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Sample records for dysfunction bacterial proliferation

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

    PubMed

    Bjornvad, Charlotte R; Thymann, Thomas; Deutz, Nicolaas E; Burrin, Douglas G; Jensen, Søren K; Jensen, Bent B; Mølbak, Lars; Boye, Mette; Larsson, Lars-Inge; Schmidt, Mette; Michaelsen, Kim F; Sangild, Per T

    2008-11-01

    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 recorded in preterm pigs fed enterally (porcine colostrum, bovine colostrum, or formula for 20-40 h), with or without a preceding 2- to 3-day TPN period (n = 435). Mucosal mass increased during TPN and further after enteral feeding to reach an intestinal mass similar to that in enterally fed pigs without TPN (+60-80% relative to birth). NEC developed only after enteral feeding but more often after a preceding TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs. 39%, both P < 0.001, n = 43-170). Further studies in 3-day-old TPN pigs fed enterally showed that formula feeding decreased villus height and nutrient digestive capacity and increased luminal lactic acid and NEC lesions, compared with colostrum (bovine or porcine, P < 0.05). Mucosal microbial diversity increased with enteral feeding, and Clostridium perfringens density was related to NEC severity. Formula feeding decreased plasma arginine, citrulline, ornithine, and tissue antioxidants, whereas tissue nitric oxide synthetase and gut permeability increased, relative to colostrum (all P < 0.05). In conclusion, enteral feeding is associated with gut dysfunction, microbial imbalance, and NEC in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum milk diets improve gut maturation and NEC resistance in preterm pigs subjected to a few days of TPN after birth. PMID:18818317

  2. Peroxisome Proliferator-Activated Receptor γ Regulates Chronic Alcohol-Induced Alveolar Macrophage Dysfunction.

    PubMed

    Yeligar, Samantha M; Mehta, Ashish J; Harris, Frank L; Brown, Lou Ann S; Hart, C Michael

    2016-07-01

    Peroxisome proliferator-activated receptor (PPAR) γ is critical for alveolar macrophage (AM) function. Chronic alcohol abuse causes AM phagocytic dysfunction and susceptibility to respiratory infections by stimulating nicotinamide adenine dinucleotide oxidases (Nox), transforming growth factor-β1, and oxidative stress in the AM. Because PPARγ inhibits Nox expression, we hypothesized that alcohol reduces PPARγ, stimulating AM dysfunction. AMs were examined from: (1) patients with alcoholism or control patients; (2) a mouse model of chronic ethanol consumption; (3) PPARγ knockout mice; or (4) MH-S cells exposed to ethanol in vitro. Alcohol reduced AM PPARγ levels and increased Nox1, -2, and -4, transforming growth factor-β1, oxidative stress, and phagocytic dysfunction. Genetic loss of PPARγ recapitulated, whereas stimulating PPARγ activity attenuated alcohol-mediated alterations in gene expression and phagocytic function, supporting the importance of PPARγ in alcohol-induced AM derangements. Similarly, PPARγ activation in vivo reduced alcohol-mediated impairments in lung bacterial clearance. Alcohol increased levels of microRNA-130a/-301a, which bind to the PPARγ 3' untranslated region to reduce PPARγ expression. MicroRNA-130a/-301a inhibition attenuated alcohol-mediated PPARγ reductions and derangements in AM gene expression and function. Alcohol-induced Toll-like receptor 4 endocytosis was reversed by PPARγ activation. These findings demonstrate that targeting PPARγ provides a novel therapeutic approach for mitigating alcohol-induced AM derangements and susceptibility to lung infection. PMID:26677910

  3. Wakayama Symposium: Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) and Meibomian Gland Dysfunction

    PubMed Central

    Jester, James V.; Brown, Donald J.

    2012-01-01

    Recently we have shown that mouse and human meibomian glands undergo specific age-related changes, including decreased acinar cell proliferation, acinar atrophy, and altered peroxisome proliferator-activated receptor gamma (PPARγ) localization from cytoplasmic-vesicular/nuclear in young mice and humans to nuclear in old mice and humans. Since PPARγ is a lipid-sensitive, nuclear receptor implicated in regulating adipocyte and sebocyte differentiation and lipogenesis, our findings suggest that PPARγ may be involved in modulating meibomian gland differentiation during aging. Based on these findings, we propose that aging of the meibomian gland results in downregulation of PPARγ, leading to decreased meibocyte differentiation and lipid synthesis, gland atrophy, and a hyposecretory meibomian gland dysfunction. PMID:23084144

  4. Bacterial Folates Provide an Exogenous Signal for C. elegans Germline Stem Cell Proliferation.

    PubMed

    Chaudhari, Snehal N; Mukherjee, Madhumati; Vagasi, Alexandra S; Bi, Gaofeng; Rahman, Mohammad M; Nguyen, Christine Q; Paul, Ligi; Selhub, Jacob; Kipreos, Edward T

    2016-07-11

    Here we describe an in vitro primary culture system for Caenorhabditis elegans germline stem cells. This culture system was used to identify a bacterial folate as a positive regulator of germ cell proliferation. Folates are a family of B-complex vitamins that function in one-carbon metabolism to allow the de novo synthesis of amino acids and nucleosides. We show that germ cell proliferation is stimulated by the folate 10-formyl-tetrahydrofolate-Glun both in vitro and in animals. Other folates that can act as vitamins to rescue folate deficiency lack this germ cell stimulatory activity. The bacterial folate precursor dihydropteroate also promotes germ cell proliferation in vitro and in vivo, despite its inability to promote one-carbon metabolism. The folate receptor homolog FOLR-1 is required for the stimulation of germ cells by 10-formyl-tetrahydrofolate-Glun and dihydropteroate. This work defines a folate and folate-related compound as exogenous signals to modulate germ cell proliferation. PMID:27404357

  5. SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation.

    PubMed

    Oliveira, Tales Lyra; Candeia-Medeiros, Návylla; Cavalcante-Araújo, Polliane M; Melo, Igor Santana; Fávaro-Pípi, Elaine; Fátima, Luciana Alves; Rocha, Antônio Augusto; Goulart, Luiz Ricardo; Machado, Ubiratan Fabres; Campos, Ruy R; Sabino-Silva, Robinson

    2016-01-01

    High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it. PMID:26902517

  6. SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation

    PubMed Central

    Oliveira, Tales Lyra; Candeia-Medeiros, Návylla; Cavalcante-Araújo, Polliane M.; Melo, Igor Santana; Fávaro-Pípi, Elaine; Fátima, Luciana Alves; Rocha, Antônio Augusto; Goulart, Luiz Ricardo; Machado, Ubiratan Fabres; Campos, Ruy R.; Sabino-Silva, Robinson

    2016-01-01

    High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it. PMID:26902517

  7. Dysfunctional telomeres induce p53-dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation.

    PubMed

    Wang, Yang; Wang, Xinwei; Flores, Elsa R; Yu, Jian; Chang, Sandy

    2016-08-01

    Aging is associated with progressive telomere shortening, resulting in the formation of dysfunctional telomeres that compromise tissue proliferation. However, dysfunctional telomeres can limit tumorigenesis by activating p53-dependent cellular senescence and apoptosis. While activation of both senescence and apoptosis is required for repress tumor formation, it is not clear which pathway is the major tumor suppressive pathway in vivo. In this study, we generated Eμ-myc; Pot1b(∆/∆) mouse to directly compare tumor formation under conditions in which either p53-dependent apoptosis or senescence is activated by telomeres devoid of the shelterin component Pot1b. We found that activation of p53-dependent apoptosis plays a more critical role in suppressing lymphoma formation than p53-dependent senescence. In addition, we found that telomeres in Pot1b(∆/∆) ; p53(-/-) mice activate an ATR-Chk1-dependent DNA damage response to initiate a robust p53-independent, p73-dependent apoptotic pathway that limited stem cell proliferation but suppressed B-cell lymphomagenesis. Our results demonstrate that in mouse models, both p53-dependent and p53-independent apoptosis are important to suppressing tumor formation. PMID:27113195

  8. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.

    PubMed

    Verbeke, Len; Farre, Ricard; Verbinnen, Bert; Covens, Kris; Vanuytsel, Tim; Verhaegen, Jan; Komuta, Mina; Roskams, Tania; Chatterjee, Sagnik; Annaert, Pieter; Vander Elst, Ingrid; Windmolders, Petra; Trebicka, Jonel; Nevens, Frederik; Laleman, Wim

    2015-02-01

    Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis. PMID:25592258

  9. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap

    PubMed Central

    Laureti, Luisa; Demol, Julien; Fuchs, Robert P.; Pagès, Vincent

    2015-01-01

    DNA Damage Tolerance (DDT) mechanisms help dealing with unrepaired DNA lesions that block replication and challenge genome integrity. Previous in vitro studies showed that the bacterial replicase is able to re-prime downstream of a DNA lesion, leaving behind a single-stranded DNA gap. The question remains of what happens to this gap in vivo. Following the insertion of a single lesion in the chromosome of a living cell, we showed that this gap is mostly filled in by Homology Directed Gap Repair in a RecA dependent manner. When cells fail to repair this gap, or when homologous recombination is impaired, cells are still able to divide, leading to the loss of the damaged chromatid, suggesting that bacteria lack a stringent cell division checkpoint mechanism. Hence, at the expense of losing one chromatid, cell survival and proliferation are ensured. PMID:26713761

  10. Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens

    PubMed Central

    Chang, Hsiao-Han; Cohen, Ted; Grad, Yonatan H.; Hanage, William P.; O'Brien, Thomas F.

    2015-01-01

    SUMMARY Many studies report the high prevalence of multiply drug-resistant (MDR) strains. Because MDR infections are often significantly harder and more expensive to treat, they represent a growing public health threat. However, for different pathogens, different underlying mechanisms are traditionally used to explain these observations, and it is unclear whether each bacterial taxon has its own mechanism(s) for multidrug resistance or whether there are common mechanisms between distantly related pathogens. In this review, we provide a systematic overview of the causes of the excess of MDR infections and define testable predictions made by each hypothetical mechanism, including experimental, epidemiological, population genomic, and other tests of these hypotheses. Better understanding the cause(s) of the excess of MDR is the first step to rational design of more effective interventions to prevent the origin and/or proliferation of MDR. PMID:25652543

  11. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap.

    PubMed

    Laureti, Luisa; Demol, Julien; Fuchs, Robert P; Pagès, Vincent

    2015-12-01

    DNA Damage Tolerance (DDT) mechanisms help dealing with unrepaired DNA lesions that block replication and challenge genome integrity. Previous in vitro studies showed that the bacterial replicase is able to re-prime downstream of a DNA lesion, leaving behind a single-stranded DNA gap. The question remains of what happens to this gap in vivo. Following the insertion of a single lesion in the chromosome of a living cell, we showed that this gap is mostly filled in by Homology Directed Gap Repair in a RecA dependent manner. When cells fail to repair this gap, or when homologous recombination is impaired, cells are still able to divide, leading to the loss of the damaged chromatid, suggesting that bacteria lack a stringent cell division checkpoint mechanism. Hence, at the expense of losing one chromatid, cell survival and proliferation are ensured. PMID:26713761

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

    PubMed

    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. PMID:26849325

  13. SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

    PubMed Central

    2015-01-01

    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. PMID:24749867

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

    PubMed Central

    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 < 0.05, all). Accumulation of polymorphonuclear neutrophils was significantly lower, while microvessel cross-sectional area was significantly higher in the telmisartan, telmisartan-GW9662, and candesartan groups compared with the I/R group (P < 0.05). ICAM-1 and VCAM-1 levels were also significantly lower, and correlated with lower NF-κB expression in these groups. The effects were the most significant in the telmisartan group compared with the telmisartan–GW9662 and candesartan groups. Telmisartan significantly increased PPARG protein expression compared with all other groups (P < 0.05, all). Conclusions Except for the typical effects of angiotensin II-receptor blocker, telmisartan improved microvascular dysfunction during myocardial I/R injury via the

  15. Tagging frogs with passive integrated transponders causes disruption of the cutaneous bacterial community and proliferation of opportunistic fungi.

    PubMed

    Antwis, Rachael E; Garcia, Gerardo; Fidgett, Andrea L; Preziosi, Richard F

    2014-08-01

    Symbiotic bacterial communities play a key role in protecting amphibians from infectious diseases including chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis. Events that lead to the disruption of the bacterial community may have implications for the susceptibility of amphibians to such diseases. Amphibians are often marked both in the wild and in captivity for a variety of reasons, and although existing literature indicates that marking techniques have few negative effects, the response of cutaneous microbial communities has not yet been investigated. Here we determine the effects of passive integrated transponder (PIT) tagging on culturable cutaneous microbial communities of captive Morelet's tree frogs (Agalychnis moreletii) and assess the isolated bacterial strains for anti-B. dendrobatidis activity in vitro. We find that PIT tagging causes a major disruption to the bacterial community associated with the skin of frogs (∼12-fold increase in abundance), as well as a concurrent proliferation in resident fungi (up to ∼200-fold increase). Handling also caused a disruption the bacterial community, although to a lesser extent than PIT tagging. However, the effects of both tagging and handling were temporary, and after 2 weeks, the bacterial communities were similar to their original compositions. We also identify two bacterial strains that inhibit B. dendrobatidis, one of which increased in abundance on PIT-tagged frogs at 1 day postmarking, while the other was unaffected. These results show that PIT tagging has previously unobserved consequences for cutaneous microbial communities of frogs and may be particularly relevant for studies that intend to use PIT tagging to identify individuals involved in trials to develop probiotic treatments. PMID:24878599

  16. Tagging Frogs with Passive Integrated Transponders Causes Disruption of the Cutaneous Bacterial Community and Proliferation of Opportunistic Fungi

    PubMed Central

    Garcia, Gerardo; Fidgett, Andrea L.; Preziosi, Richard F.

    2014-01-01

    Symbiotic bacterial communities play a key role in protecting amphibians from infectious diseases including chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis. Events that lead to the disruption of the bacterial community may have implications for the susceptibility of amphibians to such diseases. Amphibians are often marked both in the wild and in captivity for a variety of reasons, and although existing literature indicates that marking techniques have few negative effects, the response of cutaneous microbial communities has not yet been investigated. Here we determine the effects of passive integrated transponder (PIT) tagging on culturable cutaneous microbial communities of captive Morelet's tree frogs (Agalychnis moreletii) and assess the isolated bacterial strains for anti-B. dendrobatidis activity in vitro. We find that PIT tagging causes a major disruption to the bacterial community associated with the skin of frogs (∼12-fold increase in abundance), as well as a concurrent proliferation in resident fungi (up to ∼200-fold increase). Handling also caused a disruption the bacterial community, although to a lesser extent than PIT tagging. However, the effects of both tagging and handling were temporary, and after 2 weeks, the bacterial communities were similar to their original compositions. We also identify two bacterial strains that inhibit B. dendrobatidis, one of which increased in abundance on PIT-tagged frogs at 1 day postmarking, while the other was unaffected. These results show that PIT tagging has previously unobserved consequences for cutaneous microbial communities of frogs and may be particularly relevant for studies that intend to use PIT tagging to identify individuals involved in trials to develop probiotic treatments. PMID:24878599

  17. The FBPase Encoding Gene glpX Is Required for Gluconeogenesis, Bacterial Proliferation and Division In Vivo of Mycobacterium marinum

    PubMed Central

    Lyu, Liangdong; Wang, Chuan; Li, Yang; Gao, Qian; Yang, Chen

    2016-01-01

    Lipids have been identified as important carbon sources for Mycobacterium tuberculosis (Mtb) to utilize in vivo. Thus gluconeogenesis bears a key role for Mtb to survive and replicate in host. A rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (FBPase) is encoded by the gene glpX. The functions of glpX were studied in M. marinum, a closely related species to Mtb. The glpX deletion strain (ΔglpX) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial proliferation. Metabolic profiles indicate an accumulation of the FBPase substrate, fructose 1, 6-bisphosphate (FBP) and altered gluconeogenic flux when ΔglpX is cultivated in a gluconeogenic carbon substrate, acetate. In both macrophages and zebrafish, the proliferation of ΔglpX was halted, resulting in dramatically attenuated virulence. Intracellular ΔglpX exhibited an elongated morphology, which was also observed when ΔglpX was grown in a gluconeogenic carbon source. This elongated morphology is also supported by the observation of unseparated multi-nucleoid cell, indicating that a complete mycobacterial division in vivo is correlated with intact gluconeogenesis. Together, our results indicate that glpX has essential functions in gluconeogenesis, and plays an indispensable role in bacterial proliferation in vivo and virulence of M. marinum. PMID:27233038

  18. A Small Volatile Bacterial Molecule Triggers Mitochondrial Dysfunction in Murine Skeletal Muscle

    PubMed Central

    Tzika, A. Aria; Constantinou, Caterina; Bandyopadhaya, Arunava; Psychogios, Nikolaos; Lee, Sangseok; Mindrinos, Michael; Martyn, J. A. Jeevendra; Tompkins, Ronald G.; Rahme, Laurence G.

    2013-01-01

    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 associated with a

  19. Bacterial factors exploit eukaryotic Rho GTPase signaling cascades to promote invasion and proliferation within their host

    PubMed Central

    Popoff, Michel R

    2014-01-01

    Actin cytoskeleton is a main target of many bacterial pathogens. Among the multiple regulation steps of the actin cytoskeleton, bacterial factors interact preferentially with RhoGTPases. Pathogens secrete either toxins which diffuse in the surrounding environment, or directly inject virulence factors into target cells. Bacterial toxins, which interfere with RhoGTPases, and to some extent with RasGTPases, catalyze a covalent modification (ADPribosylation, glucosylation, deamidation, adenylation, proteolysis) blocking these molecules in their active or inactive state, resulting in alteration of epithelial and/or endothelial barriers, which contributes to dissemination of bacteria in the host. Injected bacterial virulence factors preferentially manipulate the RhoGTPase signaling cascade by mimicry of eukaryotic regulatory proteins leading to local actin cytoskeleton rearrangement, which mediates bacterial entry into host cells or in contrast escape to phagocytosis and immune defense. Invasive bacteria can also manipulate RhoGTPase signaling through recognition and stimulation of cell surface receptor(s). Changes in RhoGTPase activation state is sensed by the innate immunity pathways and allows the host cell to adapt an appropriate defense response. PMID:25203748

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

    PubMed Central

    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

  1. An Extracellular Bacterial Pathogen Modulates Host Metabolism to Regulate its Own Sensing and Proliferation

    PubMed Central

    Baruch, Moshe; Belotserkovsky, Ilia; Hertzog, Baruch B.; Ravins, Miriam; Dov, Eran; McIver, Kevin S.; Le Breton, Yoann S.; Zhou, Yiting; Youting, Catherine Cheng; Hanski, Emanuel

    2014-01-01

    SUMMARY Successful infection depends on the ability of the pathogen to gain nutrients from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS) causes a vast array of human diseases. By using the quorum sensing sil system as a reporter, we found that during adherence to host cells GAS delivers streptolysin toxins creating endoplasmic reticulum stress. This in turn, increases asparagine (ASN) synthetase expression and the production of ASN. The released ASN is sensed by the bacteria altering the expression of ~17% of GAS genes of which about 1/3 are dependent on the two-component system TrxSR. The expression of the streptolysin toxins is strongly upregulated whereas genes linked to proliferation are downregulated in ASN absence. Asparaginase a widely used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS proliferation in a mouse model of human bacteremia. These results delineate a pathogenic pathway and propose a new therapeutic strategy against GAS infections. PMID:24439371

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

    PubMed

    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. PMID:27533297

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

    PubMed Central

    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

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

    PubMed

    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. PMID:26927959

  5. Early administration of probiotics alters bacterial colonization and limits diet-induced gut dysfunction and severity of necrotizing enterocolitis in preterm pigs.

    PubMed

    Siggers, Richard H; Siggers, Jayda; Boye, Mette; Thymann, Thomas; Mølbak, Lars; Leser, Thomas; Jensen, Bent B; Sangild, Per T

    2008-08-01

    Following preterm birth, bacterial colonization and enteral formula feeding predispose neonates to gut dysfunction and necrotizing enterocolitis (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 (2 d) with porcine colostrum (COLOS; n = 5), formula (FORM; n = 9), or formula with probiotics (FORM-P; Bifidobacterium animalis and Lactobacillus: L. acidophilus, L. casei, L. pentosus, L. plantarum; n = 13). Clinical NEC scores were reduced (P < 0.05) in FORM-P (2.0 +/- 0.2) and COLOS groups (1.7 +/- 0.5) compared with FORM pigs (3.4 +/- 0.6). Lower NEC scores were associated with elevated intestinal weight, mucosa proportion, villus height, RNA integrity, and brush border aminopeptidase A and N activities, and lower gastric organic acid concentration in the FORM-P and COLOS groups (P < 0.05). Diversity of the mucosa-associated bacteria in the distal small intestine was similar among formula-fed pigs, yet the abundance of specific bacterial groups differed between FORM-P and FORM pigs. FORM-P pigs had lower colonization density of a potential pathogen, Clostridium perfringens, and had commensal Lactobacillus bacteria more closely associated with enterocytes along the villus-crypt axis relative to FORM pigs. These results suggest that probiotic administration immediately after birth promotes the colonization of a beneficial commensal microbiota capable of limiting the formula-induced mucosal atrophy, dysfunction, and pathogen load in preterm neonates, thereby reducing the incidence and severity of NEC. PMID:18641188

  6. Antagonist of peroxisome proliferator-activated receptor {gamma} induces cerebellar amyloid-{beta} levels and motor dysfunction in APP/PS1 transgenic mice

    SciTech Connect

    Du, Jing; Sun, Bing; Chen, Kui; Fan, Li; Wang, Zhao

    2009-07-03

    Recent evidences show that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is involved in the modulation of the amyloid-{beta} (A{beta}) cascade causing Alzheimer's disease (AD) and treatment with PPAR{gamma} agonists protects against AD pathology. However, the function of PPAR{gamma} steady-state activity in A{beta} cascade and AD pathology remains unclear. In this study, an antagonist of PPAR{gamma}, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPAR{gamma} activity in cerebellum. The results show that inhibition of PPAR{gamma} significantly induced A{beta} levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of A{beta}. Since cerebellum is spared from significant A{beta} accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPAR{gamma} steady-state activity in protection of cerebellum against AD pathology.

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

    PubMed Central

    Tian, Jun; Pinto, Jayant M.; Cui, Xiaolan; Zhang, Henghui; Li, Li; Liu, Yulong; Wu, Chan; Wei, Yongxiang

    2016-01-01

    Background 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. Objective 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. Methods 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. Results 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

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

    PubMed Central

    Czikora, Istvan; Sridhar, Supriya; Gorshkov, Boris; Alieva, Irina B.; Kasa, Anita; Gonzales, Joyce; Potapenko, Olena; Umapathy, Nagavedi S.; Pillich, Helena; Rick, Ferenc G.; Block, Norman L.; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Schally, Andrew V.; Lucas, Rudolf

    2014-01-01

    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 endothelial 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 (GHRH-R) 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 protein kinase A (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 (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α 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-α 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-α-induced pathway in the presence of PLY, the

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

    PubMed

    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. PMID:27058607

  10. Urinary Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Urinary Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... dysfunction is normal following initial therapy for localized prostate cancer. But it’s important to realize that not all ...

  11. Bacterial senescence: protein oxidation in non-proliferating cells is dictated by the accuracy of the ribosomes

    PubMed Central

    Ballesteros, Manuel; Fredriksson, Åsa; Henriksson, Jaqueline; Nyström, Thomas

    2001-01-01

    We have investigated the causal factors behind the age-related oxidation of proteins during arrest of cell proliferation. A proteomic approach demonstrated that protein oxidation in non-proliferating cells is observed primarily for proteins being produced in a number of aberrant isoforms. Also, these cells exhibited a reduced translational fidelity as demonstrated by both proteomic analysis and genetic measurements of nonsense suppression. Mutants harboring hyperaccurate ribosomes exhibited a drastically attenuated protein oxidation during growth arrest. In contrast, oxidation was augmented in mutants with error-prone ribosomes. Oxidation increased concomitantly with a reduced rate of translation, indicating that the production of aberrant, and oxidized proteins, is not the result of titration of the co-translational folding machinery. The age-related accumulation of the chaperones, DnaK and GroEL, was drastically attenuated in the hyperaccurate rpsL mutant, demonstrating that the reduced translational fidelity in growth-arrested cells may also be a primary cause for the induction of the heat shock regulon. The data point to an alternative way of approaching the causal factors involved in protein oxidation in eukaryotic G0 cells. PMID:11566891

  12. Bacterial lipopolysaccharide induces actin reorganization, intercellular gap formation, and endothelial barrier dysfunction in pulmonary vascular endothelial cells: concurrent F-actin depolymerization and new actin synthesis.

    PubMed

    Goldblum, S E; Ding, X; Brann, T W; Campbell-Washington, J

    1993-10-01

    Bacterial lipopolysaccharide (LPS) influences pulmonary vascular endothelial barrier function in vitro. We studied whether LPS regulates endothelial barrier function through actin reorganization. Postconfluent bovine pulmonary artery endothelial cell monolayers were exposed to Escherichia coli 0111:B4 LPS 10 ng/ml or media for up to 6 h and evaluated for: 1) transendothelial 14C-albumin flux, 2) F-actin organization with fluorescence microscopy, 3) F-actin quantitation by spectrofluorometry, and 4) monomeric G-actin levels by the DNAse 1 inhibition assay. LPS induced increments in 14C-albumin flux (P < 0.001) and intercellular gap formation at > or = 2-6 h. During this same time period the endothelial F-actin pool was not significantly changed compared to simultaneous media controls. Mean (+/- SE) G-actin (micrograms/mg total protein) was significantly (P < 0.002) increased compared to simultaneous media controls at 2, 4, and 6 h but not at 0.5 or 1 h. Prior F-actin stabilization with phallicidin protected against the LPS-induced increments in G-actin (P = 0.040) as well as changes in barrier function (P < 0.0001). Prior protein synthesis inhibition unmasked an LPS-induced decrement in F-actin (P = 0.0044), blunted the G-actin increment (P = 0.010), and increased LPS-induced changes in endothelial barrier function (P < 0.0001). Therefore, LPS induces pulmonary vascular endothelial F-actin depolymerization, intercellular gap formation, and barrier dysfunction. Over the same time period, LPS increased total actin (P < 0.0001) and new actin synthesis (P = 0.0063) which may be a compensatory endothelial cell response to LPS-induced F-actin depolymerization. PMID:8408232

  13. Bowel Dysfunction

    MedlinePlus

    ... PCF Spotlight Glossary African American Men Living with Prostate Cancer Bowel Dysfunction Side Effects Urinary Dysfunction Bowel Dysfunction ... rectal worse. Back to Side Effects Print | Understanding Prostate Cancer Research Faces of Prostate Cancer About PCF Take ...

  14. Down-regulation of the mitochondrial matrix peptidase ClpP in muscle cells causes mitochondrial dysfunction and decreases cell proliferation.

    PubMed

    Deepa, Sathyaseelan S; Bhaskaran, Shylesh; Ranjit, Rojina; Qaisar, Rizwan; Nair, Binoj C; Liu, Yuhong; Walsh, Michael E; Fok, Wilson C; Van Remmen, Holly

    2016-02-01

    The caseinolytic peptidase P (ClpP) is the endopeptidase component of the mitochondrial matrix ATP-dependent ClpXP protease. ClpP degrades unfolded proteins to maintain mitochondrial protein homeostasis and is involved in the initiation of the mitochondrial unfolded protein response (UPR(mt)). Outside of an integral role in the UPR(mt), the cellular function of ClpP is not well characterized in mammalian cells. To investigate the role of ClpP in mitochondrial function, we generated C2C12 muscle cells that are deficient in ClpP using siRNA or stable knockdown using lentiviral transduction. Reduction of ClpP levels by ~70% in C2C12 muscle cells resulted in a number of mitochondrial alterations including reduced mitochondrial respiration and reduced oxygen consumption rate in response to electron transport chain (ETC) complex I and II substrates. The reduction in ClpP altered mitochondrial morphology, changed the expression level of mitochondrial fission protein Drp1 and blunted UPR(mt) induction. In addition, ClpP deficient cells showed increased generation of reactive oxygen species (ROS) and decreased membrane potential. At the cellular level, reduction of ClpP impaired myoblast differentiation, cell proliferation and elevated phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) suggesting an inhibition of translation. Our study is the first to define the effects of ClpP deficiency on mitochondrial function in muscle cells in vitro. In addition, we have uncovered novel effects of ClpP on mitochondrial morphology, cell proliferation and protein translation pathways in muscle cells. PMID:26721594

  15. Telomerase Reverse Transcriptase and Peroxisome Proliferator-Activated Receptor γ Co-Activator-1α Cooperate to Protect Cells from DNA Damage and Mitochondrial Dysfunction in Vascular Senescence.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2015-10-01

    Reduced telomere length with increasing age in dividing cells has been implicated in contributing to the pathologies of human aging, which include cardiovascular and metabolic disorders, through induction of cellular senescence. Telomere shortening results from the absence of telomerase, an enzyme required to maintain telomere length. Telomerase reverse transcriptase (TERT), the protein subunit of telomerase, is expressed only transiently in a subset of adult somatic cells, which include stem cells and smooth muscle cells. A recent report from Xiong and colleagues demonstrates a pivotal role for the transcription co-factor peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) in maintaining TERT expression and preventing vascular senescence and atherosclerosis in mice. Ablation of PGC-1α reduced TERT expression and increased DNA damage and reactive oxygen species (ROS), resulting in shortened telomeres and vascular senescence. In the ApoE(-/-) mouse model of atherosclerosis, forced expression of PGC-1α increased expression of TERT, extended telomeres, and reversed genomic DNA damage, vascular senescence, and the development of atherosclerotic plaques. Alpha lipoic acid (ALA) stimulated expression of PGC-1α and TERT and reversed DNA damage, vascular senescence, and atherosclerosis, similarly to ectopic expression of PGC-1α. ALA stimulated cyclic adenosine monophosphate (cAMP) signaling, which in turn activated the cAMP response element-binding protein (CREB), a co-factor for PGC-1α expression. The possibility that ALA might induce TERT to extend telomeres in human cells suggests that ALA may be useful in treating atherosclerosis and other aging-related diseases. However, further investigation is needed to identify whether ALA induces TERT in human cells, which cell types are susceptible, and whether such changes have clinical significance. PMID:26414604

  16. Diastolic Dysfunction

    PubMed Central

    Jeong, Euy-Myoung; Dudley, Samuel C.

    2016-01-01

    Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction. PMID:25746522

  17. Mitochondrial Dysfunction in Cancer

    PubMed Central

    Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F.

    2013-01-01

    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 established 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 significance 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 of mitochondria 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 knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment. PMID:24350057

  18. Erectile dysfunction.

    PubMed

    Yafi, Faysal A; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P; Hellstrom, Wayne J G

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man's quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner's sexual experience and the couple's quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  19. Restoring Functional Status: A Long-Term Case Report of Severe Lung and Ventilatory Muscle Pump Dysfunction Involving Recurrent Bacterial Pneumonias

    PubMed Central

    Sobush, Dennis C.; Laatsch, Linda; Lipchik, Randolph J.

    2012-01-01

    Background and Purpose Prolonged mechanical ventilation contributes to immobility and deconditioning making efforts to safely discontinue ventilator support desirable. This case report documents how implementing physical therapy treatment interventions, based on the Guide to Physical Therapist Practice, can help to restore a person's functional status even after multiple years of mechanical ventilation dependency. Case Description A patient (female; aged 63 years) with severe restrictive and obstructive ventilatory impairment has survived 34 recurrent pneumonias involving 6 bacterial pathogens while being mechanically ventilated at home. A 3-year study was approved and informed consent obtained for a home exercise program of resistive extremity and inspiratory muscle training along with exercise reconditioning. Tolerable distances walked, maximal inspiratory and expiratory pressures, hours spent on versus off mechanical ventilation, activities performed within and around her home, and community excursions taken were charted. Outcomes Daily time tolerated off the ventilator improved from less than one to 12 hours, distance walked in 6 minutes increased 33%, and maximal inspiratory and expiratory pressures improved 62% and 9.6% respectively. These improvements made out-of-home social excursions possible. Discussion and Conclusions This patient's functional status improved following multiple physical therapy interventions dictated by the evaluation of initial physical therapy examination findings according to the Guide to Physical Therapist Practice. Long term mechanical ventilator dependency in the home environment did not exclude this patient from achieving clinically significant gains in functional status even when having severe restrictive and obstructive ventilator impairment. PMID:22833704

  20. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  1. Ejaculatory dysfunction.

    PubMed

    Phillips, Elizabeth; Carpenter, Christina; Oates, Robert D

    2014-02-01

    Ejaculatory dysfunction may occur after many different disorders ranging from traumatic spinal cord injury to diabetes mellitus. With an understanding of the many facets and nuances of the ejaculatory apparatus, both anatomic and neurologic, the well-versed clinician can proceed along a safe, efficient, and appropriate treatment algorithm to help affected men and their partners achieve parenthood. PMID:24286771

  2. Erectile Dysfunction

    MedlinePlus

    ... or vascular problems, will have a more difficult time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile nerves running alongside the penis stimulate the ... blood to rush in. At the same time, tiny valves at the base of the penis ...

  3. Memory dysfunction.

    PubMed

    Amici, Serena

    2012-01-01

    Memory is the cognitive ability that allows to acquire, store and recall information; its dysfunction is called amnesia and can be a presentation of unilateral ischemic stroke in the territory of the posterior cerebral and anterior choroidal artery as well as subarachnoid hemorrhage. PMID:22377863

  4. Sensory Dysfunction

    MedlinePlus

    ... to Web version Sensory Dysfunction Overview Why are smell and taste important? Your senses of smell and taste let you fully enjoy the scents ... bitter and sour. Flavor involves both taste and smell. For example, because a person is able to ...

  5. Dysfunctional voiding.

    PubMed

    Chiozza, M L

    2002-01-01

    Wetting may be considered the Cinderella of paediatric medicine. Before discussing dysfunctional voiding, the milestones of the normal development of continence in the child and the definitions used to describe this topic are presented. Bladder storage requires (1): accommodation of increasing volumes of urine at low intravesical pressure and with appropriate sensation; (2): a bladder outlet that is closed and not modified during increase in intra-abdominal pressure; (3): absence of involuntary bladder contractions. Development of continence in the child involves three independent factors maturing concomitantly: (1) development of normal bladder capacity; (2) maturation of urethral sphincter function; (3) development of neural control over bladder-sphincter function. All these processes are discussed. Abnormalities of any of these maturational sequences, which run parallel and overlapping, may result in clinically evident abnormalities of bladder sphincter control. Although dysfunctional voiding (DV) in children is very common its prevalence has not been well studied and, to date, and its origin is not well known. In a correct evaluation of functional voiding we must take into account different elements: the bladder capacity (that increases during the first 8 years of life roughly 30 ml per year), the micturition frequency, post-void residual volumes, bladder dynamics, urinary flow rates. Thus the correct assessment of children with lower urinary tract dysfunction should include a detailed history. Signs of DV range from urge syndrome to complex incontinence patterns during the day and the night. In addition to incontinence problems, children may have frequency, urgency, straining to void, weak or interrupted urinary stream, urinary tract infections (UTIs) and chronic constipation with or without encopresis. DV are also referred in enuretic children who wet the bed more than one time per night and have a functional bladder capacity lower than attended for age

  6. [Revisiting meibomian gland dysfunction].

    PubMed

    Baudouin, C

    2014-12-01

    Meibomian gland dysfunctions (MGD) are frequent affections, sometimes asymptomatic, more often responsible for disabling, potentially severe, manifestations. MGD is indeed the most frequent cause of dry eye, through the induction of tear film instability. However, eyelid inflammation, microbial proliferation that modifies melting temperature of meibum, frequent association with skin diseases, as well as potentially severe corneal complications make them complex multifactorial disorders. Complementary mechanisms combine to actually result in a vicious circle, or more accurately a double vicious cycle. The first one is self-stimulated by the microbiological changes, which create their own conditions for MGD development. The second one is related to tear film instability that results from MGD and is also self-stimulated through hyperosmolarity and inflammatory phenomena, which are both consequence and cause of dry eye. We herein propose a new pathophysiological schema on MGD, in order to better identify mechanisms and more efficiently target therapeutics. PMID:25455142

  7. Carbohydrate Metabolism Is Perturbed in Peroxisome-deficient Hepatocytes Due to Mitochondrial Dysfunction, AMP-activated Protein Kinase (AMPK) Activation, and Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Suppression*

    PubMed Central

    Peeters, Annelies; Fraisl, Peter; van den Berg, Sjoerd; Ver Loren van Themaat, Emiel; Van Kampen, Antoine; Rider, Mark H.; Takemori, Hiroshi; van Dijk, Ko Willems; Van Veldhoven, Paul P.; Carmeliet, Peter; Baes, Myriam

    2011-01-01

    Hepatic peroxisomes are essential for lipid conversions that include the formation of mature conjugated bile acids, the degradation of branched chain fatty acids, and the synthesis of docosahexaenoic acid. Through unresolved mechanisms, deletion of functional peroxisomes from mouse hepatocytes (L-Pex5−/− mice) causes severe structural and functional abnormalities at the inner mitochondrial membrane. We now demonstrate that the peroxisomal and mitochondrial anomalies trigger energy deficits, as shown by increased AMP/ATP and decreased NAD+/NADH ratios. This causes suppression of gluconeogenesis and glycogen synthesis and up-regulation of glycolysis. As a consequence, L-Pex5−/− mice combust more carbohydrates resulting in lower body weights despite increased food intake. The perturbation of carbohydrate metabolism does not require a long term adaptation to the absence of functional peroxisomes as similar metabolic changes were also rapidly induced by acute elimination of Pex5 via adenoviral administration of Cre. Despite its marked activation, peroxisome proliferator-activated receptor α (PPARα) was not causally involved in these metabolic perturbations, because all abnormalities still manifested when peroxisomes were eliminated in a peroxisome proliferator-activated receptor α null background. Instead, AMP-activated kinase activation was responsible for the down-regulation of glycogen synthesis and induction of glycolysis. Remarkably, PGC-1α was suppressed despite AMP-activated kinase activation, a paradigm not previously reported, and they jointly contributed to impaired gluconeogenesis. In conclusion, lack of functional peroxisomes from hepatocytes results in marked disturbances of carbohydrate homeostasis, which are consistent with adaptations to an energy deficit. Because this is primarily due to impaired mitochondrial ATP production, these L-Pex5-deficient livers can also be considered as a model for secondary mitochondrial hepatopathies. PMID

  8. Altered T Lymphocyte Proliferation upon Lipopolysaccharide Challenge Ex Vivo

    PubMed Central

    Poujol, Fanny; Monneret, Guillaume; Pachot, Alexandre; Textoris, Julien; Venet, Fabienne

    2015-01-01

    Context Sepsis is characterized by the development of adaptive immune cell alterations, which intensity and duration are associated with increased risk of health-care associated infections and mortality. However, pathophysiological mechanisms leading to such lymphocyte dysfunctions are not completely understood, although both intrinsic lymphocyte alterations and antigen-presenting cells (APCs) dysfunctions are most likely involved. Study The aim of the current study was to evaluate whether lipopolysaccharide (LPS, mimicking initial Gram negative bacterial challenge) could directly impact lymphocyte function after sepsis. Therefore, we explored ex-vivo the effect of LPS priming on human T lymphocyte proliferation induced by different stimuli. Results We showed that LPS priming of PBMCs reduced T cell proliferative response and altered IFNγ secretion after stimulation with OKT3 but not with phytohaemagglutinin or anti-CD2/CD3/CD28-coated beads stimulations. Interestingly only LPS priming of monocytes led to decreased T cell proliferative response as opposed to LPS priming of lymphocytes. Importantly, LPS priming was associated with reduced expression of HLA-DR, CD86 and CD64 on monocytes but not with the modification of CD3, CTLA4, PD-1 and CD28 expressions on lymphocytes. Finally, IFNγ stimulation restored monocytes accessory functions and T cell proliferative response to OKT3. Conclusion We conclude that LPS priming does not directly impact lymphocyte functions but reduces APC’s capacity to activate T cells. This recapitulates ex vivo indirect mechanisms participating in sepsis-induced lymphocyte alterations and suggests that monocyte-targeting immunoadjuvant therapies in sepsis may also help to improve adaptive immune dysfunctions. Direct mechanisms impacting lymphocytes being also at play during sepsis, the respective parts of direct versus indirect sepsis-induced lymphocyte alterations remain to be evaluated in clinic. PMID:26642057

  9. Sexual Dysfunction and Infertility

    MedlinePlus

    ... American Society for Reproductive Medicine Sexual dysfunction and infertility What is sexual dysfunction and how common is ... and 40% of women. For couples dealing with infertility, it is even more common. Often, people ignore ...

  10. Bacterial Sialidase

    NASA Technical Reports Server (NTRS)

    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.

  11. Erectile Dysfunction in Systemic Sclerosis.

    PubMed

    Jaeger, Veronika K; Walker, Ulrich A

    2016-08-01

    Erectile dysfunction (ED) is a major issue in systemic sclerosis (SSc) as it is observed in around 80 to 90 % of men with this connective tissue disease. ED greatly impacts the quality of life and should be actively addressed as a common complication. Whereas ED in the general population is usually associated with risk factors for atherosclerosis as well as cardiovascular disease, the main aetiology of ED in SSc is microangiopathic. In SSc, the blood flow is reduced in the small penile arteries due to corporal fibrosis and myointimal proliferation. There are no data on the prevention of ED in SSc. On-demand phosphodiesterase-5 inhibitors have little effect in improving erectile function, but daily or alternate day regimens of long-acting phosphodiesterase-5 inhibitors provide a measurable, although often limited, benefit. When intracavernous prostaglandin E1 injections are also ineffective, the implantation of a penile prosthesis should be considered as an option. PMID:27402106

  12. Increased Production of Lysozyme Associated with Bacterial Proliferation in Barrett's Esophagitis, Chronic Gastritis, Gluten-induced Atrophic Duodenitis (Celiac Disease), Lymphocytic Colitis, Collagenous Colitis, Ulcerative Colitis and Crohn's Colitis.

    PubMed

    Rubio, Carlos A

    2015-12-01

    The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory. PMID:26637845

  13. Germ Cells Need Folate to Proliferate.

    PubMed

    Walker, Amy K

    2016-07-11

    In this issue of Developmental Cell, Chaudhari and colleagues (2016) use a novel method to create an in vitro proliferative cell line from tumorous C. elegans germ cells, and in the process discover that bacterial folates act as signals for proliferation, independent of their roles as vitamins. PMID:27404353

  14. [Neurogenic erectile dysfunction].

    PubMed

    Ramos, Antonio Sánchez; Durán, Juan Antonio Godino; Oliviero, Antonio

    2010-10-01

    Neurogenic erectile dysfunction is a consequence of alterations in neural pathways, autonomic, somatic, the combination of both or brain components that induce erection. This review aims to explain the physiopathological mechanisms of the most frequent neurological alterations causing erectile dysfunction and sexual disorders. PMID:20978292

  15. [Pharmacotherapy of erectile dysfunction].

    PubMed

    Kovalev, V A; Koroleva, S V; Kamalov, A A

    2000-01-01

    Among the drugs used to treat erectile dysfunction most common are prostaglandins El, viagra, iochimbin, vasodilators and desaggregants, vitamins, biogenic stimulators, etc. The comparative analysis of their efficacy was made in 360 patients with erectile dysfunction, primarily at subcompensated stage, aged 17-83 years. Organic and psychogenic erectile dysfunctions were diagnosed in 69 and 31% of the patients, respectively. Intracavernous injections of prostaglandin El (Caverject) were effective in 74%, transurethral alprostadil (MUSE) when adjusting the dose--in 38.7% of the patients. Iochimbin in patients with organic and psychogenic forms of erectile dysfunctions was effective in 25 and 40% of patients, respectively. In 26.3 and 19% of such patients the response was obtained after use of the combination including xantinol, nicotinate, trental, biogenic stimulators and adaptogens. Viagra was effective in 60 and 77.3% of patients with psychogenic and organic erectile dysfunctions, respectively. PMID:16856460

  16. Insect endosymbiont proliferation is limited by lipid availability

    PubMed Central

    Herren, Jeremy K; Paredes, Juan C; Schüpfer, Fanny; Arafah, Karim; Bulet, Philippe; Lemaitre, Bruno

    2014-01-01

    Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with Drosophila melanogaster. S. poulsonii resides extracellularly in the hemolymph, where it must acquire metabolites to sustain proliferation. In this study, we find that Spiroplasma proliferation specifically depletes host hemolymph diacylglyceride, the major lipid class transported by the lipoprotein, Lpp. RNAi-mediated knockdown of Lpp expression, which reduces the amount of circulating lipids, inhibits Spiroplasma proliferation demonstrating that bacterial proliferation requires hemolymph-lipids. Altogether, our study shows that an insect endosymbiont acquires specific lipidic metabolites from the transport lipoproteins in the hemolymph of its host. In addition, we show that the proliferation of this endosymbiont is limited by the availability of hemolymph lipids. This feature could limit endosymbiont over-proliferation under conditions of host nutrient limitation as lipid availability is strongly influenced by the nutritional state. DOI: http://dx.doi.org/10.7554/eLife.02964.001 PMID:25027439

  17. Insect endosymbiont proliferation is limited by lipid availability.

    PubMed

    Herren, Jeremy K; Paredes, Juan C; Schüpfer, Fanny; Arafah, Karim; Bulet, Philippe; Lemaitre, Bruno

    2014-01-01

    Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with Drosophila melanogaster. S. poulsonii resides extracellularly in the hemolymph, where it must acquire metabolites to sustain proliferation. In this study, we find that Spiroplasma proliferation specifically depletes host hemolymph diacylglyceride, the major lipid class transported by the lipoprotein, Lpp. RNAi-mediated knockdown of Lpp expression, which reduces the amount of circulating lipids, inhibits Spiroplasma proliferation demonstrating that bacterial proliferation requires hemolymph-lipids. Altogether, our study shows that an insect endosymbiont acquires specific lipidic metabolites from the transport lipoproteins in the hemolymph of its host. In addition, we show that the proliferation of this endosymbiont is limited by the availability of hemolymph lipids. This feature could limit endosymbiont over-proliferation under conditions of host nutrient limitation as lipid availability is strongly influenced by the nutritional state. PMID:25027439

  18. Genetics Home Reference: surfactant dysfunction

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions surfactant dysfunction surfactant dysfunction Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Surfactant dysfunction is a lung disorder that causes breathing ...

  19. Bacterial Proteasomes

    PubMed Central

    Jastrab, Jordan B.; Darwin, K. Heran

    2015-01-01

    Interest in bacterial proteasomes was sparked by the discovery that proteasomal degradation is required for the pathogenesis of Mycobacterium tuberculosis, one of the world's deadliest pathogens. Although bacterial proteasomes are structurally similar to their eukaryotic and archaeal homologs, there are key differences in their mechanisms of assembly, activation, and substrate targeting for degradation. In this article, we compare and contrast bacterial proteasomes with their archaeal and eukaryotic counterparts, and we discuss recent advances in our understanding of how bacterial proteasomes function to influence microbial physiology. PMID:26488274

  20. Endothelial dysfunction: a comprehensive appraisal

    PubMed Central

    Esper, Ricardo J; Nordaby, Roberto A; Vilariño, Jorge O; Paragano, Antonio; Cacharrón, José L; Machado, Rogelio A

    2006-01-01

    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 vasodilatation produced by drugs that

  1. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  2. Chronic pelvic floor dysfunction.

    PubMed

    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. PMID:25108498

  3. Eustachian Tube Dysfunction

    MedlinePlus

    ... flying (because of altitude changes). Riding in elevators, driving through mountains or diving may also make your symptoms worse. Causes & Risk Factors What causes eustachian tube dysfunction? The most common ...

  4. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  5. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  6. Sexual Dysfunction in Women

    PubMed Central

    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. PMID:21248971

  7. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  8. Genitourinary dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2010-01-15

    Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:20077468

  9. Bacterial Keratitis

    MedlinePlus

    ... very quickly, and if left untreated, can cause blindness. The bacteria usually responsible for this type of ... to intense ultraviolet radiation exposure, e.g. snow blindness or welder's arc eye). Next Bacterial Keratitis Symptoms ...

  10. PGC-1α, Mitochondrial Dysfunction and Huntington’s Disease

    PubMed Central

    Johri, Ashu; Chandra, Abhishek; Beal, M. Flint

    2013-01-01

    The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington’s disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional master co-regulator of mitochondrial biogenesis, metabolism and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1α in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD. PMID:23602910

  11. Nuclear Proliferation Challenges

    SciTech Connect

    Professor William Potter

    2005-11-28

    William C. Potter, Director of the Center for Non Proliferation Studies and the Center for Russian and Eurasian Studies at the Monterey Institute of International Studies, will present nuclear proliferation challenges following the 2005 Nuclear Non-Proliferation Treaty (NPT) Review Conference. In addition to elucidating reasons for, and implications of, the conference’s failure, Dr. Potter will discuss common ground between nuclear proliferation and terrorism issues and whether corrective action can be taken.

  12. Hop Shoot Proliferation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hop shoot proliferation disease has been described in Poland., and is associated with phytoplasma infection. Hop shoot proliferation occurs rarely and seems to be of little economic concern in most regions of hop production. Hop shoot proliferation is thought to be caused by aster yellows phytoplas...

  13. Neutrophil dysfunction and increased susceptibility to infection.

    PubMed

    Ottonello, L; Dapino, P; Pastorino, G; Dallegri, F; Sacchetti, C

    1995-09-01

    A critical evaluation of 3 years' experience using laboratory screening to detect neutrophil dysfunction is described. Neutrophil dysfunctions in patients with recurrent bacterial infections were investigated by using the following screening tests: (1) neutrophil chemotaxis towards N-formylmethionyl peptides (FMLP) and the complement fragment C5a; (2) neutrophil production of superoxide anions (O2-) in response to phorbol myristate acetate and opsonized zymosan particles; and (3) examination of May-Grünwald and myeloperoxidase cytochemical staining of peripheral blood smears. These tests were carried out in 100 patients suffering from infections and suspected of having altered neutrophil functional competence. A minority of patients was found to have well defined neutrophil dysfunction syndromes: chronic granulomatous disease (four cases), Chediak-Higashi disease (one case) and myeloperoxidase deficiency (one case). Of the remaining 94 patients, in whom infections localized to airways and/or skin predominated, 53 cases were found to have impaired chemotaxis (41 cases) or partial defects of the O2- production. Defects of chemotaxis toward FMLP and those towards both FLMP and C5a were the most frequent abnormalities. No defect was found in the other 41 patients. Moreover, impaired neutrophil chemotaxis was found in some patients with selective IgA deficiency (five cases) or immotile cilia syndrome (seven cases). The results suggest that (a) additional screening tests are required to ameliorate the efficiency of the diagnostic work-up of the patients suspected to have neutrophil dysfunction; and (b) further evaluation, also at the molecular level, should be considered at least in selected cases of non-classified neutrophil dysfunction in order to clarify diagnosis and plan rational therapeutic strategies. PMID:7498244

  14. Dysfunctional Uterine Bleeding

    PubMed Central

    Casper, Robert F.

    1983-01-01

    Dysfunctional uterine bleeding is most commonly associated with chronic anovulation. Early diagnosis of anovulation is important; the induction of regular withdrawal periods using a progestin such as Provera prevents the development of endometrial hyperplasia with the subsequent inevitable occurrence of a heavy, frightening vaginal bleed. The etiology of dysfunctional uterine bleeding occurring during ovulatory cycles is unknown and all medical therapies at present are necessarily experimental. Hysterectomy is probably the treatment of choice for women who have finished their childbearing career and in whom persisting menorrhagia during ovulatory cycles results in anemia. PMID:21283453

  15. Dysfunctional endothelial cells directly stimulate cancer inflammation and metastasis

    PubMed Central

    Franses, Joseph W.; Drosu, Natalia C.; Gibson, William J.; Chitalia, Vipul C.; Edelman, Elazer R.

    2013-01-01

    Although the influence of context-dependent endothelial cell regulation of vascular disease and repair is well-established, the privileged roles endothelial cells play as paracrine regulators of tumor progression has only recently become appreciated. We hypothesized that if the same endothelial physiology governs vascular and cancer biology then endothelial cell control in cancer should follow endothelial regulation of vascular health. Healthy endothelial cells promote vascular repair and inhibit tumor invasiveness and metastasis; dysfunctional endothelial cells have the opposite effects. We now ask if dysfunctionally activated endothelial cells will promote cancer cell inflammatory signaling and aggressive properties. Indeed, while factors released from quiescent ECs induce balanced inflammatory signaling, correlating with decreased proliferation and invasiveness, factors released from dysfunctional ECs robustly activated NF-κB and STAT3 signaling within cancer cells, correlating with increased in vitro invasiveness and decreased proliferation and survival. Furthermore, matrix-embedded dysfunctional endothelial cells stimulated intratumoral pro-inflammatory signaling and spontaneous metastasis, while simultaneously slowing net primary tumor growth, when implanted adjacent to Lewis lung carcinoma tumors. These studies may broaden our realization of the roles of endothelial function and dysfunction, increase understanding and control of the tumor microenvironment, and facilitate optimization of anti-angiogenic and vascular-modifying therapies in cancer and related diseases. PMID:23463345

  16. Effect of Vibration on Bacterial Growth and Antibiotic Resistance

    NASA Technical Reports Server (NTRS)

    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.

  17. Endothelin and endothelial dysfunction.

    PubMed

    Masaki, Tomoh; Sawamura, Tatsuya

    2006-03-01

    Nitric oxide (NO) and endothelin (ET) produced in endothelial cells are leading molecules which regulate vascular function. Failure of the physiological balance between these two molecules is usually referred to as endothelial dysfunction. ET was initially identified as a potent vasoconstrictive peptide. Three ET isoforms and two ET receptors have been identified. One of the isoforms, ET-1, plays a significant role in many cardiovascular diseases. On the other hand, oxidized low-density lipoprotein (oxLDL) is known to induce endothelial dysfunction. The endothelial receptor for oxLDL was cloned, and named lectin-like oxidized receptor-1 (LOX-1). Activation of LOX-1 generates reactive oxygen species (ROS), and acivates a transcriptional factor, nuclear factor κB (NFκB), resulting in down-regulation of NO and up-regulation of ET-1. LOX-1 might be a key molecule in the generation of endothelial dysfunction. In endothelial dysfunction, ET-1 is an aggravating factor of cardiovascular diseases. PMID:25792766

  18. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  19. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    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…

  20. Bacterial Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of bacterial agents reside in and around the environment that can cause illness and death in a poultry flock. Many cause disseminated disease while others exert more local effects such as the respiratory or gastrointestinal tract. The host, for our current purposes the laying hen, has de...

  1. Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes.

    PubMed

    Martin, Lukas; Peters, Carsten; Schmitz, Susanne; Moellmann, Julia; Martincuks, Antons; Heussen, Nicole; Lehrke, Michael; Müller-Newen, Gerhard; Marx, Gernot; Schuerholz, Tobias

    2015-12-01

    The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide-induced mitochondrial dysfunction; however myocardial dysfunction is not restricted to gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared with unstimulated cells (P < 0.0001 and P < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared with unstimulated cells (P = 0.1174 and P = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared with unstimulated cells (P < 0.0001 and P = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared with cells stimulated with HS-free serum (P < 0.0001). Expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) and their co-activators PGC-1α, which regulate mitochondrial function, were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1α mRNA-levels compared with HS-free serum (P = 0.0082, P = 0.0128, and P = 0.0185, respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1α (all P < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting that HS may be targets of therapeutics in septic

  2. [Erectile and Ejaculatory Dysfunction].

    PubMed

    Gross, Oliver; Sulser, Tullio; Eberli, Daniel

    2015-11-25

    The inability to achieve an erection of the penis sufficient for sexual activity is called erectile dysfunction (ED). In most cases, the diagnosis can be made by medical history. The prevalence of ED in men at the age of 65 has been reported to be up to 50%. Premature ejaculation has a prevalence, up to 20% and is the most frequent ejaculatory dysfunction. The etiology of ED can involve psychological, vascular, neurogenic, hormonal or urogenital pathologies. The main pathophysiological mechanisms of ED are vascular disorders such as diabetes mellitus and atherosclerosis. Because of the common pathophysiology, patients diagnosed with ED should have a diagnostic work-up for systemic vascular pathologies to prevent concomitant cardiac events. Treatment options include invasive and non-invasive procedures. PMID:26602851

  3. Thyroid dysfunction and subfertility

    PubMed Central

    2015-01-01

    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. PMID:26816871

  4. Preclinical Diastolic Dysfunction

    PubMed Central

    Wan, Siu-Hin; Vogel, Mark W.; Chen, Horng H

    2014-01-01

    Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed. PMID:24291270

  5. [Bacterial vaginosis].

    PubMed

    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. PMID:27474242

  6. Role of UCP2 in the protective effects of PPARβ/δ activation on lipopolysaccharide-induced endothelial dysfunction.

    PubMed

    Toral, Marta; Romero, Miguel; Jiménez, Rosario; Robles-Vera, Iñaki; Tamargo, Juan; Martínez, María Carmen; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2016-06-15

    Bacterial endotoxin lipopolysaccharide (LPS) activates inflammatory pathways, induces cytokine expression in the endothelium, augments reactive oxygen species (ROS) production in the vascular wall, and induces endothelial dysfunction. The aim of the present study was to analyze the effects of peroxisome proliferator-activated receptor (PPAR)β/δ activation on LPS-induced inflammation, oxidative stress and endothelial dysfunction and to determine whether uncoupling protein-2 (UCP2) plays a role in these effects. In vivo, the PPARβ/δ agonist GW0742 treatment prevented the LPS-induced reduction in aortic relaxation, the increase in vascular ROS production, the upregulation of NOX1, NOX2, p47(phox), and p22(phox) mRNA levels, and the endoplasmic reticulum (ER) stress markers in mice. We show that in mouse aortic endothelial cells (MAECs), GW0742 prevented the decreased A23187-stimulated nitric oxide (NO) production, and the increased intracellular ROS levels caused by exposure to LPS in vitro. The PPARβ/δ antagonist GSK0660 abolished all these in vivo and in vitro protective effects induced by GW0742. This agonist also restored the reduced expression of UCP2 and mitofusin-2 induced by LPS. The effects of GW0742 on NO and ROS production in MAEC exposed to LPS were abolished by the UCP2 inhibitor genipin or by siRNA targeting UCP-2. Genipin also suppressed the expressional changes on NADPH oxidase and ER stress markers induced by GW0742. In conclusion, PPARβ/δ activation restored the LPS-induced endothelial dysfunction by upregulation of UCP2, with the subsequent alleviation of ER stress and NADPH oxidase activity, thus reducing intracellular ROS production and increasing NO bioavailability. PMID:27179975

  7. Bacterial cell biology outside the streetlight.

    PubMed

    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. PMID:27306428

  8. Bacterial cell biology outside the streetlight

    PubMed Central

    2016-01-01

    Summary 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. PMID:27306428

  9. Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction.

    PubMed

    Ramatchandirin, Balamurugan; Sadasivam, Mohanraj; Kannan, Arun; Prahalathan, Chidambaram

    2016-04-01

    Bacterial lipopolysaccharide (LPS) is the most important contributing factor in pathogenesis of bacterial infection in male accessory glands; and it has shown to inhibit testicular steroidogenesis and induce apoptosis. The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis. LC-540 Leydig cells treated with LPS (10 µg/ml) showed impaired steroidogenesis and increased cellular apoptosis. The mRNA and protein expression of SIRT4 were decreased in LPS treated cells when compared to controls. The obtained data suggest that the c-Jun N-terminal kinase (JNK) activation suppresses SIRT4 expression in LPS treated Leydig cells. Furthermore, the overexpression of SIRT4 prevented LPS induced impaired steroidogenesis and cellular apoptosis by improving mitochondrial function. These findings provide valuable information that SIRT4 regulates LPS mediated Leydig cell dysfunction. PMID:26365714

  10. Environmental enteric dysfunction: An overview

    PubMed Central

    Crane, Rosie J.; Jones, Kelsey D. J.; Berkley, James A.

    2015-01-01

    Background Environmental enteric dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries. Understanding of EED and its possible consequences for health is currently limited. Objective A narrative review of the current understanding of EED: epidemiology, pathogenesis, therapies, and relevance to child health. Methods Searches for key papers and ongoing trials were conducted using PUBMED 1966–June 2014; ClinicalTrials.gov; the WHO Clinical Trials Registry; the Cochrane Library; hand searches of the references of retrieved literature; discussions with experts; and personal experience from the field. Results EED is established during infancy and is associated with poor sanitation, certain gut infections, and micronutrient deficiencies. Helicobacter pylori infection, small intestinal bacterial overgrowth (SIBO), abnormal gut microbiota, undernutrition, and toxins may all play a role. EED is usually asymptomatic, but it is important due to its association with stunting. Diagnosis is frequently by the dual sugar absorption test, although other biomarkers are emerging. EED may partly explain the reduced efficacy of oral vaccines in low- and middle-income countries and the increased risk of serious infection seen in children with undernutrition. Conclusions Despite its potentially significant impacts, it is currently unclear exactly what causes EED and how it can be treated or prevented. Ongoing trials involve nutritional supplements, water and sanitation interventions, and immunomodulators. Further research is needed to better understand this condition, which is of likely crucial importance for child health and development in low- and middle-income settings. PMID:25902619

  11. Management of ejaculatory dysfunction.

    PubMed

    McMahon, C G

    2014-02-01

    Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20-30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well-controlled, evidence-based studies have demonstrated the efficacy and safety of selective serotonin re-uptake inhibitors in delaying ejaculation, confirming their role as first-line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large-scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side-effects or are yet considered experimental in nature. PMID:24528812

  12. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population. PMID:26441369

  13. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  14. Bacterial Games

    NASA Astrophysics Data System (ADS)

    Frey, Erwin; Reichenbach, Tobias

    Microbial laboratory communities have become model systems for studying the complex interplay between nonlinear dynamics of evolutionary selection forces, stochastic fluctuations arising from the probabilistic nature of interactions, and spatial organization. Major research goals are to identify and understand mechanisms that ensure viability of microbial colonies by allowing for species diversity, cooperative behavior and other kinds of "social" behavior. A synthesis of evolutionary game theory, nonlinear dynamics, and the theory of stochastic processes provides the mathematical tools and conceptual framework for a deeper understanding of these ecological systems. We give an introduction to the modern formulation of these theories and illustrate their effectiveness, focusing on selected examples of microbial systems. Intrinsic fluctuations, stemming from the discreteness of individuals, are ubiquitous, and can have important impact on the stability of ecosystems. In the absence of speciation, extinction of species is unavoidable, may, however, take very long times. We provide a general concept for defining survival and extinction on ecological time scales. Spatial degrees of freedom come with a certain mobility of individuals. When the latter is sufficiently high, bacterial community structures can be understood through mapping individual-based models, in a continuum approach, onto stochastic partial differential equations. These allow progress using methods of nonlinear dynamics such as bifurcation analysis and invariant manifolds. We conclude with a perspective on the current challenges in quantifying bacterial pattern formation, and how this might have an impact on fundamental research in nonequilibrium physics .

  15. Diastolic dysfunction in cirrhosis.

    PubMed

    Møller, Søren; Wiese, Signe; Halgreen, Hanne; Hove, Jens D

    2016-09-01

    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 stiffness of the cirrhotic heart may decrease the compliance and result in DD. The prevalence of DD in cirrhotic patients averages about 50 %. It can be evaluated by transmitral Doppler echocardiography, tissue Doppler echocardiography, and cardiac magnetic resonance imaging. There seems to be a relation between DD and the severity of liver dysfunction and the presence of ascites. After liver transplantation, DD worsens the prognosis and increases the risk of graft rejection, but DD improves after few months. Insertion of a transjugular intrahepatic portosystemic shunt increases left ventricular diastolic volumes, and DD is a predictor of poorer survival in these patients. Future studies should aim at disclosing pathophysiological mechanisms behind the developing of DD in cirrhosis in relation to patient characteristics, development of complications, treatment, and risk associated with interventional procedures. PMID:27075496

  16. Mitochondrial dysfunction during sepsis.

    PubMed

    Azevedo, Luciano Cesar Pontes

    2010-09-01

    Sepsis and multiple organ failure remain leading causes of death in intensive care patients. Recent advances in our understanding of the pathophysiology of these syndromes include a likely prominent role for mitochondria. Patient studies have shown that the degree of mitochondrial dysfunction is related to the eventual outcome. Associated mechanisms include damage to mitochondria or inhibition of the electron transport chain enzymes by nitric oxide and other reactive oxygen species (the effects of which are amplified by co-existing tissue hypoxia), hormonal influences that decrease mitochondrial activity, and downregulation of mitochondrial protein expression. Notably, despite these findings, there is minimal cell death seen in most affected organs, and these organs generally regain reasonably normal function should the patient survive. It is thus plausible that multiple organ failure following sepsis may actually represent an adaptive state whereby the organs temporarily 'shut down' their normal metabolic functions in order to protect themselves from an overwhelming and prolonged insult. A decrease in energy supply due to mitochondrial inhibition or injury may trigger this hibernation/estivation-like state. Likewise, organ recovery may depend on restoration of normal mitochondrial respiration. Data from animal studies show histological recovery of mitochondria after a septic insult that precedes clinical improvement. Stimulation of mitochondrial biogenesis could offer a new therapeutic approach for patients in multi-organ failure. This review will cover basic aspects of mitochondrial function, mechanisms of mitochondrial dysfunction in sepsis, and approaches to prevent, mitigate or speed recovery from mitochondrial injury. PMID:20509844

  17. Sexual dysfunction in uremia.

    PubMed

    Palmer, B F

    1999-06-01

    In summary, sexual dysfunction is a common finding in both men and women with chronic renal failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently accompany the chronic renal failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamicpituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first-line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic renal failure. PMID:10361878

  18. JPRS report. Proliferation issues

    SciTech Connect

    1992-03-26

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies.

  19. Client attributions for sexual dysfunction.

    PubMed

    Fichten, C S; Spector, I; Libman, E

    1988-01-01

    This investigation examined attributions for sexual dysfunctions made by 63 individuals and 21 of their partners who presented at a sex therapy service for the following problems: erectile dysfunction, premature ejaculation, and female orgasmic dysfunctions. All participants completed measures of marital adjustment, locus of control, depression and a questionnaire which assessed: attributions of responsibility for the sexual problem, perceived control over sexual functioning, distress, effort made to improve the sexual relationship, and expectations about the efficacy of sex therapy for the problem. Results indicate that both identified patients and their partners, regardless of the dysfunction, blamed the sexual problem on the "dysfunctional individual" rather than on the circumstances or the partner. With respect to the partners, husbands of women with orgasmic dysfunction were more likely to blame themselves than the circumstances, while the opposite was true for wives of males with erectile difficulties. Individuals experiencing the dysfunction perceived themselves and their partners as having little, but equal control over the identified patient's sexuality. Correlational analyses indicate that in identified patients, the better the quality of the marital relationship, the greater the self-blame and the lower the partner blame. Those with happy marriages also made greater efforts to improve their sexual relationship and had higher expectations of success with therapy. The implications of the results for research on the role of attributions in sexual dysfunction and for assessment of cognitive factors in sexually dysfunctional individuals and their partners is discussed. PMID:3172253

  20. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    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. PMID:27143888

  1. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    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.

  2. [Towards bacterial detection in labile blood products].

    PubMed

    Morel, P

    2005-06-01

    Bacterial contamination of blood components represents today the highest infectious risk in blood transfusion, the risk is particularly high when it affects platelet concentrates. The prevention methods developed over the past ten years (donor selection, phlebotomy site preparation, first 30 ml diversion, systematic leuko-reduction...) which aimed at limiting the introduction of bacteria in donations and bacterial proliferation, has reduced the risk of transfusion reaction due to the bacterial contamination. Improving strategies for reducing the risks of bacterial contamination is one of the priorities of the French National Blood Transfusion Service (l'Etablissement français du sang - EFS). It is essential to improve existent prevention methods and develop the implication of all the actors (from donation to transfusion) involved in the prevention of this risk. Bacterial detection or pathogens inactivation are now available and are able to reduce (for detection) or prevent (for inactivation) the occurrence of reaction due to bacterial contamination of PC. Up to now, the choice is in favour of bacterial detection. Three methods (BacT/Alert, BioMerieux; eBDS, Pall; ScanSystem, Hemosystem) of detection of bacterial contamination in PC can be generalised now. Adaptations, need for their implementation are acceptable, especially concerning PC availability. PMID:15894499

  3. Meibomian gland dysfunction: hyperkeratinization or atrophy?

    PubMed

    Jester, James V; Parfitt, Geraint J; Brown, Donald J

    2015-01-01

    Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes. PMID:26817690

  4. Bacterial Hydrodynamics

    NASA Astrophysics Data System (ADS)

    Lauga, Eric

    2016-01-01

    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 micrometer 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, I review the biomechanics of bacterial motility and look ahead to future challenges.

  5. Sexual dysfunctions and psychoanalysis.

    PubMed

    Levine, E M; Ross, N

    1977-06-01

    The authors examine the major factors involved in recent changes in the social standards and attitudes related to homosexuality. The principal influences investigated include the misconstrued emphasis given to the humanist ideology, which properly stresses the dignity of the individual; the social sciences' relativization of the cultural norms defining homosexuality; the influence of the mass media in disseminating these perspectives and thereby tending to create an acceptable image of homosexuality, and the tendency of all these changes to result in a substantial increase in public acceptance and tolerance of homosexuality. The authors suggest that this trend in public opinion has begun to isolate psychoanalytic knowledge, to reduce its status and acceptability among the public, and to replace it with popular views concerning the meaning of sexual dysfunctions. PMID:869030

  6. Endothelial dysfunction and antioxidants.

    PubMed

    Duvall, W Lane

    2005-03-01

    The vascular endothelium plays a crucial role in the physiology of blood vessels and the pathological processes of atherosclerotic disease and acute coronary syndromes. Endothelial dysfunction is the core problem; it is an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide activity in the vessel wall, which results in impairment in the regulation of vascular homeostasis. Further understanding of its mechanisms of action and possible therapeutic targets will be of great importance. The group of antioxidant vitamins, A, C and E, would seem uniquely situated to reduce cardiovascular events by improving endothelial function by reducing the concentration of reactive oxygen species in the vessel wall and by preventing oxidative modification of low-density lipoprotein. Unfortunately, despite extensive studies in both observational and randomized trials, the weight of evidence points to little or no benefit from antioxidant therapy. PMID:15770336

  7. [Reactive airways dysfunction syndrome].

    PubMed

    Costa, R; Orriols, R

    2005-01-01

    Reactive airways dysfunction syndrome, better known as RADS, was described as a clinical entity consisting in the appearance of bronchial asthma due to massive toxic inhalation. The term was coined and recognised for the first time in 1985. Since then different publications have verified new cases as well as different causal agents. It usually arises from an accident at the work place and in closed or poorly ventilated spaces, where high concentrations of irritant products are inhaled in the form of gas, smoke or vapour. In the following minutes or hours symptoms of bronchial obstruction appear in an acute form, with bronchial hyperresponsiveness persisting for months or years. The affected patients do not show a recurrence of symptoms following exposure to non-toxic doses of the same agent that started the symptoms. This is why diagnosis is based on clinical manifestations as it is not reproducible through a provocation test. PMID:15915173

  8. Telomere dysfunction and chromothripsis.

    PubMed

    Ernst, Aurélie; Jones, David T W; Maass, Kendra K; Rode, Agata; Deeg, Katharina I; Jebaraj, Billy Michael Chelliah; Korshunov, Andrey; Hovestadt, Volker; Tainsky, Michael A; Pajtler, Kristian W; Bender, Sebastian; Brabetz, Sebastian; Gröbner, Susanne; Kool, Marcel; Devens, Frauke; Edelmann, Jennifer; Zhang, Cindy; Castelo-Branco, Pedro; Tabori, Uri; Malkin, David; Rippe, Karsten; Stilgenbauer, Stephan; Pfister, Stefan M; Zapatka, Marc; Lichter, Peter

    2016-06-15

    Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. PMID:26856307

  9. HIV and neurocognitive dysfunction.

    PubMed

    Spudich, Serena

    2013-09-01

    The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists despite ART remains a challenge to the community of patients, providers and investigators aiming to optimize quality of life for those living with HIV. Cognitive dysfunction in treated HIV may reflect early irreversible CNS injury accrued before ART is typically initiated, ongoing low-level CNS infection and progressive injury in the setting of ART, or comborbidities including effects of treatment which may confound the beneficial reduction in viral replication and immune activation effected by ART. PMID:23860944

  10. [Sexual dysfunction in torture victims].

    PubMed

    Theilade, Lotte D Arlø

    2002-10-01

    Sexual dysfunction is seen in up to 51% of torture victims. The torture victim seldom reports anything about having been tortured but often consults the health care system because of a somatic problem which may seem unrelated to torture. Therefore, it is important that doctors are aware of the possible correlation. Symptoms and findings may be both physical and psychical. The torture may be both sexual and non-sexual as well as physical and non-physical. Social, cultural and individual factors also influence the development of sexual dysfunction in a torture victim. The factors that cause sexual dysfunction and the identification of any direct causal relations are discussed. There are indications that sexual torture has a greater impact on the development of sexual dysfunction than other types of torture and it seems that sexual dysfunction is a result of many factors. PMID:12407879

  11. Dysfunctional uterine bleeding (DUB).

    PubMed

    Bulletti, C; Flamigni, C; Prefetto, R A; Polli, V; Giacomucci, E

    1994-09-30

    Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB. PMID:7978956

  12. Bacterial vaginosis.

    PubMed Central

    Spiegel, C A

    1991-01-01

    Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed. PMID:1747864

  13. [Hormonal etiology in erectile dysfunction].

    PubMed

    Jabaloyas, José María Martínez

    2010-10-01

    The proper function of erection mechanisms depend on correct interrelationship between psychological, vascular, neurological and hormonal factors. Endocrine diseases affect sexual function, and sexual dysfunction may be one of the symptoms of some hormonal anomalies. Diabetes mellitus is the endocrine disease most frequently causing erectile dysfunction due to the frequent vascular and neurological complications associated. It is important to determine blood glucose in the initial evaluation of a male with erectile dysfunction, as well as to try an adequate control of blood glucose levels to avoid worsening. Diabetic male erectile dysfunction is multifactorial, more severe and has worse response to oral treatment. Hyperprolactinemia causes disorders of the sexual sphere because it produces a descent of testosterone. In these cases, sexual symptoms are treated by correcting the levels of prolactin. Routine determination of prolactin is not clear and it seems it should be determined when testosterone levels are diminished. Thyroid hormone disorders (both hyper and hypotyroidism) are associated with erectile dysfunction, which will subside in half the patients with thyroid hormone normalization. The role of adrenal hormones in erectile function is not clear and their routine determination is not considered in the diagnostic evaluation of erectile dysfunction. The role of estradiol in the regulation of the erection mechanism is not well known either, although it is known that high levels may cause erectile dysfunction. Among endocrine-metabolic disorders we point out dyslipemias, with hypercholesterolemia as an important risk factor for erectile dysfunction and, though its correction may prevent vascular system deterioration, the role of statins in erectile dysfunction is not clear. PMID:20978293

  14. [Thyroid dysfunction during pregnancy].

    PubMed

    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. PMID:25433782

  15. Primary Graft Dysfunction

    PubMed Central

    Christie, Jason D

    2014-01-01

    Primary graft dysfunction (PGD) is a syndrome encompassing a spectrum of mild to severe lung injury that occurs within the first 72 hours after lung transplantation. PGD is characterized by pulmonary edema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. In recent years, new knowledge has been generated on risks and mechanisms of PGD. Following ischemia and reperfusion, inflammatory and immunological injury-repair responses appear to be key controlling mechanisms. In addition, PGD has significant impact on short- and long-term outcomes; therefore, the choice of donor organ is impacted by this potential adverse consequence. Improved methods of reducing PGD risk and efforts to safely expand the pool are being developed. Ex-vivo lung perfusion is a strategy which may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review will detail recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers and state-of-the-art technical developments affecting PGD. (158 words) PMID:23821506

  16. Bacterial tyrosinases.

    PubMed

    Claus, Harald; Decker, Heinz

    2006-01-01

    Tyrosinases are nearly ubiquitously distributed in all domains of life. They are essential for pigmentation and are important factors in wound healing and primary immune response. Their active site is characterized by a pair of antiferromagnetically coupled copper ions, CuA and CuB, which are coordinated by six histidine residues. Such a "type 3 copper centre" is the common feature of tyrosinases, catecholoxidases and haemocycanins. It is also one of several other copper types found in the multi-copper oxidases (ascorbate oxidase, laccase). The copper pair of tyrosinases binds one molecule of atmospheric oxygen to catalyse two different kinds of enzymatic reactions: (1) the ortho-hydroxylation of monophenols (cresolase activity) and (2) the oxidation of o-diphenols to o-diquinones (catecholase activity). The best-known function is the formation of melanins from L-tyrosine via L-dihydroxyphenylalanine (L-dopa). The complicated hydroxylation mechanism at the active centre is still not completely understood, because nothing is known about their tertiary structure. One main reason for this deficit is that hitherto tyrosinases from eukaryotic sources could not be isolated in sufficient quantities and purities for detailed structural studies. This is not the case for prokaryotic tyrosinases from different Streptomyces species, having been intensively characterized genetically and spectroscopically for decades. The Streptomyces tyrosinases are non-modified monomeric proteins with a low molecular mass of ca. 30kDa. They are secreted to the surrounding medium, where they are involved in extracellular melanin production. In the species Streptomyces, the tyrosinase gene is part of the melC operon. Next to the tyrosinase gene (melC2), this operon contains an additional ORF called melC1, which is essential for the correct expression of the enzyme. This review summarizes the present knowledge of bacterial tyrosinases, which are promising models in order to get more insights in

  17. JPRS report proliferation issues

    SciTech Connect

    1991-11-18

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) China; (2) Indonesia; (3) Bulgaria; (4) Brazil, Cuba; (5) Egypt, India, Iran, Iraq, Israel, Pakistan; (6) Soviet Union; and (7) France, Germany, United Kingdom, Italy, Norway.

  18. Cell Proliferation in Neuroblastoma.

    PubMed

    Stafman, Laura L; Beierle, Elizabeth A

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  19. Proliferation: Threat and response

    SciTech Connect

    1996-04-01

    ;Table of Contents: Section I: The Regional Proliferation Challenge; Northeast Asia; The Middle East and North Africa; The Former Soviet Union: Russia, Ukrane, Kazakstan, And Belarus; South Asia; The International Threat: Dangers from Terrorism, Insurgencies, Civil Wars, And Organized Crime; Section II: Department of Defense Response; Technical Annex: Accessible Technologies; Glossary.

  20. Controlling nuclear proliferation

    SciTech Connect

    Sweet, W.

    1981-07-17

    Nuclear non-proliferation policy depends on the 1968 Non-Proliferation Treaty, in which countries promise not to acquire nuclear weapons in exchange for open access to peaceful nuclear technology, and a system of international safeguards that are imposed on exported nuclear equipment and facilities operated by parties to the treaty. Critics have feared all along that non-nuclear countries might circumvent or exploit the system to obtain nuclear weapons and that the Atoms for Peace plan would spread the very technology it sought to control. The nuclear weapons states would like everyone else to believe that atomic bombs are undesirable, but they continue to rely on the bombs for their own defense. Israel's raid on Iraq's nuclear reactor focused world attention on the proliferation problem and helped to broaden and sterengthen its prospects. It also highlighted the weakness that there are no effective sanctions against violators. Until the international community can ageee on enforcement measures powerful enough to prevent nuclear proliferation, individual countries may be tempted to follow Israel's example, 19 references.

  1. Cell Proliferation in Neuroblastoma

    PubMed Central

    Stafman, Laura L.; Beierle, Elizabeth A.

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  2. Blockade of Urotensin II Receptor Prevents Vascular Dysfunction

    PubMed Central

    Kim, Young-Ae; Lee, Dong Gil; Yi, Kyu Yang; Lee, Byung Ho; Jung, Yi-Sook

    2016-01-01

    Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/ kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction. PMID:27582556

  3. Blockade of Urotensin II Receptor Prevents Vascular Dysfunction.

    PubMed

    Kim, Young-Ae; Lee, Dong Gil; Yi, Kyu Yang; Lee, Byung Ho; Jung, Yi-Sook

    2016-09-01

    Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/ kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction. PMID:27582556

  4. Molecular bases of proliferation of Francisella tularensis in Arthropod vectors

    PubMed Central

    Asare, Rexford; Akimana, Christine; Jones, Snake; Kwaik, Yousef Abu

    2010-01-01

    Summary Arthropod vectors are important vehicles for transmission of Francisella tularensis between mammals, but very little is known about the F. tularensis-arthropod vector interaction. Drosophila melanogaster has been recently developed as an arthropod vector model for F. tularensis. We have shown that intracellular trafficking of F. tularensis within human monocytes-derived macrophages and D. melanogaster-derived S2 cells is very similar. Within both evolutionarily distant host cells, the Francisella-containing phagosome matures to a late endosome-like phagosome with limited fusion to lysosomes followed by rapid bacterial escape into the cytosol where the bacterial proliferate. To decipher the molecular bases of intracellular proliferation of F. tularensis within arthropod-derived cells, we screened a comprehensive library of mutants of F. tularensis subsp novicida for their defect in intracellular proliferation within D. melanogaster-derived S2 cells. Our data show that 394 genes, representing 22% of the genome, are required for intracellular proliferation within D. melanogaster-derived S2 cells, including many of the Francisella Pathogenicity Island (FPI) genes that are also required for proliferation within mammalian macrophages. Functional gene classes that exhibit growth defect include metabolic (25%), FPI (2%), Type IV pili (1%), transport (16%) and DNA modification (5%). Among 168 most defective mutants in intracellular proliferation in S2 cells, 80 are defective in lethality and proliferation within adult D. melanogaster. The observation that only 135 of the 394 mutants that are defective in S2 cells are also defective in human macrophages indicates that F. tularensis utilize common as well as distinct mechanisms to proliferate within mammalian and arthropod cells. Our studies will facilitate deciphering the molecular aspects of F. tularensis-arthropod vector interaction and its patho-adaptation to infect mammals. PMID:20482589

  5. Diagnostic evaluation of erectile dysfunction.

    PubMed

    Miller, T A

    2000-01-01

    Erectile dysfunction, the persistent inability to attain or maintain penile erection sufficient for sexual intercourse, affects millions of men to various degrees. The majority of cases have an organic etiology, most commonly vascular disease that decreases blood flow into the penis. Regardless of the primary cause, erectile dysfunction can have a negative impact on self-esteem, quality of life and interpersonal relationships. The initial step in evaluation is a detailed medical and social history, including a review of medication use. Discussion with the patient's sexual partner may clarify exacerbating issues. The physical examination focuses on the cardiovascular, neurologic and urogenital systems. Laboratory tests are useful to screen for common etiologic factors and, when indicated, to identify hypogonadal syndromes. Appropriate evaluation of erectile dysfunction leads to accurate advice, management and referral of patients with erectile dysfunction. PMID:10643952

  6. Emotional dysfunctions in neurodegenerative diseases.

    PubMed

    Löffler, Leonie A K; Radke, Sina; Morawetz, Carmen; Derntl, Birgit

    2016-06-01

    Neurodegenerative diseases are characterized primarily by motor signs but are also accompanied by emotional disturbances. Because of the limited knowledge about these dysfunctions, this Review provides an overview of emotional competencies in Huntington's disease (HD), Parkinson's disease (PD), and multiple sclerosis (MS), with a focus on emotion recognition, emotion regulation, and depression. Most studies indicate facial emotion recognition deficits in HD and PD, whereas data for MS are inconsistent. On a neural level, dysfunctions of amygdala and striatum, among others, have been linked to these impairments. These dysfunctions also tap brain regions that are part of the emotion regulation network, suggesting problems in this competency, too. Research points to dysfunctional emotion regulation in MS, whereas findings for PD and HD are missing. The high prevalence of depression in all three disorders emphasizes the need for effective therapies. Research on emotional disturbances might improve treatment, thereby increasing patients' and caregivers' well-being. PMID:26011035

  7. Surgical Procedures for Vestibular Dysfunction

    MedlinePlus

    ... Rated Nonprofit! Volunteer. Donate. Review. Surgical Procedures for Vestibular Dysfunction When is surgery necessary? When medical treatment ... organ (cochlea) is also sacrificed with this procedure. Vestibular nerve section A vestibular nerve section is a ...

  8. The Dysfunctions of Bureaucratic Structure.

    ERIC Educational Resources Information Center

    Duttweiler, Patricia Cloud

    1988-01-01

    Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

  9. Thyroid dysfunction and pregnancy outcomes

    PubMed Central

    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

  10. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible. PMID:27012985

  11. Management of erectile dysfunction.

    PubMed

    Heidelbaugh, Joel J

    2010-02-01

    Erectile dysfunction (ED) is the most common sexual problem in men. The incidence increases with age and affects up to one third of men throughout their lives. It causes a substantial negative impact on intimate relationships, quality of life, and self-esteem. History and physical examination are sufficient to make a diagnosis of ED in most cases, because there is no preferred, first-line diagnostic test. Initial diagnostic workup should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. First-line therapy for ED consists of lifestyle changes, modifying drug therapy that may cause ED, and pharmacotherapy with phosphodiesterase type 5 inhibitors. Obesity, sedentary lifestyle, and smoking greatly increase the risk of ED. Phosphodiesterase type 5 inhibitors are the most effective oral drugs for treatment of ED, including ED associated with diabetes mellitus, spinal cord injury, and antidepressants. Intraurethral and intracavernosal alprostadil, vacuum pump devices, and surgically implanted penile prostheses are alternative therapeutic options when phosphodiesterase type 5 inhibitors fail. Testosterone supplementation in men with hypogonadism improves ED and libido, but requires interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels because of an increased risk of prostate adenocarcinoma. Cognitive behavior therapy and therapy aimed at improving relationships may help to improve ED. Screening for cardiovascular risk factors should be considered in men with ED, because symptoms of ED present on average three years earlier than symptoms of coronary artery disease. Men with ED are at increased risk of coronary, cerebrovascular, and peripheral vascular diseases. PMID:20112889

  12. Bacterial differentiation.

    PubMed

    Shapiro, L; Agabian-Keshishian, N; Bendis, I

    1971-09-01

    technique can be used to select for mutants blocked in the various stages of morphogenesis. 3) Temperature-sensitive mutants of Caulobacter that are restricted in macromolecular synthesis and development at elevated temperatures have been isolated. 4) Genetic exchange in the Calflobacter genus has been demonstrated and is now being defined. Two questions related to control processes can now readily be approached experimentally. (i) Is the temporal progression of events occurring during bacterial differentiation controlled by regulator gene products? (ii) Is the differentiation cycle like a biosynthetic pathway where one event must follow another? The availability of temperature-sensitive mutants blocked at various stages of development permits access to both questions. An interesting feature of the differentiation cycle is that the polar organelle may represent a special segregated unit which is operative in the control of the differentiation process. Perhaps the sequential morphogenic changes exhibited by Caulobacter are dependent on the initial synthesis of this organelle. Because the ultimate expression of cell changes are dependent on selective protein synthesis, specific messenger RNA production-either from DNA present in an organelle or from the chromosome-may prove to be a controlling factor in cell differentiation. We have begun studies with RNA polymerase purified from Caulobacter crescentus to determine whether cell factors or alterations in the enzyme structure serve to change the specificity of transcription during the cell cycle. Control of sequential cell changes at the level of transcription has long been postulated and has recently been substantiated in the case of Bacillus sporulation (6). The Caulobacter bacteria now present another system in which direct analysis of these control mechanisms is feasible. PMID:5572165

  13. JPRS report proliferation issues

    SciTech Connect

    1991-12-13

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa; (2) China; (3) North and South Korea, Taiwan; (4) Hungary; (5) Brazil; (6) India, Iran, Israel, Pakistan; (7) Soviet Union; and (8) Austria, Germany, United Kingdom.

  14. JPRS report proliferation issues

    SciTech Connect

    1991-11-07

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa; (2) China; (3) North and South Korea, Japan; (4) Bulgaria, Czechoslovakia; (5) Argentina, Brazil; (6) India, Iran, Israel, Pakistan, Libya, Iraq, Egypt; (7) Soviet Union; and (8) Belgium, Germany, United Kingdom, Netherlands, France.

  15. JPRS report proliferation issues

    SciTech Connect

    1991-12-02

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa; (2) China; (3) North and South Korea, Taiwan; (4) Hungary, Yugoslavia; (5) Brazil, Argentina; (6) Afghanistan, India, Iran, Iraq, Israel, Pakistan; (7) Soviet Union; and (8) France, Germany, Italy, Switzerland.

  16. JPRS report proliferation issues

    SciTech Connect

    1991-09-27

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa, Namibia; (2) China; (3) South Korea, Australia, Indonesia, Japan, Philippines; (4) Yugoslavia; (5) Brazil, Argentina, Cuba; (6) India, Libya, Pakistan; (7) Soviet Union; and (8) France, Germany, Netherlands.

  17. Telomere dysfunction and Tumor Suppression-the Senescence Connection

    PubMed Central

    Deng, Yibin; Chan, Suzanne; Chang, Sandy

    2013-01-01

    Long lived organisms such as humans have evolved several intrinsic tumor suppressor mechanisms to combat the slew of oncogenic somatic mutations that constantly arise in proliferating stem cell compartments. One of these anti-cancer barriers is the telomere, a specialized nucleoprotein that caps the ends of eukaryotic chromosome. Impaired telomere function activates the canonical DNA damage response pathway that engages p53 to initiate apoptosis or replicative senescence. Here, we discuss how p53-dependent senescence induced by dysfunctional telomeres may be as potent as apoptosis in suppressing tumorigenesis in vivo. PMID:18500246

  18. Citrobacter rodentium mouse model of bacterial infection.

    PubMed

    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. PMID:27606775

  19. Prostatic Disease and Sexual Dysfunction

    PubMed Central

    2011-01-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, and the treatments may cause sexual dysfunction. Aging is also an important factor in the deterioration of the quality of life of men. Deterioration of quality of life caused by prostate diseases may be affected not only by the prostate diseases themselves but also by the sexual dysfunction caused by the prostate diseases secondarily. Thus, consideration of these points at the time of treatment of prostate disease is required. Therapies suitable to each condition should be selected with an understanding of the close association of prostate diseases and associated sexual dysfunction with the quality of life of males. PMID:21750746

  20. [Treatment Options for Executive Dysfunction].

    PubMed

    Müller, S V

    2016-09-01

    The concept of executive function is a so-called umbrella concept, so that it includes many different and in some cases mutually contradictory higher-level organizational abilities such as planning, monitoring, inhibition and control of action. Typically, the cause of an executive dysfunction is an underlying lesion in the prefrontal cortex or subcortical regions. Deficits in executive functions appear in the fields of cognition as well as behavior. Diagnosis requires the use of a wide-ranging repertoire of tests and questionnaires making it a time-consuming process. Different therapeutic approaches addressing the diverse symptoms of executive dysfunction, both positive and negative, are available. These include modification and manipulation of the environment and practice of cognitive repetitive procedures. The former are implemented particularly in cases of severely impaired persons. The latter are used in persons in whom cognitive dysfunctions are the dominating symptoms of the disorder.The operational area of therapeutic approaches using paper and pencil as well as computer programs limits them to treatment of cognitive dysfunction. If behavioral disturbances dominate the clinical picture, other procedures should be used.The effectiveness of cognitive therapy of executive dysfunction is well demonstrated according to the criteria of evidence-based medicine (EBM). PMID:27607068

  1. Prostatic disease and sexual dysfunction.

    PubMed

    Kim, Sae Woong

    2011-06-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, and the treatments may cause sexual dysfunction. Aging is also an important factor in the deterioration of the quality of life of men. Deterioration of quality of life caused by prostate diseases may be affected not only by the prostate diseases themselves but also by the sexual dysfunction caused by the prostate diseases secondarily. Thus, consideration of these points at the time of treatment of prostate disease is required. Therapies suitable to each condition should be selected with an understanding of the close association of prostate diseases and associated sexual dysfunction with the quality of life of males. PMID:21750746

  2. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications.

    PubMed

    Cibor, Dorota; Domagala-Rodacka, Renata; Rodacki, Tomasz; Jurczyszyn, Artur; Mach, Tomasz; Owczarek, Danuta

    2016-01-21

    Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases. PMID:26811647

  3. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications

    PubMed Central

    Cibor, Dorota; Domagala-Rodacka, Renata; Rodacki, Tomasz; Jurczyszyn, Artur; Mach, Tomasz; Owczarek, Danuta

    2016-01-01

    Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases. PMID:26811647

  4. Environmental Enteric Dysfunction Includes a Broad Spectrum of Inflammatory Responses and Epithelial Repair Processes

    PubMed Central

    Yu, Jinsheng; Ordiz, M. Isabel; Stauber, Jennifer; Shaikh, Nurmohammad; Trehan, Indi; Barnell, Erica; Head, Richard D.; Maleta, Ken; Tarr, Phillip I.; Manary, Mark J.

    2015-01-01

    Background & Aims Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study tested a novel microarray method to overcome limitation of RNA sequencing to interrogate the host transcriptome in feces in Malawian children with EED. Methods In 259 children, EED was measured by lactulose permeability (%L). After isolating low copy numbers of host messenger RNA, the transcriptome was reliably and reproducibly profiled, validated by polymerase chain reaction. Messenger RNA copy number then was correlated with %L and differential expression in EED. The transcripts identified were mapped to biological pathways and processes. The children studied had a range of %L values, consistent with a spectrum of EED from none to severe. Results We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B cells, and mediators that dampen cellular responses to hormones. EED-associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial, and parasitic microbes. Several mucins, regulatory factors, and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than in normal children. Conclusions EED represents the activation of diverse elements of the immune system and is associated with widespread intestinal barrier disruption. Differentially expressed transcripts, appropriately enumerated, should be explored as potential biomarkers. PMID:26973864

  5. Clinical neurology and executive dysfunction.

    PubMed

    Filley, C M

    2000-01-01

    Executive function is a uniquely human ability that permits an individual to plan, carry out, and monitor a sequence of actions that is intended to accomplish a goal. This crucial neurobehavioral capacity depends on the integrity of the frontal lobes, most importantly the dorsolateral prefrontal cortices and their connections. Executive dysfunction is associated with a wide range of neurologic disorders that affect these regions. In this paper, executive dysfunction is considered from the perspective of behavioral neurology, and the lesion method is employed to illustrate this impairment in a diverse group of disorders. Frontal system damage leading to disturbed executive function is common and clinically significant. Recognition of this syndrome is critical for ensuring the correct diagnosis, accurate prognosis, and appropriate treatment of affected patients. Executive dysfunction also represents an intriguing aspect of brain-behavior relationships and offers important insights into one of the highest cerebral functions. PMID:10879543

  6. Cognitive dysfunction in multiple sclerosis.

    PubMed

    Guimarães, Joana; Sá, Maria José

    2012-01-01

    In Multiple Sclerosis (MS) prevalence studies of community and clinical samples, indicate that 45-60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing, and visual-spatial abilities); the pathophysiological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities. PMID:22654782

  7. Developmental pathways of motor dysfunction.

    PubMed

    Kleven, Gale A; Bellinger, Seanceray A

    2015-05-01

    Recent evidence has revealed unique patterns of behavioral development after prenatal insult similar to those outlined in studies of adult metabolic dysfunction after prenatal malnutrition. The hallmark features of this Developmental Pathway include a prenatal insult to the nervous system (environmental or genetic) followed by a period of Silent Vulnerability, where no or few functional deficits are observed, and finally emergence of later dysfunction. Possible mechanisms leading to later dysfunction from prenatal insult may include secondary or cascade effects due to the timing of prenatal insults relative to later developing structures in the brain. Methods best employed to study the mechanisms of these pathways are microgenetic and longitudinal designs that include behavioral assessment during the prenatal period of development, and animal models such as the guinea pig. PMID:25864561

  8. Fibrosis and Adipose Tissue Dysfunction

    PubMed Central

    Sun, Kai; Tordjman, Joan; Clément, Karine; Scherer, Philipp E.

    2013-01-01

    Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent pro-fibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction. PMID:23954640

  9. Does stress induce bowel dysfunction?

    PubMed

    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. PMID:24881644

  10. Cell proliferation is reduced in the hippocampus in schizophrenia

    PubMed Central

    Allen, Katherine M; Fung, Samantha J; Shannon Weickert, Cynthia

    2015-01-01

    Objective: The molecular and cellular basis of structural and functional abnormalities of the hippocampus found in schizophrenia is currently unclear. Postnatal neurogenesis contributes to hippocampal function in animal models and is correlated with hippocampal volume in primates. Reduced hippocampal cell proliferation has been previously reported in schizophrenia, which may contribute to hippocampal dysfunction. Method: We measured the cell proliferation marker, Ki67, in post-mortem hippocampal tissue from patients with schizophrenia (n = 10) and matched controls (n = 16). Ki67-labelled cells were counted within the dentate gyrus and hilus on sections taken from the anterior hippocampus. Results: We replicated the finding of a significant reduction in Ki67+ cells/mm2 in schizophrenia cases compared to controls (t24 = 2.1, p = 0.023). In our relatively small sample, we did not find a relationship between Ki67+ cells and age overall, or between Ki67 + cells and duration of illness or antipsychotic treatment in people with schizophrenia. Conclusion: Our results confirm that reduced hippocampal cell proliferation may be present in schizophrenia. Restoring hippocampal neurogenesis may be a potential therapeutic target for the treatment of hippocampal dysfunction in schizophrenia. PMID:26113745

  11. Initiatives for proliferation prevention

    SciTech Connect

    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.

  12. Estrogens and Male Lower Urinary Tract Dysfunction

    PubMed Central

    Wynder, Jalissa L.; Nicholson, Tristan M.; DeFranco, Donald B.

    2016-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology and affect the majority of men at some time during their lives. The development of BPH/LUTS is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD). While the precise molecular etiology remains unclear, estrogens have been implicated in the development and maintenance of BPH. Numerous endogenous and exogenous estrogens exist in humans. These estrogens act via multiple estrogen receptors to promote or inhibit prostatic hyperplasia and other BPH-associated processes. The prostate is an estrogen target tissue, and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of estrogen action directly affecting prostate growth and differentiation in the context of BPH is an understudied area and remains to be elucidated. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation illustrating their potential roles in the development of BPH as therapy. More work will be required to identify estrogen signaling pathways associated with LUTD in order to develop more efficacious drugs for BPH treatment and prevention. PMID:26156791

  13. Peroxisome proliferator-activated receptor {alpha}-independent peroxisome proliferation

    SciTech Connect

    Zhang Xiuguo; Tanaka, Naoki . E-mail: naopi@hsp.md.shinshu-u.ac.jp; Nakajima, Takero; Kamijo, Yuji; Gonzalez, Frank J.; Aoyama, Toshifumi

    2006-08-11

    Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR{alpha}-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPAR{alpha} dependence in the assay system. Surprisingly, a novel type of PPAR{alpha}-independent peroxisome proliferation and enlargement was uncovered in PPAR{alpha}-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11{alpha}, might be associated with the PPAR{alpha}-independent peroxisome proliferation at least in part.

  14. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    PubMed

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. PMID:27426491

  15. Sexual dysfunction in infertile women

    PubMed Central

    Zare, Zahra; Amirian, Malihe; Golmakani, Nahid; Mazlom, Reza; Laal Ahangar, Mojtaba

    2016-01-01

    Background: Sexual problems have different effects on the life of people by influencing their interpersonal and marital relationships and satisfaction. Relationship between sexual dysfunctions and infertility can be mutual. Sexual dysfunction may cause difficulty conceiving but also attempts to conceive, may cause sexual dysfunction. Objective: This paper compares sexual dysfunction in fertile and infertile women. Materials and Methods: In this cross-sectional study, 110 infertile couples referring to Montasarieh Infertility Clinic and 110 fertile couples referring to five healthcare centers in Mashhad were selected by class cluster sampling method. Data collection tools included demographic questionnaire and Glombok-Rust Inventory of Sexual Satisfaction. Data were analyzed through descriptive and analytical statistical methods by SPSS. Results: There was no significant difference in total score of sexual problems and other dimensions of sexual problems (except infrequency) in fertile 28.9 (15.5) and infertile 29.0 (15.4) women. Fertile women had more infrequency than infertile women (p=0.002). Conclusion: There was no significant difference between fertile and infertile women in terms of sexual problems. Paying attention to sexual aspects of infertility and presence of programs for training of sexual skills seems necessary for couples. PMID:27200422

  16. Current Concepts in Ejaculatory Dysfunction

    PubMed Central

    Wolters, Jeffrey P; Hellstrom, Wayne J. G

    2006-01-01

    Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the α1-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality. PMID:17215997

  17. [Cognitive dysfunction in Parkinson's disease].

    PubMed

    Maruyama, T

    2000-10-01

    The neuropsychological impairments associated with Parkinson's disease(PD) have been often documented. However, the pathological mechanisms underlying cognitive dysfunction are hardly solved, as compared with motor dysfunction. Moreover, the precise relationships between the two dysfunctions have remained aloof. This paper attempts to clarify three specific domains of isolated cognitive impairments: dysexecutive syndrome, memory disturbance, and bradyphrenia, which are specifically observed in PD. It especially discusses the neuropsychological relationships between these impairments and the stages of illness. Several neuropsychological experiments to examine these three domains of cognitive impairments were conducted. Significant results were obtained in the following: set-shifting and divergent thinking were significantly impaired in both the early group and the advanced group; while set-maintaining, procedural learning, and cognitive speed, were only significantly disturbed in the advanced group. The failure to acquire procedural skills and the slowing of cognitive speed, were correlated with decreased attention of working memory in the advanced group. These results indicate that the shifting of cognitive sets maybe disturbed in the embryonic stage of the disease. The results also indicated that other cognitive dysfunctions might manifest themselves during the advanced stages due to attentional deficits. In conclusion, it is possible that other neurotransmitters maybe involved in the progressive degeneration of other systems in addition to the dopaminergic system. For example: serotoninergic, noradrenergic and cholinergic systems. Therefore, further research is required to establish which neurotransmitters are involved in their corresponding cognitive impairments in PD. PMID:11068439

  18. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    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.

  19. Posterior Tibial Tendon Dysfunction (PTTD)

    MedlinePlus

    ... ACFAS | Información en Español Advanced Search Home » Foot & Ankle Conditions » Posterior Tibial Tendon Dysfunction (PTTD) Text Size ... the arch, and an inward rolling of the ankle. As the condition progresses, the symptoms will change. ...

  20. Learning Disabilities: A Neurophysiological Dysfunction.

    ERIC Educational Resources Information Center

    Cruickshank, William M.

    1983-01-01

    The author reviews the controversy over definitions of learning disabilities and posits two "givens" in any defintion of the condition: that all learning is neurological, and that learning is conditioning. He proposes a definition based on neuropsychological dysfunction which can be translated into an educational regimen. (CL)

  1. The changing proliferation threat

    SciTech Connect

    Sopko, J.F.

    1996-12-31

    Technological advances and new adversaries with new motives have reduced the relevancy and effectiveness of the American nonproliferation strategy that was developed during the Cold War. The Cold War`s end and the breakup of the Soviet Union have created new proliferation dangers even as they have reduced others. The familiar balance of nuclear terror that linked the superpowers and their client states for nearly 50 years in a choreographed series of confrontations has given way to a much less predictable situation, where weapons of unthinkable power appear within the grasp of those more willing to use them. Rogue nations and {open_quotes}clientless{close_quotes} states, terrorist groups, religious cults, ethnic minorities, disaffected political groups, and even individuals appear to have jointed a new arms race toward mass destruction. The author describes recent events that suggest the new trends and a serious challenge to US national security.

  2. Activation of GPR30 inhibits cardiac fibroblast proliferation.

    PubMed

    Wang, Hao; Zhao, Zhuo; Lin, Marina; Groban, Leanne

    2015-07-01

    The incidence of left ventricular diastolic dysfunction significantly increases in postmenopausal women suggesting the association between estrogen loss and diastolic dysfunction. The in vivo activation of G protein-coupled estrogen receptor (GPR30) attenuates the adverse effects of estrogen loss on cardiac fibrosis and diastolic dysfunction in mRen2.Lewis rats. This study was designed to address the effects of GPR30 on cardiac fibroblast proliferation in rats. The expression of GPR30 in cardiac fibroblasts isolated from adult Sprague-Dawley rats was confirmed by RT-PCR, Western blot analysis, and immunofluorescence staining. Results from BrdU incorporation assays, cell counting, carboxyfluorescein diacetate succinimidyl ester labeling in conjunction with flow cytometry, and Ki-67 staining showed that treatment with G1, a specific agonist of GPR30, inhibited cardiac fibroblast proliferation in a dose-dependent manner, which was associated with decreases in CDK1 and cyclin B1 protein expressions. In the GPR30-KO cells, BrdU incorporation, and CDK1 and cyclin B1 expressions significantly increased when compared to GPR30-intact cells. G1 had no effect on BrdU incorporation, CDK1 and cyclin B1 mRNA levels in GPR30-KO cells. In vivo studies showed increases in CDK1 and cyclin B1 mRNA levels, Ki-67-positive cells, and the immunohistochemistry staining of vimentin, a fibroblast marker, in the left ventricles from ovariectomized mRen2.Lewis rats versus hearts from ovary-intact littermates; 2 weeks of G1 treatment attenuated these adverse effects of estrogen loss. This study demonstrates that GPR30 is expressed in rat cardiac fibroblasts, and activation of GPR30 limits proliferation of these cells likely via suppression of the cell cycle proteins, cyclin B1, and CDK1. PMID:25893735

  3. [Endothelial dysfunction in patients with primary hypertension and hyperhomocysteinemia].

    PubMed

    Baszczuk, Aleksandra; Kopczyński, Zygmunt; Thielemann, Anna

    2014-01-01

    It is widely accepted that endothelial dysfunction is the basis of the development of cardiovascular diseases, including hypertension. With regard to hypertension, endothelial dysfunction is concerned mainly with impaired vascular expansion; however, it is also related to the intensity of the development of atherosclerosis and thrombosis. Among the factors that cause damage to the endothelium, along with classic risk factors, is hyperhomocysteinemia. Hyperhomocysteinemia promotes the formation of oxygen radicals, lowering the oxidation-reduction potential, adversely affects the biosynthesis and function of vasodilator factors in the vascular wall, contributes to the inhibition of endothelial cell division with intense myocyte proliferation and migration, and impairs production of extracellular matrix components in the vascular wall. In addition, high levels of homocysteine and its derivatives contribute to the modification of LDL and HDL particles, inflammation and disorders in coagulation and fibrinolysis. Biochemical effects of the impact of hyperhomocysteinemia on endothelium can lead to damage of endothelial cells, dysfunction of diastolic function of vessels and reduction of their flexibility through its influence on vascular wall remodeling. These changes lead to an increase in blood pressure, strengthening the development of hypertension and target organ damage in patients with this disease. PMID:24491900

  4. A mechanism for trauma induced muscle wasting and immune dysfunction

    NASA Astrophysics Data System (ADS)

    Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

    A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

  5. Bacterial infections in cirrhosis: A critical review and practical guidance

    PubMed Central

    Bunchorntavakul, Chalermrat; Chamroonkul, Naichaya; Chavalitdhamrong, Disaya

    2016-01-01

    Bacterial infection is common and accounts for major morbidity and mortality in cirrhosis. Patients with cirrhosis are immunocompromised and increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. Once infection develops, the excessive response of pro-inflammatory cytokines on a pre-existing hemodynamic dysfunction in cirrhosis further predispose the development of serious complications such as shock, acute-on-chronic liver failure, renal failure, and death. Spontaneous bacterial peritonitis and bacteremia are common in patients with advanced cirrhosis, and are important prognostic landmarks in the natural history of cirrhosis. Notably, the incidence of infections from resistant bacteria has increased significantly in healthcare-associated settings. Serum biomarkers such as procalcitonin may help to improve the diagnosis of bacterial infection. Preventive measures (e.g., avoidance, antibiotic prophylaxis, and vaccination), early recognition, and proper management are required in order to minimize morbidity and mortality of infections in cirrhosis. PMID:26962397

  6. Nest Material Shapes Eggs Bacterial Environment

    PubMed Central

    Ruiz-Castellano, Cristina; Tomás, Gustavo; Ruiz-Rodríguez, Magdalena; Martín-Gálvez, David; Soler, Juan José

    2016-01-01

    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. PMID:26871451

  7. Nest Material Shapes Eggs Bacterial Environment.

    PubMed

    Ruiz-Castellano, Cristina; Tomás, Gustavo; Ruiz-Rodríguez, Magdalena; Martín-Gálvez, David; Soler, Juan José

    2016-01-01

    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. PMID:26871451

  8. Mitochondrial Regulation of Cell Cycle and Proliferation

    PubMed Central

    Antico Arciuch, Valeria Gabriela; Elguero, María Eugenia; Poderoso, Juan José

    2012-01-01

    Abstract Eukaryotic mitochondria resulted from symbiotic incorporation of α-proteobacteria into ancient archaea species. During evolution, mitochondria lost most of the prokaryotic bacterial genes and only conserved a small fraction including those encoding 13 proteins of the respiratory chain. In this process, many functions were transferred to the host cells, but mitochondria gained a central role in the regulation of cell proliferation and apoptosis, and in the modulation of metabolism; accordingly, defective organelles contribute to cell transformation and cancer, diabetes, and neurodegenerative diseases. Most cell and transcriptional effects of mitochondria depend on the modulation of respiratory rate and on the production of hydrogen peroxide released into the cytosol. The mitochondrial oxidative rate has to remain depressed for cell proliferation; even in the presence of O2, energy is preferentially obtained from increased glycolysis (Warburg effect). In response to stress signals, traffic of pro- and antiapoptotic mitochondrial proteins in the intermembrane space (B-cell lymphoma-extra large, Bcl-2-associated death promoter, Bcl-2 associated X-protein and cytochrome c) is modulated by the redox condition determined by mitochondrial O2 utilization and mitochondrial nitric oxide metabolism. In this article, we highlight the traffic of the different canonical signaling pathways to mitochondria and the contributions of organelles to redox regulation of kinases. Finally, we analyze the dynamics of the mitochondrial population in cell cycle and apoptosis. Antioxid. Redox Signal. 16, 1150–1180. PMID:21967640

  9. Biofilms’ Role in Planktonic Cell Proliferation

    PubMed Central

    Bester, Elanna; Wolfaardt, Gideon M.; Aznaveh, Nahid B.; Greener, Jesse

    2013-01-01

    The detachment of single cells from biofilms is an intrinsic part of this surface-associated mode of bacterial existence. Pseudomonas sp. strain CT07gfp biofilms, cultivated in microfluidic channels under continuous flow conditions, were subjected to a range of liquid shear stresses (9.42 mPa to 320 mPa). The number of detached planktonic cells was quantified from the effluent at 24-h intervals, while average biofilm thickness and biofilm surface area were determined by confocal laser scanning microscopy and image analysis. Biofilm accumulation proceeded at the highest applied shear stress, while similar rates of planktonic cell detachment was maintained for biofilms of the same age subjected to the range of average shear rates. The conventional view of liquid-mediated shear leading to the passive erosion of single cells from the biofilm surface, disregards the active contribution of attached cell metabolism and growth to the observed detachment rates. As a complement to the conventional conceptual biofilm models, the existence of a biofilm surface-associated zone of planktonic cell proliferation is proposed to highlight the need to expand the traditional perception of biofilms as promoting microbial survival, to include the potential of biofilms to contribute to microbial proliferation. PMID:24201127

  10. Adult Children of Dysfunctional Families: Childhood Roles.

    ERIC Educational Resources Information Center

    Jenkins, Stephen J.; And Others

    1993-01-01

    Used retrospective accounts to compare adult children of alcoholics (ACOAs), adults who experienced stressful events in childhood not involving parental alcoholism (A-D+), and adults with no reported dysfunction in family of origin (A-D-) with regard to dysfunctional roles adopted as children. Dysfunctional role adoption was more frequent in ACOA…

  11. Cardiac dysfunction and prenatal exposure to venlafaxine.

    PubMed

    Araújo, Ana R; Marçal, Mónica; Tuna, Madalena; Anjos, Rui

    2016-04-01

    Venlofaxine, a widely used antidepressant, is known to cause a withdrawal syndrome. We present a case of neonatal transient ventricular dysfunction in a neonate exposed to venlafaxine in utero. Other causes of ventricular dysfunction were excluded. Neonatal ventricular dysfunction can be a possible side effect of maternal use of this drug. PMID:27099733

  12. Focally regulated endothelial proliferation and cell death in human synovium.

    PubMed Central

    Walsh, D. A.; Wade, M.; Mapp, P. I.; Blake, D. R.

    1998-01-01

    Angiogenesis and vascular insufficiency each may support the chronic synovial inflammation of rheumatoid arthritis. We have shown by quantitative immunohistochemistry and terminal uridyl deoxynucleotide nick end labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis compared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. Markers of proliferation were associated with foci immunoreactive for vascular endothelial growth factor and integrin alpha(v)beta3, whereas cell death was observed in foci in which immunoreactivities for these factors were weak or absent. No association was found with thrombospondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal expression of angiogenic and endothelial survival factors. Increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. Images Figure 1 Figure 3 Figure 4 PMID:9502411

  13. Mitochondria: Redox Metabolism and Dysfunction

    PubMed Central

    Kang, Jia; Pervaiz, Shazib

    2012-01-01

    Mitochondria are the main intracellular location for fuel generation; however, they are not just power plants but involved in a range of other intracellular functions including regulation of redox homeostasis and cell fate. Dysfunction of mitochondria will result in oxidative stress which is one of the underlying causal factors for a variety of diseases including neurodegenerative diseases, diabetes, cardiovascular diseases, and cancer. In this paper, generation of reactive oxygen/nitrogen species (ROS/RNS) in the mitochondria, redox regulatory roles of certain mitochondrial proteins, and the impact on cell fate will be discussed. The current state of our understanding in mitochondrial dysfunction in pathological states and how we could target them for therapeutic purpose will also be briefly reviewed. PMID:22593827

  14. [Sexual dysfunction among patients with psychiatric disorders].

    PubMed

    Soldati, Lorenzo

    2016-03-16

    Scientific literature shows that sexual dysfunction is more common in patients suffering from psychiatric illness as opposed to the general population. It also shows that the prevalence of sexual dysfunction is underestimated by professionals, partly because patients rarely talk spontaneously about their dysfunctions. However, sexual dysfunction has an impact on patients' mental health. Furthermore, some psychotropic medication, antidepressants and antipsychotics in particular, can hinder sexual functioning and induce sexual dysfunction. These harmful effects can, in turn, reduce patients' compliance with their medical treatments. It is therefore important that practitioners take into account their patients' sexual experience. PMID:27149715

  15. Global proliferation of cephalopods.

    PubMed

    Doubleday, Zoë A; Prowse, Thomas A A; Arkhipkin, Alexander; Pierce, Graham J; Semmens, Jayson; Steer, Michael; Leporati, Stephen C; Lourenço, Sílvia; Quetglas, Antoni; Sauer, Warwick; Gillanders, Bronwyn M

    2016-05-23

    Human activities have substantially changed the world's oceans in recent decades, altering marine food webs, habitats and biogeochemical processes [1]. Cephalopods (squid, cuttlefish and octopuses) have a unique set of biological traits, including rapid growth, short lifespans and strong life-history plasticity, allowing them to adapt quickly to changing environmental conditions [2-4]. There has been growing speculation that cephalopod populations are proliferating in response to a changing environment, a perception fuelled by increasing trends in cephalopod fisheries catch [4,5]. To investigate long-term trends in cephalopod abundance, we assembled global time-series of cephalopod catch rates (catch per unit of fishing or sampling effort). We show that cephalopod populations have increased over the last six decades, a result that was remarkably consistent across a highly diverse set of cephalopod taxa. Positive trends were also evident for both fisheries-dependent and fisheries-independent time-series, suggesting that trends are not solely due to factors associated with developing fisheries. Our results suggest that large-scale, directional processes, common to a range of coastal and oceanic environments, are responsible. This study presents the first evidence that cephalopod populations have increased globally, indicating that these ecologically and commercially important invertebrates may have benefited from a changing ocean environment. PMID:27218844

  16. Thyroid dysfunction from antineoplastic agents.

    PubMed

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

    2011-11-01

    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

  17. Insulin dysfunction and Tau pathology

    PubMed Central

    El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

    2013-01-01

    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 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. PMID:24574966

  18. Mitochondrial dysfunction and organophosphorus compounds

    SciTech Connect

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    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.

  19. Amiodarone-induced thyroid dysfunction.

    PubMed

    Danzi, Sara; Klein, Irwin

    2015-05-01

    Amiodarone is an effective medication for the treatment of cardiac arrhythmias. Originally developed for the treatment of angina, it is now the most frequently prescribed antiarrhythmia drug despite the fact that its use is limited because of potential serious side effects including adverse effects on the thyroid gland and thyroid hormones. Although the mechanisms of action of amiodarone on the thyroid gland and thyroid hormone metabolism are poorly understood, the structural similarity of amiodarone to thyroid hormones, including the presence of iodine moieties on the inner benzene ring, may play a role in causing thyroid dysfunction. Amiodarone-induced thyroid dysfunction includes amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH). The AIT develops more commonly in iodine-deficient areas and AIH in iodine-sufficient areas. The AIT type 1 usually occurs in patients with known or previously undiagnosed thyroid dysfunction or goiter. The AIT type 2 usually occurs in normal thyroid glands and results in destruction of thyroid tissue caused by thyroiditis. This is the result of an intrinsic drug effect from the amiodarone itself. Mixed types are not uncommon. Patients with cardiac disease receiving amiodarone treatment should be monitored for signs of thyroid dysfunction, which often manifest as a reappearance of the underlying cardiac disease state. When monitoring patients, initial tests should include the full battery of thyroid function tests, thyroid-stimulating hormone, thyroxine, triiodothyronine, and antithyroid antibodies. Mixed types of AIT can be challenging both to diagnose and treat and therapy differs depending on the type of AIT. Treatment can include thionamides and/or glucocorticoids. The AIH responds favorably to thyroid hormone replacement therapy. Amiodarone is lipophilic and has a long half-life in the body. Therefore, stopping the amiodarone therapy usually has little short-term benefit. PMID:24067547

  20. Facial bacterial infections: folliculitis.

    PubMed

    Laureano, Ana Cristina; Schwartz, Robert A; Cohen, Philip J

    2014-01-01

    Facial bacterial infections are most commonly caused by infections of the hair follicles. Wherever pilosebaceous units are found folliculitis can occur, with the most frequent bacterial culprit being Staphylococcus aureus. We review different origins of facial folliculitis, distinguishing bacterial forms from other infectious and non-infectious mimickers. We distinguish folliculitis from pseudofolliculitis and perifolliculitis. Clinical features, etiology, pathology, and management options are also discussed. PMID:25441463

  1. Neuromuscular dysfunction in nonbacterial prostatitis.

    PubMed

    Hellstrom, W J; Schmidt, R A; Lue, T F; Tanagho, E A

    1987-08-01

    Although chronic nonbacterial prostatitis is common, the condition remains poorly understood and refractory to treatment. Another approach, i.e., a urodynamic explanation, seems warranted. The underlying cause of the symptoms may be an inappropriate spasm of of the distal urethra/external sphincteric unit, leading to increased pressure in the prostatic urethra with a resultant reflux of urine into the prostatic ducts. The presence of urine (sterile or infected) could induce ductal and periductal inflammation, which could further aggravate spasm of the involved pelvic musculature, exacerbating the voiding dysfunction. We present 3 patients in whom this sequence of events was documented radiographically and urodynamically. Consequently, treatment involved modulation of the dysfunction of the distal urethra/external sphincteric unit: (1) reeducation by reassurance and biofeedback was the initial line of therapy; (2) pharmacologic manipulation using alpha-blockers (to affect smooth and striated muscle irritability) and striated muscle relaxants was next tried; (3) finally, in unremitting symptoms, we used selective sacral-root electro-stimulation, successfully fatiguing the involved muscles and relieving the voiding dysfunction. PMID:3497475

  2. Gut dysfunction in Parkinson's disease.

    PubMed

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-01

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  3. Binge eating and menstrual dysfunction

    PubMed Central

    Ålgars, Monica; Huang, Lu; Von Holle, Ann F.; Peat, Christine M.; Thornton, Laura; Lichtenstein, Paul; Bulik, Cynthia M.

    2014-01-01

    Objective The relation between eating disorders and menstrual function has been widely studied, but it is unknown whether the behavior of binge eating itself is related to menstrual dysfunction. Methods The 11,503 women included in this study were from the Swedish Twin study of Adults: Genes and Environment. The associations between menstrual dysfunction and binge eating were analyzed using logistic regression or multiple linear regression models with generalized estimation equations. Results Women who reported lifetime binge eating were more likely to report either amenorrhea or oligomenorrhea than women who reported no binge eating. These results persisted when controlling for compensatory behaviors including self-induced vomiting, laxative use, and diuretic use. No differences between women with and without a history of binge eating were observed for age at menarche. Conclusion Even when controlling for the effect of compensatory behaviors, the behavior of binge eating is associated with menstrual dysfunction. Metabolic and endocrinological factors could underlie this association. Careful evaluation of menstrual status is warranted for women with all eating disorders, not just anorexia nervosa. PMID:24360136

  4. Gut dysfunction in Parkinson's disease

    PubMed Central

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  5. Demonstrating Bacterial Flagella.

    ERIC Educational Resources Information Center

    Porter, John R.; And Others

    1992-01-01

    Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

  6. From proliferation to proliferation: monocyte lineage comes full circle

    PubMed Central

    Swirski, Filip K.; Hilgendorf, Ingo; Robbins, Clinton S.

    2014-01-01

    Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of monocyte lineage was bound to a stepwise model that favored an inverse relationship between cellular proliferation and differentiation. Sophisticated molecular and surgical cell tracking tools have transformed our thinking about monocyte topo-ontogeny and function. Here, we discuss how recent studies focusing on progenitor proliferation and differentiation, monocyte mobilization and recruitment, and macrophage differentiation and proliferation are reshaping knowledge of monocyte lineage in steady state and disease. PMID:24435095

  7. A western type of bacterial gill disease

    USGS Publications Warehouse

    Fish, F.F.

    1935-01-01

    The first reference to a pathological condition of the gill tissues of salmonid fishes was made by Osburn in 1910. This author in describing a progressive infolding of the opercula of trout, commonly known to hatcherymen as "short gill covers," mentioned a marked proliferation on the gill epithelium as accompanying this condition. Osburn assumed that the club-like appearance of the gill filaments due to the proliferated epithelium was the result of continual irritation of the delicate gill tissue in the absence of the usual protection offered by the normal opercula. Although such a conclusion seems quite logical, it is also possible that Osburn was dealing with "short gill covers" complicated by the unknown bacterial gill disease which was subsequently described by Davis.

  8. Perspectives of bacterial ACC deaminase in phytoremediation.

    PubMed

    Arshad, Muhammad; Saleem, Muhammad; Hussain, Sarfraz

    2007-08-01

    Phytoremediation of contaminated soil and water environments is regulated and coordinated by the plant root system, yet root growth is often inhibited by pollutant-induced stress. Prolific root growth could maximize rates of hyperaccumulation of inorganic contaminants or rhizodegradation of organic pollutants, and thus accelerate phytoremediation. Accelerated ethylene production in response to stress induced by contaminants is known to inhibit root growth and is considered as a major limitation in improving phytoremediation efficiency. Recent work shows that bacterial 1-aminocyclopropane-1-carboxylate (ACC) deaminase regulates ethylene levels in plants by metabolizing its precursor ACC into alpha-ketobutyric acid and ammonia. Plants inoculated with ACC deaminase bacteria or transgenic plants that express bacterial ACC deaminase genes can regulate their ethylene levels and consequently contribute to a more extensive root system. Such proliferation of roots in contaminated soil can lead to enhanced uptake of heavy metals or rhizodegradation of xenobiotics. PMID:17573137

  9. Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases.

    PubMed

    Yue, Li; Yao, Hongwei

    2016-08-01

    Mitochondria are dynamic organelles, which couple the various cellular processes that regulate metabolism, cell proliferation and survival. Environmental stress can cause mitochondrial dysfunction and dynamic changes including reduced mitochondrial biogenesis, oxidative phosphorylation and ATP production, as well as mitophagy impairment, which leads to increased ROS, inflammatory responses and cellular senescence. Oxidative stress, inflammation and cellular senescence all have important roles in the pathogenesis of chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and bronchopulmonary dysplasia. In this review, we discuss the current state on how mitochondrial dysfunction affects inflammatory responses and cellular senescence, the mechanisms of mitochondrial dysfunction underlying the pathogenesis of chronic lung diseases and the potential of mitochondrial transfer and replacement as treatments for these diseases. PMID:27189175

  10. Metabolic dysfunction in lymphocytes promotes postoperative morbidity.

    PubMed

    Edwards, Mark R; Sultan, Pervez; del Arroyo, Ana Gutierrez; Whittle, John; Karmali, Shamir N; Moonesinghe, S Ramani; Haddad, Fares S; Mythen, Michael G; Singer, Mervyn; Ackland, Gareth L

    2015-09-01

    Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61-82 years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (≤1.3 x 10(9)·l(-1); <20% white cell count; prevalence 15-18%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1-2.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26-65%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1β in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic

  11. Asthma: vocal cord dysfunction (VCD) and other dysfunctional breathing disorders.

    PubMed

    Balkissoon, Ron; Kenn, Klaus

    2012-12-01

    Vocal cord dysfunction (VCD) and dysfunctional breathing (DB) disorders may mimic or coexist with asthma, leading to overtreatment with corticosteroids with consequent morbidity. Iatrogenic complications can be averted by early and correct diagnosis. VCD, also termed paradoxical vocal fold motion disorder (PVFMD), is characterized by intermittent paradoxical adduction of the vocal cords, mainly during inspiration, leading to airflow obstruction and dyspnea. Patients with VCD may have repetitive emergency room visits due to acute dyspnea (mimicking exacerbations of asthma). In the seminal descriptions of VCD, young women (often with psychiatric issues) predominated; however, other groups at increased risk for developing VCD include elite athletes, military recruits, and individuals exposed to irritants (inhaled or aspirated). Chronic postnasal drip, laryngopharyngeal reflux (LPR), and gastroesophageal reflux (GER) may lead to laryngeal hyperresponsiveness. The diagnosis of VCD may be difficult because physical exam and spirometry may be normal between episodes. During symptomatic episodes, spirometry typically reveals variable extrathoracic airway obstruction (truncated inspiratory flow volume loop). The gold standard for identifying VCD is flexible fiberoptic rhinolaryngoscopy. Management of VCD includes identification and treatment of underlying disorders (eg, chronic postnasal drip, LPR, GER, anxiety, depression) and a multidisciplinary approach (including highly trained speech therapists). Speech therapy and biofeedback play a critical role in teaching techniques to override various dysfunctional breathing habits. When postnasal drip, LPR, or GER coexist, these disorders should be aggressively treated. With successful therapy, corticosteroids can often be discontinued. During severe, acute episodes of VCD, therapeutic strategies include heliox (80% helium/20% oxygen), topical lidocaine, anxiolytics, and superior laryngeal blocks with Clostridium botulinum toxin

  12. Bacterial Ion Channels.

    PubMed

    Compton, Emma L R; Mindell, Joseph A

    2010-09-01

    Bacterial ion channels were known, but only in special cases, such as outer membrane porins in Escherichia coli and bacterial toxins that form pores in their target (bacterial or mammalian) membranes. The exhaustive coverage provided by a decade of bacterial genome sequencing has revealed that ion channels are actually widespread in bacteria, with homologs of a broad range of mammalian channel proteins coded throughout the bacterial and archaeal kingdoms. This review discusses four groups of bacterial channels: porins, mechano-sensitive (MS) channels, channel-forming toxins, and bacterial homologs of mammalian channels. The outer membrane (OM) of gram-negative bacteria blocks access of essential nutrients; to survive, the cell needs to provide a mechanism for nutrients to penetrate the OM. Porin channels provide this access by forming large, nonspecific aqueous pores in the OM that allow ions and vital nutrients to cross it and enter the periplasm. MS channels act as emergency release valves, allowing solutes to rapidly exit the cytoplasm and to dissipate the large osmotic disparity between the internal and external environments. MS channels are remarkable in that they do this by responding to forces exerted by the membrane itself. Some bacteria produce toxic proteins that form pores in trans, attacking and killing other organisms by virtue of their pore formation. The review focuses on those bacterial toxins that kill other bacteria, specifically the class of proteins called colicins. Colicins reveal the dangers of channel formation in the plasma membrane, since they kill their targets with exactly that approach. PMID:26443789

  13. Vimentin in Bacterial Infections.

    PubMed

    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-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection. PMID:27096872

  14. Vimentin in Bacterial Infections

    PubMed Central

    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-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection. PMID:27096872

  15. Fungal and Bacterial Diseases.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal and bacterial diseases are important constraints to production. Recognition of diseases and information on their biology is important in disease management. This chapter is aimed at providing diagnostic information on fungal and bacterial diseases of sugar beet and their biology, epidemiolo...

  16. Pharmacotherapy of Sexual Dysfunctions : Current Status

    PubMed Central

    Avasthi, Ajith; Biswas, Parthasarathy

    2004-01-01

    The sexual dysfunctions are one of the most prevalent conditions. Sexual dysfunctions can have profound effect on the psychological well-being of an individual and the psychosexual relationship of a couple. Management of the sexual dysfunction should be preceded by an accurate diagnosis reached after a complete medical and sexual history and physical examination. Current focus of researchers has been on understanding the pathophysiology of erectile dysfunction, premature ejaculation and other sexual dysfunctions that can help in developing newer pharmacological cures for these conditions. Recently, a number of clinical trials have studied the potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in the treatment of Erectile Dysfunction (ED) and Premature Ejaculation (PME). The introduction of PDE-5 inhibitors like sildenafil, vardenafil and tadalafil has revolutionized the treatment of sexual dysfunctions. This review focuses on the recent pharmacological advances in the treatment of common sexual dysfunctions like ED and PME with special focus on the role of PDE-5 inhibitors. Also discussed is the pharmacological treatment of other less prevalent and recognized disorders like female sexual dysfunction, drug induced sexual dysfunction etc. PMID:21224902

  17. [Cognitive dysfunction in cardiovascular diseases].

    PubMed

    Ladwig, Karl-Heinz

    2016-08-01

    A multitude of modifiable risk factors during the median phase of life are often causative for cognitive dysfunction (CD) in old age. High evidence exists for cigarette smoking, diabetes, physical inactivity and sleeping disorders. Single large scale population based studies proof it for hypertension, hypercholesterinemia and depression, conflicting evidence exists for obesity and work stress. Little attention is paid to the close association between cardiovascular disease conditions and CD, particularly for atrial fibrillation, heart failure and for older patients with coronary heart disease. Undetected CD may be responsible for non-adherence and failure of self-care programs in chronic heart patients. PMID:27557067

  18. Nonpharmacologic Treatment of Erectile Dysfunction

    PubMed Central

    Montague, Drogo K

    2002-01-01

    Nonpharmacologic treatment for erectile dysfunction (ED) includes sex therapy, the use of vacuum erection devices, penile prosthesis implantation, and penile vascular surgery. Sex therapy is indicated for psychogenic ED and is at times a useful adjunct for other treatments in men with mixed psychogenic and organic ED. Vacuum erection devices produce usable erections in over 90% of patients; however, patient and partner acceptability is an issue. Three-piece inflatable penile prostheses create flaccidity and an erection that comes close to that which occurs naturally. Penile vascular surgery has shown greatest efficacy in young men with vasculogenic ED resulting from pelvic or perineal trauma. PMID:16986016

  19. Male sexual dysfunction in Asia.

    PubMed

    Ho, Christopher Ck; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-07-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  20. Cerebrovascular Dysfunction in Preeclamptic Pregnancies

    PubMed Central

    Hammer, Erica S.; Cipolla, Marilyn J.

    2016-01-01

    Preeclampsia is a hypertensive, multi-system disorder of pregnancy that affects several organ systems, including the maternal brain. Cerebrovascular dysfunction during preeclampsia can lead to cerebral edema, seizures, stroke and potentially maternal mortality. This review will discuss the effects of preeclampsia on the cerebrovasculature that may adversely affect the maternal brain, including cerebral blood flow (CBF) autoregulation and blood-brain barrier disruption, and the resultant clinical outcomes including posterior reversible encephalopathy syndrome (PRES) and maternal stroke. Potential long-term cognitive outcomes of preeclampsia and the role of the cerebrovasculature are also reviewed. PMID:26126779

  1. Male sexual dysfunction in Asia

    PubMed Central

    Ho, Christopher CK; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-01-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  2. Medical treatment of erectile dysfunction.

    PubMed Central

    Burns-Cox, N.; Gingell, C.

    1998-01-01

    There has been a tremendous increase in demand for the treatment of erectile dysfunction in the last 10 years. This has occurred partly because of a greater understanding and awareness by both the general public and clinicians, and also because there now exists a range of effective treatments. The choice of treatments is increasing rapidly and novel delivery systems which may be more patient-friendly than intracavernosal injections are now becoming available. We review the published data on effectiveness and safety of the currently available treatments and discuss recent advances in oral therapy, as these drugs are likely to become available in the near future. Images Figure 1 Figure 2 PMID:9799886

  3. Conservative management of voiding dysfunction

    PubMed Central

    Patel, Anita

    2007-01-01

    This review article discusses the efficacy of various conservative therapies in the management of voiding dysfunction with special reference to urinary incontinence. The article emphasizes the fact that conservative therapies have limited side effects and they do not jeopardize future treatment options. Behaviour therapy, pelvic floor therapy and biofeedback; electrical and magnetic stimulation are discussed here individually. Though there is unanimous agreement that these therapies improve quality of life, complete cure is rare. All therapies work better in conjunction with each other rather than in isolation. The review also highlights the need for randomized controlled trials of better methodology. PMID:19675794

  4. Nuclear Proliferation and Grand Challenges

    SciTech Connect

    McCarthy, Kathy

    2009-01-01

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  5. Nuclear Proliferation and Grand Challenges

    ScienceCinema

    McCarthy, Kathy

    2013-05-28

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  6. The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation.

    PubMed

    Martin-Gandul, C; Mueller, N J; Pascual, M; Manuel, O

    2015-12-01

    Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community-acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction. PMID:26474168

  7. ABC transporters: bacterial exporters.

    PubMed Central

    Fath, M J; Kolter, R

    1993-01-01

    The ABC transporters (also called traffic ATPases) make up a large superfamily of proteins which share a common function and a common ATP-binding domain. ABC transporters are classified into three major groups: bacterial importers (the periplasmic permeases), eukaryotic transporters, and bacterial exporters. We present a comprehensive review of the bacterial ABC exporter group, which currently includes over 40 systems. The bacterial ABC exporter systems are functionally subdivided on the basis of the type of substrate that each translocates. We describe three main groups: protein exporters, peptide exporters, and systems that transport nonprotein substrates. Prototype exporters from each group are described in detail to illustrate our current understanding of this protein family. The prototype systems include the alpha-hemolysin, colicin V, and capsular polysaccharide exporters from Escherichia coli, the protease exporter from Erwinia chrysanthemi, and the glucan exporters from Agrobacterium tumefaciens and Rhizobium meliloti. Phylogenetic analysis of the ATP-binding domains from 29 bacterial ABC exporters indicates that the bacterial ABC exporters can be divided into two primary branches. One branch contains the transport systems where the ATP-binding domain and the membrane-spanning domain are present on the same polypeptide, and the other branch contains the systems where these domains are found on separate polypeptides. Differences in substrate specificity do not correlate with evolutionary relatedness. A complete survey of the known and putative bacterial ABC exporters is included at the end of the review. PMID:8302219

  8. Meibomian Gland Dysfunction: Endocrine Aspects

    PubMed Central

    Sahin, Ozlem G.; Kartal, Elçin; Taheri, Nusret

    2011-01-01

    Purpose. To compare the hormone levels of patients with seborrheic meibomian gland dysfunction with controls. Procedures. This is a retrospective case-control study involving 50 patients and 50 controls. Blood workup for hormones was studied in both groups by using macroELISA (enzyme-linked immunosorbent assay). Statistical evaluation was done by using SPSS 15.0 independent samples t-test. Results. There were statistically significant differences of serum testosterone and dehydroepiandrosterone sulphate levels between patients and controls (P = 0.000). Female gender showed statistically significant differences of serum thyroid-stimulating hormone and prolactin levels between patients and controls (P = 0.014 and P = 0.043), in addition to serum testosterone and dehydroepiandrosterone sulphate levels (P = 0.000 and P = 0.001). However, male gender showed statistically significant differences of only serum testosterone and dehydroepiandrosterone sulphate levels between patients and controls. (P = 0.003 and P = 0.003 resp.). Conclusions. Increased serum levels of testosterone and dehydroepiandrosterone sulphate in both genders should be considered as diagnostic markers for seborrheic meibomian gland dysfunction. PMID:24533183

  9. Mitochondrial dysfunction in heart failure

    PubMed Central

    Rosca, Mariana G.; Hoppel, Charles L.

    2013-01-01

    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 cylic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction. PMID:22948484

  10. Mitochondrial dysfunction in cancer chemoresistance.

    PubMed

    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. PMID:25107705

  11. Immune surveillance for ERAAP dysfunction.

    PubMed

    Nagarajan, Niranjana A; Shastri, Nilabh

    2013-09-01

    The ER aminopeptidase associated with antigen processing, ERAAP (or ERAP1), is essential for trimming peptides that are presented by MHC class I molecules. ERAP1 is inhibited by human cytomegalovirus, and ERAP1 polymorphisms are associated with autoimmune diseases. How the immune system detects ERAAP dysfunction, however, is unknown. We have shown previously that ERAAP-deficient cells present an immunogenic pMHC I repertoire, that elicits CD8+ T cell response in WT mice. Additionally, we discovered that the WT CD8+ T cells recognized novel peptides presented by non-classical, or MHC class Ib, molecules on ERAAP-deficient cells. The MHC Ib restricted WT CD8 T cells eliminated ERAAP-deficient cells in vitro and in vivo. We identified the FL9 peptide, presented by Qa-1(b), a MHC class Ib molecule exclusively on ERAAP-deficient cells. Remarkably, T cells specific for the FL9-Qa-1(b) complex were frequent in naïve WT mice, and had an antigen-experienced phenotype. Thus, novel non-classical pQa-1(b) complexes direct cytotoxic T cells to target cells with defective peptide processing in the endoplasmic reticulum. Here, we discuss the implications of our findings, and the possible roles of pMHC Ib-specific T cells in immune surveillance for ERAAP dysfunction. PMID:23433779

  12. Olfactory dysfunction in Alzheimer’s disease

    PubMed Central

    Zou, Yong-ming; Lu, Da; Liu, Li-ping; Zhang, Hui-hong; Zhou, Yu-ying

    2016-01-01

    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. PMID:27143888

  13. Bacterial challenges in food

    PubMed Central

    Collee, J. G.

    1974-01-01

    Qualitative and quantitative aspects of bacterial challenges that might be encountered in food are discussed with reference to recognized and relatively unrecognized hazards. Mechanisms of pathogenicity are reviewed and the populations at risk are noted. The bacterial content of food as it is served at table merits more study. The challenge of prevention by education is discussed. Indirect bacterial challenges in our food are considered. The real challenge of diagnosis depends upon an awareness of a complex range of conditions; the importance of effective communication with efficient laboratory and epidemiological services is stressed. There is an increasing need for care in the preparation and distribution of food. PMID:4467860

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed Central

    Mansilla Pareja, Maria Eugenia; 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. PMID:24137567

  16. Bacterial Wound Culture

    MedlinePlus

    ... Home Visit Global Sites Search Help? Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  17. Bacterial Nail Infection (Paronychia)

    MedlinePlus

    ... in people who work in the health care industry. Chronic paronychia is most common in adult women and those who work in places where their hands are kept moist, such as food handlers. Signs and Symptoms Bacterial nail infection most ...

  18. Small bowel bacterial overgrowth

    MedlinePlus

    Overgrowth - intestinal bacteria; Bacterial overgrowth - intestine ... Unlike the large intestine, the small intestine does not have a high number of bacteria. When there are too many bacteria in the ...

  19. Bacterial surface adaptation

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:26537128

  1. Deciphering the bacterial glycocode: recent advances in bacterial glycoproteomics

    PubMed Central

    Longwell, Scott A.; Dube, Danielle H.

    2012-01-01

    Bacterial glycoproteins represent an attractive target for new antibacterial treatments, as they are frequently linked to pathogenesis and contain distinctive glycans that are absent in humans. Despite their potential therapeutic importance, many bacterial glycoproteins remain uncharacterized. This review focuses on recent advances in deciphering the bacterial glycocode, including metabolic glycan labeling to discover and characterize bacterial glycoproteins, lectin-based microarrays to monitor bacterial glycoprotein dynamics, crosslinking sugars to assess the roles of bacterial glycoproteins, and harnessing bacterial glycosylation systems for the efficient production of industrially important glycoproteins. PMID:23276734

  2. Bistability and Bacterial Infections

    PubMed Central

    Malka, Roy; Shochat, Eliezer; Rom-Kedar, Vered

    2010-01-01

    Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection. PMID:20463954

  3. An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis.

    PubMed

    Birsoy, Kıvanç; Wang, Tim; Chen, Walter W; Freinkman, Elizaveta; Abu-Remaileh, Monther; Sabatini, David M

    2015-07-30

    The mitochondrial electron transport chain (ETC) enables many metabolic processes, but why its inhibition suppresses cell proliferation is unclear. It is also not well understood why pyruvate supplementation allows cells lacking ETC function to proliferate. We used a CRISPR-based genetic screen to identify genes whose loss sensitizes human cells to phenformin, a complex I inhibitor. The screen yielded GOT1, the cytosolic aspartate aminotransferase, loss of which kills cells upon ETC inhibition. GOT1 normally consumes aspartate to transfer electrons into mitochondria, but, upon ETC inhibition, it reverses to generate aspartate in the cytosol, which partially compensates for the loss of mitochondrial aspartate synthesis. Pyruvate stimulates aspartate synthesis in a GOT1-dependent fashion, which is required for pyruvate to rescue proliferation of cells with ETC dysfunction. Aspartate supplementation or overexpression of an aspartate transporter allows cells without ETC activity to proliferate. Thus, enabling aspartate synthesis is an essential role of the ETC in cell proliferation. PMID:26232224

  4. Novel factors modulating human β-cell proliferation.

    PubMed

    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. PMID:27615134

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

    ERIC Educational Resources Information Center

    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…

  6. Diabetes and Retinal Vascular Dysfunction

    PubMed Central

    Shin, Eui Seok; Sorenson, Christine M.; Sheibani, Nader

    2014-01-01

    Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR). We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR. PMID:25667739

  7. Environmental Enteric Dysfunction in Children.

    PubMed

    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. PMID:26974416

  8. Hypoparathyroidism presenting as cognitive dysfunction

    PubMed Central

    Kumar, Gunjan; Kaur, Darshpreet; Aggarwal, Puneet; Khurana, Tilak

    2013-01-01

    Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education. PMID:23709145

  9. Psychopathy: cognitive and neural dysfunction

    PubMed Central

    R. Blair, R. James

    2013-01-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause—ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder. PMID:24174892

  10. Dysfunctional attention in autistic savants.

    PubMed

    Casey, B J; Gordon, C T; Mannheim, G B; Rumsey, J M

    1993-11-01

    A dysfunctional attention hypothesis of the basis of savant skills was tested with a series of computerized tasks that assessed the ability to divide, shift, direct, and sustain attention. Ten healthy men with pervasive developmental disorders and unusual calendar-calculating skill, and 10 age- and sex-matched controls were tested. There were four general findings. First, the savants and controls did not differ on a measure of visual sustained attention. Second, the savants failed to detect rare auditory targets significantly more than did the controls. Third, the savants were unable to efficiently divide their attention when required to detect both visual and auditory targets simultaneously. Finally, deficient orienting or a deficit in shifting selective attention from one stimulus location to another was evidenced in overall slower reaction times for the savants across tasks requiring shifts and redirecting of attention. This deficit was attributed to an inability to disengage attention as a result of deficient orienting and overselectivity. PMID:8120129

  11. Coronary microvascular dysfunction: an update

    PubMed Central

    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

  12. Sleep Dysfunction and Gastrointestinal Diseases

    PubMed Central

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A.; Borum, Marie L.

    2015-01-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  13. Neddylation dysfunction in Alzheimer's disease.

    PubMed

    Chen, Yuzhi; Neve, Rachael L; Liu, Helena

    2012-11-01

    Ubiquitin-dependent proteolysis is a major mechanism that downregulates misfolded proteins or those that have finished a programmed task. In the last two decades, neddylation has emerged as a major regulatory pathway for ubiquitination. Central to the neddylation pathway is the amyloid precursor protein (APP)-binding protein APP-BP1, which together with Uba3, plays an analogous role to the ubiquitin-activating enzyme E1 in nedd8 activation. Activated nedd8 covalently modifies and activates a major class of ubiquitin ligases called Cullin-RING ligases (CRLs). New evidence suggests that neddylation also modifies Type-1 transmembrane receptors such as APP. Here we review the functions of neddylation and summarize evidence suggesting that dysfunction of neddylation is involved in Alzheimer's disease. PMID:22805479

  14. Balance Dysfunction in Parkinson's Disease

    PubMed Central

    Rinalduzzi, Steno; Missori, Paolo; Fattapposta, Francesco; Currà, Antonio

    2015-01-01

    Stability and mobility in functional motor activities depend on a precise regulation of phasic and tonic muscular activity that is carried out automatically, without conscious awareness. The sensorimotor control of posture involves a complex integration of multisensory inputs that results in a final motor adjustment process. All or some of the components of this system may be dysfunctional in Parkinsonian patients, rendering postural instability one of the most disabling features of Parkinson's disease (PD). Balance control is critical for moving safely in and adapting to the environment. PD induces a multilevel impairment of this function, therefore worsening the patients' physical and psychosocial disability. In this review, we describe the complex ways in which PD impairs posture and balance, collecting and reviewing the available experimental evidence. PMID:25654100

  15. [Conservative therapy of erectile dysfunction].

    PubMed

    Trottmann, M; Marcon, J; Pompe, S; Strobach, D; Becker, A J; Stief, C G

    2015-05-01

    The erectile dysfunction (ED) with a prevalence of 19.2% and a steep age-related increase up to 53.4% in men over 70 years is a common sexual disorder. Especially after market launch of the phosphodiesterase 5 inhibitors the possibility of an easy-to-use and well-tolerated therapy is available. In case of nonresponse, vasoactive substances can be applied in different forms. In case of an additional hypogonadism, testosterone substitution is indicated. Simultaneously the causes of ED should always be treated, including a change of lifestyle with elimination of exogenous noxa. The use of mechanic tools as single or combination therapy can lead to improved erection. This article provides a critical overview of the latest conservative therapy options, it explains previous unsuccessful therapeutic trials and gives an outlook into potential ED therapy concepts of the future. PMID:25987332

  16. [Topical therapy in erectile dysfunction].

    PubMed

    Floth, A

    2000-01-01

    All forms of pharmacological therapy result in a relaxation of the corporeal smooth muscle. Intracorporeal injection of vasoactive drugs was introduced around 15 years ago and still is the most effective therapy in erectile dysfunction. Resulting in a consistent success rate of 70-80% this form of therapy will find numerous applications, even after the introduction of effective oral agents such as sildenafil. Prostaglandin E1 and--less frequently used--the combination of papaverine and phentolamine are the mainstay of intracorporeal injection therapy. Intraurethral prostaglandin (MUSE) has recently become available and is somewhat less effective than injection therapy. Externally applied drugs (nitroglycerin paste on the penile shaft and minoxidil solution on the glans penis) have not succeeded in the long run. Vacuum erection devices represent a form of physical topical therapy that is very versatile and also effective but rather infrequently applied. PMID:10746290

  17. Sleep Dysfunction and Gastrointestinal Diseases.

    PubMed

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  18. Noradrenergic dysfunction in Alzheimer's disease

    PubMed Central

    Gannon, Mary; Che, Pulin; Chen, Yunjia; Jiao, Kai; Roberson, Erik D.; Wang, Qin

    2015-01-01

    The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed. PMID:26136654

  19. The neuropathy of erectile dysfunction.

    PubMed

    Bleustein, C B; Arezzo, J C; Eckholdt, H; Melman, A

    2002-12-01

    These studies were intended to explore the relationship between autonomic neuropathy and erectile dysfunction (ED). Sensory thresholds reflecting the integrity of both large diameter, myelinated neurons (ie pressure, touch, vibration) and small diameter axons (ie hot and cold thermal sensation) were determined on the penis and finger. Data were compared across subjects with and without ED, controlling for age, hypertension and diabetes. The correlation of specific thresholds scores and IIEF values were also examined. Seventy-three patients who visited the academic urology clinics at Montefiore hospital were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire: 20 subjects had no complaints of ED and scored within the 'normal' range on the IIEF. Patients were subsequently tested on their index finger and glans penis for vibration (Biothesiometer), pressure (Semmes-Weinstein monofilaments), spatial perception (Tactile Circumferential Discriminator), and warm and cold thermal thresholds (Physitemp NTE-2). Sensation of the glans penis, as defined by the examined sensory thresholds, was significantly diminished in patients with ED and these differences remained significant when controlling for age, diabetes and hypertension. In contrast, thresholds on the index finger were equivalent in the ED and non-ED groups. Threshold and IIEF scores were highly correlated, consistent with an association between diminished sensation and decreasing IIEF score (worse erectile functioning). These relations also remained significant when controlling for age, diabetes and hypertension. The findings demonstrate dysfunction of large and small diameter nerve fibers in patients with ED of all etiologies. Further, the neurophysiologic measures validate the use of the IIEF as an index of ED, as objective findings of sensory neuropathy were highly correlated with worse IIEF scores. The sensory

  20. Male Pseudoheterosexuality and Minimal Sexual Dysfunction

    ERIC Educational Resources Information Center

    Gutstadt, Joseph P.

    1976-01-01

    There is often a correlation between "pseudoheterosexuality" and minor sexual dysfunction. Insight alone is not sufficient to provide relief, but when the patient can be helped to a comfortable acceptance of his homosexual feelings as a normal and healthy facet of his personality, very often the dysfunction is relieved. (Author)

  1. Towards an Analysis of Dysfunctional Grammar

    ERIC Educational Resources Information Center

    Rigaudeau-McKenna, B.

    2005-01-01

    This article applies Systemic Functional Linguistics (SFL) to the study of language dysfunction. It demonstrates the potential that Systemic Functional analysis can offer to one aspect of the analysis of language dysfunction--the failure to realise complexes of clauses. For the purpose of analysis, new concepts and new measures have been created.…

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

    PubMed

    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. PMID:26608185

  3. Nuclear proliferation: toward global restraint

    SciTech Connect

    Not Available

    1984-01-01

    A year-long study by the United Nations Association of the USA (UNA-USA) on the problem of proliferation analyzed the policy issues and developed recommendations for US and international policy. The consensus report concludes that old approaches are no longer sufficient. Renewed efforts must avoid the spread of nuclear weapons to additional countries. Efforts must focus on raising the costs of and decreasing the incentives for acquiring nuclear weapons. The report defines five categories of feasible policy initiatives: (1) strengthen the International Atomic Energy Agency's credibility as a nuclear watchdog, (2) reaffirm US and international support for the Non-Proliferation Treaty, (3) develop a comprehensive US non-proliferation policy, (4) renew efforts to develop nuclear-weapons-free zones, and (5) develop nonproliferation confidence-building measures.

  4. Calcium signaling and cell proliferation.

    PubMed

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. PMID:26275497

  5. [The cognitive dysfunction in Parkinson's disease].

    PubMed

    Kanazawa, Akira

    2004-09-01

    Parkinson's disease (PD) is a slowly progressive disorder which begins with motor symptoms. Several cognitive deficits can be observed in nondemented patients with PD during their history. The core symptom in the cognitive deficits in PD is the executive dysfunction. Neuropsychological tests such as Wisconsin Card Sorting Test, Trail Making Test are used to measure the degree of this dysfunction. Executive dysfunction is thought related to abnormalities in the dorsolateral prefrontal circuit which largely passes through the caudate nucleus. The dysfunction emerges as the pathology spreads to the nigrocaudate project corresponding to Hoehn & Yahr stage II-III. Effective therapy for cognitive dysfunction in PD remains elusive, however donepezil, Attention Process Training, Music therapy and Transcranial magnetic stimulation have been reported to have partial efficacy. PMID:15462384

  6. Proliferation of mutators in A cell population.

    PubMed Central

    Mao, E F; Lane, L; Lee, J; Miller, J H

    1997-01-01

    A Lac- strain of Escherichia coli that reverts by the addition of a G to a G-G-G-G-G-G sequence was used to study the proliferation of mutators in a bacterial culture. Selection for the Lac+ phenotype, which is greatly stimulated in mismatch repair-deficient strains, results in an increase in the percentage of mutators in the selected population from less than 1 per 100,000 cells to 1 per 200 cells. All the mutators detected were deficient in the mismatch repair system. Mutagenesis results in a similar increase in the percentage of mutators. Mutagenesis combined with a single selection can result in a population of more than 50% mutators when a sample of several thousand cells is grown out and selected. Mutagenesis combined with two or more successive selections can generate a population that is 100% mutator. These experiments are discussed in relation to ideas that an early step in carcinogenesis is the creation of a mutator phenotype. PMID:8990293

  7. Bacterial interactions in pathogenic subgingival plaque.

    PubMed

    Ng, Hong Min; Kin, Lin Xin; Dashper, Stuart G; Slakeski, Nada; Butler, Catherine A; Reynolds, Eric C

    2016-05-01

    Chronic periodontitis has a polymicrobial biofilm aetiology. Polymicrobial biofilms are complex, dynamic microbial communities formed by two or more bacterial species that are important for the persistence and proliferation of participating microbes in the environment. Interspecies adherence, which often involves bacterial surface-associated molecules, and communications are essential in the spatial and temporal development of a polymicrobial biofilm, which in turn is necessary for the overall fitness of a well-organized multispecies biofilm community. In the oral cavity, interactions between key oral bacterial species, including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, are essential for the progression of chronic periodontitis. In vivo, P. gingivalis and T. denticola are frequently found to co-exist in deep periodontal pockets and have been co-localized to the superficial layers of subgingival plaque as microcolony blooms adjacent to the pocket epithelium, suggesting possible interbacterial interactions that contribute towards disease. The motility and chemotactic ability of T. denticola, although not considered as classic virulence factors, are likely to be important in the synergistic biofilm formation with P. gingivalis. In vitro, P. gingivalis and T. denticola display a symbiotic relationship in nutrient utilization and growth promotion. Together these data suggest there is an intimate relationship between these two species that has evolved to enhance their survival and virulence. PMID:26541672

  8. How bacterial pathogens colonize their hosts and invade deeper tissues.

    PubMed

    Ribet, David; Cossart, Pascale

    2015-03-01

    Bacterial pathogens have evolved a wide range of strategies to colonize and invade human organs, despite the presence of multiple host defense mechanisms. In this review, we will describe how pathogenic bacteria can adhere and multiply at the surface of host cells, how some bacteria can enter and proliferate inside these cells, and finally how pathogens may cross epithelial or endothelial host barriers and get access to internal tissues, leading to severe diseases in humans. PMID:25637951

  9. Bacterial start site prediction.

    PubMed

    Hannenhalli, S S; Hayes, W S; Hatzigeorgiou, A G; Fickett, J W

    1999-09-01

    With the growing number of completely sequenced bacterial genes, accurate gene prediction in bacterial genomes remains an important problem. Although the existing tools predict genes in bacterial genomes with high overall accuracy, their ability to pinpoint the translation start site remains unsatisfactory. In this paper, we present a novel approach to bacterial start site prediction that takes into account multiple features of a potential start site, viz., ribosome binding site (RBS) binding energy, distance of the RBS from the start codon, distance from the beginning of the maximal ORF to the start codon, the start codon itself and the coding/non-coding potential around the start site. Mixed integer programing was used to optimize the discriminatory system. The accuracy of this approach is up to 90%, compared to 70%, using the most common tools in fully automated mode (that is, without expert human post-processing of results). The approach is evaluated using Bacillus subtilis, Escherichia coli and Pyrococcus furiosus. These three genomes cover a broad spectrum of bacterial genomes, since B.subtilis is a Gram-positive bacterium, E.coli is a Gram-negative bacterium and P. furiosus is an archaebacterium. A significant problem is generating a set of 'true' start sites for algorithm training, in the absence of experimental work. We found that sequence conservation between P. furiosus and the related Pyrococcus horikoshii clearly delimited the gene start in many cases, providing a sufficient training set. PMID:10446249

  10. Nuclear Proliferation Technology Trends Analysis

    SciTech Connect

    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.