City, Abu Dhabi, UAEAbstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain

  8. Vaccination-related shoulder dysfunction.

    Science.gov (United States)

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

    We present two cases of shoulder pain and weakness following influenza and pneumococcal vaccine injections provided high into the deltoid muscle. Based on ultrasound measurements, we hypothesize that vaccine injected into the subdeltoid bursa caused a periarticular inflammatory response, subacromial bursitis, bicipital tendonitis and adhesive capsulitis. Resolution of symptoms followed corticosteroid injections to the subacromial space, bicipital tendon sheath and glenohumeral joint, followed by physical therapy. We conclude that the upper third of the deltoid muscle should not be used for vaccine injections, and the diagnosis of vaccination-related shoulder dysfunction should be considered in patients presenting with shoulder pain following a vaccination.

  9. Mitochondrial dysfunctions in Parkinson's disease.

    Science.gov (United States)

    Gautier, C A; Corti, O; Brice, A

    2014-05-01

    Neurodegenerative disorders (ND) include a wide spectrum of diseases characterized by progressive neuronal dysfunctions or degeneration. With an estimated cost of 135 billion € in 2010 in the European Union (Olesen et al., 2012), they put an enormous economic as well as social burden on modern societies. Hence, they have been the subject of a huge amount of research for the last fifty years. For many of these diseases, our understanding of their profound causes is incomplete and this hinders the discovery of efficient therapies. ND form a highly heterogeneous group of diseases affecting various neuronal subpopulations reflecting different origins and different pathological mechanisms. However, some common themes in the physiopathology of these disorders are emerging. There is growing evidence that mitochondrial dysfunctions play a pivotal role at some point in the course of neurodegeneration. In some cases (e.g. Alzheimer's disease, amyotrophic lateral sclerosis), impairment of mitochondrial functions probably occurs late in the course of the disease. In a subset of ND, current evidence suggests that mitochondrial dysfunctions play a more seminal role in neuronal demise. Parkinson's disease (PD) presents one of the strongest cases based in part on post-mortem studies that have shown mitochondrial impairment (e.g. reduced complex I activity) and oxidative damage in idiopathic PD brains. The occurrence of PD is largely sporadic, but clinical syndromes resembling sporadic PD have been linked to specific environmental insults or to mutations in at least 5 distinct genes (α-synuclein, parkin, DJ-1, PINK1 and LRRK2). It is postulated that the elucidation of the pathogenic mechanisms underlying the selective dopaminergic degeneration in familial and environmental Parkinsonism should provide important clues to the pathogenic mechanisms responsible for idiopathic PD. Hence, numerous cellular and animal models of the disease have been generated that mimic these

  10. 泡菜乳酸菌筛选鉴别及耐受性和促益生菌增殖的研究%Study on Selection and Identification of Lactic Bacteria and Its Tolerance and the Proliferation in Probiotic Bacterial in Pickles

    Institute of Scientific and Technical Information of China (English)

    赵立彬; 刘凌; 童军茂; 陈功; 余文华

    2009-01-01

    In order to look for the effective approach of beneficial function in Chinese traditional pickled vegetables, the Lactic bacteria from traditional pickles are isolated and selected by lineation on slab. The tolerances are inspected in simulation of gastrointestinal tract. The Bifidobacterium proliferation and the strain identification are carried out in the selected high tolerance bacteria strains. The viable counts of tow Lactic bacteria are above 10~6 CFU/mL after keeping 2 hours in the simulation of the environment of gastric juices(pH 2. 5-4. 5) and the viable counts are almost unchanged after keeping 4 hours in the simulation of the environment of 0. 3% gall. The Bifidobacterium proliferations are promoted by Lactic Acid Bacteria in the six hours fermentation. By examining the morphosis, measuring the metabolic organic acids in gas chromatography and the G + C contents in DNA with denaturation temperature, it is demonstrated that the selected desired strains are homofermentation Lactic bacteria.%以寻求提高我国传统发酵型腌渍蔬菜益生作用的有效途径为目的,采用平板划线分离的方法从典型泡菜产品中分离筛选乳酸菌,考察其在模拟人体胃肠环境条件下的耐受能力,选择耐受力强的菌株进行双歧杆菌增殖试验和菌株分类鉴别.结果显示:2株乳酸菌在pH为2.5-4.5的模拟胃液环境中停留2 h活菌数仍达10~6CFU/mL以上,在0.3%的模拟肠道胆汁环境停留4h活菌数仍保持在初始状态;发酵时间6h内乳酸菌株对长双歧杆菌生长有促进作用.经形态特征观察、气相色谱检测代谢有机酸种类和热变性温度法测定DNA中G+C(鸟嘌呤+胞嘧啶)含量,确认筛选出的优质菌株为同型发酵乳杆菌属.

  11. The bacterial lipocalins.

    Science.gov (United States)

    Bishop, R E

    2000-10-18

    The lipocalins were once regarded as a eukaryotic protein family, but new members have been recently discovered in bacteria. The first bacterial lipocalin (Blc) was identified in Escherichia coli as an outer membrane lipoprotein expressed under conditions of environmental stress. Blc is distinguished from most lipocalins by the absence of intramolecular disulfide bonds, but the presence of a membrane anchor is shared with two of its closest homologues, apolipoprotein D and lazarillo. Several common features of the membrane-anchored lipocalins suggest that each may play an important role in membrane biogenesis and repair. Additionally, Blc proteins are implicated in the dissemination of antibiotic resistance genes and in the activation of immunity. Recent genome sequencing efforts reveal the existence of at least 20 bacterial lipocalins. The lipocalins appear to have originated in Gram-negative bacteria and were probably transferred horizontally to eukaryotes from the endosymbiotic alpha-proteobacterial ancestor of the mitochondrion. The genome sequences also reveal that some bacterial lipocalins exhibit disulfide bonds and alternative modes of subcellular localization, which include targeting to the periplasmic space, the cytoplasmic membrane, and the cytosol. The relationships between bacterial lipocalin structure and function further illuminate the common biochemistry of bacterial and eukaryotic cells.

  12. Bacteroides uniformis CECT 7771 Ameliorates Metabolic and Immunological Dysfunction in Mice with High-Fat-Diet Induced Obesity

    Science.gov (United States)

    Gauffin Cano, Paola; Santacruz, Arlette; Moya, Ángela; Sanz, Yolanda

    2012-01-01

    Background Associations have been made between obesity and reduced intestinal numbers of members of the phylum Bacteroidetes, but there is no direct evidence of the role these bacteria play in obesity. Herein, the effects of Bacteroides uniformis CECT 7771 on obesity-related metabolic and immune alterations have been evaluated. Methods and Findings Adult (6–8 week) male wild-type C57BL-6 mice were fed a standard diet or a high-fat-diet HFD to induce obesity, supplemented or not with B. uniformis CECT 7771 for seven weeks. Animal weight was monitored and histologic, biochemical, immunocompetent cell functions, and features of the faecal microbiota were analysed after intervention. The oral administration of B. uniformis CECT 7771 reduced body weight gain, liver steatosis and liver cholesterol and triglyceride concentrations and increased small adipocyte numbers in HFD-fed mice. The strain also reduced serum cholesterol, triglyceride, glucose, insulin and leptin levels, and improved oral tolerance to glucose in HFD fed mice. The bacterial strain also reduced dietary fat absorption, as indicated by the reduced number of fat micelles detected in enterocytes. Moreover, B. uniformis CECT 7771 improved immune defence mechanisms, impaired in obesity. HFD-induced obesity led to a decrease in TNF-α production by peritoneal macrophages stimulated with LPS, conversely, the administration of B. uniformis CECT 7771 increased TNF-α production and phagocytosis. Administering this strain also increased TNF-α production by dendritic cells (DCs) in response to LPS stimulation, which was significantly reduced by HFD. B. uniformis CECT 7771 also restored the capacity of DCs to induce a T-cell proliferation response, which was impaired in obese mice. HFD induced marked changes in gut microbiota composition, which were partially restored by the intervention. Conclusions Altogether, the findings indicate that administration of B. uniformis CECT 7771 ameliorates HFD-induced metabolic

  13. Bacteroides uniformis CECT 7771 ameliorates metabolic and immunological dysfunction in mice with high-fat-diet induced obesity.

    Directory of Open Access Journals (Sweden)

    Paola Gauffin Cano

    Full Text Available BACKGROUND: Associations have been made between obesity and reduced intestinal numbers of members of the phylum Bacteroidetes, but there is no direct evidence of the role these bacteria play in obesity. Herein, the effects of Bacteroides uniformis CECT 7771 on obesity-related metabolic and immune alterations have been evaluated. METHODS AND FINDINGS: Adult (6-8 week male wild-type C57BL-6 mice were fed a standard diet or a high-fat-diet HFD to induce obesity, supplemented or not with B. uniformis CECT 7771 for seven weeks. Animal weight was monitored and histologic, biochemical, immunocompetent cell functions, and features of the faecal microbiota were analysed after intervention. The oral administration of B. uniformis CECT 7771 reduced body weight gain, liver steatosis and liver cholesterol and triglyceride concentrations and increased small adipocyte numbers in HFD-fed mice. The strain also reduced serum cholesterol, triglyceride, glucose, insulin and leptin levels, and improved oral tolerance to glucose in HFD fed mice. The bacterial strain also reduced dietary fat absorption, as indicated by the reduced number of fat micelles detected in enterocytes. Moreover, B. uniformis CECT 7771 improved immune defence mechanisms, impaired in obesity. HFD-induced obesity led to a decrease in TNF-α production by peritoneal macrophages stimulated with LPS, conversely, the administration of B. uniformis CECT 7771 increased TNF-α production and phagocytosis. Administering this strain also increased TNF-α production by dendritic cells (DCs in response to LPS stimulation, which was significantly reduced by HFD. B. uniformis CECT 7771 also restored the capacity of DCs to induce a T-cell proliferation response, which was impaired in obese mice. HFD induced marked changes in gut microbiota composition, which were partially restored by the intervention. CONCLUSIONS: Altogether, the findings indicate that administration of B. uniformis CECT 7771 ameliorates HFD

  14. Multiple sclerosis and sexual dysfunction

    Institute of Scientific and Technical Information of China (English)

    Zhen-Ni Guo; Si-Yuan He; Hong-Liang Zhang; Jiang Wu; Yi Yang

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions.The underlying pathogenesis of MS remains largely unclear.However,it is currently accepted as a T cell-mediated autoimmune disease.Among other clinical manifestations,sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder.SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic,physiologic,biologic,medical and psychological factors.SD arises primarily from lesions affecting the neural pathways involved in physiologic function.In addition,psychological factors,the side effects of medications and physical symptoms such as fatigue,muscular weakness,menstrual changes,pain and concerns about bladder and bowel incontinence may also be involved.Since MS primarily affects young people,SD secondary to MS may have a great impact on quality of life.Thus,maintaining a healthy sexual life with MS is an important priority.The treatment of SD requires multidisciplinary teamwork and cooperation among specialists,individual patients,partners and the society.

  15. Mitochondrial dysfunction in heart failure.

    Science.gov (United States)

    Rosca, Mariana G; Hoppel, Charles L

    2013-09-01

    Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction.

  16. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  17. Mitochondrial dysfunction in cancer chemoresistance.

    Science.gov (United States)

    Guaragnella, Nicoletta; Giannattasio, Sergio; Moro, Loredana

    2014-11-01

    Mitochondrial dysfunction has been associated with cancer development and progression. Recent evidences suggest that pathogenic mutations or depletion of the mitochondrial genome can contribute to development of chemoresistance in malignant tumors. In this review we will describe the current knowledge on the role of mitochondrial dysfunction in the development of chemoresistance in cancer. We will also discuss the significance of this research topic in the context of development of more effective, targeted therapeutic modalities and diagnostic strategies for cancer patients, with a particular focus on the potential use of PARP inhibitors in cancer patients displaying mitochondrial DNA mutations. We will discuss recent studies highlighting the importance of the cross-talk between the tumor microenvironment and mitochondrial functionality in determining selective response to certain chemotherapeutic drugs. Finally, owing to the similarities between cancer and yeast cell metabolism, we will point out the use of yeast as a model system to study cancer-related genes and for anti-cancer drugs screening. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Apraxia and Motor Dysfunction in Corticobasal Syndrome

    OpenAIRE

    Burrell, James R.; Michael Hornberger; Steve Vucic; Kiernan, Matthew C.; Hodges, John R.

    2014-01-01

    Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impai...

  19. The treatment of autonomic dysfunction in tetanus

    Directory of Open Access Journals (Sweden)

    T van den Heever

    2017-07-01

    Full Text Available We report a case of generalised tetanus in a 50-year-old female patient after sustaining a wound to her right lower leg. She developed autonomic dysfunction, which included labile hypertension alternating with hypotension and sweating. The autonomic dysfunction was treated successfully with a combination of morphine sulphate infusion, magnesium sulphate, and clonidine. She also received adrenaline and phenylephrine infusions as needed for hypotension. We then discuss the pathophysiology, clinical features and treatment options of autonomic dysfunction.

  20. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG

    2016-06-01

    Full Text Available As the survival of patients with multiple system atrophy (MSA is prolonged, patients may present cognitive dysfunction or even dementia in addition to autonomic dysfunction, damage of extrapyramidal system and cerebellar ataxia. This article made a brief summary on the research progress of MSA combined with cognitive dysfunction reported at home and abroad. DOI: 10.3969/j.issn.1672-6731.2016.06.003

  1. Proliferation Vulnerability Red Team report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E. [and others

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  2. Lipoproteins of Bacterial Pathogens▿

    Science.gov (United States)

    Kovacs-Simon, A.; Titball, R. W.; Michell, S. L.

    2011-01-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  3. Intestinal dysfunction associated with acute thoracolumbar fractures.

    Science.gov (United States)

    Peschiera, J L; Beerman, S P

    1990-03-01

    The frequency of intestinal dysfunction, particularly intestinal ileus, among patients with acute thoracolumbar fractures and no neurologic compromise was assessed. We reviewed the medical records of 70 patients who met specific criteria. Only four (6%) of these patients developed intestinal dysfunction, manifested by vomiting, abdominal distention, diminished bowel sounds, or an intestinal ileus documented by an abdominal roentgenogram. Conservative initial nutritional management of the patients did not reduce the incidence of intestinal dysfunction. This study suggests that patients with acute thoracolumbar fractures and no neurologic compromise are not at substantial risk of intestinal dysfunction and that nasogastric suction and restriction of oral intake are unnecessary in the initial management of these patients.

  4. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

    Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

  5. The relationship between depression and erectile dysfunction.

    Science.gov (United States)

    Seidman, S N; Roose, S P

    2000-06-01

    Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

  6. Diagnosis of bacterial vaginosis

    Directory of Open Access Journals (Sweden)

    Đukić Slobodanka

    2013-01-01

    Full Text Available Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2­producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent’s scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up­to­date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short­term and long­term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  7. Bacterial blight of cotton

    Directory of Open Access Journals (Sweden)

    Aïda JALLOUL

    2015-04-01

    Full Text Available Bacterial blight of cotton (Gossypium ssp., caused by Xanthomonas citri pathovar malvacearum, is a severe disease occurring in all cotton-growing areas. The interactions between host plants and the bacteria are based on the gene-for-gene concept, representing a complex resistance gene/avr gene system. In light of the recent data, this review focuses on the understanding of these interactions with emphasis on (1 the genetic basis for plant resistance and bacterial virulence, (2 physiological mechanisms involved in the hypersensitive response to the pathogen, including hormonal signaling, the oxylipin pathway, synthesis of antimicrobial molecules and alteration of host cell structures, and (3 control of the disease.

  8. Bacterial glycosyltransferase toxins.

    Science.gov (United States)

    Jank, Thomas; Belyi, Yury; Aktories, Klaus

    2015-12-01

    Mono-glycosylation of host proteins is a common mechanism by which bacterial protein toxins manipulate cellular functions of eukaryotic target host cells. Prototypic for this group of glycosyltransferase toxins are Clostridium difficile toxins A and B, which modify guanine nucleotide-binding proteins of the Rho family. However, toxin-induced glycosylation is not restricted to the Clostridia. Various types of bacterial pathogens including Escherichia coli, Yersinia, Photorhabdus and Legionella species produce glycosyltransferase toxins. Recent studies discovered novel unexpected variations in host protein targets and amino acid acceptors of toxin-catalysed glycosylation. These findings open new perspectives in toxin as well as in carbohydrate research.

  9. Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells

    Science.gov (United States)

    Jiménez-Palomares, Margarita; López-Acosta, José Francisco; Villa-Pérez, Pablo; Moreno-Amador, José Luis; Muñoz-Barrera, Jennifer; Fernández-Luis, Sara; Heras-Pozas, Blanca; Perdomo, Germán; Bernal-Mizrachi, Ernesto

    2015-01-01

    Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation. We hypothesized that cyclin C overexpression would induce β-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional β-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [3H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected β-cell death by TUNEL, β-cell differentiation by RT-PCR, and β-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human β-cell proliferation. This augmented proliferation did not induce β-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing β-cell regeneration. PMID:25564474

  10. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    Science.gov (United States)

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling.

  11. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

    Science.gov (United States)

    Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

    2013-05-01

    This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

  12. Proliferation behavior of E. coli in a three-dimensional in vitro tumor model.

    Science.gov (United States)

    Elliott, Nelita; Lee, Tae; You, Lingchong; Yuan, Fan

    2011-06-01

    Advances in genetic engineering of non-pathogenic Escherichia coli (E. coli) have made this organism an attractive candidate for gene delivery vehicle. However, proliferation and transport behaviors of E. coli in three-dimensional (3D) tumor environment are still unclear. To this end, we developed a novel microfluidics-based tumor model that permitted direct in situ visualization of E. coli in a 3D environment with densely packed tumor cells (B16.F10 or EMT6). The E. coli was engineered to co-express two proteins invasin and mCherry (inv(+)) so that they had the ability to enter mammalian cells and could be visualized via fluorescence microscopy. E. coli expressing mCherry alone (inv(-)) was used as the control counterpart. The inv(-) bacteria proliferated to a higher extent than inv(+) bacteria in both the 3D tumor model and a 2D monolayer culture model. Meanwhile, the proliferation appeared to be tumor cell type dependent since bacteria did not proliferate as well in the EMT6 model compared to the B16.F10 model. These differences in bacterial proliferation were likely to be caused by inhibitors secreted by tumor cells, as suggested by our data from the bacterial-tumor cell monolayer co-culture experiment. The bacterial proliferation provided a driving force for E. coli spreading in the 3D interstitial space of tumors. These findings are useful for researchers to develop novel strategies for improvement of bacteria-mediated oncolysis or gene delivery in cancer treatment.

  13. [Combination therapy of prostatitis-associated copulative dysfunction].

    Science.gov (United States)

    Bliumberg, B I; Shatylko, T V; Tverdokhleb, S A; Fomkin, R N; Voskoboĭnikova, I V

    2014-01-01

    Chronic prostatitis is characterized by clinical polymorphism, that may include pain, dysuria, asthenovegetative syndrome, and others. Symptoms associated with impaired copulatory cycle in chronic prostatitis have a significant impact on the quality of life of patient. Sexual dysfunction and sexuality cessation can exacerbate the inflammation of the prostate gland and worsen the underlying disease. The study included 60 patients diagnosed with chronic bacterial prostatitis, complicated by sexual disorders. Patients were divided into two comparable groups of 30 persons. Control group ofpatients received standard antibacterial therapy; study group ofpatients in addition received phytodrug prostanorm. At the end of treatment, higher IIEF-5 scores, increasing number of lecithin granules in the prostate secretion, as well as reducing the severity of irritative symptoms were registered in the study group.

  14. [Cashmere goat bacterial artificial chromosome recombination and cell transfection system].

    Science.gov (United States)

    Huang, Tian; Cao, Zhongyang; Yang, Yaohui; Cao, Gengsheng

    2016-03-01

    The Cashmere goat is mainly used to produce cashmere, which is very popular for its delicate fiber, luscious softness and natural excellent warm property. Keratin associated protein (KAP) and bone morphogenetic protein (BMP) of the Cashmere goat play an important role in the proliferation and development of cashmere fiber follicle cells. Bacterial artificial chromosome containing kap6.3, kap8.1 and bmp4 genes were used to increase the production and quality of Cashmere. First, we constructed bacterial artificial chromosomes by homology recombination. Then Tol2 transposon was inserted into bacterial artificial chromosomes that were then transfected into Cashmere goat fibroblasts by Amaxa Nucleofector technology according to the manufacture's instructions. We successfully constructed the BAC-Tol2 vectors containing target genes. Each vector contained egfp report gene with UBC promoter, Neomycin resistant gene for cell screening and two loxp elements for resistance removing after transfected into cells. The bacterial artificial chromosome-Tol2 vectors showed a high efficiency of transfection that can reach 1% to 6% with a highest efficiency of 10%. We also obtained Cashmere goat fibroblasts integrated exogenous genes (kap6.3, kap8.1 and bmp4) preparing for the clone of Cashmere goat in the future. Our research demonstrates that the insertion of Tol2 transposons into bacterial artificial chromosomes improves the transfection efficiency and accuracy of bacterial artificial chromosome error-free recombination.

  15. Microbial activity and bacterial community structure during degradation of microcystins

    DEFF Research Database (Denmark)

    Christoffersen, K.; Lyck, Susanne; Winding, A.

    2002-01-01

    Degradation of realistic microcystin concentrations in lake water with indigenous bacteria was studied in laboratory and field experiments following inoculation with lysed toxic algal material containing microcystin primarily from Microcystis sp. or purified commercial microcystin-LR to microcosms...... experiment to evaluate the effects of organic lysates on bacterial proliferation in the absence of microcystin. An exponential decline of the dissolved toxins was observed in all cases with toxins present, and the degradation rates ranged between 0.5 and 1.0 d(-1). No lag phases were observed but slow...... including microcystins, and this resulted in a net accumulation of bacterial cells. The heterotrophic nanoflagellates responded quickly to the bacterial growth and probably consumed a considerable amount of the bacteria. The microbial activities returned to initial values within 5 to 6 d as the toxins...

  16. Inside the Spiral of Dysfunction: The Personal Consequences of Working for a Dysfunctional Leader

    Science.gov (United States)

    Shuck, Brad; Rose, Kevin; Bergman, Matt

    2015-01-01

    Dysfunctional leaders suffocate others with coercive power and ego, are unpredictable, and often lack self-awareness about their dysfunction. Dysfunctional leaders are incredibly difficult to work with and can cause a series of cascading personal consequences for employees who work with them. This Perspectives in Human Resource Development essay…

  17. Diabetes and sexual dysfunction: current perspectives

    Directory of Open Access Journals (Sweden)

    Maiorino MI

    2014-03-01

    Full Text Available Maria Ida Maiorino,1 Giuseppe Bellastella,1 Katherine Esposito2 1Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; 2Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Abstract: Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. Keywords: diabetes mellitus, diabetes complications, erectile dysfunction, female sexual dysfunction, lifestyle changes

  18. New determinants of prognosis in bacterial infections in cirrhosis

    Science.gov (United States)

    Acevedo, Juan; Fernández, Javier

    2014-01-01

    Despite major advances in the knowledge and management of liver diseases achieved in recent decades, decompensation of cirrhosis still carries a high burden of morbidity and mortality. Bacterial infections are one of the main causes of decompensation. It is very important for clinical management to be aware of the population with the highest risk of poor outcome. This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently. Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines. Moreover, it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and, in infected patients, with the degree of sepsis. It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection, severe sepsis, hepatorenal syndrome and death. We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis. PMID:24966596

  19. Environmental Enteric Dysfunction in Children.

    Science.gov (United States)

    Syed, Sana; Ali, Asad; Duggan, Christopher

    2016-07-01

    Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

  20. Olfactory dysfunction in Down's Syndrome.

    Science.gov (United States)

    Murphy, C; Jinich, S

    1996-01-01

    Down's Syndrome subjects over 40 years old show neuropathology similar to that of Alzheimer's disease. The olfactory system is particularly vulnerable in Alzheimer's disease, both anatomically and functionally. Several measures of sensory and cognitive functioning were studied in the older Down's Syndrome patient, with the hypothesis of significant olfactory dysfunction. Participants were 23 Down's subjects, and 23 controls. The Dementia Rating Scale showed mean scores of 103 for Down's subjects and 141 for controls. Down's subjects showed significant deficits in odor detection threshold, odor identification, and odor recognition memory. Normal performance in a taste threshold task, similar to the olfactory threshold task in subject demands, suggested that the Down's syndrome subjects' poor performance was not due to task demands. Deficits in olfaction may provide a sensitive and early indicator of the deterioration and progression of the brain in older subjects with Down's Syndrome.

  1. Muscle dysfunction in male hypogonadism.

    Science.gov (United States)

    Chauhan, A K; Katiyar, B C; Misra, S; Thacker, A K; Singh, N K

    1986-05-01

    Twenty-eight consecutive male patients with primary and secondary hypogonadism (14 each) were evaluated clinically and electrophysiologically for muscle dysfunction. Although generalised muscle weakness was initially reported by only 9 patients, on direct questioning, it was recorded in 19. Objective weakness was found in 13 patients and it involved both the proximal and distal limb muscles. Quantitative electromyography showed evidence of myopathy in the proximal muscle in 25 patients, i.e., reduced MUP duration and amplitude with increased polyphasia in the deltoid and the gluteus maximus. There were no denervation potentials. None of the patients showed clinical neuropathy or NCV abnormalities. Thus, the profile of muscle involvement in hypogonadism closely simulates limb-girdle muscular dystrophy and other endocrine myopathies. The incidence of muscle involvement was higher in secondary hypogonadism. Diminished androgens in primary hypogonadism and diminished growth hormone in the secondary hypogonadism are probably responsible for the myopathy.

  2. Animal models of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Snehlata V Gajbhiye

    2015-01-01

    Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

  3. Flibanserin for female sexual dysfunction.

    Science.gov (United States)

    Reviriego, C

    2014-08-01

    Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women. Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. Clinically, flibanserin has exhibited some encouraging results in terms of its ability to increase the frequency of satisfying sexual events, and the intensity of sexual desire. However, adverse events such as dizziness, nausea, fatigue and somnolence, typical of a centrally acting drug, are also frequently related to flibanserin treatment.

  4. Coronary microvascular dysfunction: an update

    Science.gov (United States)

    Crea, Filippo; Camici, Paolo G.; Bairey Merz, Cathleen Noel

    2014-01-01

    Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy. PMID:24366916

  5. Nutraceuticals, aging, and cognitive dysfunction.

    Science.gov (United States)

    Head, Elizabeth; Zicker, Steven C

    2004-01-01

    Decline in cognitive function that accompanies aging in dogs might have a biological basis, and many of the disorders associated with aging in canines might be preventable through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants might be one class of nutraceutical that benefits aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which can lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes might lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs; however, determining which compounds, combinations, dosage ranges, when to initiate intervention, and long-term effects constitute critical gaps in knowledge about this subject.

  6. Ambulatory anaesthesia and cognitive dysfunction

    DEFF Research Database (Denmark)

    Rasmussen, Lars S; Steinmetz, Jacob

    2015-01-01

    serious adverse outcomes, hence difficult to obtain sound scientific evidence for avoiding complications. RECENT FINDINGS: Few studies have assessed recovery of cognitive function after ambulatory surgery, but it seems that both propofol and modern volatile anaesthetics are rational choices for general...... anaesthesia in the outpatient setting. Cognitive complications such as delirium and postoperative cognitive dysfunction are less frequent in ambulatory surgery than with hospitalization. SUMMARY: The elderly are especially susceptible to adverse effects of the hospital environment such as immobilisation......, sleep deprivation, unfamiliar surroundings, and medication errors. Enhanced recovery programmes (fast-track regimens) may allow earlier discharge which is probably beneficial for the elderly. Frailty is becoming an increasingly important concept that needs to be clinically considered in elderly patients...

  7. Thyroid dysfunction in infertile women

    Directory of Open Access Journals (Sweden)

    S G Perminova

    2011-12-01

    Full Text Available Objective. To study the rate and structure of thyroid diseases in infertile women and to asses their reproductive system depending upon the thyroid pathology. Subjects and methods. The study was based on the results of screening of T status of 496 women with infertility (main group and 80 fertile women (control group. Traditional methods of diagnosis of infertility were used along with special methods of investigation including assessment of function and structure of T (TTH, fT4, fT3, AT-TPO, AT-rTTH, ultrasound examination of T, thin-niddle aspirational biopsy, scintigraphy of T. A complex evaluation of the reproductive system status in infertile women was done depending on the type of T pathology. Results. Infertile women were found to suffer from thyroid dysfunction 3.8 times as more often as fertile ones (48% and 12.5%, p <0.05. Its structure included mainly AT-TPO carrier phenomenon in combination with ultrasound markers of thyroid autoimmunity (24%, hypothyroidism following thyroid autoimmunity (9.4% demonstrating itself as clinical (0.8%, subclinical (8.6%, and euthyroid (7.8% goiters. The portion of women with infertility and hyperthyroidism was small (0.6%. An association of thyroid autoimmunity with idiopathic infertility, endometriosis, endocrine infertility was found. Conclusion. It is necessary to perform a screening assessment of the function and structure of T in infertile women within diagnostic search for the reasons of infertility and in-time correction of the revealed thyroid dysfunction.

  8. Test Performance Related Dysfunctional Beliefs

    Directory of Open Access Journals (Sweden)

    Recep TÜTÜNCÜ

    2012-11-01

    Full Text Available Objective: Examinations by using tests are very frequently used in educational settings and successful studying before the examinations is a complex matter to deal with. In order to understand the determinants of success in exams better, we need to take into account not only emotional and motivational, but also cognitive aspects of the participants such as dysfunctional beliefs. Our aim is to present the relationship between candidates’ characteristics and distorted beliefs/schemata just before an examination. Method: The subjects of the study were 30 female and 30 male physicians who were about to take the medical specialization exam (MSE in Turkey. Dysfunctional Attitude Scale (DAS and Young Schema Questionnaire Short Form (YSQ-SF were applied to the subjects. The statistical analysis was done using the F test, Mann-Whitney, Kruskal-Wallis, chi-square test and spearman’s correlation test. Results: It was shown that some of the DAS and YSQ-SF scores were significantly higher in female gender, in the group who could not pass the exam, who had repetitive examinations, who had their first try taking an examination and who were unemployed at the time of the examination. Conclusion: Our findings indicate that candidates seeking help before MSE examination could be referred for cognitive therapy or counseling even they do not have any psychiatric diagnosis due to clinically significant cognitive distortion. Measurement and treatment of cognitive distortions that have negative impact on MSE performance may improve the cost-effectiveness and mental well being of the young doctors.

  9. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

    2017-01-01

    Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

  10. Seizures Complicating Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-09-01

    Full Text Available The clinical data of 116 patients, 1 month to <5 years of age, admitted for bacterial meningitis, and grouped according to those with and without seizures during hospitalization, were compared in a study at Buddhist Dalin Tzu Chi General Hospital, Chang Gung Memorial Hospital and other centers in Taiwan.

  11. Bacterial fingerprints across Europe

    NARCIS (Netherlands)

    Glasner, Corinna

    2014-01-01

    Bacterial pathogens, such as Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae (CPE), impose major threats to human health worldwide. Both have a ‘Jekyll & Hyde’ character, since they can be present as human commensals, but can also become harmful invasive pathogens especially

  12. Bacterial cell factoriest

    NARCIS (Netherlands)

    Kranenburg, van Richard

    2017-01-01

    The research of Bacterial Cell Factories aims to apply bacteria for production of biobased chemicals from renewable resources. The focus lies on thermophilic Gram-positives. This group of relatively unexplored thermophiles has many relevant characteristics that make them attractive as production

  13. Mechanisms used for genomic proliferation by thermophilic group II introns.

    Directory of Open Access Journals (Sweden)

    Georg Mohr

    Full Text Available Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelements hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting approximately 1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases.

  14. Understanding taste dysfunction in patients with cancer.

    Science.gov (United States)

    McLaughlin, Laura; Mahon, Suzanne M

    2012-04-01

    Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.

  15. Olfactory dysfunction in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zou YM

    2016-04-01

    Full Text Available Yong-ming Zou, Da Lu, Li-ping Liu, Hui-hong Zhang, Yu-ying Zhou Department of Neurology, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China Abstract: Alzheimer’s disease (AD is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. Keywords: olfactory dysfunction, Alzheimer’s disease, olfactory testing, progress

  16. Endothelial Dysfunction in Renal Failure: Current Update.

    Science.gov (United States)

    Radenkovic, Miroslav; Stojanovic, Marko; Prostran, Milica

    2016-01-01

    Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.

  17. Diastolic dysfunction in the critically ill patient.

    Science.gov (United States)

    Suárez, J C; López, P; Mancebo, J; Zapata, L

    2016-11-01

    Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  18. Attachment, borderline personality, and romantic relationship dysfunction.

    Science.gov (United States)

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  19. Lack of awareness of erectile dysfunction in many men with risk factors for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Magee Michelle

    2010-11-01

    Full Text Available Abstract Background Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate. Methods Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m2] or waist circumference ≥40 inches, and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF were administered. Results Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053, of whom 54% (399/744 had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range number of risk factors was 2.9 ± 1.7 (3-8 in the "yes" group, 3.2 ± 1.7 (3-9 in the "unsure" group, and 2.6 ± 1.5 (2-8 in the "no" group. Conclusion Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction. Trial registration ClinicalTrials.gov Identifier NCT00343200.

  20. Formation of bacterial nanocells

    Science.gov (United States)

    Vainshtein, Mikhail; Kudryashova, Ekaterina; Suzina, Natalia; Ariskina, Elena; Voronkov, Vadim

    1998-07-01

    Existence of nanobacteria received increasing attention both in environmental microbiology/geomicro-biology and in medical microbiology. In order to study a production of nanoforms by typical bacterial cells. Effects of different physical factors were investigated. Treatment of bacterial cultures with microwave radiation, or culturing in field of electric current resulted in formation a few types of nanocells. The number and type of nanoforms were determined with type and dose of the treatment. The produced nanoforms were: i) globules, ii) clusters of the globules--probably produced by liaison, iii) nanocells coated with membrane. The viability of the globules is an object opened for doubts. The nanocells discovered multiplication and growth on solidified nutrient media. The authors suggest that formation of nanocells is a common response of bacteria to stress-actions produced by different agents.

  1. Cooperative Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2009-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a novel optimization algorithm based on the social foraging behavior of E. coli bacteria. This paper presents a variation on the original BFO algorithm, namely, the Cooperative Bacterial Foraging Optimization (CBFO, which significantly improve the original BFO in solving complex optimization problems. This significant improvement is achieved by applying two cooperative approaches to the original BFO, namely, the serial heterogeneous cooperation on the implicit space decomposition level and the serial heterogeneous cooperation on the hybrid space decomposition level. The experiments compare the performance of two CBFO variants with the original BFO, the standard PSO and a real-coded GA on four widely used benchmark functions. The new method shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  2. Bacterial Colony Optimization

    Directory of Open Access Journals (Sweden)

    Ben Niu

    2012-01-01

    Full Text Available This paper investigates the behaviors at different developmental stages in Escherichia coli (E. coli lifecycle and developing a new biologically inspired optimization algorithm named bacterial colony optimization (BCO. BCO is based on a lifecycle model that simulates some typical behaviors of E. coli bacteria during their whole lifecycle, including chemotaxis, communication, elimination, reproduction, and migration. A newly created chemotaxis strategy combined with communication mechanism is developed to simplify the bacterial optimization, which is spread over the whole optimization process. However, the other behaviors such as elimination, reproduction, and migration are implemented only when the given conditions are satisfied. Two types of interactive communication schemas: individuals exchange schema and group exchange schema are designed to improve the optimization efficiency. In the simulation studies, a set of 12 benchmark functions belonging to three classes (unimodal, multimodal, and rotated problems are performed, and the performances of the proposed algorithms are compared with five recent evolutionary algorithms to demonstrate the superiority of BCO.

  3. Targeting bacterial toxins.

    Science.gov (United States)

    Ivarsson, Mattias E; Leroux, Jean-Christophe; Castagner, Bastien

    2012-04-23

    Protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. Lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. Despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. This Review presents the state of the art in bacterial toxin targeted drug development with a critical consideration of achieved breakthroughs and withstanding challenges. The discussion focuses on A-B-type protein toxins secreted by four species of bacteria, namely Clostridium difficile (toxins A and B), Vibrio cholerae (cholera toxin), enterohemorrhagic Escherichia coli (Shiga toxin), and Bacillus anthracis (anthrax toxin), which are the causative agents of diseases for which treatments need to be improved. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Bacterial assays for recombinagens.

    Science.gov (United States)

    Hoffmann, G R

    1992-12-01

    Two principal strategies have been used for studying recombinagenic effects of chemicals and radiation in bacteria: (1) measurement of homologous recombination involving defined alleles in a partially diploid strain, and (2) measurement of the formation and loss of genetic duplications in the bacterial chromosome. In the former category, most methods involve one allele in the bacterial chromosome and another in a plasmid, but it is also possible to detect recombination between two chromosomal alleles or between two extrachromosomal alleles. This review summarizes methods that use each of these approaches for detecting recombination and tabulates data on agents that have been found to be recombinagenic in bacteria. The assays are discussed with respect to their effectiveness in testing for recombinagens and their potential for elucidating mechanisms underlying recombinagenic effects.

  5. Bacterial transformation of terpenoids

    Science.gov (United States)

    Grishko, V. V.; Nogovitsina, Y. M.; Ivshina, I. B.

    2014-04-01

    Data on the bacterial transformation of terpenoids published in the literature in the past decade are analyzed. Possible pathways for chemo-, regio- and stereoselective modifications of terpenoids are discussed. Considerable attention is given to new technological approaches to the synthesis of terpenoid derivatives suitable for the use in the perfume and food industry and promising as drugs and chiral intermediates for fine organic synthesis. The bibliography includes 246 references.

  6. Spontaneous bacterial peritonitis

    OpenAIRE

    Al Amri Saleh

    1995-01-01

    Spontaneous bacterial peritonitis (SBP) is an infection of the ascitic fluid without obvious intra-abdominal source of sepsis; usually complicates advanced liver disease. The pathogenesis of the disease is multifactorial: low ascitic protein-content, which reflects defi-cient ascitic fluid complement and hence, reduced opsonic activity is thought to be the most important pathogenic factor. Frequent and prolonged bacteremia has been considered as another pertinent cause of SBP. This disease is...

  7. Modelling bacterial speciation

    OpenAIRE

    2006-01-01

    A central problem in understanding bacterial speciation is how clusters of closely related strains emerge and persist in the face of recombination. We use a neutral Fisher–Wright model in which genotypes, defined by the alleles at 140 house-keeping loci, change in each generation by mutation or recombination, and examine conditions in which an initially uniform population gives rise to resolved clusters. Where recombination occurs at equal frequency between all members of the population, we o...

  8. Psychogenic erectile dysfunction. Classification and management.

    Science.gov (United States)

    Rosen, R C

    2001-05-01

    Psychogenic factors are involved alone or in combination with organic causes in a substantial number of cases of erectile dysfunction. Epidemiologic studies have implicated the role of depressed mood, loss of self-esteem, and other psychosocial stresses in the cause of erectile dysfunction. A new definition and classification of psychogenic erectile dysfunction has been proposed based on recent clinical and research findings. According to this new classification, psychogenic erectile dysfunction is categorized as generalized or situational type, with subcategories of each type proposed. Traditional treatment approaches for psychogenic erectile dysfunction have included anxiety reduction and desensitization procedures, cognitive-behavioral interventions, guided sexual stimulation techniques, and couples' or relationship counseling. Recently, these approaches increasingly have been combined with pharmacologic therapy such as sildenafil. Special situations have been identified in which combining psychosocial interventions with medical therapy is recommended. These situations include problems of sexual initiation, low sexual desire, other sexual dysfunctions, and significant couples' or relationship problems. More research is needed on the role of psychosocial interventions in the treatment of erectile dysfunction.

  9. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

    Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

  10. Neglected bacterial zoonoses.

    Science.gov (United States)

    Chikeka, I; Dumler, J S

    2015-05-01

    Bacterial zoonoses comprise a group of diseases in humans or animals acquired by direct contact with or by oral consumption of contaminated animal materials, or via arthropod vectors. Among neglected infections, bacterial zoonoses are among the most neglected given emerging data on incidence and prevalence as causes of acute febrile illness, even in areas where recognized neglected tropical diseases occur frequently. Although many other bacterial infections could also be considered in this neglected category, five distinct infections stand out because they are globally distributed, are acute febrile diseases, have high rates of morbidity and case fatality, and are reported as commonly as malaria, typhoid or dengue virus infections in carefully designed studies in which broad-spectrum diagnoses are actively sought. This review will focus attention on leptospirosis, relapsing fever borreliosis and rickettsioses, including scrub typhus, murine typhus and spotted fever group rickettsiosis. Of greatest interest is the lack of distinguishing clinical features among these infections when in humans, which confounds diagnosis where laboratory confirmation is lacking, and in regions where clinical diagnosis is often attributed to one of several perceived more common threats. As diseases such as malaria come under improved control, the real impact of these common and under-recognized infections will become evident, as will the requirement for the strategies and allocation of resources for their control.

  11. Adaptive Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2011-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a recently developed nature-inspired optimization algorithm, which is based on the foraging behavior of E. coli bacteria. Up to now, BFO has been applied successfully to some engineering problems due to its simplicity and ease of implementation. However, BFO possesses a poor convergence behavior over complex optimization problems as compared to other nature-inspired optimization techniques. This paper first analyzes how the run-length unit parameter of BFO controls the exploration of the whole search space and the exploitation of the promising areas. Then it presents a variation on the original BFO, called the adaptive bacterial foraging optimization (ABFO, employing the adaptive foraging strategies to improve the performance of the original BFO. This improvement is achieved by enabling the bacterial foraging algorithm to adjust the run-length unit parameter dynamically during algorithm execution in order to balance the exploration/exploitation tradeoff. The experiments compare the performance of two versions of ABFO with the original BFO, the standard particle swarm optimization (PSO and a real-coded genetic algorithm (GA on four widely-used benchmark functions. The proposed ABFO shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  12. Mitochondrial dysfunction in neuromuscular disorders.

    Science.gov (United States)

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

  13. Myofascial Pain Dysfunction Syndrome (MPDS

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2010-10-01

    Full Text Available Introduction: Myofascial Pain Dysfunction Syndrome (MPDS is one of the most important causes of the orofacial pain. The main purpose of this study was to evaluate 40 related variables in this regard. Materials and Methods: Thirty nine patients with MPDS were evaluated in this study. Different factors including age, gender, occupation, marital status, sensitivity of masticatory muscles, maximum opening of the mouth, deviation, deflection, involvement of temporomandibular joint, habit, parafunction, malocclusion, neck pain, headache, earache and history of jaw involvement, etc were analyzed in this  evaluation. Results: In our study, 39 patients (32 females and 7 males, 20-40 years old, with the average age of 35 ± 13.32 years were studied. 51% were housewives and 74.4% were married. The most common involvements were Clicking (74.4%, pain in temporomandibular joint (54%, headache (46.2%, earache (41%, neck-pain (35.9%, trouble in the mouth opening (71.8%, malocclusion Class I (74.4%, cross bite and deep bite (25%, clenching (64.1% and involvement of masseter and lateral pterygoid muscle (84%. Conclusion: Since MPDS consists of variable symptoms, it might be very difficult to provide any definite diagnosis and treatment. Therefore the more the specialists extend their knowledge and information about this disorder, the more they will make the best decision in this regard.

  14. Polyphenols in preventing endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Sylwia Biegańska-Hensoldt

    2017-03-01

    Full Text Available One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions.Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS and increased production of nitric oxide (NO and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules – sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  15. Erectile dysfunction in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Imen Gorsane

    2016-01-01

    Full Text Available Erectile dysfunction (ED is a common problem seen among patients on hemodialysis (HD, but it is still a taboo subject in our country. The attention given to this sexual problem remained low, and the prevalence of ED among these patients has not been well characterized. We carried out this study in order to determine the prevalence and severity of ED in HD patients. We conducted a descriptive cross-sectional study in our HD unit in March 2013. ED was evaluated using the International Index Erection Function. Thirty patients with a mean age of 49.1 years were eligible for this study. The main causes of chronic kidney disease were hypertension (62.5% and diabetes (41.6%. The prevalence of ED was 80%, including 33.3% severe ED. Plasma levels of gonadotropins: luteinizing hormone (LH, follicule-stimulating hormone were in the standards except for one patient who had an elevated level of LH. Prolactin was elevated in four cases. ED was present in 8.4% of patients before the discovery of renal failure and in 91.6% of patients at the beginning of dialysis. For 19 patients (79.1%, the ED had increased during the dialysis sessions. A significant number of our HD patients presented with ED of varying degrees. Nephrologists should pay attention to the problem of ED in order to improve the quality of their life.

  16. Neurostimulation for Neurogenic Bowel Dysfunction

    Directory of Open Access Journals (Sweden)

    J. Worsøe

    2013-01-01

    Full Text Available Background. Loss of normal bowel function caused by nerve injury, neurological disease or congenital defects of the nervous system is termed neurogenic bowel dysfunction (NBD. It usually includes combinations of fecal incontinence, constipation, abdominal pain and bloating. When standard treatment of NBD fails surgical procedures are often needed. Neurostimulation has also been investigated, but no consensus exists about efficacy or clinical use. Methods. A systematic literature search of NBD treated by sacral anterior root stimulation (SARS, sacral nerve stimulation (SNS, peripheral nerve stimulation, magnetic stimulation, and nerve re-routing was made in Pubmed, Embase, Scopus, and the Cochrane Library. Results. SARS improves bowel function in some patients with complete spinal cord injury (SCI. Nerve re-routing is claimed to facilitate defecation through mechanical stimulation of dermatomes in patients with complete or incomplete SCI or myelomeningocele. SNS can reduce NBD in selected patients with a variety of incomplete neurological lesions. Peripheral stimulation using electrical stimulation or magnetic stimulation may represent non-invasive alternatives. Conclusion. Numerous methods of neurostimulation to treat NBD have been investigated in pilot studies or retrospective studies. Therefore, larger controlled trials with well-defined inclusion criteria and endpoints are recommended before widespread clinical use of neurostimulation against NBD.

  17. Sarcomere Dysfunction in Nemaline Myopathy.

    Science.gov (United States)

    de Winter, Josine M; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood. Therefore, no therapeutic treatment is available yet.Eleven implicated genes have been identified: ten genes encode proteins that are either components of thin filament, or are thought to contribute to stability or turnover of thin filament proteins. The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. It is at this level of contraction - thin-thick filament interaction - where muscle weakness originates in NM patients.This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. Insight into the contribution of sarcomeric dysfunction to muscle weakness in NM, across the genes involved, will direct towards the development of targeted therapeutic strategies.

  18. Sleep apnoea and metabolic dysfunction

    Directory of Open Access Journals (Sweden)

    Maria R. Bonsignore

    2013-09-01

    Full Text Available Obstructive sleep apnoea (OSA is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and non-alcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patients.

  19. Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia

    National Research Council Canada - National Science Library

    Skeldon, Sean C; Detsky, Allan S; Goldenberg, S Larry; Law, Michael R

    2015-01-01

    .... Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes...

  20. Male Sexual Dysfunction and Chronic Kidney Disease

    Science.gov (United States)

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  1. Etiology and Management of Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Narendra Kumar Muthugaduru Shivarudrappa

    2009-09-01

    Full Text Available Sexual dysfunction is the impairment or disruption of any of the three phases of normal sexual functioning, including loss of libido, impairment of physiological arousal and loss, delay or alteration of orgasm. Each one of these can be affected by an orchestra of factors like senility, medical and surgical illnesses, medications and drugs of abuse. Non-pharmacological therapy is the main stay in the treatment of sexual dysfunction and drugs are used as adjuncts for a quicker and better result. Management in many of the cases depends on the primary cause. Here is a review of the major etiological factors of sexual dysfunction and its management

  2. Sexual dysfunction within an adult developmental perspective.

    Science.gov (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  3. Velo-pharyngeal dysfunction: Evaluation and management

    Directory of Open Access Journals (Sweden)

    Marsh Jeffrey

    2009-10-01

    Full Text Available Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention.

  4. Cell death and cell proliferation in mouse submandibular gland during early post-irradiation phase.

    Directory of Open Access Journals (Sweden)

    Bralic,Marina

    2005-08-01

    Full Text Available

    The effects of irradiation on different cell compartments in the submandibular gland were analyzed in adult C57BL/6 mice exposed to X-ray irradiation and followed up for 10 days. Apoptosis was quantified using the terminal deoxynucleotidyl transferase (TdT-mediated dUTP-digoxigenin nick end labeling method (TUNEL. Cell proliferation was detected using immunohistochemistry for proliferating cell nuclear antigen (PCNA. Radiation-induced apoptosis occurred rapidly, reaching a maximum 3 days post-irradiation. The percentage of apoptotic cells increased with the irradiation dose. At day 1 post-irradiation, cell proliferation was significantly reduced in comparison to sham-irradiated controls. After post-irradiation arrest of the cell cycle, proliferation increased in all gland compartments, reaching a maximum at day 6 post-irradiation. The proliferation response corresponded to the dose of irradiation. We suggest that the reason for gland dysfunction could be the coexistence of high apoptotic and proliferative activity in the irradiated gland.

  5. TBK1 protects vacuolar integrity during intracellular bacterial infection.

    Directory of Open Access Journals (Sweden)

    Andrea L Radtke

    2007-03-01

    Full Text Available TANK-binding kinase-1 (TBK1 is an integral component of Type I interferon induction by microbial infection. The importance of TBK1 and Type I interferon in antiviral immunity is well established, but the function of TBK1 in bacterial infection is unclear. Upon infection of murine embryonic fibroblasts with Salmonella enterica serovar Typhimurium (Salmonella, more extensive bacterial proliferation was observed in tbk1(-/- than tbk1(+/+ cells. TBK1 kinase activity was required for restriction of bacterial infection, but interferon regulatory factor-3 or Type I interferon did not contribute to this TBK1-dependent function. In tbk1(-/-cells, Salmonella, enteropathogenic Escherichia coli, and Streptococcus pyogenes escaped from vacuoles into the cytosol where increased replication occurred, which suggests that TBK1 regulates the integrity of pathogen-containing vacuoles. Knockdown of tbk1 in macrophages and epithelial cells also resulted in increased bacterial localization in the cytosol, indicating that the role of TBK1 in maintaining vacuolar integrity is relevant in different cell types. Taken together, these data demonstrate a requirement for TBK1 in control of bacterial infection distinct from its established role in antiviral immunity.

  6. The development of permafrost bacterial communities under submarine conditions

    Science.gov (United States)

    Mitzscherling, Julia; Winkel, Matthias; Winterfeld, Maria; Horn, Fabian; Yang, Sizhong; Grigoriev, Mikhail N.; Wagner, Dirk; Overduin, Pier P.; Liebner, Susanne

    2017-07-01

    Submarine permafrost is more vulnerable to thawing than permafrost on land. Besides increased heat transfer from the ocean water, the penetration of salt lowers the freezing temperature and accelerates permafrost degradation. Microbial communities in thawing permafrost are expected to be stimulated by warming, but how they develop under submarine conditions is completely unknown. We used the unique records of two submarine permafrost cores from the Laptev Sea on the East Siberian Arctic Shelf, inundated about 540 and 2500 years ago, to trace how bacterial communities develop depending on duration of the marine influence and pore water chemistry. Combined with geochemical analysis, we quantified total cell numbers and bacterial gene copies and determined the community structure of bacteria using deep sequencing of the bacterial 16S rRNA gene. We show that submarine permafrost is an extreme habitat for microbial life deep below the seafloor with changing thermal and chemical conditions. Pore water chemistry revealed different pore water units reflecting the degree of marine influence and stages of permafrost thaw. Millennia after inundation by seawater, bacteria stratify into communities in permafrost, marine-affected permafrost, and seabed sediments. In contrast to pore water chemistry, the development of bacterial community structure, diversity, and abundance in submarine permafrost appears site specific, showing that both sedimentation and permafrost thaw histories strongly affect bacteria. Finally, highest microbial abundance was observed in the ice-bonded seawater unaffected but warmed permafrost of the longer inundated core, suggesting that permafrost bacterial communities exposed to submarine conditions start to proliferate millennia after warming.

  7. Chronic Inhibition of PPAR-γ Signaling Induces Endothelial Dysfunction In The Juvenile Lamb

    Science.gov (United States)

    Sharma, Shruti; Barton, Jubilee; Rafikov, Ruslan; Aggarwal, Saurabh; Kuo, Hsuan-Chang; Oishi, Peter E.; Datar, Sanjeev A.; Fineman, Jeffrey R; Black, Stephen M.

    2013-01-01

    We have recently shown that the development of endothelial dysfunction in lambs with increased pulmonary blood flow (PBF) correlates with a decrease in peroxisome proliferator activated receptor-γ (PPAR-γ) signaling. Thus, in this study we determined if the loss of PPAR-γ signaling is necessary and sufficient to induce endothelial dysfunction by exposing lambs with normal PBF to the PPAR-γ antagonist, GW9662. Two-weeks of exposure to GW9662 significantly decreased both PPAR-γ protein and activity. In addition, although eNOS protein and nitric oxide metabolites (NOx) were significantly increased, endothelial dependent pulmonary vasodilation in response to acetylcholine was attenuated, indicative of endothelial dysfunction. To elucidate whether downstream mediators of vasodilation were impaired we examined soluble guanylate cyclase (sGC)- α and β subunit protein, cGMP levels, and phosphodiesterase 5 (PDE5) protein and activity, but we found no significant changes. However, we found that peroxynitrite levels were significantly increased in GW9662-treated lambs and this correlated with a significant increase in protein kinase G-1α (PKG-1α) nitration and a reduction in PKG activity. Peroxynitrite is formed by the interaction of NO with superoxide and we found that there was a significant increase in superoxide generation in GW9662-treated lambs. Further, we identified dysfunctional mitochondria as the primary source of the increased superoxide. Finally, we found that the mitochondrial dysfunction was due to a disruption in carnitine metabolism. We conclude that loss of PPAR-γ signaling is sufficient to induce endothelial dysfunction confirming its important role in maintaining a healthy vasculature. PMID:23257346

  8. Cellular proliferation and hypusine synthesis.

    Science.gov (United States)

    Torrelio, B M; Paz, M A; Gallop, P M

    1984-10-01

    Hypusine (N(-)-(4-amino-2-hydroxybutyl) lysine), a spermidine-dependent post-translational protein modification, is synthesized by various mammalian cells in culture. Experiments described in this paper demonstrated a relationship between rates of cellular growth and the synthesis of hypusine. Cells that divide at fast rates have a high rate of hypusine synthesis. In kinetic experiments, a positive relationship is evident between the rates of protein, DNA and hypusine synthesis. Cells seeded at high density, growing non-exponentially, synthesized less hypusine than logarithmically growing cells seeded at low density. Slowing the growth rate of cells by modification of the external milieu also results in a decreased rate of hypusine synthesis. These results provide additional evidence of the association of hypusine with cell proliferation in cultured cell lines and suggest a possible role for this unusual post-translational modification in the complex macromolecular events leading to cellular growth.

  9. Proliferation resistance fuel cycle technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Ko, W. I

    1999-02-01

    The issues of dual use in nuclear technology are analysed for nuclear fuel cycle with special focus on uranium enrichment and spent fuel reprocessing which are considered as the most sensitive components in terms of vulnerability to diversion. Technical alternatives to mitigrate the vulnerability, as has been analysed in depth during the NASAP and INFCE era in the late seventies, are reviewed to characterize the DUPIC fuel cycle alternative. On the other hand, the new realities in nuclear energy including the disposition of weapon materials as a legacy of cold war are recast in an angle of nuclear proliferation resistance and safeguards with a discussion on the concept of spent fuel standard concept and its compliance with the DUPIC fuel cycle technology. (author)

  10. Proliferation resistance: issues, initiatives and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, Joseph F [Los Alamos National Laboratory

    2009-01-01

    The vision of a nuclear renaissance has highlighted the issue of proliferation resistance. The prospects for a dramatic growth in nuclear power may depend on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance. The GenIV International Forum (GIF) and others have devoted attention and resources to proliferation resistance. However, the hope of finding a way to make the peaceful uses of nuclear energy resistant to proliferation has reappeared again and again in the history of nuclear power with little practical consequence. The concept of proliferation resistance has usually focused on intrinsic (technological) as opposed to extrinsic (institutional) factors. However, if there are benefits that may yet be realized from reactors and other facilities designed to minimize proliferation risks, it is their coupling with effective safeguards and other nonproliferation measures that likely will be critical. Proliferation resistance has also traditionally been applied only to state threats. Although there are no technologies that can wholly eliminate the risk of proliferation by a determined state, technology can play a limited role in reducing state threats and perhaps in eliminating many non-state threats. These and other issues are not academic. They affect efforts to evaluate proliferation resistance, including the methodology developed by GIF's Proliferation Resistance and Physical Protection (PR&PP) Working Group as well as the proliferation resistance initiatives that are being pursued or may be developed in the future. This paper will offer a new framework for thinking about proliferation resistance issues, including the ways the output of the methodology could be developed to inform the decisions that states, the International Atomic Energy (IAEA) and others will have to make in order to fully realize the promise of a nuclear renaissance.

  11. Mitochondrial dysfunction in myofibrillar myopathy.

    Science.gov (United States)

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  12. Oral sensory dysfunction following radiotherapy.

    Science.gov (United States)

    Bearelly, Shethal; Wang, Steven J; Cheung, Steven W

    2017-10-01

    To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls. Cross-sectional cohort comparison. Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts. Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB. 3b. Laryngoscope, 127:2282-2286, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Endocrine dysfunction in hereditary hemochromatosis.

    Science.gov (United States)

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

  14. Temporomandibular dysfunction and headache disorder.

    Science.gov (United States)

    Speciali, José G; Dach, Fabíola

    2015-02-01

    It has been well established that primary headaches (especially migraine, chronic migraine, and tension-type headache) and temporomandibular dysfunction (TMD) are comorbid diseases, with the presence of one of them in a patient increasing the prevalence of the others. The relationship between the 2 diseases may involve the sharing of common physiopathological aspects. Studies about the treatment of this disease association have shown that a simultaneous therapeutic approach to the 2 diseases is more effective than the separate treatment of each. As a consequence, specialists in orofacial pain are now required to know the criteria for the diagnosis of headaches, and headache physicians are required to know the semiologic aspects of orofacial pain. Nevertheless, a headache may be attributed to TMD, instead be an association of 2 problems - TMD and primary headaches - in these cases a secondary headache, described in item 11.7 of the International Classification of Headache Disorders, is still a controversial topic. Attempts to determine the existence of this secondary headache with a specific or suggestive phenotype have been frustrated. The conclusion that can be reached based on the few studies published thus far is that this headache has a preferential unilateral or bilateral temporal location and migraine-like or tension-type headache-like clinical characteristics. In the present review, we will consider the main aspects of the TMD-headache relationship, that is, comorbidity of primary headaches and TMD and clinical aspects of the headaches attributed to TMD from the viewpoint of the International Headache Society and of a group of specialists in orofacial pain. This paper aims to explore our understanding of the association between TMD and headaches in general and migraine in particular.

  15. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Gui-Zhen [Department of Health, Linyi People' s Hospital, Shandong University, Shandong (China); Tian, Wei [Department of Nursing, Linyi Oncosurgical Hospital, Shandong (China); Fu, Hai-Tao [Department of Ophthalmology, Linyi People' s Hospital, Shandong University, Shandong (China); Li, Chao-Peng, E-mail: lcpcn@163.com [Eye Institute of Xuzhou, Jiangsu (China); Liu, Ban, E-mail: liuban@126.com [Department of Cardiology, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai (China)

    2016-02-26

    Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.

  16. Erectile Dysfunction: Viagra and Other Oral Medications

    Science.gov (United States)

    ... loss or vision loss. Some men have had sudden loss of hearing or loss of vision after taking one of ... taking an oral erectile dysfunction medication and have sudden loss of hearing or vision, seek prompt medical attention. An erection ...

  17. Questionnaires for assessment of female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Rellini, Alessandra; Pfaus, James G;

    2011-01-01

    There are many methods to evaluate female sexual function and dysfunction (FSD) in clinical and research settings, including questionnaires, structured interviews, and detailed case histories. Of these, questionnaires have become an easy first choice to screen individuals into different categories...

  18. Animal models of brain dysfunction in phenylketonuria

    NARCIS (Netherlands)

    Martynyuk, A. E.; van Spronsen, F. J.; Van der Zee, E. A.

    2010-01-01

    Phenylketonuria (PKU) is a metabolic disorder that results in significant brain dysfunction if untreated. Although phenylalanine restricted diets instituted at birth have clearly improved PKU outcomes, neuropsychological deficits and neurological changes still represent substantial problems. The spe

  19. Erectile Dysfunction: A Sign of Heart Disease?

    Science.gov (United States)

    ... High cholesterol. A high level of low-density lipoprotein (LDL, or "bad") cholesterol can lead to atherosclerosis. ... Erectile-Dysfunction-and-High-Blood-Pressure_UCM_301827_Article.jsp. Accessed July 8, 2015. Ma RCW, et ...

  20. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was

  1. Sexual dysfunction in women with epilepsy.

    Science.gov (United States)

    Harden, Cynthia L

    2008-03-01

    Sexual dysfunction in women with epilepsy (WWE) is an important comorbidity. A significant minority of WWE have markedly decreased sexual interest and it appears that orgasmic dysfunction occurs more frequently in WWE than in control women. Enzyme-inducing antiepileptic drugs can adversely affect sexual functioning by decreasing bioactive testosterone levels. Temporal lobe epilepsy of right-sided versus left-sided origin may also be a risk factor for sexual dysfunction. In addition to these factors, emerging evidence suggests that the serotonin transporter protein is related to temporal lobe epilepsy and it is postulated that this transporter may play a role in altered sexual functioning in epilepsy, perhaps through the serotonergic effects of antiepileptic drugs (AEDs). Strategies for modifying the contributors to sexual dysfunction in WWE will be discussed as well as the role of the neurologist in initiating management of this challenging comorbidity.

  2. [Endothelial dysfunction in pathogenesis of duodenal ulcer].

    Science.gov (United States)

    Oparin, A G; Oparin, A A

    2002-01-01

    It is shown that in patients with ulcer associated with Helicobacter pylori (HP) there is a close correlation between the severity of the lesion of gastroduodenal protective mucous barrier and that of endothelial dysfunction manifesting in elevated level of endothelin-1, serum levels of TBK-active products, inhibition of blood flow and narrowing of the celiac trunk. The correlation becomes stronger with expanding contamination of gastroduodenal mucosa with HP. Thus, HP may participate in breaking the protective mucous barrier in endothelial dysfunction.

  3. Modeling Cognitive Dysfunction in Neurofibromatosis-1

    OpenAIRE

    Diggs-Andrews, Kelly A.; David H Gutmann

    2013-01-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, Neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and mechanistically dissect the molecular and cellular bases underlying cognitive dysfunction. In this review, we ...

  4. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging.Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction fol...

  5. Trichotillomania In A Patient With Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Aswathi Krishna

    2016-10-01

    Full Text Available Trichotillomania is a chronic psychiatric disorder characterized by pulling out one's own hair, which results in an obvious loss of hair. Hair pulling was first described in Henri Allopeau in 1889. The term "trichotillomania" comes from the Greek words "thrix" - hair, "tillein" - to pull and "Mania" madness or frenzy. 30 year old man presented with complaints of hairpulling behavior and associated erectile dysfunction. His hairpulling behavior improved on treating his sexual dysfunction.

  6. Functional and Dysfunctional rumination in alcohol dependence

    OpenAIRE

    Grynberg, Delphine; Briane, Yasmine; Timary, Philippe De; Maurage, Pierre; 16th International Society of Addiction Medicine Annual Meeting

    2014-01-01

    Previous findings have shown that rumination predicts alcohol abuse independently of depression. However, the literature does not inform about the relationships between alcohol dependence and functional and dysfunctional rumination. It has indeed been suggested that there exist a functional form of rumination(concrete thinking) and a dysfunctional form of rumination (abstract thinking). In this study, our aim is to evaluate if alcohol dependence is similarly associated with functional/constru...

  7. Eosinophilic gastroenteritis with ascites and hepatic dysfunction

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Jin-Ming Chen; Qin Du

    2007-01-01

    Eosinophilic gastroenteritis is a rare gastrointestinal disorder with eosinophilic infiltration of the gastrointestinal wall and various gastrointestinal dysfunctions. Diagnosis requires a high index of suspicion and exclusion of various disorders that are associated with peripheral eosinophilia.We report a case of eosinophilic gastroenteritis, which had features of the predominant subserosal type presenting with ascites and hepatic dysfunction, and which responded to a course of low-dose steroid.

  8. SECONDARY MITOCHONDRIAL DYSFUNCTION IN ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    Y. A. Vasyuk

    2015-12-01

    Full Text Available So-called “metabolic” direction has been developing intensively during last decades. Its aim is the theoretical and practical analysis of the role of metabolic disorders in initiation and progression of many diseases. The pathogenic peculiarities of acute coronary syndrome (ACS which result in developing of secondary mitochondrial dysfunction are considered as a subject of this review. The methods of laboratory diagnosis of mitochondrial dysfunction and possibilities of its pharmaceutical correction in patients with ACS are reviewed.

  9. Endothelial dysfunction and inflammation in asymptomatic proteinuria

    OpenAIRE

    Paisley, K.E.; Beaman, M; Tooke, J. E.; Mohamed-Ali, V; Lowe, G. D. O.; Shore, A C

    2003-01-01

    Background. Proteinuria is associated with vascular risk and a systemic increase in vascular permeability. Endothelial dysfunction occurs early in atherosclerosis and modulates vascular permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular permeability in proteinuria reflects systemic endothelial dysfunction and chronic inflammation. Methods. Twenty-one patients with asymptomatic proteinuria (1.29 g/24 h; range 0.18 to 3.17...

  10. Temporomandibular Joint Dysfunction: A Dental Overview

    OpenAIRE

    Hillier, Clyde D.

    1985-01-01

    Temporomandibular joint dysfunction is common and often acutely painful. Because of the large and diverse symptom complex created by this disorder, patients frequently first seek relief from their physician rather than their dentist. In this article temporomandibular joint (TMJ) dysfunction is defined and the presenting signs and symptoms are discussed. Their etiology is described in relation to the anatomy of the temporomandibular joint. Examination techniques can help in the differential di...

  11. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  12. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  13. Peri-operative cognitive dysfunction and protection

    DEFF Research Database (Denmark)

    Steinmetz, J; Rasmussen, L S

    2016-01-01

    Cognition may decline after surgery. Postoperative delirium, especially when hyperactive, may be easily recognised, whereas cognitive dysfunction is subtle and can only be detected using neuropsychological tests. The causes for these two conditions are largely unknown, although they share risk...... reduce the rate of delirium in the elderly, but in spite of promising findings in animal experiments, no intervention reduces postoperative cognitive dysfunction in humans....

  14. Radiology of bacterial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Vilar, Jose E-mail: vilar_jlu@gva.es; Domingo, Maria Luisa; Soto, Cristina; Cogollos, Jonathan

    2004-08-01

    Bacterial pneumonia is commonly encountered in clinical practice. Radiology plays a prominent role in the evaluation of pneumonia. Chest radiography is the most commonly used imaging tool in pneumonias due to its availability and excellent cost benefit ratio. CT should be used in unresolved cases or when complications of pneumonia are suspected. The main applications of radiology in pneumonia are oriented to detection, characterisation and follow-up, especially regarding complications. The classical classification of pneumonias into lobar and bronchial pneumonia has been abandoned for a more clinical classification. Thus, bacterial pneumonias are typified into three main groups: Community acquired pneumonia (CAD), Aspiration pneumonia and Nosocomial pneumonia (NP).The usual pattern of CAD is that of the previously called lobar pneumonia; an air-space consolidation limited to one lobe or segment. Nevertheless, the radiographic patterns of CAD may be variable and are often related to the causative agent. Aspiration pneumonia generally involves the lower lobes with bilateral multicentric opacities. Nosocomial Pneumonia (NP) occurs in hospitalised patients. The importance of NP is related to its high mortality and, thus, the need to obtain a prompt diagnosis. The role of imaging in NP is limited but decisive. The most valuable information is when the chest radiographs are negative and rule out pneumonia. The radiographic patterns of NP are very variable, most commonly showing diffuse multifocal involvement and pleural effusion. Imaging plays also an important role in the detection and evaluation of complications of bacterial pneumonias. In many of these cases, especially in hospitalised patients, chest CT must be obtained in order to better depict these associate findings.

  15. Bacterial mitotic machineries

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Ebersbach, Gitte;

    2004-01-01

    Here, we review recent progress that yields fundamental new insight into the molecular mechanisms behind plasmid and chromosome segregation in prokaryotic cells. In particular, we describe how prokaryotic actin homologs form mitotic machineries that segregate DNA before cell division. Thus, the Par......M protein of plasmid R1 forms F actin-like filaments that separate and move plasmid DNA from mid-cell to the cell poles. Evidence from three different laboratories indicate that the morphogenetic MreB protein may be involved in segregation of the bacterial chromosome....

  16. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  17. Spontaneous bacterial peritonitis

    Directory of Open Access Journals (Sweden)

    Al Amri Saleh

    1995-01-01

    Full Text Available Spontaneous bacterial peritonitis (SBP is an infection of the ascitic fluid without obvious intra-abdominal source of sepsis; usually complicates advanced liver disease. The pathogenesis of the disease is multifactorial: low ascitic protein-content, which reflects defi-cient ascitic fluid complement and hence, reduced opsonic activity is thought to be the most important pathogenic factor. Frequent and prolonged bacteremia has been considered as another pertinent cause of SBP. This disease is associated with high mortality and recurrence. Therefore, orompt recognition and institution of therapy and plan of prophylaxis is vital.

  18. Thyroid hormone dysfunction during pregnancy: A review

    Science.gov (United States)

    Alemu, Aynadis; Terefe, Betelihem; Abebe, Molla; Biadgo, Belete

    2016-01-01

    Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, preeclampsia, preterm delivery and reduced intellectual function in the offspring. Epidemiological data have shown the significant role of maternal thyroid hormone in fetal neurologic development and maternal health. It has been suggested that the deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. Pregnancy poses an important challenge to the maternal thyroid gland as hormone requirements are increased during gestation as a result of an increase in thyroid- binding globulin, the stimulatory effect of HCG on TSH receptors, and increased peripheral thyroid hormone requirements. Maternal thyroid dysfunction is associated with increased risk for early abortion, preterm delivery, neonatal morbidity and other obstetrical complications. Early diagnosis for thyroid dysfunction of pregnant women and treatment of thyroid dysfunction during pregnancy is important and cost effective to avoid both fetal and maternal complications secondary to thyroid dysfunction. Therefore the aim of this review was to assess the thyroid function changes occurring during pregnancy, the different disorders with their maternal and fetal implications, the laboratory diagnosis and the best ways of management of these conditions. PMID:27981252

  19. Mitochondrial Dysfunction in Lysosomal Storage Disorders

    Directory of Open Access Journals (Sweden)

    Mario de la Mata

    2016-10-01

    Full Text Available Lysosomal storage diseases (LSDs describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS, where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm, diminished ATP production and increased generation of reactive oxygen species (ROS. Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD, the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase. Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer and glucosylsphingosine (GlcSph in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.

  20. Vascular endothelial dysfunction and pharmacological treatment

    Institute of Scientific and Technical Information of China (English)

    Jin; Bo; Su

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smo-king, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide(NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease.

  1. Rho kinase regulates induction of T-cell immune dysfunction in abdominal sepsis.

    Science.gov (United States)

    Hasan, Z; Palani, K; Zhang, S; Lepsenyi, M; Hwaiz, R; Rahman, M; Syk, I; Jeppsson, B; Thorlacius, Henrik

    2013-07-01

    T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present study, we hypothesized that Rho kinase signaling might regulate induction of T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were treated with the specific Rho kinase inhibitor Y-27632 (5 mg/kg of body weight) prior to cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation, and percentage of regulatory T cells (CD4(+) CD25(+) Foxp3(+)) were determined by flow cytometry. Formation of gamma interferon (IFN-γ) and interleukin 4 (IL-4) in the spleen and plasma levels of HMBG1, IL-17, and IL-6 were quantified by use of enzyme-linked immunosorbent assay (ELISA). It was found that CLP evoked apoptosis and decreased proliferation in splenic CD4 T cells. Inhibition of Rho kinase activity decreased apoptosis and enhanced proliferation of CD4 T cells in septic animals. In addition, CLP-evoked induction of regulatory T cells in the spleen was abolished by Rho kinase inhibition. CLP reduced the levels of IFN-γ and IL-4 in the spleen. Pretreatment with Y-27632 inhibited the sepsis-induced decrease in IFN-γ but not IL-4 formation in the spleen. CLP increased plasma levels of high-mobility group box 1 (HMGB1) by 20-fold and IL-6 by 19-fold. Inhibition of Rho kinase decreased this CLP-evoked increase of HMGB1, IL-6, and IL-17 levels in the plasma by more than 60%, suggesting that Rho kinase regulates systemic inflammation in sepsis. Moreover, we observed that pretreatment with Y-27632 abolished CLP-induced bacteremia. Together, our novel findings indicate that Rho kinase is a powerful regulator of T-cell immune dysfunction in abdominal sepsis. Thus, targeting Rho kinase signaling might be a useful strategy to improve T-cell immunity in patients with abdominal sepsis.

  2. Macrophage peroxisome proliferator-activated receptor γ deficiency delays skin wound healing through impairing apoptotic cell clearance in mice

    OpenAIRE

    Chen, H.; Shi, R.; Luo, B.; Yang, X.; Qiu, L; Xiong, J.; Jiang, M; Y. Liu; Zhang, Z; Wu, Y

    2015-01-01

    Skin wound macrophages are key regulators of skin repair and their dysfunction causes chronic, non-healing skin wounds. Peroxisome proliferator-activated receptor gamma (PPARγ) regulates pleiotropic functions of macrophages, but its contribution in skin wound healing is poorly defined. We observed that macrophage PPARγ expression was upregulated during skin wound healing. Furthermore, macrophage PPARγ deficiency (PPARγ-knock out (KO)) mice exhibited impaired skin wound healing with reduced co...

  3. ChREBP Mediates Glucose Repression of Peroxisome Proliferator-activated Receptor {alpha} Expression in Pancreatic {beta}-Cells

    DEFF Research Database (Denmark)

    Boergesen, Michael; Poulsen, Lars la Cour; Schmidt, Søren Fisker;

    2011-01-01

    Chronic exposure to elevated levels of glucose and fatty acids leads to dysfunction of pancreatic β-cells by mechanisms that are only partly understood. The transcription factor peroxisome proliferator-activated receptor α (PPARα) is an important regulator of genes involved in fatty acid metaboli...... of glucose repression of PPARα gene expression in pancreatic β-cells, suggesting that ChREBP may be important for glucose suppression of the fatty acid oxidation capacity of β-cells....

  4. Proliferation after the Iraq war; La proliferation apres la guerre d'Irak

    Energy Technology Data Exchange (ETDEWEB)

    Daguzan, J.F

    2004-09-15

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  5. Arterial ageing: from endothelial dysfunction to vascular calcification.

    Science.gov (United States)

    Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

    2017-05-01

    Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  6. Dermatitis herpetiformis and neurological dysfunction.

    Science.gov (United States)

    Wills, A J; Turner, B; Lock, R J; Johnston, S L; Unsworth, D J; Fry, L

    2002-02-01

    Dermatitis herpetiformis and coeliac disease are gluten sensitive diseases, which have common immunopathological and genetic mechanisms. Neuropsychiatric complications have been reported in up to 26% of patients with coeliac disease. This is probably an overestimate, because of the chance associations with some common neurological conditions such as epilepsy. The pathogenesis is speculative but it has been postulated that gluten is neurotoxic possibly via immune mechanisms. The frequency of neurological dysfunction in patients with dermatitis herpetiformis has not been characterised. Patients with dermatitis herpetiformis might be expected to be particularly susceptible to neuronal damage as some continue to consume gluten when their dermatological symptoms are controlled by dapsone. Thirty five patients were recruited with dermatitis herpetiformis from dermatology clinics at St Mary's Hospital, London and Queen's Medical Centre, Nottingham and investigated for evidence of neurological abnormality. All patients underwent a full neurological examination and were asked about their neurological and general medical history by means of a structured questionnaire. Serum samples were taken and screened for the presence of anti-neuronal antibodies (anti-Hu and Yo) as well as anti-gliadin (IgA and G) anti-endomysial (IgA), and anti-tissue transglutaminase (IgA) antibodies. Neurophysiological tests were carried out where appropriate. Only two patients were identified with unexplained neurological abnormalities (one essential tremor, and one chorea). Two other patients had a history of migraine. The patient with chorea also had borderline/equivocally positive anti-Hu antibodies by immunofluorescence assay. All other samples were negative for anti-neuronal antibodies. Fifteen patients were positive for anti-gliadin antibodies (IgA and/or IgG), four for anti-endomysial antibodies (monkey oesophagus or umbilical cord), and six for anti-tissue transglutaminase antibodies. The

  7. Is it time to target gut dysbiosis and immune dysfunction in the therapy of hepatic encephalopathy?

    Science.gov (United States)

    Shawcross, Debbie L

    2015-05-01

    The development of overt hepatic encephalopathy (HE) in a patient with cirrhosis confers a damning prognosis with a 1-year mortality approaching 64%. This complex neuropsychiatric syndrome arises as a consequence of a dysfunctional gut-liver-brain axis. HE has been largely neglected over the past 30 years, with the reliance on therapies aimed at lowering ammonia production or increasing metabolism following the seminal observation that the hepatic urea cycle is the major mammalian ammonia detoxification pathway and is key in the pathogenesis of HE. The relationship with ammonia is more clear-cut in acute liver failure; but in cirrhosis, it has become apparent that inflammation is a key driver and that a disrupted microbiome resulting in gut dysbiosis, bacterial overgrowth and translocation, systemic endotoxemia and immune dysfunction may be more important drivers. Therefore, it is important to re-focus our efforts into developing therapies that modulate the disrupted microbiome or alleviating its downstream consequences.

  8. Antimicrobials for bacterial bioterrorism agents.

    Science.gov (United States)

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  9. Control of cell proliferation by Myc

    DEFF Research Database (Denmark)

    Bouchard, C; Staller, P; Eilers, M

    1998-01-01

    Myc proteins are key regulators of mammalian cell proliferation. They are transcription factors that activate genes as part of a heterodimeric complex with the protein Max. This review summarizes recent progress in understanding how Myc stimulates cell proliferation and how this might contribute...

  10. Corneal cellular proliferation and wound healing

    OpenAIRE

    Gan, Lisha

    2000-01-01

    Background. Cellular proliferation plays an important role in both physiological and pathological processes. Epithelial hyperplasia in the epithelium, excessive scar formation in retrocorneal membrane formation and neovascularization are examples of excessive proliferation of cornea cells. Lack of proliferative ability causes corneal degeneration. The degree of proliferative and metabolic activity will directly influence corneal transparency and very evidently refractive res...

  11. Teaching Activities on Horizontal Nuclear Proliferation.

    Science.gov (United States)

    Zola, John

    1990-01-01

    Provides learning activities concerning the horizontal proliferation of nuclear weapons. Includes step-by-step directions for four activities: (1) the life cycle of nuclear weapons; (2) nuclear nonproliferation: pros and cons; (3) the nuclear power/nuclear weapons connection; and (4) managing nuclear proliferation. (NL)

  12. Nuclear Proliferation as a Global Values Issue.

    Science.gov (United States)

    Nelson, Jack L.

    1990-01-01

    Presents a classroom activity designed to involve students in critical thinking and values inquiry concerning the horizontal nuclear proliferation. Provides a set of global values, explaining the conflict between them and nuclear proliferation. Uses indicators, hypothesis development, and testing. Provides sources for material evidence to use in…

  13. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1995-11-17

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

  14. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1995-11-17

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

  15. Proliferation resistance of small modular reactors fuels

    Energy Technology Data Exchange (ETDEWEB)

    Polidoro, F.; Parozzi, F. [RSE - Ricerca sul Sistema Energetico,Via Rubattino 54, 20134, Milano (Italy); Fassnacht, F.; Kuett, M.; Englert, M. [IANUS, Darmstadt University of Technology, Alexanderstr. 35, D-64283 Darmstadt (Germany)

    2013-07-01

    In this paper the proliferation resistance of different types of Small Modular Reactors (SMRs) has been examined and classified with criteria available in the literature. In the first part of the study, the level of proliferation attractiveness of traditional low-enriched UO{sub 2} and MOX fuels to be used in SMRs based on pressurized water technology has been analyzed. On the basis of numerical simulations both cores show significant proliferation risks. Although the MOX core is less proliferation prone in comparison to the UO{sub 2} core, it still can be highly attractive for diversion or undeclared production of nuclear material. In the second part of the paper, calculations to assess the proliferation attractiveness of fuel in typical small sodium cooled fast reactor show that proliferation risks from spent fuel cannot be neglected. The core contains a highly attractive plutonium composition during the whole life cycle. Despite some aspects of the design like the sealed core that enables easy detection of unauthorized withdrawal of fissile material and enhances proliferation resistance, in case of open Non-Proliferation Treaty break-out, weapon-grade plutonium in sufficient quantities could be extracted from the reactor core.

  16. Bladder Dysfunction and Urinary Incontinence

    Directory of Open Access Journals (Sweden)

    F. faizi

    2009-01-01

    Full Text Available   "nIn the name of God. Dear colleagues, ladies and gentlemen, it is a great honor to be here. Bladder dysfunction is serious enough to seek serious help. If you may know I am working in a private clinic which it is impossible to follow the patients so this lecture is based on unusual and rare cases who came to me. Bladder dysfunction (BD is common among 30% of young and old people who are suffering from it, however it is more common in old ages. According to a research, women are more involved as in men which prostate has a role is more common. The usual cases were: "n1. A young girl, aged 20, who had to wake up five times during the night to micturate. "n2. Also a lady said when I roll in bed I wet myself. "n3. A young lady who always had to use a pad. "n4. A man said I can’t use underground. "n5. I cannot go out since I have to micturate every hour. "n6. One said I have to wake up every hour at night. "n7. Young people say we have to micturate 3-4 times at night. "n8. A young man said as soon as I feel to micturate I empty my bladder before I’ve reached the WC and I wet myself to the ankle, how could I have a job? "n9. Some women wet themselves when they cough. "nIn order to know and diagnosis, the physiology of bladder function must be known. "nThe bladder is divided into two parts: "nThe Dom, which is innervated by Beta-Adrenergic. It relaxes the bladder in order to comply the urine. "nFrom the orifice of the urether and posterior ridge of the trigon to the bladder neck or internal sphincter. The prostatic urethra plays a major role in conti- nence. It has two parts,   "n1: From the bladder neck to V.M. this is enclaved by extension of detrusor muscles like a sleeve. These muscles contract during ejaculation to prevent retrograde ejaculation. "nDistal urethra from V.M. to the external sphincter which is covered by voluntary muscles. "nThe internal pressure of the urethra is higher than the bladder. If the pressure of the bladder rises

  17. The endocannabinoid system drives neural progenitor proliferation.

    Science.gov (United States)

    Aguado, Tania; Monory, Krisztina; Palazuelos, Javier; Stella, Nephi; Cravatt, Benjamin; Lutz, Beat; Marsicano, Giovanni; Kokaia, Zaal; Guzmán, Manuel; Galve-Roperh, Ismael

    2005-10-01

    The discovery of multipotent neural progenitor (NP) cells has provided strong support for the existence of neurogenesis in the adult brain. However, the signals controlling NP proliferation remain elusive. Endocannabinoids, the endogenous counterparts of marijuana-derived cannabinoids, act as neuromodulators via presynaptic CB1 receptors and also control neural cell death and survival. Here we show that progenitor cells express a functional endocannabinoid system that actively regulates cell proliferation both in vitro and in vivo. Specifically, NPs produce endocannabinoids and express the CB1 receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). CB1 receptor activation promotes cell proliferation and neurosphere generation, an action that is abrogated in CB1-deficient NPs. Accordingly, proliferation of hippocampal NPs is increased in FAAH-deficient mice. Our results demonstrate that endocannabinoids constitute a new group of signaling cues that regulate NP proliferation and thus open novel therapeutic avenues for manipulation of NP cell fate in the adult brain.

  18. Ptpmt1 induced by HIF-2α regulates the proliferation and glucose metabolism in erythroleukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qin-Qin [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China); Qinghai Provincial People' s Hospital, Xining (China); Xiao, Feng-Jun; Sun, Hui-Yan [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Shi, Xue-Feng [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China); Qinghai Provincial People' s Hospital, Xining (China); Wang, Hua; Yang, Yue-Feng; Li, Yu-Xiang [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Wang, Li-Sheng, E-mail: wangls@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Ge, Ri-Li, E-mail: geriligao@hotmail.com [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China)

    2016-03-18

    Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. - Highlights: • Hypoxia induces upregulation of HIF-1α, HIF-2α and Ptpmt1; HIF-2a induces Ptpmt1 upregulation in TF-1 cells. • PTPMT-1 inhibition reduces growth and induces apoptosis of TF-1 cells. • PTPMT1 inhibition downregulates Glut-1, Glut-3 expression and reduces glucose consumption.

  19. Apraxia and motor dysfunction in corticobasal syndrome.

    Directory of Open Access Journals (Sweden)

    James R Burrell

    Full Text Available BACKGROUND: Corticobasal syndrome (CBS is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM, is associated with motor system dysfunction and limb apraxia in CBS. METHODS: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R, with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. RESULTS: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices. CONCLUSIONS: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and

  20. Apraxia and motor dysfunction in corticobasal syndrome.

    Science.gov (United States)

    Burrell, James R; Hornberger, Michael; Vucic, Steve; Kiernan, Matthew C; Hodges, John R

    2014-01-01

    Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS. Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold apraxia correlated with atrophy of the pre-motor and parietal cortices. Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy.

  1. Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood.

    Science.gov (United States)

    Chen, Z P; Cai, Y; Phillipson, J D

    1994-12-01

    Three in-vitro assays have been adopted to examine the cytotoxicity and anti-bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to examine its effect upon the proliferation of endothelial cells. The sap was found not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a potent anti-bacterial activity. The sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

  2. Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2016-09-01

    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

  3. Cigarette smoke-induced disruption of pulmonary barrier and bacterial translocation drive tumor-associated inflammation and growth.

    Science.gov (United States)

    Jungnickel, C; Wonnenberg, B; Karabiber, O; Wolf, A; Voss, M; Wolf, L; Honecker, A; Kamyschnikow, A; Herr, C; Bals, R; Beisswenger, C

    2015-09-15

    Microorganisms have an important role in tumorgenesis by the induction of inflammation and by a direct impact on tumor cells. Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and microbial colonization. We asked whether bacterial pathogens act as tumor promoters during CS-induced pulmonary inflammation. In a metastatic lung cancer (LC) model, Lewis lung carcinoma (LLC) cells were injected in mice to initiate the growth of tumors in the lung. Exposure to the combination of cigarette smoke (CS) and nontypeable Haemophilus influenzae (NTHi) synergistically increased metastatic growth. Lung levels of albumin and LDH, translocation of bacterial factors into tumor tissue, tumor inflammation, and tumor proliferation were significantly increased in mice exposed to CS in combination with NTHi. Bacterial pathogens increased the proliferation of cultured LLC cells and human cancer cell lines. Metastatic growth induced by the exposure to CS in combination with NTHi was reduced in mice deficient for IL-17. Our data provide evidence that CS-induced loss of pulmonary barrier integrity allows bacterial factors to translocate into tumor tissue and to regulate tumor-associated inflammation and tumor proliferation. Translocation of bacterial factors in tumor tissue links CS-induced inflammation with tumor proliferation.

  4. Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

    OpenAIRE

    DeLay, Kenneth Jackson; Nutt,Max; McVary, Kevin T.

    2016-01-01

    The link between lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and sexual dysfunction is well established. Sexual dysfunction can encompass both ejaculatory dysfunction (EjD) and erectile dysfunction (ED). Ejaculatory dysfunction can consist of premature ejaculation, delayed ejaculation, retrograde ejaculation, anejaculation, decreased force of ejaculation and pain upon ejaculation. The impact of different medical and surgical therapies on ejaculatory fun...

  5. Bacterial polyhydroxyalkanoates: Still fabulous?

    Science.gov (United States)

    Możejko-Ciesielska, Justyna; Kiewisz, Robert

    2016-11-01

    Bacterial polyhydroxyalkanoates (PHA) are polyesters accumulated as carbon and energy storage materials under limited growth conditions in the presence of excess carbon sources. They have been developed as biomaterials with unique properties for the past many years being considered as a potential substitute for conventional non-degradable plastics. Due to the increasing concern towards global climate change, depleting petroleum resource and problems with an utilization of a growing number of synthetic plastics, PHAs have gained much more attention from industry and research. These environmentally friendly microbial polymers have great potential in biomedical, agricultural, and industrial applications. However, their production on a large scale is still limited. This paper describes the backgrounds of PHAs and discussed the current state of knowledge on the polyhydroxyalkanoates. Ability of bacteria to convert different carbon sources to PHAs, the opportunities and challenges of their introduction to global market as valuable renewable products have been also discussed.

  6. Epigenetics and bacterial infections.

    Science.gov (United States)

    Bierne, Hélène; Hamon, Mélanie; Cossart, Pascale

    2012-12-01

    Epigenetic mechanisms regulate expression of the genome to generate various cell types during development or orchestrate cellular responses to external stimuli. Recent studies highlight that bacteria can affect the chromatin structure and transcriptional program of host cells by influencing diverse epigenetic factors (i.e., histone modifications, DNA methylation, chromatin-associated complexes, noncoding RNAs, and RNA splicing factors). In this article, we first review the molecular bases of the epigenetic language and then describe the current state of research regarding how bacteria can alter epigenetic marks and machineries. Bacterial-induced epigenetic deregulations may affect host cell function either to promote host defense or to allow pathogen persistence. Thus, pathogenic bacteria can be considered as potential epimutagens able to reshape the epigenome. Their effects might generate specific, long-lasting imprints on host cells, leading to a memory of infection that influences immunity and might be at the origin of unexplained diseases.

  7. Pathophysiology of muscle dysfunction in COPD.

    Science.gov (United States)

    Gea, Joaquim; Agustí, Alvar; Roca, Josep

    2013-05-01

    Muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD) and may involve both respiratory and locomotor (peripheral) muscles. The loss of strength and/or endurance in the former can lead to ventilatory insufficiency, whereas in the latter it limits exercise capacity and activities of daily life. Muscle dysfunction is the consequence of complex interactions between local and systemic factors, frequently coexisting in COPD patients. Pulmonary hyperinflation along with the increase in work of breathing that occur in COPD appear as the main contributing factors to respiratory muscle dysfunction. By contrast, deconditioning seems to play a key role in peripheral muscle dysfunction. However, additional systemic factors, including tobacco smoking, systemic inflammation, exercise, exacerbations, nutritional and gas exchange abnormalities, anabolic insufficiency, comorbidities and drugs, can also influence the function of both respiratory and peripheral muscles, by inducing modifications in their local microenvironment. Under all these circumstances, protein metabolism imbalance, oxidative stress, inflammatory events, as well as muscle injury may occur, determining the final structure and modulating the function of different muscle groups. Respiratory muscles show signs of injury as well as an increase in several elements involved in aerobic metabolism (proportion of type I fibers, capillary density, and aerobic enzyme activity) whereas limb muscles exhibit a loss of the same elements, injury, and a reduction in fiber size. In the present review we examine the current state of the art of the pathophysiology of muscle dysfunction in COPD.

  8. From "bacterial-toxin treated simutaneously" to "four syndromes and four methods"——improvement and integration of the syndrome-differentating thinking for treating multiple organ dysfunction syndrome with integrated traditional Chinese and western medicine%从"菌毒并治"到"四证四法"——关于中西医结合治疗多器官功能障碍综合征辨证思路的深入与完善

    Institute of Scientific and Technical Information of China (English)

    曹书华; 王今达; 李银平

    2005-01-01

    @@ 多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)发病急,病情进展迅速,病死率极高,是危重病医学领域内的尖端课题.天津市急救医学研究所自20世纪70年代起就开始了以中西医结合方法治疗MODS的探索.

  9. Vegetative Proliferation and Secondary Proliferated Inflorescences Development in Grass Ischaemum barbatum Retz

    Institute of Scientific and Technical Information of China (English)

    Guo-Hua Ma; Xue-Lin Huang; Bunn Eric

    2006-01-01

    We report the vegetative proliferation and new phenomenon of "secondary proliferated inflorescences" in the grass Ischaemum barbatum Retz, as determined by anatomical analysis of prepared sections of inflorescences. Leaves and shoots could be developed from the original spikelets of inflorescences and plantlets developed when these shoots were transplanted to moist soil. "Secondary proliferated inflorescences" is the first name here because some inflorescences that developed inadequacy are grown from the spikelet on the mother inflorescence. Our investigation showed that this form of vegetative proliferation and secondary proliferated inflorescences development of I. barbatum has arisen following late autumn fires of the previous year. It is suggested that the sudden onset of a fire could lead to a hormone imbalance or a chemical induction, which results in ephemeral vegetative proliferation even secondary proliferated inflorescences development in wild populations.

  10. Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins.

    Science.gov (United States)

    Hoppe, T; Kraus, D; Novak, N; Probstmeier, R; Frentzen, M; Wenghoefer, M; Jepsen, S; Winter, J

    2016-10-01

    The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.

  11. Harmine stimulates proliferation of human neural progenitors

    Science.gov (United States)

    Dakic, Vanja; Maciel, Renata de Moraes; Drummond, Hannah; Nascimento, Juliana M.; Trindade, Pablo

    2016-01-01

    Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo. PMID:27957390

  12. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  13. Bacterial sepsis in the neonate.

    Science.gov (United States)

    Rubarth, Lori Baas; Christensen, Carla M; Riley, Cheryl

    2017-09-21

    Neonatal bacterial infections leading to sepsis occur frequently in the first few days or weeks of life. NPs must be able to recognize the early signs of sepsis and understand the need for rapid evaluation and treatment. This article discusses antibiotic treatments for various types and locations of bacterial infections and sepsis in the neonate.

  14. Pelvic radiotherapy and sexual dysfunction in women

    DEFF Research Database (Denmark)

    Jensen, Pernille Tine; Froeding, Ligita Paskeviciute

    2015-01-01

    of life (QOL) issues; sexual functioning has proved to be one of the most important aspects of concern in long-term survivors. METHODS: An updated literature search in PubMed was performed on pelvic radiotherapy and female sexual functioning/dysfunction. Studies on gynaecological, urological...... and gastrointestinal cancers were included. The focus was on the period from 2010 to 2014, on studies using PROs, on potential randomized controlled trials (RCTs) where female sexual dysfunction (FSD) at least constituted a secondary outcome, and on studies reporting from modern radiotherapy modalities. RESULTS...... during the next five years. Several newer studies confirm that health care professionals are still reluctant to discuss treatment induced sexual dysfunction with patients. CONCLUSIONS: Pelvic radiotherapy has a persistent deteriorating effect on the vaginal mucosa impacting negatively on the sexual...

  15. Pain related sexual dysfunction after inguinal herniorrhaphy

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Møhl, Bo; Bay-Nielsen, Morten

    2006-01-01

    To determine the incidence of pain related sexual dysfunction 1 year after inguinal herniorrhaphy and to assess the impact pain has on sexual function. In contrast to the well-described about 10% risk of chronic wound related pain after inguinal herniorrhaphy, chronic genital pain, dysejaculation......, and sexual dysfunction have only been described sporadically. The aim was therefore to describe these symptoms in a questionnaire study. A nationwide detailed questionnaire study in September 2004 of pain related sexual dysfunction in all men aged 18-40 years undergoing inguinal herniorrhaphy between October...... 2002 and June 2003 (n=1015) based upon the nationwide Danish Hernia Database collaboration. The response rate was 68.4%. Combined frequent and moderate or severe pain from the previous hernia site during activity was reported by 187 patients (18.4%). Pain during sexual activity was reported by 224...

  16. Stent graft placement for dysfunctional arteriovenous grafts

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Shin, Byung Seok; Ohm, Joon Young; Ahn, Moon Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2015-07-15

    This study aimed to evaluate the usefulness and outcomes of stent graft use in dysfunctional arteriovenous grafts. Eleven patients who underwent stent graft placement for a dysfunctional hemodialysis graft were included in this retrospective study. Expanded polytetrafluoroethylene covered stent grafts were placed at the venous anastomosis site in case of pseudoaneurysm, venous laceration, elastic recoil or residual restenosis despite the repeated angioplasty. The patency of the arteriovenous graft was evaluated using Kaplan-Meier analysis. Primary and secondary mean patency was 363 days and 741 days. Primary patency at 3, 6, and 12 months was 82%, 73%, and 32%, respectively. Secondary patency at the 3, 6, 12, 24, and 36 months was improved to 91%, 82%, 82%, 50%, and 25%, respectively. Fractures of the stent graft were observed in 2 patients, but had no effect on the patency. Stent graft placement in dysfunctional arteriovenous graft is useful and effective in prolonging graft patency.

  17. Modeling cognitive dysfunction in neurofibromatosis-1.

    Science.gov (United States)

    Diggs-Andrews, Kelly A; Gutmann, David H

    2013-04-01

    Cognitive dysfunction, including significant impairments in learning, behavior, and attention, is found in over 10% of children in the general population. However, in the common inherited cancer predisposition syndrome, neurofibromatosis type 1 (NF1), the prevalence of these cognitive deficits approaches 70%. As a monogenic disorder, NF1 provides a unique genetic tool to identify and dissect mechanistically the molecular and cellular bases underlying cognitive dysfunction. In this review, we discuss Nf1 fly and mouse systems that mimic many of the cognitive abnormalities seen in children with NF1. Further, we describe discoveries from these models that have uncovered defects in the regulation of Ras activity, cAMP generation, and dopamine homeostasis as key mechanisms important for cognitive dysfunction in children with NF1.

  18. DELINQUENT BEHAVIOUR OF CHILDREN FROM DYSFUNCTIONAL FAMILIES

    Directory of Open Access Journals (Sweden)

    Sandra Bateva

    2014-12-01

    Full Text Available The subject of my research in the paper are the children from dysfunctional families, primarily their delinquent behavior, education and moral, actually, who takes care of them and who undertakes the family roles and whether this care is sufficient for building these personalities.This research approaches towards the study of the delinquent behavior of children from dysfunctional families. It examines to what extent the educational level of parents, the material condition, the health condition, the leisure time, the average monthly income of the family, the available permanent goods, the educational resources, the social communications within the very family, all affect the delinquent behavior of children from dysfunctional families. 

  19. Inherited Causes of Exocrine Pancreatic Dysfunction

    Directory of Open Access Journals (Sweden)

    Peter R Durie

    1997-01-01

    Full Text Available The exocrine pancreas is functionally immature at birth. Protease function is probably adequate, but lipase activity approximates 5% to 10% of adult values in the newborn and remains low in infancy. Pancreatic amylase secretion is essentially absent at birth and remains low through the first years of life. Functional disturbances of the exocrine pancreas are less frequent in childhood than in adult life. Causes of pancreatic dysfunction in childhood can be divided in two general categories: hereditary conditions, which directly affect the pancreas; and acquired disorders, in which loss of pancreatic function is a secondary phenomenon. Most inherited causes of pancreatic dysfunction are due to a generalized disorder. Cystic fibrosis is, by far, the most common inherited cause of disturbed pancreatic function among Caucasian children. All other inherited causes of exocrine pancreatic dysfunction (eg, Johanson-Blizzard syndrome are uncommon or rare.

  20. AB271. Sexual dysfunction in chronic prostatitis

    Science.gov (United States)

    Cho, In-Rae

    2016-01-01

    Chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS), or NIH category III prostatitis, is a clinical syndrome characterized by genital/ pelvic pain and lower urinary tract symptoms in the absence of urinary tract infection. CPPS is the most common prostatic disease in men younger than 50 years of age and the third most common in men older than 50 years of age. CP/CPPS is a complex entity with unclear etiology. Many articles reported that the high percentage of patients with CP/CPPS had sexual dysfunction. The most common symptoms of sexual dysfunction in chronic prostatitis patients are erectile dysfunction (ED), painful ejaculation and premature ejaculation. So we will discuss about ED and ejaculation problems in CP/CPPS patients.

  1. Effectiveness of tolterodine in nonneurogenic voiding dysfunction.

    Science.gov (United States)

    Babu, Ramesh

    2006-11-01

    The efficacy of tolterodine was analysed in children with non-neurogenic voiding dysfunction, using dysfunctional voiding symptom score (DVSS). Of 44 patients (mean age 9.3 yrs; M:F = 25:19), 36 received long acting tolterodine tartrate at a dose of 2mg OD and 8 at a dose of 4mg OD. The mean (SD) DVSS before and after the treatment was 17.1 (2.8) and 12.0 (2.4). There was a significant improvement in the mean DVSS score at the end of the treatment (Students t test P tolterodine is effective in children with voiding dysfunction. The single daily dose has good compliance and minimal side effect profile.

  2. Financial incentives for reducing proliferation risks

    Energy Technology Data Exchange (ETDEWEB)

    Weise, Rachel A.; Hund, Gretchen

    2016-08-15

    This article submitted for publication to the Bulletin of Atomic Scientists explains the possible financial incentives for financial institutions and large integrators to reduce nuclear proliferation risks by including anti-proliferation measures in their due diligence and requiring their suppliers to meet heightened compliance standards. Because manufacturers of dual-use nuclear goods are diverse and numerous outreach is difficult. However, financial institutions and large integrators work with nearly all dual-use manufacturers, making financial institutions and integrators well-positioned to increase awareness of proliferation and trafficking risks throughout the nuclear supply chain

  3. Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress?

    Science.gov (United States)

    Fortunato, Rodrigo S; Ferreira, Andrea C F; Hecht, Fabio; Dupuy, Corinne; Carvalho, Denise P

    2014-05-01

    Thyroid diseases, such as autoimmune disease and benign and malignant nodules, are more prevalent in women than in men, but the mechanisms involved in this sex difference is still poorly defined. H₂O₂ is produced at high levels in the thyroid gland and regulates parameters such as cell proliferation, migration, survival, and death; an imbalance in the cellular oxidant-antioxidant system in the thyroid may contribute to the greater incidence of thyroid disease among women. Recently, we demonstrated the existence of a sexual dimorphism in the thyrocyte redox balance, characterized by higher H₂O₂ production, due to higher NOX4 and Poldip2 expression, and weakened enzymatic antioxidant defense in the thyroid of adult female rats compared with male rats. In addition, 17β-estradiol administration increased NOX4 mRNA expression and H₂O₂ production in thyroid PCCL3 cells. In this review, we discuss the possible involvement of oxidative stress in estrogen-related thyroid pathophysiology. Our current hypothesis suggests that a redox imbalance elicited by estrogen could be involved in the sex differences found in the prevalence of thyroid dysfunctions.

  4. ATRX dysfunction induces replication defects in primary mouse cells.

    Directory of Open Access Journals (Sweden)

    David Clynes

    Full Text Available The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.

  5. ATRX dysfunction induces replication defects in primary mouse cells.

    Science.gov (United States)

    Clynes, David; Jelinska, Clare; Xella, Barbara; Ayyub, Helena; Taylor, Stephen; Mitson, Matthew; Bachrati, Csanád Z; Higgs, Douglas R; Gibbons, Richard J

    2014-01-01

    The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.

  6. Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yaron Ilan

    2012-01-01

    Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease,including cirrhosis and its complications.Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections,major complications and also play a role in the pathogenesis of chronic liver disorders.Levels of bacterial lipopolysaccharide,a component of gram-negative bacteria,are increased in the portal and/or systemic circulation in several types of chronic liver disease.Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation.Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH).Bacterial overgrowth,immune dysfunction,alteration of the luminal factors,and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications.A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases.These may suggest new targets for potential therapeutic interventions for the treatment of NASH.Here,we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.

  7. [Urinary tract dysfunction in older patients].

    Science.gov (United States)

    Verdejo, Carlos; Méndez, Santiago; Salinas, Jesús

    2016-11-18

    Urinary tract dysfunction in older patients has a multifactorial aetiology and is not a uniform clinical condition. Changes due to physiological ageing as well as comorbidity and polypharmacy, can produce several dynamic conditions such as urinary incontinence and urinary retention. Lower urinary tract symptoms increase with age in both sexes and are a major problem in older patients due to their medical and psychosocial consequences. For these reasons, in assessing urinary dysfunction in older patients, we should consider external circumstances such as polypharmacy, poor mobility, affective and cognitive disorders and also accessibility to housing. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Sexual Dysfunction Due to Psychotropic Medications.

    Science.gov (United States)

    Clayton, Anita H; Alkis, Andrew R; Parikh, Nishant B; Votta, Jennifer G

    2016-09-01

    Sexual functioning is important to assess in patients with psychiatric illness as both the condition and associated treatment may contribute to sexual dysfunction (SD). Antidepressant medications, mood stabilizers, antipsychotics, and antianxiety agents may be associated with SD related to drug mechanism of action. Sexual adverse effects may be related to genetic risk factors, impact on neurotransmitters and hormones, and psychological elements. Effective strategies to manage medication-induced sexual dysfunction are initial choice of a drug unlikely to cause SD, switching to a different medication, and adding an antidote to reverse SD. Appropriate interventions should be determined on a clinical case-by-case basis.

  9. The female athlete triad and endothelial dysfunction.

    Science.gov (United States)

    Lanser, Erica M; Zach, Karie N; Hoch, Anne Z

    2011-05-01

    A tremendous increase in the number of female athletes of all ages and abilities has occurred in the past 35 years. In general, sports and athletic competition produce healthier and happier women. However, explosion in participation has revealed clear gender-specific injuries and medical conditions unique to the female athlete. This article focuses on the latest advances in our knowledge of the female athlete triad and the relationship between athletic-associated amenorrhea and endothelial dysfunction. Treatment of vascular dysfunction with folic acid is also discussed.

  10. Mitochondrial dysfunction underlying outer retinal diseases

    DEFF Research Database (Denmark)

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali

    2017-01-01

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer...... retina pathologies, which can be classified as primary and secondary mitochondrial disorders. This review highlights the importance of oxidative stress and mitochondrial DNA damage, underlying outer retinal disorders. Indeed, the metabolically active photoreceptors/RPE are highly prone to these hallmarks...... of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells....

  11. Liver dysfunction and anti-thyroid therapy

    Directory of Open Access Journals (Sweden)

    Danae A Papachristos

    2015-01-01

    Full Text Available Thioamides have been used in the management of hyperthyroidism for over 50 years. Liver dysfunction is a rare but important side effect associated with their use. Recently, cases of liver failure associated with propylthiouracil have prompted the Federal Drug Administration to issue a Boxed Warning to the label of propylthiouracil regarding its risk of potentially fatal liver injury and acute liver failure in adults and children. Herein, we present a case to underline the importance of recognising the similar potential for severe hepatic dysfunction with the use of other thioamides.

  12. Structure of bacterial respiratory complex I.

    Science.gov (United States)

    Berrisford, John M; Baradaran, Rozbeh; Sazanov, Leonid A

    2016-07-01

    Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536 kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

  13. Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression.

    Science.gov (United States)

    Tang, Ming-Ming; Lin, Wen-Juan; Pan, Yu-Qin; Guan, Xi-Ting; Li, Ying-Cong

    2016-07-01

    Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation.

  14. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    Science.gov (United States)

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  15. Handbook for nuclear non-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok

    1997-05-01

    This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs.

  16. Eosinophils induce airway smooth muscle cell proliferation.

    Science.gov (United States)

    Halwani, Rabih; Vazquez-Tello, Alejandro; Sumi, Yuki; Pureza, Mary Angeline; Bahammam, Ahmed; Al-Jahdali, Hamdan; Soussi-Gounni, Abdelillah; Mahboub, Bassam; Al-Muhsen, Saleh; Hamid, Qutayba

    2013-04-01

    Asthma is characterized by eosinophilic airway inflammation and remodeling of the airway wall. Features of airway remodeling include increased airway smooth muscle (ASM) mass. However, little is known about the interaction between inflammatory eosinophils and ASM cells. In this study, we investigated the effect of eosinophils on ASM cell proliferation. Eosinophils were isolated from peripheral blood of mild asthmatics and non-asthmatic subjects and co-cultured with human primary ASM cells. ASM proliferation was estimated using Ki-67 expression assay. The expression of extracellular matrix (ECM) mRNA in ASM cells was measured using quantitative real-time PCR. The role of eosinophil derived Cysteinyl Leukotrienes (CysLTs) in enhancing ASM proliferation was estimated by measuring the release of leukotrienes from eosinophils upon their direct contact with ASM cells using ELISA. This role was confirmed either by blocking eosinophil-ASM contact or co-culturing them in the presence of leukotrienes antagonist. ASM cells co-cultured with eosinophils, isolated from asthmatics, but not non-asthmatics, had a significantly higher rate of proliferation compared to controls. This increase in ASM proliferation was independent of their release of ECM proteins but dependent upon eosinophils release of CysLTs. Eosinophil-ASM cell to cell contact was required for CysLTs release. Preventing eosinophil contact with ASM cells using anti-adhesion molecules antibodies, or blocking the activity of eosinophil derived CysLTs using montelukast inhibited ASM proliferation. Our results indicated that eosinophils contribute to airway remodeling during asthma by enhancing ASM cell proliferation and hence increasing ASM mass. Direct contact of eosinophils with ASM cells triggers their release of CysLTs which enhance ASM proliferation. Eosinophils, and their binding to ASM cells, constitute a potential therapeutic target to interfere with the series of biological events leading to airway remodeling

  17. Airway Epithelium Stimulates Smooth Muscle Proliferation

    OpenAIRE

    Malavia, Nikita K.; Raub, Christopher B.; Mahon, Sari B.; Brenner, Matthew; Reynold A Panettieri; George, Steven C.

    2009-01-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air–liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (...

  18. Evolution of Bacterial Suicide

    Science.gov (United States)

    Tchernookov, Martin; Nemenman, Ilya

    2013-03-01

    While active, controlled cellular suicide (autolysis) in bacteria is commonly observed, it has been hard to argue that autolysis can be beneficial to an individual who commits it. We propose a theoretical model that predicts that bacterial autolysis is evolutionarily advantageous to an individualand would fixate in physically structured environments for stationary phase colonies. We perform spatially resolved agent-based simulations of the model, which predict that lower mixing in the environment results in fixation of a higher autolysis rate from a single mutated cell, regardless of the colony's genetic diversity. We argue that quorum sensing will fixate as well, even if initially rare, if it is coupled to controlling the autolysis rate. The model does not predict a strong additional competitive advantage for cells where autolysis is controlled by quorum sensing systems that distinguish self from nonself. These predictions are broadly supported by recent experimental results in B. subtilisand S. pneumoniae. Research partially supported by the James S McDonnell Foundation grant No. 220020321 and by HFSP grant No. RGY0084/2011.

  19. Bacterial degradation of aminopyrine.

    Science.gov (United States)

    Blecher, H; Blecher, R; Wegst, W; Eberspaecher, J; Lingens, F

    1981-11-01

    1. Four strains of bacteria growing with aminopyrine as sole source of carbon were isolated from soil and were identified as strains of Phenylobacterium immobilis. 2. Strain M13 and strain E, the type species of Phenylobacterium immobilis (DSM 1986), which had been isolated by enrichment with chloridazon (5-amino-4-chloro-2-phenyl-2H-pyridazin-3-one) were used to investigate the bacterial degradation of aminopyrine. 3. Three metabolites were isolated and identified as: 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-2-(2,3-dihydro-2,3-dihydroxy-4,6-cyc lohexadien-1-yl)-3H-pyrazol-3-one, 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-2-(2,3-dihydroxyphenyl)-3H-pyrazol-3 -one and 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-3H-pyrazol-3-one. 4. An enzyme extract from cells of strain m13 was shown to further metabolize the catechol derivative of aminopyrine, with the formation of 2-pyrone-6-carboxylic acid. 5. Results indicate that the benzene ring of aminopyrine is the principal site of microbial metabolism.

  20. Electromagnetism of Bacterial Growth

    Science.gov (United States)

    Ainiwaer, Ailiyasi

    2011-10-01

    There has been increasing concern from the public about personal health due to the significant rise in the daily use of electrical devices such as cell phones, radios, computers, GPS, video games and television. All of these devices create electromagnetic (EM) fields, which are simply magnetic and electric fields surrounding the appliances that simultaneously affect the human bio-system. Although these can affect the human system, obstacles can easily shield or weaken the electrical fields; however, magnetic fields cannot be weakened and can pass through walls, human bodies and most other objects. The present study was conducted to examine the possible effects of bacteria when exposed to magnetic fields. The results indicate that a strong causal relationship is not clear, since different magnetic fields affect the bacteria differently, with some causing an increase in bacterial cells, and others causing a decrease in the same cells. This phenomenon has yet to be explained, but the current study attempts to offer a mathematical explanation for this occurrence. The researchers added cultures to the magnetic fields to examine any effects to ion transportation. Researchers discovered ions such as potassium and sodium are affected by the magnetic field. A formula is presented in the analysis section to explain this effect.

  1. Bacterial endocarditis prophylaxis.

    Science.gov (United States)

    Blanco-Carrión, Andrés

    2004-01-01

    Bacterial endocarditis (BE) is a disease resulting from the association of morphological alterations of the heart and bacteraemia originating from different sources that at times can be indiscernible (infectious endocarditis). It is classified on the basis of the morphological alteration involved, depending on the clinical manifestations and course of illness, which varies according to the causative microorganism and host conditions (for example, it is characteristic in I.V. drug users). The most common microorganisms involved are: Streptococcus viridans (55%), Staphylococcus aureus (30%), Enterococcus (6%) and HACEK bacteria (corresponding to the initials: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and Kingella), although on occasions it can also be caused by fungi. The oral microbiological flora plays a very important role in the aetiopathogenesis of BE, given that the condition may be of oral or dental origin. This paper will deal with the prevention of said bacteraemia. Prophylaxis will be undertaken using amoxicillin or clindamycin according to action protocols, with special emphasis placed on oral hygiene in patients with structural defects of the heart.

  2. Proliferation of cultured mouse choroid plexus epithelial cells.

    Directory of Open Access Journals (Sweden)

    Basam Z Barkho

    Full Text Available The choroid plexus (ChP epithelium is a multifunctional tissue found in the ventricles of the brain. The major function of the ChP epithelium is to produce cerebrospinal fluid (CSF that bathes and nourishes the central nervous system (CNS. In addition to the CSF, ChP epithelial cells (CPECs produce and secrete numerous neurotrophic factors that support brain homeostasis, such as adult hippocampal neurogenesis. Accordingly, damage and dysfunction to CPECs are thought to accelerate and intensify multiple disease phenotypes, and CPEC regeneration would represent a potential therapeutic approach for these diseases. However, previous reports suggest that CPECs rarely divide, although this has not been extensively studied in response to extrinsic factors. Utilizing a cell-cycle reporter mouse line and live cell imaging, we identified scratch injury and the growth factors insulin-like growth factor 1 (IGF-1 and epidermal growth factor (EGF as extrinsic cues that promote increased CPEC expansion in vitro. Furthermore, we found that IGF-1 and EGF treatment enhances scratch injury-induced proliferation. Finally, we established whole tissue explant cultures and observed that IGF-1 and EGF promote CPEC division within the intact ChP epithelium. We conclude that although CPECs normally have a slow turnover rate, they expand in response to external stimuli such as injury and/or growth factors, which provides a potential avenue for enhancing ChP function after brain injury or neurodegeneration.

  3. Managing Proliferation Issues with Iran

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, C. Richard; Saltiel, David H.

    2002-02-15

    . Russian policy, in particular, will continue to play a vital role in determining the extent to which Iran is able to pursue WMD options. Without a fundamental change in the regional security environment, however, there is little reason to expect changes in Iranian WMD and missile policies, and the United States, acting alone and short of war, cannot prevent Iran from ultimately developing WMD and delivery systems. Furthermore, U.S. policies that take a tougher line with Russia, China and North Korea are not likely to lead to more restraint among these potential sources of WMD and missile technology. In the absence of engagement with Iran, unilateral U.S. economic sanctions will remain the principal, if flawed, U.S. policy tool for seeking to prevent Iran from acquiring WMD. The rationale is that by discouraging trade and investment, particularly in Iran's energy sector, the government of Iran will have less revenue to pursue proliferation. Without broad international support for economic isolation, however, such an effort may hinder Iran's WMD programs, though it cannot block them. Finally, options are needed to deal with major failures in nonproliferation efforts. These options include measures to deter Iranian use of WMD, to defend against their use if deterrence fails, and to destroy Iranian WMD capabilities should the need arise.

  4. Ubiquitin-proteasome system in cardiac dysfunction

    OpenAIRE

    Mearini, Giulia; Schlossarek, Saskia; Willis, Monte S.; Carrier, Lucie

    2008-01-01

    Ubiquitin-proteasome system in cardiac dysfunction correspondance: Corresponding author. Tel.: +49 40 42803 7208; fax: +49 40 42803 5925. (Carrier, Lucie) (Carrier, Lucie) Institute of Experimental and Clinical Pharmacology and Toxicology--> , University Medical Center Hamburg-Eppendorf--> , Hamburg--> - GERMANY (Mearini, Giulia) Institute of Experimental and Clinical Pharmacology and...

  5. Cycloserine induced psychosis with hepatic dysfunction

    Directory of Open Access Journals (Sweden)

    Vishal R Tandon

    2015-01-01

    Full Text Available With the increase in the cases of multidrug resistance tuberculosis, second line anti-tubercular drugs like the cycloserine are being prescribed frequently. Isoniazid and ethambutol are reported to cause psychosis like state; however, few reports of cycloserine induced psychosis are available. To the best of our knowledge, this is the first case of cycloserine induced psychosis with hepatic dysfunction.

  6. Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-yi; WANG Fang; FENG Jie-xiong

    2013-01-01

    Objective Based on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients,it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC.However,the published studies regarding the role of intestinal ischemia in NEC are controversial.The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC,and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC.Data sources The studies cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis".Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.Results Immature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable.When neonates are subjected to stress,endothelial cell dysfunction occurs and results in vasoconstriction of arterioles,inflammatory cell infiltration and activation in venules,and endothelial barrier disruption in capillaries.The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion,and may eventually progress to intestinal necrosis.Conclusion Intestinal ischemia plays an important role through the whole course of NEC.New therapeutic agents targeting intestinal ischemia,like HB-EGF,are promising therapeutic agents for the treatment of NEC.

  7. New Diagnostic Terminology for Minimal Brain Dysfunction.

    Science.gov (United States)

    Shaywitz, Bennett A.; And Others

    1979-01-01

    Minimal brain dysfunction has been redefined by the American Psychological Association as attention deficit disorder (ADD) and subdivided into categories with and without hyperactivity. The revised 'Diagnostic and Statistical Manual' (DSM III) is now undergoing field trials. Journal Availability: C. V. Mosby Company, 11830 Westline Industrial…

  8. Early diastolic filling dynamics in diastolic dysfunction

    Directory of Open Access Journals (Sweden)

    Crean Peter A

    2003-07-01

    Full Text Available Abstract Background The aim of the study was to determine the relationship between the rate of peak early mitral inflow velocity and the peak early diastolic mitral annular tissue velocities in normal controls and to compare them with subjects with diastolic dysfunction. Methods The relationship between early passive diastolic transmitral flow and peak early mitral annular velocity in the normal and in diastolic dysfunction was studied. Two groups comprising 22 normal controls and 25 patients with diastolic dysfunction were studied. Results Compared with the normal group, those with diastolic dysfunction had a lower E/A ratio (0.7 ± 0.2 vs. 1.9 ± 0.5, p 2 vs. 871 ± 128.1 cm/sec2, p Conclusions This investigation provides information on the acceleration of early diastolic filling and its relationship to mitral annular peak tissue velocity (Ea recorded by Doppler tissue imaging. It supports not only the premise that recoil is an important mechanism for rapid early diastolic filling but also the existence of an early diastolic mechanism in normal.

  9. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down...

  10. Lower urinary tract dysfunction in children

    NARCIS (Netherlands)

    Klijn, AJ

    2016-01-01

    Lower urinary tract dysfunction in children can have many faces. It can present with incontinenece for urine, urinary tract infections or even constipation or loosing stools. All kinds of factors influencing the function of the pelvic floor muscle tension can have an impact on the lower urinary trac

  11. Characterizing postoperative cognitive dysfunction in the elderly

    NARCIS (Netherlands)

    Hovens, Iris Bertha

    2015-01-01

    In the Netherlands, yearly more than 400.000 elderly patients undergo surgery. An estimated ten percent of these patients develops long-lasting postoperative cognitive dysfunction (POCD), associated with a reduced quality of life, increased dependency and worse prognosis. Currently, there is no

  12. EXTRACTION, ORTHODONTIC TREATMENT, AND CRANIOMANDIBULAR DYSFUNCTION

    NARCIS (Netherlands)

    DIBBETS, JMH; VANDERWEELE, LT

    1991-01-01

    Signs and symptoms attributed to craniomandibular dysfunction (CMD) were registered in the Groningen longitudinal prospective study over a 15-year period. It is concluded that none of the three treatment types-removable appliances, Begg mechanics, and chin cups-should be considered causal factors fo

  13. Syllable Structure in Dysfunctional Portuguese Children's Speech

    Science.gov (United States)

    Candeias, Sara; Perdigao, Fernando

    2010-01-01

    The goal of this work is to investigate whether children with speech dysfunctions (SD) show a deficit in planning some Portuguese syllable structures (PSS) in continuous speech production. Knowledge of which aspects of speech production are affected by SD is necessary for efficient improvement in the therapy techniques. The case-study is focused…

  14. Minor neurological dysfunction in children with dyslexia

    NARCIS (Netherlands)

    Punt, Marja; De Jong, Marianne; De Groot, Erik; Hadders-Algra, Mijna

    2010-01-01

    AIM To improve understanding of brain function in children with severe dyslexia in terms of minor neurological dysfunctions (MNDs). METHOD One hundred and four children (81 males, 23 females; age range 7-12y; mean age 9y 7mo, SD 1y 2mo;) with severe dyslexia (the presence of a Full-scale IQ score of

  15. Hepatitis C Virus-Induced Mitochondrial Dysfunctions

    Directory of Open Access Journals (Sweden)

    Birke Bartosch

    2013-03-01

    Full Text Available Chronic hepatitis C is characterized by metabolic disorders and a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that lead in the long term to hepatocellular carcinoma. Many lines of evidence suggest that mitochondrial dysfunctions, including modification of metabolic fluxes, generation and elimination of oxidative stress, Ca2+ signaling and apoptosis, play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV proteins localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory, probably due to the use of artificial expression and replication systems. In vivo studies are hampered by the fact that innate and adaptive immune responses will overlay mitochondrial dysfunctions induced directly in the hepatocyte by HCV. Thus, the molecular aspects underlying HCV-induced mitochondrial dysfunctions and their roles in viral replication and the associated pathology need yet to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems.

  16. Feeding and Swallowing Dysfunction in Genetic Syndromes

    Science.gov (United States)

    Cooper-Brown, Linda; Copeland, Sara; Dailey, Scott; Downey, Debora; Petersen, Mario Cesar; Stimson, Cheryl; Van Dyke, Don C.

    2008-01-01

    Children with genetic syndromes frequently have feeding problems and swallowing dysfunction as a result of the complex interactions between anatomical, medical, physiological, and behavioral factors. Feeding problems associated with genetic disorders may also cause feeding to be unpleasant, negative, or even painful because of choking, coughing,…

  17. Endothelial Dysfunction in Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Curtis M. Steyers

    2014-06-01

    Full Text Available Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD. As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α, reactive oxygen species, oxidized LDL (low density lipoprotein, autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.

  18. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  19. Opioid-Induced Constipation and Bowel Dysfunction

    DEFF Research Database (Denmark)

    Müller-Lissner, Stefan; Bassotti, Gabrio; Coffin, Benoit

    2016-01-01

    OBJECTIVE:  To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. SETTING:  Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inh...

  20. Chorioretinopathy and pituitary dysfunction. The CPD syndrome.

    Science.gov (United States)

    Judisch, G F; Lowry, R B; Hanson, J W; McGillivary, B C

    1981-02-01

    Four reports of a rare syndrome characterized by severe, early-onset chorioretinopathy, trichosis, and evidence of pituitary dysfunction are reviewed. Recently obtained follow-up information about these four patients is presented. A new example of this disease, the fifth case to be reported, to our knowledge, is described.

  1. Cardiovascular autonomic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Ziemssen, Tjalf; Reichmann, Heinz

    2010-02-15

    Symptoms of cardiovascular dysautonomia are a common occurrence in Parkinson's disease (PD). In addition to this dysautonomia as part of PD itself, dysfunction of the autonomic nervous system (ANS) can be triggered as a side-effect of drug treatment interacting with the ANS or - if prominent and early - an indication of a different disease such as multiple system atrophy (MSA). Various diagnostic tests are available to demonstrate autonomic failure. While autonomic function tests can differentiate parasympathetic from sympathetic dysfunction, cardiac imaging can define the pathophysiologically involved site of a lesion. Standard tests such as 24-h ambulatory blood pressure measurements can identify significant autonomic failure which needs treatment. The most frequent and disturbing symptom of cardiovascular autonomic dysfunction is orthostatic hypotension. Symptoms include generalized weakness, light-headiness, mental "clouding" up to syncope. Factors like heat, food, alcohol, exercise, activities which increase intrathoraric pressure (e.g. defecation, coughing) and certain drugs (e.g. vasodilators) can worsen a probably asymptomatic orthostatic hypotension. Non-medical and medical therapies can help the patient to cope with a disabling symptomatic orthostatic hypotension. Supine hypertension is often associated with orthostatic hypotension. The prognostic role of cardiovagal and baroreflex dysfunction is still not yet known.

  2. Dimensions of working memory dysfunction in schizophrenia.

    NARCIS (Netherlands)

    Pukrop, R.; Matuschek, E.; Ruhrmann, S.; Brockhaus, A.; Tendolkar, I.; Bertsch, A.; Klosterkötter, J.

    2003-01-01

    The aim of this study was to investigate the underlying structure of eight working memory tests used to assess prefrontal dysfunction in schizophrenia research [Letter-Number Span (LNS), Digit-Symbol Test (DST), Trail-Making Test B (TMT-B), Delayed Response Task (DRT) for spatial working memory, Sub

  3. In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood.

    Science.gov (United States)

    Ricke, William A; Lee, Calvin W; Clapper, Tyler R; Schneider, Andrew J; Moore, Robert W; Keil, Kimberly P; Abler, Lisa L; Wynder, Jalissa L; López Alvarado, Arnaldo; Beaubrun, Isaac; Vo, Jenny; Bauman, Tyler M; Ricke, Emily A; Peterson, Richard E; Vezina, Chad M

    2016-04-01

    Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV-cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 μg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 β-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone-induced urinary tract dysfunction later in life.

  4. Renal heparan sulfate proteoglycans modulate fibroblast growth factor 2 signaling in experimental chronic transplant dysfunction.

    Science.gov (United States)

    Katta, Kirankumar; Boersema, Miriam; Adepu, Saritha; Rienstra, Heleen; Celie, Johanna W A M; Mencke, Rik; Molema, Grietje; van Goor, Harry; Berden, Jo H M; Navis, Gerjan; Hillebrands, Jan-Luuk; van den Born, Jacob

    2013-11-01

    Depending on the glycan structure, proteoglycans can act as coreceptors for growth factors. We hypothesized that proteoglycans and their growth factor ligands orchestrate tissue remodeling in chronic transplant dysfunction. We have previously shown perlecan to be selectively up-regulated in the glomeruli and arteries in a rat renal transplantation model. Using the same model, here we present quantitative RT-PCR profiling data on proteoglycans and growth factors from laser-microdissected glomeruli, arterial tunicae mediae, and neointimae at 12 weeks after transplantation. In glomeruli and neointimae of allografts, selective induction of the matrix heparan sulfate proteoglycan perlecan was observed, along with massive accumulation of fibroblast growth factor 2 (FGF2). Profiling the heparan sulfate polysaccharide side chains revealed conversion from a non-FGF2-binding heparan sulfate phenotype in control and isografted kidneys toward a FGF2-binding phenotype in allografts. In vitro experiments with perlecan-positive rat mesangial cells showed that FGF2-induced proliferation is dependent on sulfation and can be inhibited by exogenously added heparan sulfate. These findings indicate that matrix proteoglycans such as perlecan serve as functional docking platforms for FGF2 in chronic transplant dysfunction. We speculate that heparin-like glycomimetics could be a promising intervention to retard development of glomerulosclerosis and neointima formation in chronic transplant dysfunction.

  5. Vascular dysfunctions following spinal cord injury.

    Science.gov (United States)

    Popa, Constantin; Popa, Florian; Grigorean, Valentin Titus; Onose, Gelu; Sandu, Aurelia Mihaela; Popescu, Mihai; Burnei, Gheorghe; Strambu, Victor; Sinescu, Crina

    2010-01-01

    The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1-L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life-threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5-T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin-angiotensin-aldosterone activity, peripheral alpha-adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein

  6. Pulmonary dysfunction in obese early adolescents

    Directory of Open Access Journals (Sweden)

    Bambang Supriyatno

    2010-08-01

    Full Text Available Aim Obesity leads to various complications, including pulmonary dysfunction. Studies on pulmonary function of obese children are limited and the results are controversial. This study was aimed to determine proportion of pulmonary dysfunction on early adolescents with obesity and to evaluate correlation between obesity degree with pulmonary dysfunction degree.Methods A cross-sectional study was conducted at the Department of Child Health, Medical School, University of Indonesia, from November 2007 to December 2008. Subjects were 10 to 12 year-old adolescents with obesity. Subjects underwent pulmonary function test (PFT to assess FEV1/FVC, FEV1, FVC, V50, and V25.Results 110 subjects fulfilled study criteria, 83 (75.5% were male and 27 (24.5% were female with median BMI 26.7 (22.6-54.7 kg/m2; 92 subjects (83.6% were superobese. History of asthma and allergic rhinitis were found in 32 (29.1% and 46 (41.8% subjects, respectively. 64 (58.2% subjects had abnormal PFT results consisting of restrictive type in 28 (25.5% subjects, obstructive in 3 (2.7%, and combined type in 33 (30%. Mean FEV1, FVC, V50, and V25 values were below normal, while mean FEV1/FVC ratio was normal. There was no statistically significant correlation between BMI and PFT parameters. No significant correlation was found between degree of obesity and the severity of pulmonary dysfunction.Conclusions Pulmonary dysfunction occurs in 58.2% obese early adolescents. The most common abnormality was combined type (30%, followed by restrictive (25.5%, and obstructive type (2.7%. There was no correlation between BMI and pulmonary function test parameters. (Med J Indones 2010;19:179-84Key words: early adolescents, obesity, pulmonary function test

  7. Transition from Cyclosporine-Induced Renal Dysfunction to Nephrotoxicity in an in Vivo Rat Model

    Directory of Open Access Journals (Sweden)

    José Sereno

    2014-05-01

    Full Text Available Cyclosporin A (CsA, a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day treatments (3 and 9 weeks, respectively. Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA, transforming growth factor beta 1 (TGF-β1, factor nuclear kappa B (NF-κβ and Tumor Protein P53 (TP53 kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR and the antigen identified by monoclonal antibody Ki-67 (Mki67, accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy.

  8. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    Science.gov (United States)

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists.

  9. Meningitis bacteriana Bacterial meningitis

    Directory of Open Access Journals (Sweden)

    Ana Teresa Alvarado Guevara

    2006-03-01

    causales son virales lo cual conlleva a las diferentes sub-clasificaciones. También en ciertos casos puede ser ocasionada por hongos, bacterias atípicas, micobacterias y parásitos.In Costa Rica the bacterial meningitis had turn into a high-priority subject in which to monitoring epidemiologist. It had been talked about in the last months, to dice an increase in the attention is published of this subject, due to this phenomenon it becomes necessary to make a revision of topic. Meningitis is an inflammation of leptomeninges and colonization of the subarachnoid cerebrospinal fluid (LCR due to different agents, which produces meningeal symptoms (ex. migraine, neck rigidity, and photophobia and pleocytosis in LCR. De pending on the variables to take into account is possible to group it in different classifications, taking into account the time of evolution are possible to be divided in acute or chronic, to first with few hours or days of beginning of the symptoms, whereas the chronicle also presents a silence course but of the disease of approximately 4 weeks of instauration. There is a difference according to its etiologic agent; they can be infectious and non-infectious. Examples of common non-infectious causes include medications (ex, nonsteroidal anti-inflammatory drugs, and antibiotics and carcinomatosis. A classification exists as well according to the causal agent. The acute bacterial meningitis remarks a bacterial origin of the syndrome, which characterizes by the by an acute onset of meningeal symptoms and neutrophilic pleocytosis. Each one of the bacteriological agents, parasitic or fungus finishes by characterizing the different presentations of the clinical features (ex, meningocóccica meningitis, Cryptococcus meningitis. Finally, there is also the aseptic meningitis, denominated in this form because it’s nonpyogenic cellular response caused by many types of agents. The patients show an acute beginning of symptoms, fever and lymphocytic pleocytosis. After

  10. AB028. New drugs for sexual dysfunction complementary medicine for sexual dysfunction in Australia

    Science.gov (United States)

    Earle, Carolyn

    2015-01-01

    Objective In Australia both oriental and western products are available as complementary medicines. Our aim was to review the current available over-the-counter (OTC) medications for sexual dysfunction and report on this market. Methods Following an earlier published review in 2010, 37 products were reviewed that were listed on the Australian Register of Therapeutic Goods (ARTG) and registered with the Therapeutic Goods Administration (TGA). These products were manufactured in Australia and laid claim to provide treatment for sexual dysfunction. A review of these products and newer products was undertaken to establish the extent of complementary medicines in Australia for sexual dysfunction and the reported clinical experience. Results As at July 2015 there were 31 Australian manufactured OTC products registered with the TGA on the ARTG for sexual dysfunction. Twenty-four were for male sexual dysfunction, 3 for female sexual dysfunction and 4 for unisex sexual dysfunction. The main herbs used in sexual health products in Australia are tribulus terrestris, panax ginseng and horny goat weed. However, complementary medicine practitioners also promote the use of gingko Bilbo, avena sativa and damiana. Many of the ingredients found in men’s products are also in the women’s products. Although review articles for complementary medicine, sexual dysfunction and libido have been written in Australia, as far as can be investigated there are no published randomized clinical trials in the area of complementary medicine and sexual function. Conclusions Complementary medicine has reached a high degree of development in Australia. But, due to the lack of properly conducted placebo-controlled clinical trials there is not a body of supporting evidence of efficacy, certification of purity, guarantee of safety, or well-documented side effects. Even though most OTC medications for sexual health have mild side effects and some also promote general health, the lack of such evidence

  11. Bacterial Communities: Interactions to Scale

    Directory of Open Access Journals (Sweden)

    Reed M. Stubbendieck

    2016-08-01

    Full Text Available In the environment, bacteria live in complex multispecies communities. These communities span in scale from small, multicellular aggregates to billions or trillions of cells within the gastrointestinal tract of animals. The dynamics of bacterial communities are determined by pairwise interactions that occur between different species in the community. Though interactions occur between a few cells at a time, the outcomes of these interchanges have ramifications that ripple through many orders of magnitude, and ultimately affect the macroscopic world including the health of host organisms. In this review we cover how bacterial competition influences the structures of bacterial communities. We also emphasize methods and insights garnered from culture-dependent pairwise interaction studies, metagenomic analyses, and modeling experiments. Finally, we argue that the integration of multiple approaches will be instrumental to future understanding of the underlying dynamics of bacterial communities.

  12. Male sexual dysfunction and infertility associated with neurological disorders

    DEFF Research Database (Denmark)

    Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L

    2012-01-01

    Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic...

  13. Dysfunctional Uterine Bleeding: Questions to Discuss with Your Doctor

    Science.gov (United States)

    ... delivered to your inbox ! When You Visit Your Doctor - Dysfunctional Uterine Bleeding Dysfunctional Uterine Bleeding Questions to Discuss with Your Doctor: Do you have regular menstrual cycles? When was ...

  14. Renal dysfunction in African patients with acute heart failure

    NARCIS (Netherlands)

    Sani, Mahmoud U.; Davison, Beth A.; Cotter, Gad; Sliwa, Karen; Edwards, Christopher; Liu, Licette; Damasceno, Albertino; Mayosi, Bongani M.; Ogah, Okechukwu S.; Mondo, Charles; Dzudie, Anastase; Ojji, Dike B.; Voors, Adrian A.

    2014-01-01

    Aims In Western countries with typically elderly ischaemic acute heart failure patients, predictors and clinical outcome of renal dysfunction and worsening renal function are well described. However, the prevalence, predictors and clinical outcome of renal dysfunction in younger, mainly hypertensive

  15. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  16. Thyroid dysfunction in type 2 diabetics seen at the University ...

    African Journals Online (AJOL)

    Chigo Okwuosa

    Summary:Thyroid dysfunction complicates the metabolic derangement observed in Diabetes ... prevalence of thyroid dysfunction in type-2 diabetics in our environment is not known. ... hypothyroidism in the rare Crow-Fucase syndrome ...

  17. Bacterial toxin-antitoxin gene system as containment control in yeast cells

    DEFF Research Database (Denmark)

    Kristoffersen, P.; Jensen, G. B.; Gerdes, K.;

    2000-01-01

    The potential of a bacterial toxin-antitoxin gene system for use in containment control in eukaryotes was explored. The Escherichia coli relE and relB genes were expressed in the yeast Saccharomyces cerevisiae, Expression of the relE gene was highly toxic to yeast cells. However, expression...... of the relB gene counteracted the effect of relE to some extent, suggesting that toxin-antitoxin interaction also occurs in S. cerevisiae, Thus, bacterial toxin-antitoxin gene systems also have potential applications in the control of cell proliferation in eukaryotic cells, especially in those industrial...

  18. Surface micropattern limits bacterial contamination

    OpenAIRE

    Mann, Ethan E.; Manna, Dipankar; Mettetal, Michael R; May, Rhea M.; Dannemiller, Elisa M; Chung, Kenneth K.; Brennan, Anthony B; Reddy, Shravanthi T

    2014-01-01

    Background Bacterial surface contamination contributes to transmission of nosocomial infections. Chemical cleansers used to control surface contamination are often toxic and incorrectly implemented. Additional non-toxic strategies should be combined with regular cleanings to mitigate risks of human error and further decrease rates of nosocomial infections. The Sharklet micropattern (MP), inspired by shark skin, is an effective tool for reducing bacterial load on surfaces without toxic additiv...

  19. Bacterial cellulose/boehmite composites

    Energy Technology Data Exchange (ETDEWEB)

    Salvi, Denise T.B. de; Barud, Hernane S.; Messaddeq, Younes; Ribeiro, Sidney J.L. [Universidade Estadual Paulista Julio de Mesquita Filho. UNESP. Instituto de Quimica de Araraquara, SP (Brazil); Caiut, Jose Mauricio A. [Universidade de Sao Paulo. Departamento de Quimica - FFCLRP/USP, Ribeirao Preto, SP (Brazil)

    2011-07-01

    Composites based on bacterial cellulose membranes and boehmite were obtained. SEM results indicate that the bacterial cellulose (BC) membranes are totally covered by boehmite and obtained XRD patterns suggest structural changes due to this boehmite addition. Thermal stability is accessed through TG curves and is dependent on boehmite content. Transparency is high comparing to pure BC as can be seen through UV-vis absorption spectroscopy. (author)

  20. Bacterial toxins: friends or foes?

    OpenAIRE

    Schmitt, C K; Meysick, K. C.; O'Brien, A D

    1999-01-01

    Many emerging and reemerging bacterial pathogens synthesize toxins that serve as primary virulence factors. We highlight seven bacterial toxins produced by well-established or newly emergent pathogenic microbes. These toxins, which affect eukaryotic cells by a variety of means, include Staphylococcus aureus alpha-toxin, Shiga toxin, cytotoxic necrotizing factor type 1, Escherichia coli heat-stable toxin, botulinum and tetanus neurotoxins, and S. aureus toxic-shock syndrome toxin. For each, we...

  1. Bacterial Chromosome Organization and Segregation

    OpenAIRE

    Toro, Esteban; Shapiro, Lucy

    2010-01-01

    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  2. [Current knowledge of bacterial vaginosis].

    Science.gov (United States)

    Djukić, Slobodanka; Opavski, Nataša; Mijač, Vera; Ranin, Lazar

    2011-01-01

    Bacterial vaginosis, earlier termed nonspecific vaginitis (anaerobic vaginosis) because of the absence of recognized pathogens, is most common vaginal syndrome of women of childbearing age affecting 15-30%. This syndrome, whose aetiology and pathogenesis remains unknown, is characterized by significant changes in the vaginal ecosystem. These changes consist of a decrease in the number of lactobacilli and a large increase in the number of anaerobic organisms. The bacteria adhere to desquamated epithelial cells with a distinctive appearance of clue cells The main complaints of women with symptomatic bacterial vaginosis include vaginal discharge and odour. However, a significant number of all women who have bacterial vaginosis deny symptoms. Bacterial vaginosis is associated with a number of gynaecologic and obstetric complications including cervicitis, cervical neoplasia, pelvic inflammatory disease, postoperative infections, and preterm labour.The diagnosis is most frequently made based on vaginal smear stained according to Gram (Nugent scoring method). Metronidazole and clindamycin are the drugs of choice for treatment of women with bacterial vaginosis. Which women should undergo treatment? According to the prevailing attitude, it should include women with symptoms. Symptomatic women with frequent relapses of bacterial vaginosisas, as a rule, have poor response to the applied therapy. To achieve better efficiency in the treatment of such women, it is necessary to have more extensive understanding of all factors in the pathogenesis of the syndrome.

  3. Current knowledge of bacterial vaginosis

    Directory of Open Access Journals (Sweden)

    Đukić Slobodanka

    2011-01-01

    Full Text Available Bacterial vaginosis, earlier termed nonspecific vaginitis (anaerobic vaginosis because of the absence of recognized pathogens, is most common vaginal syndrome of women of childbearing age affecting 15-30%. This syndrome, whose aetiology and pathogenesis remains unknown, is characterized by significant changes in the vaginal ecosystem. These changes consist of a decrease in the number of lactobacilli and a large increase in the number of anaerobic organisms. The bacteria adhere to desquamated epithelial cells with a distinctive appearance of clue cells The main complaints of women with symptomatic bacterial vaginosis include vaginal discharge and odour. However, a significant number of all women who have bacterial vaginosis deny symptoms. Bacterial vaginosis is associated with a number of gynaecologic and obstetric complications including cervicitis, cervical neoplasia, pelvic inflammatory disease, postoperative infections, and preterm labour. The diagnosis is most frequently made based on vaginal smear stained according to Gram (Nugent scoring method. Metronidazole and clindamycin are the drugs of choice for treatment of women with bacterial vaginosis. Which women should undergo treatment? According to the prevailing attitude, it should include women with symptoms. Symptomatic women with frequent relapses of bacterial vaginosisas, as a rule, have poor response to the applied therapy. To achieve better efficiency in the treatment of such women, it is necessary to have more extensive understanding of all factors in the pathogenesis of the syndrome.

  4. Neutrophil function in healthy aged horses and horses with pituitary dysfunction.

    Science.gov (United States)

    McFarlane, Dianne; Hill, Kim; Anton, Jason

    2015-06-15

    Immunosuppression leading to opportunist bacterial infection is a well-recognized sequela of equine pituitary pars intermedia dysfunction (PPID). The mechanisms responsible for immune dysfunction in PPID however, are as of yet poorly characterized. Horses with PPID have high concentrations of hormones known to impact immune function including α-melanocyte stimulating hormone (α-MSH) and insulin. α-MSH and related melanocortins have been shown in rodents and people to impair neutrophil function by decreasing superoxide production (known as oxidative burst activity), migration and adhesion. The goal of this study was to determine if neutrophil function is impaired in horses with PPID and, if so, to determine if plasma α-MSH or insulin concentration correlated with the severity of neutrophil dysfunction. Specifically, neutrophil phagocytosis, oxidative burst activity, chemotaxis and adhesion were assessed. Results of this study indicate that horses with PPID have reduced neutrophil function, characterized by decreased oxidative burst activity and adhesion. In addition, chemotaxis was greater in healthy aged horses than in young horses or aged horses with PPID. Plasma insulin: α-MSH ratio, but not individual hormone concentration was correlated to neutrophil oxidative burst activity. In summary, neutrophil function is impaired in horses with PPID, likely due to altered hormone concentrations and may contribute to increased risk of opportunistic infections. Whether regulation of hormone concentration profiles in horses with PPID using therapeutic intervention improves neutrophil function and reduces infections needs to be explored.

  5. CXCL12/CXCR4-Axis Dysfunctions: Markers of the Rare Immunodeficiency Disorder WHIM Syndrome

    Directory of Open Access Journals (Sweden)

    Françoise Bachelerie

    2010-01-01

    Full Text Available The WHIM syndrome features susceptibility to human Papillomavirus infection-induced warts and carcinomas, hypogammaglobulinemia, recurrent bacterial infections, B and T-cell lymphopenia, and neutropenia associated with retention of senescent neutrophils in the bone marrow (i.e. myelokathexis. This rare disorder is mostly linked to inherited heterozygous autosomal dominant mutations in the gene encoding CXCR4, a G protein coupled receptor with a unique ligand, the chemokine CXCL12/SDF-1. Some individuals who have full clinical forms of the syndrome carry a wild type CXCR4 gene. In spite of this genetic heterogeneity, leukocytes from WHIM patients share in common dysfunctions of the CXCR4-mediated signaling pathway upon exposure to CXCL12. Dysfunctions are characterized by impaired desensitization and receptor internalization, which are associated with enhanced responses to the chemokine. Our increasing understanding of the mechanisms that account for the aberrant CXCL12/CXCR4-mediated responses is beginning to provide insight into the pathogenesis of the disorder. As a result we can expect to identify markers of the WHIM syndrome, as well as other disorders with WHIM-like features that are associated with dysfunctions of the CXCL12/CXCR4 axis.

  6. Identification of glucocorticoid-regulated genes that control cell proliferation during murine respiratory development.

    Science.gov (United States)

    Bird, Anthony D; Tan, Kheng H; Olsson, P Fredrik; Zieba, Malgorzata; Flecknoe, Sharon J; Liddicoat, Douglas R; Mollard, Richard; Hooper, Stuart B; Cole, Timothy J

    2007-11-15

    Glucocorticoids play a vital role in fetal respiratory development and act via the intracellular glucocorticoid receptor (GR) to regulate transcription of key target genes. GR-null mice die at birth due to respiratory dysfunction associated with hypercellularity and atelectasis. To identify events associated with this lung phenotype we examined perinatal cellular proliferation rates and apoptotic indices. We demonstrate that compared to wild-type controls, day 18.5 postcoitum (p.c.) GR-null mouse lungs display significantly increased cell proliferation rates (1.8-fold P < 0.05) and no change in apoptosis. To examine underlying molecular mechanisms, we compared whole genome expression profiles by microarray analysis at 18.5 days p.c. Pathways relating to cell proliferation, division and cell cycle were significantly down-regulated while pathways relating to carbohydrate metabolism, kinase activities and immune responses were significantly up-regulated. Differential levels of gene expression were verified by quantitative-RT-PCR and/or Northern analysis. Key regulators of proliferation differentially expressed in the lung of 18.5 p.c. GR-null lungs included p21 CIP1 (decreased 2.9-fold, P < 0.05), a negative regulator of the cell cycle, and Mdk (increased 6.0-fold, P < 0.05), a lung growth factor. The more under-expressed genes in 18.5 p.c. GR-null lungs included Chi3l3 (11-fold, P < 0.05), a macrophage inflammatory response gene and Ela1 (9.4-fold, P < 0.05), an extracellular matrix remodeling enzyme. Our results demonstrate that GR affects the transcriptional status of a number of regulatory processes during late fetal lung development. Amongst these processes is cell proliferation whereby GR induces expression of cell cycle repressors while suppressing induction of a well characterized cell cycle stimulator.

  7. Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway.

    Science.gov (United States)

    Noblet, Jillian N; Goodwill, Adam G; Sassoon, Daniel J; Kiel, Alexander M; Tune, Johnathan D

    2016-05-01

    Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway.

  8. Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ya C Wu

    Full Text Available Hydrogen sulfide (H(2S is a gaseous bacterial metabolite that reaches high levels in the large intestine. In the present study, the effect of H(2S on the proliferation of normal and cancerous colon epithelial cells was investigated. An immortalized colon epithelial cell line (YAMC and a panel of colon cancer cell lines (HT-29, SW1116, HCT116 were exposed to H(2S at concentrations similar to those found in the human colon. H(2S inhibited normal and cancerous colon epithelial cell proliferation as measured by MTT assay. The anti-mitogenic effect of H(2S was accompanied by G(1-phase cell cycle arrest and the induction of the cyclin-dependent kinase inhibitor p21(Cip. Moreover, exposure to H(2S led to features characteristic of autophagy, including increased formation of LC3B(+ autophagic vacuoles and acidic vesicular organelles as determined by immunofluorescence and acridine orange staining, respectively. Abolition of autophagy by RNA interference targeting Vps34 or Atg7 enhanced the anti-proliferative effect of H(2S. Further mechanistic investigation revealed that H(2S stimulated the phosphorylation of AMP-activated protein kinase (AMPK and inhibited the phosphorylation of mammalian target of rapamycin (mTOR and S6 kinase. Inhibition of AMPK significantly reversed H(2S-induced autophagy and inhibition of cell proliferation. Collectively, we demonstrate that H(2S inhibits colon epithelial cell proliferation and induces protective autophagy via the AMPK pathway.

  9. Gut microbial colonization orchestrates TLR2 expression, signaling and epithelial proliferation in the small intestinal mucosa.

    Directory of Open Access Journals (Sweden)

    Nives Hörmann

    Full Text Available The gut microbiota is an environmental factor that determines renewal of the intestinal epithelium and remodeling of the intestinal mucosa. At present, it is not resolved if components of the gut microbiota can augment innate immune sensing in the intestinal epithelium via the up-regulation of Toll-like receptors (TLRs. Here, we report that colonization of germ-free (GF Swiss Webster mice with a complex gut microbiota augments expression of TLR2. The microbiota-dependent up-regulation of components of the TLR2 signaling complex could be reversed by a 7 day broad-spectrum antibiotic treatment. TLR2 downstream signaling via the mitogen-activated protein kinase (ERK1/2 and protein-kinase B (AKT induced by bacterial TLR2 agonists resulted in increased proliferation of the small intestinal epithelial cell line MODE-K. Mice that were colonized from birth with a normal gut microbiota (conventionally-raised; CONV-R showed signs of increased small intestinal renewal and apoptosis compared with GF controls as indicated by elevated mRNA levels of the proliferation markers Ki67 and Cyclin D1, elevated transcripts of the apoptosis marker Caspase-3 and increased numbers of TUNEL-positive cells per intestinal villus structure. In accordance, TLR2-deficient mice showed reduced proliferation and reduced apoptosis. Our findings suggest that a tuned proliferation response of epithelial cells following microbial colonization could aid to protect the host from its microbial colonizers and increase intestinal surface area.

  10. [How Does Lower Urinary Tract Dysfunction Affekt Female Sexuality?].

    Science.gov (United States)

    Anding, R; Kirschner-Hermanns, R; Rantell, A; Wiedemann, A

    2016-08-01

    With increasing age many women suffer from lower urinary tract dysfunction (LUTD) and female sexual dysfunction. An increasing body of evidence supports an association between the 2 conditions. Especially women with urodynamically proved detrusor hyperactivity suffer from sexual dysfunction and there is some evidence that in patients with stress incontinence sexual health improves after successful surgery.

  11. Sexual dysfunctions in men treated for testicular cancer

    DEFF Research Database (Denmark)

    Rosendal, Susanne; Kristensen, Ellids; Giraldi, Annamaria G E

    2008-01-01

    Patients treated for testicular cancer have increased risk of ejaculatory, orgasmic and erectile dysfunction compared with healthy men. The underlying relations are unclear. This review describes sexual dysfunctions that are associated with various treatment modalities. One meta-analysis and 11...... for understanding sexual dysfunctions in patients with testicular cancer....

  12. Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance.

    Science.gov (United States)

    Clavel, Thomas; Desmarchelier, Charles; Haller, Dirk; Gérard, Philippe; Rohn, Sascha; Lepage, Patricia; Daniel, Hannelore

    2014-07-01

    The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions.

  13. Inhibitory effect for proliferation of oral bacteria in dogs by tooth brushing and application of toothpaste

    Science.gov (United States)

    WATANABE, Kazuhiro; KIJIMA, Saku; NONAKA, Chie; MATSUKAWA, Yuki; YAMAZOE, Kazuaki

    2016-01-01

    To investigate inhibitory effect for oral bacterial proliferation, we divided 12 dogs into 3 groups; scaling alone (C; control group), brushing (B) and application of toothpaste (P). Before scaling (Pre) and at 0 to 8 weeks after scaling (0–8 w), we collected oral bacteria from the dental surface every week and counted them using a bacterial counter. The results demonstrated a significant reduction in the number of oral bacteria for group B relative to Pre and group C, as well as for group P relative to group C at 5–7 w. Consequently, brushing may inhibit an increase in the number of oral bacteria, and toothpaste may be effective at a certain level, although not more than that of brushing. PMID:27062999

  14. Dysfunction of Rapid Neural Adaptation in Dyslexia.

    Science.gov (United States)

    Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

    2016-12-21

    Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Transient renal dysfunction with reversible splenial lesion.

    Science.gov (United States)

    Watanabe, Toru; Matsuda, Tomoka; Kitagata, Ryoichi; Tajima, Iwao; Ono, Hiroyuki; Hirano, Keiko; Shirai, Masami; Endoh, Akira; Hongo, Teruaki

    2014-10-01

    We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.

  16. [Endothelial dysfunction in hypertension--clinical implications].

    Science.gov (United States)

    Kosmala, Wojciech

    2002-04-01

    Endothelial cells produce both vasodilatating compounds as nitric oxide, prostacycline, endothelial derived hyperpolarising factor and counteracting substances known as endothelial derived contracting factors: endothelin, tromboxan A2, prostaglandin H2, free oxygen radicals. Natural balance between both groups affects blood perfusion of various tissues and constitutes important element in blood pressure control. More and more attention is paid to endothelial dysfunction in patogenesis of hypertension. In a number of studies endothelial dysfunction in hypertensive patients was found out as decreased release of nitric oxide or increased production of endothelin. Principle mechanism of impaired function of endothelium in hypertension seems to be decreased production and increased degradation of nitric oxide mainly due to free oxygen radicals. Favorable effects in improvement of endothelial function were achieved by using ACE inhibitors, AT1 receptor blockers and calcium channel antagonists.

  17. Microalbuminuria, endothelial dysfunction and cardiovascular risk

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B

    2000-01-01

    Microalbuminuria was originally considered to be an important new risk factor for diabetic nephropathy. More recently, it has been convincingly shown that microalbuminuria is also an independent risk factor for cardiovascular morbidity and mortality in Type 1 and Type 2 diabetic patients. Even...... in the non-diabetic background population, microalbuminuria is a risk factor for cardiovascular mortality. What is the link between increased loss of albumin in urine and cardiovascular disease and mortality? As microalbuminuria is apparently associated with increased universal vascular sieving of albumin...... of functional in vivo tests of endothelial dysfunction have been performed in Type 1 and Type 2 diabetic patients as well as in normal controls. Overall, these studies indicate the existence of a functional vascular dysfunction in Type 1 diabetic patients and normal controls with microalbuminuria, which may...

  18. The current treatment of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2016-10-01

    Full Text Available Erectile dysfunction (ED is the inability to achieve and maintain an erection sufficient for satisfactory sexual intercourse. It is the most frequent sexual dysfunction in elderly men and its prevalence increases with age. Ever since ED was recognized as a real health problem, several treatment options became available and some of them proved to be very efficient. PDE5 inhibitors are the mainstay treatment of ED. However, other treatment options such as intracorporal injections, surgery, vacuum devices and prosthesis are also available for patients who are unresponsive to PDE5 inhibitors. Since none of the treatment options available so far has proven ideal, research in the field of sexual medicine continues. The aim of this paper is to review the most advances in the treatment of ED.

  19. Effects of cigarette smoking on erectile dysfunction.

    Science.gov (United States)

    Kovac, J R; Labbate, C; Ramasamy, R; Tang, D; Lipshultz, L I

    2015-12-01

    Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new smokers, smoking rates remain stubbornly high in certain demographics with 20% of all American middle-aged men smoking. In addition to the well-established harmful effects of smoking (i.e. coronary artery disease and lung cancer), the past three decades have led to a compendium of evidence being compiled into the development of a relationship between cigarette smoking and erectile dysfunction. The main physiologic mechanism that appears to be affected includes the nitric oxide signal transduction pathway. This review details the recent literature linking cigarette smoking to erectile dysfunction, epidemiological associations, dose dependency and the effects of smoking cessation on improving erectile quality.

  20. Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation

    Science.gov (United States)

    Chang, Chao-Chien; Duann, Yeh-Fang; Yen, Ting-Lin; Chen, Yu-Ying; Jayakumar, Thanasekaran; Ong, Eng-Thiam; Sheu, Joen-Rong

    2014-01-01

    Background Aberrant vascular smooth muscle cell (VSMC) proliferation and cerebral endothelial cell (CEC) dysfunction contribute significantly in the pathogenesis of cardiovascular diseases. Therefore, inhibition of these cellular events would be by candidate agents for treating these diseases. In the present study, the mechanism of anti-proliferative and anti-inflammatory effects of andrographolides, a novel nuclear factor-κB inhibitor, was investigated in VSMC and CEC cells. Methods VSMCs and CECs were isolated from rat artery and mouse brain, respectively, and cultured before experimentation. The effect of andro on platelet-derived growth factor-BB (PDGF-BB) induced VSMC cell proliferation was evaluated by cell number, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of extracellular signal regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA), and the effects on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and, cyclooxygenase-2 (COX2) were detected by Western blotting. Results Andro significantly inhibited PDGF-BB (10 ng/ml) induced cell proliferation in a concentration (20-100 μM) dependent manner, which may be due to reducing the expression of ERK1/2, and by inhibiting the expression of PCNA. Andro also remarkably diminished LPS-induced iNOS and COX2 expression. Conclusions The results of this study suggested that the effects of andro against VSMCs proliferation and CECs dysfunction may represent a promising approach for treatment of vascular diseases. PMID:27122804

  1. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C. [ed.

    1993-09-07

    Two essays are included in this booklet. Their titles are ``The Dynamics of the NPT Extension Decision`` and ``North Korea`s Nuclear Gambit.`` The first paper discusses the conference to be held in 1995 to review the Nuclear Non-Proliferation Treaty (NPT) which will decide whether the treaty shall continue in force indefinitely, or shall be extended for an additional fixed period or periods. Topics relevant to this discussion are: Arms control issues, the nuclear test ban, the limited test ban treaty, the French nuclear testing moratorium, former Soviet nuclear weapons, Iraq, North Korea, nuclear-weapon-free zones, security, controls on nuclear weapon materials, peaceful uses of nuclear energy, safeguards, politics, and organizational and procedural issues. The second paper examines short, medium, and long term issues entailed in Korea`s nuclear proliferation. Topics considered include: Korean unification, North Korean politics, the nuclear issue as leverage, and the Nuclear Non- Proliferation Treaty.

  2. Neuropsychological Dysfunction among HIV Infected Drug Abusers

    Directory of Open Access Journals (Sweden)

    Ramani S. Durvasula

    2006-01-01

    Full Text Available Human immunodeficiency virus (HIV has been documented to cause direct and indirect central nervous system dysfunction that can be observed as a progressive decline in neuropsychological functioning in a large proportion of persons with HIV and AIDS. Neuropsychological decline in individuals with HIV is characterized by cognitive and motor slowing, attentional deficits, executive dysfunction and memory impairment (characterized by intact recognition and deficits in learning and delayed recall. Dementia occurs in a relatively small proportion of HIV infected individuals, though milder NP deficits are observed in 30-50% of persons with advanced disease. Recent evidence suggests that drug users, especially stimulant users, are at risk for accelerated progression of their HIV disease, including a greater risk of neuropsychological dysfunction. Methamphetamine may potentiate HIV Tat protein mediated neurotoxicity giving rise to striatal proinflammatory cytokine stimulation and activation of redox-regulated transcription factors. Oxidative stress due to mitochondrial dysfunction is another candidate process underlying the synergistic effects of stimulant use and HIV. Damage to neurotransmitter systems including the dopaminergic, serotonergic and glutamatergic systems which are affected by both stimulant use and HIV is an alternate explanation. Methamphetamine has also been shown to impede the effectiveness of HAART, which could then in turn allow for more rapid HIV disease progression. A greater prevalence of psychiatric disorders, particularly mood, anxiety and substance use disorders are also observed in HIV positive samples relative to the general population. The changing nature of the HIV pandemic is an ongoing challenge to investigators and clinicians working in this field. Emerging issues requiring additional attention are study of the interactive effects of normal aging and HIV on neurocognition as well as study of the effects of co

  3. Sexuality and Sexual Dysfunctions in Bipolar Disorder

    OpenAIRE

    Zeynep Namli; Gonca Karakus; Lut Tamam; Mehmet Emin Demirkol

    2016-01-01

    In the clinical course of bipolar disorder, there is a reduction in sexual will during depressive episodes and inappopriate sexual experiences and hypersexuality occurs during manic episodes. Up to now, studies focused on sexual side effects of drugs. Sexual violence, sexually transmitted diseases, contraception methods, unplanned pregnancies need to be assessed carefully in bipolar disorder patients. This review focused on sexuality and sexual dysfunctions in the course of bipolar disorder. ...

  4. Sexual dysfunction in chronic renal failure.

    Science.gov (United States)

    Soffer, O

    1980-12-01

    Sexual dysfunction in end-stage renal disease is a troublesome, multifactorial disorder. Abnormality of the hypothalamo-pituitary-gonadal axis is but one of the causes leading to the impotence and infertility commonly encountered in chronic renal failure. Short of kidney transplantation, no therapy is available. Though infertility is the rule in end-stage renal disease, successful fatherhood and deliveries have occurred on rare occasions.

  5. Methodological issues of postoperative cognitive dysfunction research

    DEFF Research Database (Denmark)

    Funder, Kamilia S; Steinmetz, Jacob; Rasmussen, Lars S

    2010-01-01

    Postoperative cognitive dysfunction (POCD) is a subtle impairment of memory, concentration, and speed of information processing. It is a frequent complication following surgery and can have a debilitating effect on patients' recovery and future prognosis. Neuropsychological testing is needed...... to reveal postoperative cognitive decline, and questionnaires are not useful for this purpose. There is a profound lack of consensus regarding the research methodology for detection of cognitive deterioration, especially the diagnostic criteria. Issues, such as baseline performance, learning effects...

  6. ATTACHMENT, BORDERLINE PERSONALITY, AND ROMANTIC RELATIONSHIP DYSFUNCTION

    OpenAIRE

    Hill, Jonathan; Stepp, Stephanie D.; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q.; Steele, Miriam; Steele, Howard; Pilkonis, Paul A.

    2011-01-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. S...

  7. Immune Dysfunction in Uremia—An Update

    OpenAIRE

    Gerald Cohen; Hörl, Walter H.

    2012-01-01

    Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense. The specific coordinated roles of polymorphonuclear leukocy...

  8. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction

    Science.gov (United States)

    Coburn, Phillip S.; Wiskur, Brandt J.; Miller, Frederick C.; LaGrow, Austin L.; Astley, Roger A.; Elliott, Michael H.; Callegan, Michelle C.

    2016-01-01

    The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is

  9. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

    Science.gov (United States)

    Coburn, Phillip S; Wiskur, Brandt J; Miller, Frederick C; LaGrow, Austin L; Astley, Roger A; Elliott, Michael H; Callegan, Michelle C

    2016-01-01

    The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is

  10. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

    Directory of Open Access Journals (Sweden)

    Phillip S Coburn

    Full Text Available The blood-retinal barrier (BRB functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE, a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3 was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB

  11. Growth hormone reduces mortality and bacterial translocation in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-de-Segura, I.A.; Miguel, E. de [`La Paz` Hospital, Madrid (Spain). Dept. of Experimental Surgery; Prieto, I. [`La Paz` Hospital, Madrid (Spain). Dept. of General and Digestive Surgery; Grande, A.G. [`La Paz` Hospital, Madrid (Spain). Dept. of Oncology Radiotherapy; Garcia, P.; Mendez, J. [`La Paz` Hospital, Madrid (Spain). Dept. of Clinical Biochemistry; Guerra, A. [`La Paz` Hospital, Madrid (Spain). Dept. of Microbiology

    1998-09-01

    Growth hormone stimulates the growth of intestinal mucosa and may reduce the severity of injury caused by radiation. Male Wistar rats underwent abdominal irradiation (12 Gy) and were treated with either human growth hormone (hGH) or saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation, and the ileal mucosal thickness, proliferation, and disaccharidase activity were assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement (29%, p<0.05). Bacterial translocation was also reduced by hGH (p<0.05). Treating irradiated rats with hGH prevented body weight loss (p<0.05). Mucosal thickness increased faster in irradiated hGH-treated animals. The proliferative index showed an increment in hGH-treated animals (p<0.05). Giving hGH to irradiated rats prevented decrease in sucrose activity, and increment in lactase activity. In conclusion, giving hGH to irradiated rats promotes the adaptative process of the intestine and acute radiation-related negative effects, including mortality, bacterial translocation, and weight loss. (orig.)

  12. PPARγ in Bacterial Infections: A Friend or Foe?

    Science.gov (United States)

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPARγ and its activation during bacterial infections, with focus on the potential of PPARγ agonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPARγ agonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system.

  13. Methylglyoxal promotes oxidative stress and endothelial dysfunction.

    Science.gov (United States)

    Sena, Cristina M; Matafome, Paulo; Crisóstomo, Joana; Rodrigues, Lisa; Fernandes, Rosa; Pereira, Paulo; Seiça, Raquel M

    2012-05-01

    Modern diets can cause modern diseases. Research has linked a metabolite of sugar, methylglyoxal (MG), to the development of diabetic complications, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether MG could directly influence endothelial function, oxidative stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 months were compared with the respective control rats. The effects of MG were investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from the different groups. Insulin resistance, NO bioavailability, glycation, a pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats significantly reduced the efficacy of NO-dependent vasorelaxation (pMethylglyoxal treated GK rats significantly aggravated endothelial dysfunction, oxidative stress, AGEs accumulation and diminished NO bioavailability when compared with control GK rats. These results indicate that methylglyoxal induced endothelial dysfunction in normal Wistar rats and aggravated the endothelial dysfunction present in GK rats. The mechanism is at least in part by increasing oxidative stress and/or AGEs formation with a concomitant increment of inflammation and a decrement in NO bioavailability. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of atherosclerosis and development of macrovascular diabetic complication.

  14. Erectile dysfunction in ankylosing spondylitis patients.

    Science.gov (United States)

    Santana, Thiago; Skare, Thelma; Delboni, Vitor Steil; Simione, Juliana; Campos, Ana Paula B; Nisihara, Renato

    2017-01-01

    Rheumatic diseases such as ankylosing spondylitis (AS) may be associated with sexual dysfunction. To study erectile function of a group of Brazilian AS patients comparing them with controls. This was a cross sectional study approved by the local Committee of Ethics in Research. The questionnaire IIEF (International Index of Erectile Function) was applied to 40 AS patients and 40 healthy controls. AS patients had determination of disease activity (through BASDAI or Bath Ankylosing Spondylitis Disease activity index), ASDAS (Ankylosing Spondylitis Disease Activity Score, MASES or Maastricht Ankylosing Spondylitis Score and SPARCC or Spondyloarthritis Research Consortium of Canada), function (through BASFI or Bath Ankylosing Spondylitis Functional Index and HAQ or Health Assessment Questionnaire) and BASMI (Bath Ankylosing Spondylitis Metrological Index). AS patients had a median score on IIEF of 22.0 (IQR=18-25) while controls had 29 (IQR=27-30) with p<0.0001 Only 17.5% of the AS patients had no erectile dysfunction, in opposite to 87.5% of controls (p<0.0001). IIEF scores had a negative association with BASDAI (p<0.0001), HAQ (p=0.05), body mass index (P=0.03), MASES (P=0.02) and SPARCC (P=0.02) in a univariate analysis. Multiple regression showed that BASDAI was the only variable independently associated with IIEF. There is a high prevalence of erectile dysfunction among AS patients that is associated with disease activity measured by BASDAI. Copyright® by the International Brazilian Journal of Urology.

  15. Role of Nanotechnology in Erectile Dysfunction Treatment.

    Science.gov (United States)

    Wang, Alice Y; Podlasek, Carol A

    2017-01-01

    The biological importance of nanotechnology-based delivery vehicles for in vivo tissue regeneration is gaining acceptance by the medical community; however, its relevance and incorporation into the treatment of sexual dysfunction are evolving and have not been well evaluated. To provide scientific evidence examining the use of state-of-the-art nanotechnology-based delivery methodology in the treatment of erectile dysfunction (ED) in animal models and in patients. This review assessed the current basic science literature examining the role of nanotechnology-based delivery vehicles in the development of potential ED therapies. There are four primary areas where nanotechnology has been applied for ED treatment: (i) topical delivery of drugs for on-demand erectile function, (ii) injectable gels into the penis to prevent morphologic changes after prostatectomy, (iii) hydrogels to promote cavernous nerve regeneration or neuroprotection, and (iv) encapsulation of drugs to increase erectile function (primarily of phosphodiesterase type 5 inhibitors). Basic science studies provide evidence for a significant and evolving role for nanotechnology in the development of therapies for ED and suggest that properly administered nano-based therapies might be advantageous for treating male sexual dysfunction. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  16. Episodic neurological dysfunction in hereditary peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Girish Baburao Kulkarni

    2015-01-01

    Full Text Available Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X was confirmed with detection of mutation in Gap Junction B1 (GJB1 gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation. Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes.

  17. Hypothalamic dysfunction following whole-brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-10-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage.

  18. Acute renal dysfunction in liver diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (MRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

  19. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Gina Rutherford

    2016-01-01

    Full Text Available Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

  20. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome.

    Science.gov (United States)

    Rutherford, Gina; Manning, Philip; Newton, Julia L

    2016-01-01

    Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

  1. Sexual dysfunction with antihypertensive and antipsychotic agents.

    Science.gov (United States)

    Smith, P J; Talbert, R L

    1986-05-01

    The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

  2. Clinical problems and levels of psychosomatic dysfunction

    Directory of Open Access Journals (Sweden)

    Clovis Martins

    1977-03-01

    Full Text Available As an introduction, some doctrinary and technical problems dealing with the complexity of the human mind and the possible approaches to investigate and treat the personality are discussed and, among them, the "medical model" is emphasized. A brief description of some cases in the author's experience are presented; they, at first, had been very difficult to diagnose. However, after some time, they were found to be of indisputable neuro-psychogenetic pathogenesis. The psychosomatic aspects of each case are analyzed, with emphasis on the different levels of pathogenic action and the means of elaboration to defend and readapt the affected personality, resulting in its final clinical expression. There are four possible levels where the primary dysfunction may act; (a physiopathologic neuronal level; (b cerebral subsystemic level; (c psychodynamic level; (d psychosocial level. The primary dysfunction, acting as a new stimulus on each of these levels, may determine in the personality pathologic responses that may assume very complex clinical situations. Many of these responses are quite different from the precipitating primary dysfunction, although there are still many evident links among them.

  3. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper was to system......BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper...... was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... with non-invasive measurements done both pre- and post-operatively and published in English. All types of non-cardiac surgery and both men and women of all ages were included. RESULTS: We found 1722 eligible studies in our search, and of these, five studies fulfilled our inclusion and exclusion criteria...

  4. The Human Vaginal Bacterial Biota and Bacterial Vaginosis

    Directory of Open Access Journals (Sweden)

    Sujatha Srinivasan

    2008-01-01

    Full Text Available The bacterial biota of the human vagina can have a profound impact on the health of women and their neonates. Changes in the vaginal microbiota have been associated with several adverse health outcomes including premature birth, pelvic inflammatory disease, and acquisition of HIV infection. Cultivation-independent molecular methods have provided new insights regarding bacterial diversity in this important niche, particularly in women with the common condition bacterial vaginosis (BV. PCR methods have shown that women with BV have complex communities of vaginal bacteria that include many fastidious species, particularly from the phyla Bacteroidetes and Actinobacteria. Healthy women are mostly colonized with lactobacilli such as Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners, though a variety of other bacteria may be present. The microbiology of BV is heterogeneous. The presence of Gardnerella vaginalis and Atopobium vaginae coating the vaginal epithelium in some subjects with BV suggests that biofilms may contribute to this condition.

  5. Preliminary calculation of proliferation resistance of Pyroprocess

    Energy Technology Data Exchange (ETDEWEB)

    Yeop, Joung Sung; Chang, Soon Heung [Korea Advanced Institute Science and Technology, Daejeon (Korea, Republic of)

    2010-10-15

    We measured the proliferation resistance of Pyroprocess by using multi-attribute utility analysis method. This methodology is intended to allow for the assessment of the effectiveness of safeguards implementation at facilities within a large-scale fuel cycle and allow for the ability to choose technologies based in part on their effectiveness to deter the proliferation of nuclear materials. Pyroprocess may be the part of new Fuel cycle that includes PWR, fuel storage facilities, Pryoprocessing facilities, SFR, fuel repository facilities. In this paper we only focused on Pyroprocessing facilities as a single process

  6. Proliferation risks; Proliferatierisico's

    Energy Technology Data Exchange (ETDEWEB)

    Carchon, R

    1998-09-01

    The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed.

  7. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-12-27

    The Director`s Series on Proliferation is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The seven papers presented in this issue cover the following topics: Should the Treaty on the Nonproliferation of Nuclear Weapons (NPT) be amended?; NPT extension - Legal and procedural issues; An Indonesian view of NPT review conference issues; The treaty of Tlatelolco and the NPT - Tools for peace and development; Perspectives on cut-off, weapons dismantlement, and security assurances; Belarus and NPT challenges; A perspective on the chemical weapons convention - Lessons learned from the preparatory commission.

  8. Does negative-pressure wound therapy influence subjacent bacterial growth? A systematic review.

    Science.gov (United States)

    Glass, Graeme E; Murphy, George R F; Nanchahal, Jagdeep

    2017-08-01

    Negative-pressure wound therapy is a ubiquitous wound management resource. The influence of NPWT on the bacterial bioburden of the subjacent wound remains unclear. We sought to examine the evidence. MEDLINE, Embase, PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles quantitatively evaluating bacterial load under NPWT. Twenty-four studies met the inclusion criteria including 4 randomised controlled trials, 8 clinical series and 12 experimental studies. Twenty studies evaluated conventional NPWT, while 4 evaluated infiltration-based NPWT. While 8 studies using conventional NPWT failed to demonstrate an observable effect on bacterial load, 7 studies reported that NPWT was inherently bacteriostatic and 5 others reported species selectivity with suppression of non-fermentative gram-negative bacilli (NFGNB), including Pseudomonas spp. Simultaneously, there was some evidence of enhanced proliferation of gram-positive cocci where the niche was cleared of NFGNB. Two of the 4 studies using infiltration-based NPWT also reported selectively impaired proliferation of Pseudomonas spp. The assumption that NPWT suppresses bacterial proliferation is oversimplified. There is evidence that NPWT exhibits species selectivity, suppressing the proliferation of NFGNB. However, this may depopulate the niche for exploitation by gram-positive cocci. This, in turn, has implications for the use of NPWT where highly virulent strains of gram-positive cocci have been isolated and the duration of NPWT therapy and frequency of dressing changes. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. A functional genetic variant (N521D in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

    Directory of Open Access Journals (Sweden)

    Naveen L Pereira

    Full Text Available To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs and myocardial structure and function in the general community.NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%. All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007 in the homozygotes G/G (43% than the A/A+A/G (28% group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03. There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

  10. p55PIK Transcriptionally Activated by MZF1 Promotes Colorectal Cancer Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Yu Deng

    2013-01-01

    Full Text Available p55PIK, regulatory subunit of class IA phosphatidylinositol 3-kinase (PI3K, plays a crucial role in cell cycle progression by interaction with tumor repressor retinoblastoma (Rb protein. A recent study showed that Rb protein can localize to the mitochondria in proliferative cells. Aberrant p55PIK expression may contribute to mitochondrial dysfunction in cancer progression. To reveal the mechanisms of p55PIK transcriptional regulation, the p55PIK promoter characteristics were analyzed. The data show that myeloid zinc finger 1, MZF1, is necessary for p55PIK gene transcription activation. ChIP (Chromatin immuno-precipitation assay shows that MZF1 binds to the cis-element “TGGGGA” in p55PIK promoter. In MZF1 overexpressed cells, the promoter activity, expression of p55PIK, and cell proliferation rate were observed to be significantly enhanced. Whereas in MZF1-silenced cells, the promoter activity and expression of p55PIK and cell proliferation level was statistically decreased. In CRC tissues, MZF1 and p55PIK mRNA expression were increased (P=0.046, P=0.047, resp.. A strong positive correlation (Rs=0.94 between MZF1 and p55PIK mRNA expression was observed. Taken together, we concluded that p55PIK is transcriptionally activated by MZF1, resulting in increased proliferation of colorectal cancer cells.

  11. Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat.

    Science.gov (United States)

    de Segura, Ignacio A Gómez; Vallejo-Cremades, María Teresa; Lomas, Jesús; Sánchez, Miriam F; Caballero, María Isabel; Largo, Carlota; De Miguel, Enrique

    2010-04-01

    Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats (n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines.

  12. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp

    2016-09-09

    Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.

  13. New Treatments for Bacterial Keratitis

    Directory of Open Access Journals (Sweden)

    Raymond L. M. Wong

    2012-01-01

    Full Text Available Purpose. To review the newer treatments for bacterial keratitis. Data Sources. PubMed literature search up to April 2012. Study Selection. Key words used for literature search: “infectious keratitis”, “microbial keratitis”, “infective keratitis”, “new treatments for infectious keratitis”, “fourth generation fluoroquinolones”, “moxifloxacin”, “gatifloxacin”, “collagen cross-linking”, and “photodynamic therapy”. Data Extraction. Over 2400 articles were retrieved. Large scale studies or publications at more recent dates were selected. Data Synthesis. Broad spectrum antibiotics have been the main stay of treatment for bacterial keratitis but with the emergence of bacterial resistance; there is a need for newer antimicrobial agents and treatment methods. Fourth-generation fluoroquinolones and corneal collagen cross-linking are amongst the new treatments. In vitro studies and prospective clinical trials have shown that fourth-generation fluoroquinolones are better than the older generation fluoroquinolones and are as potent as combined fortified antibiotics against common pathogens that cause bacterial keratitis. Collagen cross-linking was shown to improve healing of infectious corneal ulcer in treatment-resistant cases or as an adjunct to antibiotics treatment. Conclusion. Fourth-generation fluoroquinolones are good alternatives to standard treatment of bacterial keratitis using combined fortified topical antibiotics. Collagen cross-linking may be considered in treatment-resistant infectious keratitis or as an adjunct to antibiotics therapy.

  14. Bacterial carbonatogenesis; La carbonatogenese bacterienne

    Energy Technology Data Exchange (ETDEWEB)

    Castanier, S. [Angers Univ., 49 (France). Faculte des Sciences; Le Metayer-Levrel, G.; Perthuisot, J.P. [Nantes Univ., 44 (France). Laboratoire de Biogeologie, Faculte des Sciences et des Techniques

    1998-12-31

    Several series of experiments in the laboratory as well as in natural conditions teach that the production of carbonate particles by heterotrophic bacteria follows different ways. The `passive` carbonatogenesis is generated by modifications of the medium that lead to the accumulation of carbonate and bicarbonate ions and to the precipitation of solid particles. The `active` carbonatogenesis is independent of the metabolic pathways. The carbonate particles are produced by ionic exchanges through the cell membrane following still poorly known mechanisms. Carbonatogenesis appears to be the response of heterotrophic bacterial communities to an enrichment of the milieu in organic matter. The active carbonatogenesis seems to start first. It is followed by the passive one which induces the growth of initially produced particles. The yield of heterotrophic bacterial carbonatogenesis and the amounts of solid carbonates production by bacteria are potentially very high as compared to autotrophic or chemical sedimentation from marine, paralic or continental waters. Furthermore, the bacterial processes are environmentally very ubiquitous; they just require organic matter enrichment. Thus, apart from purely evaporite and autotrophic ones, all Ca and/or Mg carbonates must be considered as from heterotrophic bacterial origin. By the way, the carbon of carbonates comes from primary organic matter. Such considerations ask questions about some interpretations from isotopic data on carbonates. Finally, bacterial heterotrophic carbonatogenesis appears as a fundamental phase in the relationships between atmosphere and lithosphere and in the geo-biological evolution of Earth. (author) 43 refs.

  15. Renal dysfunction and coronary disease: a high-risk combination.

    Science.gov (United States)

    Schiele, Francois

    2009-01-01

    Chronic kidney dysfunction is recognized as a risk factor for atherosclerosis and complicates strategies and treatment. Therefore, it is important for cardiologists not only to detect and measure potential kidney dysfunction, but also to know the mechanisms by which the heart and kidney interact, and recognize that in cases of acute coronary syndrome, the presence of renal dysfunction increases the risk of death. The detection and classification of kidney dysfunction into 5 stages is based on the estimated glomerular filtration rate (GFR). The presence of hypertension, endothelial dysfunction, dyslipidemia, inflammation, activation of the renin-angiotensin system and specific calcifications are the main mechanisms by which renal dysfunction can induce or compound cardiovascular disease. The magnitude of renal dysfunction is related to the cardiovascular risk; a linear relation links the extent of GFR decrease and the risk of cardiovascular events. Renal dysfunction and acute coronary syndromes are a dangerous combination: more common comorbidities, more frequent contraindications for effective drugs and higher numbers of drug-related adverse events such as bleeding partially explain the higher mortality in patients with renal dysfunction. In addition, despite higher risk, patients with renal dysfunction often receive fewer guideline-recommended treatments even in the absence of contraindications. Renal dysfunction induces and promotes atherosclerosis by various pathophysiologic pathways and is associated with other cardiovascular risk factors and underuse of appropriate therapy. Therefore, the assessment of renal function is an important step in the risk evaluation of patients with coronary artery disease.

  16. Proliferation kinetics of paramecium tetraurelia in balloon-borne experiments

    Energy Technology Data Exchange (ETDEWEB)

    Croute, F.; Soleilhavoup, J.P.; Vidal, S.; Rousseille, R.; Planel, H.

    1982-06-01

    Experiments were carried out to demonstrate the effect of cosmic radiation, at a balloon-flight ceiling of about 36,500 m (120,000 ft) on single-cell organism proliferation. Paramecium tetraurelia were placed in air-tight containers and maintained at 25 degrees +/- 0.1 degrees C. Cellular growth was determined by cell count, either after recovery or during the flight, by means of an automatic fixation device. Dosimetry was performed by a tissue equivalent proportional counter and was of about 0.5 mrad/h. Flight ceiling duration ranged from 48 min - 22 h. A secondary stimulating effect of growth rate, preceded by a temporary decrease, was observed after recovery. Because of the high bacterial concentration in the trans-Mediterranean flight culture medium, the temporary drop of the growth rate, due to the radiolysis products, disappears. Researchers consider that the stimulating effect can be the result of enzymatic intracellular scavenging of radiolysis products generated in the cell.

  17. Delirium is associated with early postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Rudolph, J.L.; Marcantonio, E.R.; Culley, D.J.

    2008-01-01

    The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects......). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative...... cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive...

  18. oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27(kip1) signaling: opposite effects of oxLDL and cholesterol loading.

    Science.gov (United States)

    Zhang, Chongxu; Adamos, Crystal; Oh, Myung-Jin; Baruah, Jugajyoti; Ayee, Manuela A A; Mehta, Dolly; Wary, Kishore K; Levitan, Irena

    2017-09-01

    Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu(2+)-oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu(2+)-oxLDL enhanced HAECs' proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu(2+)-oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27(kip1)). Both Cu(2+)-oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu(2+)- and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27(kip1) Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis. Copyright © 2017 the American Physiological Society.

  19. Bacterial Degradation of Aromatic Compounds

    Directory of Open Access Journals (Sweden)

    Qing X. Li

    2009-01-01

    Full Text Available Aromatic compounds are among the most prevalent and persistent pollutants in the environment. Petroleum-contaminated soil and sediment commonly contain a mixture of polycyclic aromatic hydrocarbons (PAHs and heterocyclic aromatics. Aromatics derived from industrial activities often have functional groups such as alkyls, halogens and nitro groups. Biodegradation is a major mechanism of removal of organic pollutants from a contaminated site. This review focuses on bacterial degradation pathways of selected aromatic compounds. Catabolic pathways of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, and benzo[a]pyrene are described in detail. Bacterial catabolism of the heterocycles dibenzofuran, carbazole, dibenzothiophene, and dibenzodioxin is discussed. Bacterial catabolism of alkylated PAHs is summarized, followed by a brief discussion of proteomics and metabolomics as powerful tools for elucidation of biodegradation mechanisms.

  20. Acute bacterial and viral meningitis.

    Science.gov (United States)

    Bartt, Russell

    2012-12-01

    Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.