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Sample records for apoptosis organ dysfunction

  1. Molecular biology of multiple organ dysfunction syndrome: injury, adaptation, and apoptosis.

    Science.gov (United States)

    Cobb, J P; Buchman, T G; Karl, I E; Hotchkiss, R S

    2000-01-01

    Injury will equal or surpass communicable disease in the year 2020 as the number one cause of lost disability-adjusted life-years worldwide. The major cause of "late death" after trauma is organ dysfunction, commonly as a complication of shock or sepsis. The pathophysiology of injury-induced organ dysfunction is poorly characterized but has been linked to systemic inflammation as a result of infection (either obvious or occult) or massive tissue injury (systemic inflammatory response syndrome, SIRS). Subsequent complications of organ dysfunction, including death, may also stem from immunosuppression characteristic of what has been called the counter-regulatory anti-inflammatory response syndrome (CARS). At the cellular level, injurious stimuli trigger adaptive stress responses that include changes in gene expression. Multiple organ dysfunction syndrome (MODS) is the summation of these stress responses to severe systemic injury, integrated at the cellular, organ, and host levels. We hypothesize that a complete understanding at the molecular level of the stress responses induced by injury will aid in the development of therapeutic strategies for treating MODS in the critically ill surgical patient. This paper reviews recent data from our Cellular Injury and Adaptation Laboratory relevant to our understanding of MODS pathophysiology, particularly as it relates to stress-induced cell death by apoptosis. Our data suggest that inhibition of stress-induced apoptosis may improve survival after severe injury.

  2. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

    Science.gov (United States)

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

  3. [Apoptosis of interstitial cells of Cajal in deep muscular layer of small intestine in rats with multiple organ dysfunction syndrome].

    Science.gov (United States)

    Xie, Mingzheng; Qi, Qinghui

    2015-06-01

    To observe the apoptosis of interstitial cells of Cajal in deep muscular layer (ICC-DMP) of small intestine in rats with multiple organ dysfunction syndrome (MODS) as a result of bacterial peritonitis, and the expression of c-kit (an ICC phenotype marker) and Bax/Bcl-2, in order to investigate the mechanism of gastrointestinal motility dysfunction in MODS. According to the random number table, 40 Wistar rats were randomly divided into two groups: control group (n=20) and MODS group (n=20). The MODS model in rats was reproduced by intraperitoneal injection of 8×10(8) cfu/mL Escherichia coli suspension 1 mL, and the control group was given the same amount of normal saline. After 24 hours, the upper small intestine was harvested for examination. Ultrastructure of ICC-DMP was observed using electron microscope. The network structure of ICC-DMP and the expression of c-kit and Bax/Bcl-2 were observed and determined with immunofluorescence and laser scanning confocal microscope. Macroscopic observation revealed that the gastrointestinal motility of rats was normal in the control group. Compared with the control group, gastro intestine was significantly expanded with parulytic ileus in MODS group. It was shown by transmission electron microscopy that intermediate filament structure of ICC-DMP was clear without swelling of mitochondria; chromatin distributed uniformly with small amounts of heterochromatin aggregated in perinuclear. Compared with the control group, intermediate filament structure of ICC-DMP was fuzzy, and mitochondria were swollen obviously in MODS group; chromatin was assembled in nucleus centre. It was shown by laser scanning confocal microscope that the network structure of ICC-DMP was clear, the expression of c-kit and Bcl-2 was strongly and overlapping; the expression of Bax was weak and scatter distributed. Compared with control group, ICC-DMP quantity in MODS group was significantly reduced (cells/HP: 15.80±2.30 vs. 25.70±3.97, t=6.819, P=0

  4. Postinjury Inflammation and Organ Dysfunction.

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    Sauaia, Angela; Moore, Frederick A; Moore, Ernest E

    2017-01-01

    The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, whereas antiinflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low-level OD may develop the persistent inflammation-immunosuppression catabolism syndrome. Although the incidence of multiple organ failure has decreased over time, it remains morbid, lethal, and resource intensive. However, single OD, especially acute lung injury, remains frequent. Treatment is limited, and prevention remains the mainstay strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Inflammatory mediator and organ dysfunction syndrome].

    Science.gov (United States)

    Shimada, H; Moriwaki, Y; Kurosawa, H; Kubota, T; Endo, I; Togo, S; Yamaoka, H

    1998-08-01

    Inflammatory mediators include endotoxin (ETX), cytokines (interleukins [ILs], tumor necrosis factors [TNFs], and interferons), eicosanoids (prostaglandins and thromboxanes), reactive oxygen species (O2-, NO, and ONOO-), complements (C3 and C4), and stress hormones (catecholamine, cortisol, vasopressin, and growth hormone). These mediators work to maintain homeostasis under stressful conditions through a complex chain reaction or cascade that results in transient tissue damage known as the inflammatory response. The inflammatory response is decreased by a negative feedback system, which consists not only of the self-inhibitory action of ETX, TNF-alpha, IL-1, and IL-8, but also of the production of antiinflammatory mediators such as IL-4, -10, -11, and -13, TGF-beta, IL-Ra, and sTNFR. If excessive stress or a second attack of stress results in a higher level of inflammation-producing mediators than of inflammation-inhibiting mediators, tissue destruction occurs due to activation and infiltration of inflammatory cells or necrosis due to endothelial injury is seen, followed by disruption of homeostasis, organ dysfunction, and organ failure (multiple organ dysfunction syndrome [MODS] or multiple organ failure [MOF] induced by SIRS). In experimental liver dysfunction after 95% hepatectomy, massive apoptosis of hepatocytes is induced by prolonged hypercytokinemia, ONOO- production, decreased mitochondrial membrane potential of hepatocytes, and decreased Bc12 levels. On the other hand, if the antiinflammatory response is greater than the inflammatory response (CARS) a compromised state and refractory infection are seen, followed by progressive, irreversible organ dysfunction (MODS or MOF induced by CARS).

  6. Indomethacin elicits proteasomal dysfunctions develops apoptosis through mitochondrial abnormalities.

    Science.gov (United States)

    Amanullah, Ayeman; Mishra, Ribhav; Upadhyay, Arun; Reddy, Pothula P; Das, Ranabir; Mishra, Amit

    2018-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that are mainly used to treat pain, inflammation, and fever via cyclooxygenase-2 (COX-2) inhibition. There are abundant findings that uncover the hidden critical chemotherapeutics potential of NSAIDs in cancer treatment. However, still the precise mechanism by which NSAIDs could be used as an effective anti-tumor agent in the prevention of carcinogenesis is not well understood. Here, we show that indomethacin, a well-known NSAID, induces proteasomal dysfunction that results in accumulation of unwanted proteins, mitochondrial abnormalities, and successively stimulate apoptosis in cells. We observed the interaction of indomethacin with proteasome and noticed the massive accumulation of intracellular ubiquitin-positive proteins, which might be due to the suppression of proteasome activities. Furthermore, we also found that exposure of indomethacin causes the accumulation of critical proteasomal substrates that consequently generate severe mitochondrial abnormalities and prompt up key apoptotic events in cells. Our results demonstrate how indomethacin affects normal proteasomal functions and induces mitochondrial apoptosis in cells. These findings also improve our current understanding of how NSAIDs can exhibit crucial anti-proliferative effects in cells. In near future, our findings may suggest a new possible strategy for the development of specific proteasome inhibitors in conjunction with other chemo-preventive anticancer agents. © 2017 Wiley Periodicals, Inc.

  7. Foodborne cereulide causes beta-cell dysfunction and apoptosis.

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    Roman Vangoitsenhoven

    Full Text Available To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function.Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6 and rat (INS-1E beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1. Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS. Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05. Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05 and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein. Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05 and reactive oxygen species increased by more than twofold (P<0.05 following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.

  8. Mitochondrial dysfunction is responsible for fatty acid synthase inhibition-induced apoptosis in breast cancer cells by PdpaMn.

    Science.gov (United States)

    Wang, Qiang; Du, Xia; Zhou, Bingjie; Li, Jing; Lu, Wenlong; Chen, Qiuyun; Gao, Jing

    2017-12-01

    Targeting cellular metabolism is becoming a hallmark to overcome drug resistance in breast cancer treatment. Activation of fatty acid synthase (FASN) has been shown to promote breast cancer cell growth. However, there is no concrete report underlying the mechanism associated with mitochondrial dysfunction in relation to fatty acid synthase inhibition-induced apoptosis in breast cancer cells. The current study is aimed at exploring the effect of the novel manganese (Mn) complex, labeled as PdpaMn, on lipid metabolism and mitochondrial function in breast cancer cells. Herein, we observed that PdpaMn displayed strong cytotoxicity on breast cancer cell lines and selectively targeted the tumor without affecting the normal organs or cells in vivo. We also observed that PdpaMn could bind to TE domain of FASN and decrease the activity and the level of expression of FASN, which is an indication that FASN could serve as a target of PdpaMn. In addition, we demonstrated that PdpaMn increased intrinsic apoptosis in breast cancer cells relayed by a suppressed the level of expression of FASN, followed by the release of mitochondrial cytochrome c and the activation of caspases-9. Instigated by the above observations, we hypothesized that PdpaMn-induced apoptosis events are dependent on mitochondrial dysfunction. Indeed, we found that mitochondrial membrane potential (MMP) collapse, mitochondrial oxygen consumption reduction and adenosine triphosphate (ATP) release were deeply repressed. Furthermore, our results showed that PdpaMn significantly increased the reactive oxygen species (ROS) production, and the protection conferred by the free radical scavenger N-acetyl-cysteine (NAC) indicates that PdpaMn-induced apoptosis through an oxidative stress-associated mechanism. More so, the above results have demonstrated that mitochondrial dysfunction participated in FASN inhibition-induce apoptosis in breast cancer cells by PdpaMn. Therefore, PdpaMn may be considered as a good candidate

  9. DNA damage and mitochondria dysfunction in cell apoptosis induced by nonthermal air plasma

    Science.gov (United States)

    Kim, G. J.; Kim, W.; Kim, K. T.; Lee, J. K.

    2010-01-01

    Nonthermal plasma is known to induce animal cell death but the mechanism is not yet clear. Here, cellular and biochemical regulation of cell apoptosis is demonstrated for plasma treated cells. Surface type nonthermal air plasma triggered apoptosis of B16F10 mouse melanoma cancer cells causing DNA damage and mitochondria dysfunction. Plasma treatment activated caspase-3, apoptosis executioner. The plasma treated cells also accumulated gamma-H2A.X, marker for DNA double strand breaks, and p53 tumor suppressor gene as a response to DNA damage. Interestingly, cytochrome C was released from mitochondria and its membrane potential was changed significantly.

  10. Proteasomal Dysfunction Induced By Diclofenac Engenders Apoptosis Through Mitochondrial Pathway.

    Science.gov (United States)

    Amanullah, Ayeman; Upadhyay, Arun; Chhangani, Deepak; Joshi, Vibhuti; Mishra, Ribhav; Yamanaka, Koji; Mishra, Amit

    2017-05-01

    Diclofenac is the most commonly used phenylacetic acid derivative non-steroidal anti-inflammatory drug (NSAID) that demonstrates significant analgesic, antipyretic, and anti-inflammatory effects. Several epidemiological studies have demonstrated anti-proliferative activity of NSAIDs and examined their apoptotic induction effects in different cancer cell lines. However, the precise molecular mechanisms by which these pharmacological agents induce apoptosis and exert anti-carcinogenic properties are not well known. Here, we have observed that diclofenac treatment induces proteasome malfunction and promotes accumulation of different critical proteasome substrates, including few pro-apoptotic proteins in cells. Exposure of diclofenac consequently elevates aggregation of various ubiquitylated misfolded proteins. Finally, we have shown that diclofenac treatment promotes apoptosis in cells, which could be because of mitochondrial membrane depolarization and cytochrome c release into cytosol. This study suggests possible beneficial insights of NSAIDs-induced apoptosis that may improve our existing knowledge in anti-proliferative interspecific strategies development. J. Cell. Biochem. 118: 1014-1027, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction.

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    Sun, Lingmei; Liao, Kai; Hang, Chengcheng; Wang, Dayong

    2017-01-01

    To investigate the effects of honokiol on induction of reactive oxygen species (ROS), antioxidant defense systems, mitochondrial dysfunction, and apoptosis in Candida albicans. To measure ROS accumulation, 2',7'-dichlorofluorescein diacetate fluorescence was used. Lipid peroxidation was assessed using both fluorescence staining and a thiobarbituric acid reactive substances (TBARS) assay. Protein oxidation was determined using dinitrophenylhydrazine derivatization. Antioxidant enzymatic activities were measured using commercially available detection kits. Superoxide dismutase (SOD) genes expression was measured using real time RT-PCR. To assess its antifungal abilities and effectiveness on ROS accumulation, honokiol and the SOD inhibitor N,N'-diethyldithiocarbamate (DDC) were used simultaneously. Mitochondrial dysfunction was assessed by measuring the mitochondrial membrane potential (mtΔψ). Honokiol-induced apoptosis was assessed using an Annexin V-FITC apoptosis detection kit. ROS, lipid peroxidation, and protein oxidation occurred in a dose-dependent manner in C. albicans after honokiol treatment. Honokiol caused an increase in antioxidant enzymatic activity. In addition, honokiol treatment induced SOD genes expression in C. albicans cells. Moreover, addition of DDC resulted in increased endogenous ROS levels and potentiated the antifungal activity of honokiol. Mitochondrial dysfunction was confirmed by measured changes to mtΔψ. The level of apoptosis increased in a dose-dependent manner after honokiol treatment. Collectively, these results indicate that honokiol acts as a pro-oxidant in C. albicans. Furthermore, the SOD inhibitor DDC can be used to potentiate the activity of honokiol against C. albicans.

  12. Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction.

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    Lingmei Sun

    Full Text Available To investigate the effects of honokiol on induction of reactive oxygen species (ROS, antioxidant defense systems, mitochondrial dysfunction, and apoptosis in Candida albicans.To measure ROS accumulation, 2',7'-dichlorofluorescein diacetate fluorescence was used. Lipid peroxidation was assessed using both fluorescence staining and a thiobarbituric acid reactive substances (TBARS assay. Protein oxidation was determined using dinitrophenylhydrazine derivatization. Antioxidant enzymatic activities were measured using commercially available detection kits. Superoxide dismutase (SOD genes expression was measured using real time RT-PCR. To assess its antifungal abilities and effectiveness on ROS accumulation, honokiol and the SOD inhibitor N,N'-diethyldithiocarbamate (DDC were used simultaneously. Mitochondrial dysfunction was assessed by measuring the mitochondrial membrane potential (mtΔψ. Honokiol-induced apoptosis was assessed using an Annexin V-FITC apoptosis detection kit.ROS, lipid peroxidation, and protein oxidation occurred in a dose-dependent manner in C. albicans after honokiol treatment. Honokiol caused an increase in antioxidant enzymatic activity. In addition, honokiol treatment induced SOD genes expression in C. albicans cells. Moreover, addition of DDC resulted in increased endogenous ROS levels and potentiated the antifungal activity of honokiol. Mitochondrial dysfunction was confirmed by measured changes to mtΔψ. The level of apoptosis increased in a dose-dependent manner after honokiol treatment.Collectively, these results indicate that honokiol acts as a pro-oxidant in C. albicans. Furthermore, the SOD inhibitor DDC can be used to potentiate the activity of honokiol against C. albicans.

  13. MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte Apoptosis and Cardiac Dysfunction

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    Hasahya Tony

    2015-01-01

    Full Text Available Aims. GATA4 depletion is a distinct mechanism by which doxorubicin leads to cardiomyocyte apoptosis, and preservation of GATA4 mitigates doxorubicin induced myocyte apoptosis and cardiac dysfunction. We investigated a novel approach of attenuating doxorubicin induced cardiac toxicity by silencing miR-208a, a heart specific microRNA known to target GATA4. Methods and Results. Eight-week-old female Balb/C mice were randomly assigned to sham, antagomir, and control groups. Antagomir group were pretreated with miR-208a antagomir 4 days before doxorubicin administration. At day 0, control and antagomir groups received 20 mg/kg of doxorubicin, while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed and hearts harvested and assessed for apoptosis and expression of miR-208a, GATA4, and BCL-2. Doxorubicin significantly upregulated miR-208a, downregulated GATA4, and increased myocyte apoptosis, with resulting decrease in cardiac function. In contrast, therapeutic silencing of miR-208a salvaged GATA4 and BCL-2 and decreased apoptosis, with improvement in cardiac function. Conclusion. Doxorubicin upregulates miR-208a and promotes cardiomyocyte apoptosis, while therapeutic silencing of miR-208a attenuates doxorubicin induced myocyte apoptosis with subsequent improvement in cardiac function. These novel results highlight the therapeutic potential of targeting miR-208a to prevent doxorubicin cardiotoxicity.

  14. Radiation-Induced Salivary Gland Dysfunction Results From p53-Dependent Apoptosis

    International Nuclear Information System (INIS)

    Avila, Jennifer L.; Grundmann, Oliver; Burd, Randy; Limesand, Kirsten H.

    2009-01-01

    Purpose: Radiotherapy for head-and-neck cancer causes adverse secondary side effects in the salivary glands and results in diminished quality of life for the patient. A previous in vivo study in parotid salivary glands demonstrated that targeted head-and-neck irradiation resulted in marked increases in phosphorylated p53 (serine 18 ) and apoptosis, which was suppressed in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Methods and Materials: Transgenic and knockout mouse models were exposed to irradiation, and p53-mediated transcription, apoptosis, and salivary gland dysfunction were analyzed. Results: The proapoptotic p53 target genes PUMA and Bax were induced in parotid salivary glands of mice at early time points after therapeutic radiation. This dose-dependent induction requires expression of p53 because no radiation-induced expression of PUMA and Bax was observed in p53-/- mice. Radiation also induced apoptosis in the parotid gland in a dose-dependent manner, which was p53 dependent. Furthermore, expression of p53 was required for the acute and chronic loss of salivary function after irradiation. In contrast, apoptosis was not induced in p53-/- mice, and their salivary function was preserved after radiation exposure. Conclusions: Apoptosis in the salivary glands after therapeutic head-and-neck irradiation is mediated by p53 and corresponds to salivary gland dysfunction in vivo

  15. Pattern of Presentation of Multiple Organ Dysfunction Syndrome in ...

    African Journals Online (AJOL)

    Background: Multiple organ dysfunction syndrome is the sequential failure of several organ systems after a trigger event, like sepsis, massive transfusions, burns, trauma and cardiogenic shock. Aim and Objectives- The pattern of presentation of multiple organ dysfunction and the risk factors associated with multiple organ ...

  16. Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

    Science.gov (United States)

    Chen, M; Zhang, Y; Yu, V C; Chong, Y-S; Yoshioka, T; Ge, R

    2014-01-01

    Isthmin (ISM) is a secreted 60-kDa protein that potently induces endothelial cell (EC) apoptosis. It suppresses tumor growth and angiogenesis in mice when stably overexpressed in cancer cells. Although αvβ5 integrin serves as a low-affinity receptor for ISM, the mechanism by which ISM mediates antiangiogenesis and apoptosis in ECs remain to be fully resolved. In this work, we report the identification of cell-surface glucose-regulated protein 78 kDa (GRP78) as a high-affinity receptor for ISM (Kd=8.6 nM). We demonstrated that ISM-GRP78 interaction triggers apoptosis not only in activated ECs but also in cancer cells expressing high level of cell-surface GRP78. Normal cells and benign tumor cells tend to express low level of cell-surface GRP78 and are resistant to ISM-induced apoptosis. Upon binding to GRP78, ISM is internalized into ECs through clathrin-dependent endocytosis that is essential for its proapoptotic activity. Once inside the cell, ISM co-targets with GRP78 to mitochondria where it interacts with ADP/ATP carriers on the inner membrane and blocks ATP transport from mitochondria to cytosol, thereby causing apoptosis. Hence, ISM is a novel proapoptotic ligand that targets cell-surface GRP78 to trigger apoptosis by inducing mitochondrial dysfunction. The restricted and high-level expression of cell-surface GRP78 on cancer cells and cancer ECs make them uniquely susceptible to ISM-targeted apoptosis. Indeed, systemic delivery of recombinant ISM potently suppressed subcutaneous 4T1 breast carcinoma and B16 melanoma growth in mice by eliciting apoptosis selectively in the cancer cells and cancer ECs. Together, this work reveals a novel ISM-GRP78 apoptosis pathway and demonstrates the potential of ISM as a cancer-specific and dual-targeting anticancer agent. PMID:24464222

  17. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-01-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

  18. Asymmetric Dimethylarginine Induced Apoptosis and Dysfunction of Endothelial Progenitor Cells: Role of Endoplasmic Reticulum Stress Pathway

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    Sheng Ye

    2017-01-01

    Full Text Available Asymmetric dimethylarginine (ADMA, an inhibitor of nitric oxide synthase, is a novel risk factor of cardiovascular disease. Endothelial progenitor cells (EPCs bear typical endothelial characteristics and are thought to contribute to neovascularization by providing new endothelial cells (ECs after arterial injury. Many studies have shown that ADMA can induce EPC apoptosis and dysfunction, but the underlying mechanism is not well understood. EPCs from umbilical cord blood were cultured in EGM-2 medium with particular growth factors and supplemented with 10% fetal bovine serum. The cells were treated with different concentrations of ADMA (5, 10, and 50 μmol/L. Endoplasmic reticulum (ER stress marker levels were examined by western blot analysis. After 24-hour incubation, ADMA induced apoptosis of EPCs and significantly decreased the proliferation, migration, and vasculogenesis capacity of EPCs. We also found that ADMA treatment activated phosphorylated protein kinase RNA-activated-like ER kinase (PERK, a stress sensor protein in the endoplasmic reticulum (ER. The activated PERK induced 78 kDa glucose-regulated protein (GRP-78 and C/EBP homologous protein (CHOP expression. Additionally, the inhibition of the ER stress pathway by Salubrinal (a specific ER stress inhibitor can attenuate ADMA-induced apoptosis of EPCs. Overall, these observations indicate that ADMA may induce the apoptosis and dysfunction of EPCs through the ER stress pathway.

  19. Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells.

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    Zerin, Tamanna; Kim, Jin-Sun; Gil, Hyo-Wook; Song, Ho-Yeon; Hong, Sae-Yong

    2015-12-01

    Methanol ingestion is neurotoxic in humans due to its metabolites, formaldehyde and formic acid. Here, we compared the cytotoxicity of methanol and its metabolites on different types of cells. While methanol and formic acid did not affect the viability of the cells, formaldehyde (200-800 μg/mL) was strongly cytotoxic in all cell types tested. We investigated the effects of formaldehyde on oxidative stress, mitochondrial respiratory functions, and apoptosis on the sensitive neuronal SK-N-SH cells. Oxidative stress was induced after 2 h of formaldehyde exposure. Formaldehyde at a concentration of 400 μg/mL for 12 h of treatment greatly reduced cellular adenosine triphosphate (ATP) levels. Confocal microscopy indicated that the mitochondrial membrane potential (MMP) was dose-dependently reduced by formaldehyde. A marked and dose-dependent inhibition of mitochondrial respiratory enzymes, viz., NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and oxidative stress-sensitive aconitase was also detected following treatment with formaldehyde. Furthermore, formaldehyde caused a concentration-dependent increase in nuclear fragmentation and in the activities of the apoptosis-initiator caspase-9 and apoptosis-effector caspase-3/-7, indicating apoptosis progression. Our data suggests that formaldehyde exerts strong cytotoxicity, at least in part, by inducing oxidative stress, mitochondrial dysfunction, and eventually apoptosis. Changes in mitochondrial respiratory function and oxidative stress by formaldehyde may therefore be critical in methanol-induced toxicity.

  20. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

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    Fang Sun

    2016-04-01

    Full Text Available Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1. TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

  1. Sesamin Ameliorates Advanced Glycation End Products-Induced Pancreatic β-Cell Dysfunction and Apoptosis

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    Xiang Kong

    2015-06-01

    Full Text Available Advanced glycation end products (AGEs, the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg and orally treated with sesamin (160 mg/kg for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM and then exposed to AGEs (200 mg/L for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67phox and p22phox, and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

  2. Platycodin D induced apoptosis and autophagy in PC-12 cells through mitochondrial dysfunction pathway

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    Zeng, Chuan-Chuan; Zhang, Cheng; Yao, Jun-Hua; Lai, Shang-Hai; Han, Bing-Jie; Li, Wei; Tang, Bing; Wan, Dan; Liu, Yun-Jun

    2016-11-01

    In this article, the in vitro cytotoxicity of platycodin D was evaluated in human PC-12, SGC-7901, BEL-7402, HeLa and A549 cancer cell lines. PC-12 cells were sensitive to platycodin D treatment, with an IC50 value of 13.5 ± 1.2 μM. Morphological and comet assays showed that platycodin D effectively induced apoptosis in PC-12 cells. Platycodin D increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Platycodin D induced cell cycle arrest at the G0/G1 phase in the PC-12 cell line. Platycodin D can induce autophagy. In addition, platycodin D can down-regulate the expression of Bcl-2 and Bcl-x, and up-regulate the levels of Bid protein in the PC-12 cells. The results demonstrated that platycodin D induced PC-12 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway.

  3. Multiple organ dysfunction caused by parathyroid adenoma‑induced ...

    African Journals Online (AJOL)

    We present a 27‑year‑old male with multiple organ dysfunction caused by parathyroid adenoma‑induced primary hyperparathyroidism (PHPT). Initially, the patient experienced a sudden onset of gastrointestinal symptoms, polyuria, polydipsia, bone pain, renal dysfunction, nephrolithiasis, and acute pancreatitis, symptoms ...

  4. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  5. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Kyuhwa; Seo, Suho; Han, Jae Yun; Ki, Sung Hwan; Shin, Sang Mi, E-mail: smshin@chosun.ac.kr

    2014-10-15

    Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2

  6. Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling.

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    Patrick Meybohm

    Full Text Available BACKGROUND: Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty pigs (28-34 kg were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21, coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group n = 7 for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01, reduced infarct size (34+/-7 versus 57+/-12%; p<0.05 and improved left ventricular function compared to normothermia (p<0.05. Hypothermia was associated with a reduction in: (i immune cell infiltration, (ii apoptosis, (iii IL-1beta and IL-6 mRNA up-regulation, and (iv IL-1beta protein expression (p<0.05. Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached. CONCLUSIONS/SIGNIFICANCE: Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis

  7. Dipyridamole reduces penile apoptosis in a rat model of post-prostatectomy erectile dysfunction

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    Omer Kutlu

    Full Text Available ABSTRACT Purpose: Despite the nerve-sparing technique, many patients suffer from erectile dysfunction after radical prostatectomy (RP due to cavernous nerve injury. The aim of this study was to evaluate dipyridamole as a potential treatment agent of post-radical prostatectomy erectile dysfunction. Material and methods: A total of 18 male Sprague-Dawley rats were randomized into three experimental Groups (SHAM+DMSO, BCNI+DMSO and BCNI+DIP. An animal model of bilateral cavernous nerve crush injury (BCNI was established to mimic the partial nerve damage during nerve-sparing RP. After creating of BCNI, dimethyl sulphoxide (DMSO was administered transperitoneally as a vehicle to SHAM+DMSO and BCNI+DMSO Groups. BCNI+DIP Group received dipyiridamole (10mg/kg/day as a solution in DMSO for 15 days. Afterwards, rats were evaluated for in vivo erectile response to cavernous nerve stimulation. Penile tissues were also analyzed biochemically for transforming growth factor-β1 (TGF-β1 level. Penile corporal apoptosis was determined by TUNEL method. Results: Erectile response was decreased in rats with BCNI and there was no significant improvement with dipyridamole treatment. TGF-β1 levels were increased in rats with BCNI and decreased with dipyridamole treatment. Dipyridamole led to reduced penile apoptosis in rats with BCNI and there was no significant difference when compared to sham operated rats. Conclusions: Although fifteen-day dipyridamole treatment has failed to improve erectile function in rats with BCNI, the decline in both TGF-β1 levels and apoptotic indices with treatment may be helpful in protecting penile morphology after cavernous nerve injury.

  8. Multiple organ dysfunction syndrome associated with Mycoplasma pneumoniae infection

    Directory of Open Access Journals (Sweden)

    Shu-Bo Zhai

    2012-03-01

    Full Text Available In this study, we report one case of a three-year-old boy infected with Mycoplasma pneumonia (MP and presenting concomitant multiple organ damage of the heart, kidney, lung and liver, among others, together with a brief review for the diagnosis and treatment of MP infection with multiple organ dysfunction syndrome (MODS.

  9. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis.

    Science.gov (United States)

    Zhang, Xiang; Dong, Hongquan; Li, Nana; Zhang, Susu; Sun, Jie; Zhang, Shu; Qian, Yanning

    2016-05-31

    Neuroinflammation plays a key role in the occurrence and development of postoperative cognitive dysfunction (POCD). Microglia, the resident immune cells in the brain, has been increasingly recognized to contribute to neuroinflammation. Although brain mast cells (MCs) are the "first responder" in the brain injury rather than microglia, little is known about the functional aspects of MCs-microglia interactions. Male Sprague-Dawley (SD) rats were injected intracerebroventricular with MC stabilizer Cromolyn (100 μg/μl), MC stimulator C48/80 (1 μg/μl), or sterile saline 30 min before open tibial fracture surgery, and the levels of neuroinflammation and memory dysfunction were tested 1 and 3 days after surgery. In addition, the effect of activated MCs on microglia and neurons was determined in vitro. Tibial fracture surgery induced MCs degranulation, microglia activation, and inflammatory factors production, which initiated the acute brain inflammatory response and neuronal death and exhibited cognitive deficit. Site-directed preinjection of the "MCs stabilizer" disodium cromoglycate (Cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced MCs degranulation, microglia activation, neuronal death, and improved cognitive function 24 h after the surgery. In vitro study, we found that the conditioned medium from lipopolysaccharide (LPS)-stimulated mast cells line (P815) could induce primary microglia activation through mitogen-activated protein kinase (MAPK) pathway signaling and subsequent production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the activated P815 could directly induce neuronal apoptosis and synapse injury with microglia independently. Cromolyn could inhibit P815 activation following improved microglia activation and neuronal loss. These results implicate that activated MCs could trigger microglia activation and neuronal damage, resulting in central nervous system (CNS) inflammation, and

  10. Low Molecular Weight Fucoidan Alleviates Cardiac Dysfunction in Diabetic Goto-Kakizaki Rats by Reducing Oxidative Stress and Cardiomyocyte Apoptosis

    Directory of Open Access Journals (Sweden)

    Xinfeng Yu

    2014-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

  11. Caudal regression in adrenocortical dysplasia (acd) mice is caused by telomere dysfunction with subsequent p53-dependent apoptosis.

    Science.gov (United States)

    Vlangos, Christopher N; O'Connor, Bridget C; Morley, Madeleine J; Krause, Andrea S; Osawa, Gail A; Keegan, Catherine E

    2009-10-15

    Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation that exhibits a pleiotropic phenotype with perinatal lethality. Mutant acd embryos have caudal truncation, vertebral segmentation defects, hydronephrosis, and limb hypoplasia, resembling humans with Caudal Regression syndrome. Acd encodes Tpp1, a component of the shelterin complex that maintains telomere integrity, and consequently acd mutant mice have telomere dysfunction and genomic instability. While the association between genomic instability and cancer is well documented, the association between genomic instability and birth defects is unexplored. To determine the relationship between telomere dysfunction and embryonic malformations, we investigated mechanisms leading to the caudal dysgenesis phenotype of acd mutant embryos. We report that the caudal truncation is caused primarily by apoptosis, not altered cell proliferation. We show that the apoptosis and consequent skeletal malformations in acd mutants are dependent upon the p53 pathway by genetic rescue of the limb hypoplasia and vertebral anomalies with p53 null mice. Furthermore, rescue of the acd phenotype by p53 deficiency is a dosage-sensitive process, as acd/acd, p53(-/-) double mutants exhibit preaxial polydactyly. These findings demonstrate that caudal dysgenesis in acd embryos is secondary to p53-dependent apoptosis. Importantly, this study reinforces a significant link between genomic instability and birth defects.

  12. The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness.

    Science.gov (United States)

    Klingensmith, Nathan J; Coopersmith, Craig M

    2016-04-01

    All elements of the gut - the epithelium, the immune system, and the microbiome - are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis.

    Directory of Open Access Journals (Sweden)

    Cheng-Ming Tsao

    Full Text Available Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg or an equivalent volume of saline. The administration of CLP rats with selegiline (i increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii reduced plasma liver and kidney dysfunction, (iii attenuated metabolic acidosis, (iv decreased neutrophil infiltration in liver and lung, and (v improved survival rate (from 44% to 65%, compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill.

  14. P2X7R antagonism after subfailure overstretch injury of blood vessels reverses vasomotor dysfunction and prevents apoptosis.

    Science.gov (United States)

    Luo, Weifeng; Feldman, Daniel; McCallister, Reid; Brophy, Colleen; Cheung-Flynn, Joyce

    2017-12-01

    Human saphenous vein (HSV) is harvested and prepared prior to implantation as an arterial bypass graft. Injury and the response to injury from surgical harvest and preparation trigger cascades of molecular events and contribute to graft remodeling and intimal hyperplasia. Apoptosis is an early response after implantation that contributes the development of neointimal lesions. Here, we showed that surgical harvest and preparation of HSV leads to vasomotor dysfunction, increased apoptosis and downregulation of the phosphorylation of the anti-apoptotic protein, Niban. A model of subfailure overstretch injury in rat aorta (RA) was used to demonstrate impaired vasomotor function, increased extracellular ATP (eATP) release, and increased apoptosis following pathological vascular injury. The subfailure overstretch injury was associated with activation of p38 MAPK stress pathway and decreases in the phosphorylation of the anti-apoptotic protein Niban. Treatment of RA after overstretch injury with antagonists to purinergic P2X7 receptor (P2X7R) antagonists or P2X7R/pannexin (PanX1) complex, but not PanX1 alone, restored vasomotor function. Inhibitors to P2X7R and PanX1 reduced stretch-induced eATP release. P2X7R/PanX1 antagonism led to decrease in p38 MAPK phosphorylation, restoration of Niban phosphorylation and increases in the phosphorylation of the anti-apoptotic protein Akt in RA and reduced TNFα-stimulated caspase 3/7 activity in cultured rat vascular smooth muscle cells. In conclusion, inhibition of P2X7R after overstretch injury restored vasomotor function and inhibited apoptosis. Treatment with P2X7R/PanX1 complex inhibitors after harvest and preparation injury of blood vessels used for bypass conduits may prevent the subsequent response to injury that lead to apoptosis and represents a novel therapeutic approach to prevent graft failure.

  15. Escin, a novel triterpene, mitigates chronic MPTP/p-induced dopaminergic toxicity by attenuating mitochondrial dysfunction, oxidative stress, and apoptosis.

    Science.gov (United States)

    Selvakumar, Govindasamy Pushpavathi; Manivasagam, Thamilarasan; Rekha, Karamkolly R; Jayaraj, Richard L; Elangovan, Namasivayam

    2015-01-01

    Parkinson's disease (PD) is a common, chronic, and debilitating neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons due to unknown factors. In the present study, we have evaluated if escin, a triterpene saponin from seeds of horse chestnut tree (Aesculus hippocastanum), offers neuroprotection against chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced toxicity using a mouse model. Chronic administration of MPTP/p deteriorated the loss of TH immunoreactivity in striatum. Subsequently, MPTP/p also enhanced oxidative stress by mitochondrial complex I inhibition, thereby ensuing dopaminergic denervation via modulation of Bcl-2, Bax, Cyto-C, and cleaved caspases expressions. However, we observed that pretreatment with escin (4 mg/kg) significantly attenuated MPTP/p-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, behavioral studies and ultrastructural analysis of mitochondria and intracellular components were in support of these findings. Therefore, we speculate that escin might be a promising candidate for the prevention of mitochondrial dysfunction-induced apoptosis in neurodegenerative disorders such as PD.

  16. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

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    Kain Vasundhara

    2011-11-01

    Full Text Available Abstract Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB, Azelnidipine (AZL on contractile dysfunction, intracellular calcium (Ca2+ cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP injection of streptozotocin (STZ. Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS, time-to-PS (TPS, time-to-relengthening (TR90, maximal velocity of shortening/relengthening (± dL/dt and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD, calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

  17. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

    Energy Technology Data Exchange (ETDEWEB)

    Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

    2014-09-01

    Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

  18. Histidine deficiency attenuates cell viability in rat intestinal epithelial cells by apoptosis via mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Tatsunobu Matsui, M.S.

    2017-06-01

    Conclusions: This is the first report showing that histidine deficiency reduced cell viability and induced apoptosis in IEC-6 cells, and that a small amount of histidine supplementation prevented and improved the IEC-6 cell injury. This is a potential new clinical treatment against intestinal and/or gastric cell injury that would improve the patient's quality of life.

  19. Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions

    DEFF Research Database (Denmark)

    Karam, Oliver; Demaret, Pierre; Duhamel, Alain

    2016-01-01

    BACKGROUND: Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration...

  20. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  1. Prevalence of multiple organ dysfunction in the pediatric intensive care unit: Pediatric Risk of Mortality III versus Pediatric Logistic Organ Dysfunction scores for mortality prediction.

    Science.gov (United States)

    Hamshary, Azza Abd Elkader El; Sherbini, Seham Awad El; Elgebaly, HebatAllah Fadel; Amin, Samah Abdelkrim

    2017-01-01

    To assess the frequency of primary multiple organ failure and the role of sepsis as a causative agent in critically ill pediatric patients; and calculate and evaluate the accuracy of the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores to predict the outcomes of critically ill children. Retrospective study, which evaluated data from patients admitted from January to December 2011 in the pediatric intensive care unit of the Children's Hospital of the University of Cairo. Out of 237 patients in the study, 72% had multiple organ dysfunctions, and 45% had sepsis with multiple organ dysfunctions. The mortality rate in patients with multiple organ dysfunction was 73%. Independent risk factors for death were mechanical ventilation and neurological failure [OR: 36 and 3.3, respectively]. The PRISM III score was more accurate than the PELOD score in predicting death, with a Hosmer-Lemeshow X2 (Chi-square value) of 7.3 (df = 8, p = 0.5). The area under the curve was 0.723 for PRISM III and 0.78 for PELOD. A multiple organ dysfunctions was associated with high mortality. Sepsis was the major cause. Pneumonia, diarrhea and central nervous system infections were the major causes of sepsis. PRISM III had a better calibration than the PELOD for prognosis of the patients, despite the high frequency of the multiple organ dysfunction syndrome.

  2. Curcumin analog EF24 induces apoptosis via ROS-dependent mitochondrial dysfunction in human colorectal cancer cells.

    Science.gov (United States)

    He, Guodong; Feng, Chen; Vinothkumar, Rajamanickam; Chen, Weiqian; Dai, Xuanxuan; Chen, Xi; Ye, Qingqing; Qiu, Chenyu; Zhou, Huiping; Wang, Yi; Liang, Guang; Xie, Yubo; Wu, Wei

    2016-12-01

    Colorectal cancer is the most commonly diagnosed malignancy with high mortality rates worldwide. Improved therapeutic strategies with minimal adverse side effects are urgently needed. In this study, the anti-tumor effects of EF24, a novel analog of the natural compound curcumin, were evaluated in colorectal cancer cells. The anti-tumor activity of EF24 on human colon cancer lines (HCT-116, SW-620, and HT-29) was determined by measures of cell cycle arrest, apoptosis, and mitochondrial function. The contribution of ROS in the EF24-induced anti-tumor activity was evaluated by measures of H 2 O 2 and pretreatment with an ROS scavenger, NAC. The findings indicated that EF24 treatment dose-dependently inhibited cell viability and caused cell cycle arrest at G2/M phase in all the tested colon cancer cell lines. Furthermore, we demonstrated that EF24 treatment induced apoptosis effectively via enhancing intracellular accumulation of ROS in both HCT-116 and SW-620 cells, but with moderate effects in HT-29 cells. We found that EF24 treatment decreased the mitochondrial membrane potential in the colon cancer cells, leading to the release of mitochondrial cytochrome c. Also, EF24 induced activation of caspases 9 and 3, causing decreased Bcl-2 protein expression and Bcl-2/Bax ratio. Pretreatment with NAC, a ROS scavenger, abrogated the EF24-induced cell death, apoptosis, cell cycle arrest, and mitochondrial dysfunction, suggesting an upstream ROS generation which was responsible for the anticancer effects of EF24. Our findings support an anticancer mechanism by which EF24 enhanced ROS accumulation in colon cancer cells, thereby resulting in mitochondrial membrane collapse and activated intrinsic apoptotic signaling. Thus, EF24 could be a potential candidate for therapeutic application of colon cancer.

  3. MORE for multiple organ dysfunction syndrome: Multiple Organ REanimation, REgeneration, and REprogramming.

    Science.gov (United States)

    Cobb, J Perren

    2010-11-01

    Those who care for the critically ill and injured rightfully celebrate the advances made by our field over its first 50 yrs. Advances in systems, tissue, and molecular engineering, together defined as "health engineering," will provide unprecedented opportunities to treat multiple organ dysfunction syndrome in the 21st century. In the future, Multiple Organ REanimation, REgeneration, and REprogramming will be responsible for new treatment approaches for those with multiple organ dysfunction syndrome; several examples are presented here. Thus, as we spent the first 50 yrs of care for the critical ill and injured learning how best to hook humans up to machines, we will spend the next 50 yrs understanding better how to liberate patients from mechanical support. It is difficult to know when these advances will be realized given that the rate of change continues to increase and the seemingly impossible goal of reprogramming fully differentiated cells was accomplished recently by manipulating a few transcription factors. It is not unrealistic to expect that in the next couple of decades that it will be possible to dedifferentiate dysfunctional somatic cells in vivo to a more robust, resistant cell phenotype. Our future should be aimed in part at refining our skill sets and refocusing (even rebranding) critical care as health engineering aimed at Multiple Organ REanimation, REgeneration, and REprogramming.

  4. Increased expression of matrix metalloproteinases in the murine zymosan-induced multiple organ dysfunction syndrome.

    NARCIS (Netherlands)

    Volman, T.J.H.; Goris, R.J.A.; Lomme, R.M.L.M.; Groot, J. de; Verhofstad, A.A.J.; Hendriks, T.

    2004-01-01

    Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue damage in several inflammatory diseases. Since the multiple organ dysfunction syndrome (MODS) is thought to result from systemic inflammation, overactivation of MMPs could contribute to the organ damage observed. The

  5. Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells.

    Science.gov (United States)

    Shen, Jian; Zhu, Yu; Huang, Kaiyuan; Jiang, Hao; Shi, Chengzhang; Xiong, Xiaoxing; Zhan, Renya; Pan, Jianwei

    2016-05-31

    Apoptosis of endothelial cells caused by reactive oxygen species plays an important role in ischemia/reperfusion injury after cerebral infarction. Buyang Huanwu Decoction (BYHWD) has been used to treat stroke and stroke-induced disability, however, the mechanism for this treatment remains unknown. In this study, we investigated whether BYHWD can protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and explored the underlying mechanisms. To investigate the effect of BYHWD on the apoptosis of HUVECs, we established a H2O2-induced oxidative stress model and detected apoptosis by Hoechst 33342 and propidium iodide staining. JC-1 and DCFH-DA assays,western blotting and electron microscopy were used to examine the mechanism of BYHWD on apoptosis. Pretreatment with BYHWD significantly inhibited H2O2-induced apoptosis and protein caspase-3 expression in a concentration-dependent manner. In addition, BYHWD reduced reactive oxygen species production and promoted endogenous antioxidant defenses. Furthermore, loss of mitochondrial membrane potential and structural disruption of mitochondria were both rescued by BYHWD. BYHWD protects HUVECs from H2O2-induced apoptosis by inhibiting oxidative stress damage and mitochondrial dysfunction. These findings indicate that BYHWD is a promising treatment for cerebral ischemia diseases.

  6. Induction of apoptosis by an oleanolic acid derivative in SMMC-7721 human hepatocellular carcinoma cells is associated with mitochondrial dysfunction.

    Science.gov (United States)

    Fan, Xinfeng; Wang, Penglong; Sun, Yaogui; Jiang, Junbing; Du, Haiyuan; Wang, Zhirui; Duan, Zhibian; Lei, Haimin; Li, Hongquan

    2018-03-01

    The aim of the present study was to investigate the effects of an oleanolic acid derivative, a novel antitumor drug, on the growth of SMMC-7721 human hepatocellular carcinoma cells and the underlying mechanism. An MTT assay was performed to determine the cytotoxicity of the oleanolic acid derivative. Cell membrane integrity was assessed using fluorescence microscopy to assess the uptake of annexin V-FITC/propidium iodide (PI). Western blotting was used to detect the apoptosis-associated proteins B cell lymphoma-2 (Bcl-2), Bax, caspase-9 and caspase-3. A spectrophotometer was used to analyze the intracellular adenosine triphosphate (ATP) expression level. The loss of mitochondrial membrane potential was detected by performing the JC-1 assay. ELISA was used to evaluate the content of cytochrome c (Cyt-C). The oleanolic acid derivative reduced the cell viability of SMMC-7721 cells in a dose- and time-dependent manner. The half maximal inhibitory concentration values of the oleanolic acid derivative in SMMC-7721 cells at 24, 48 and 72 h were 26.80, 11.85, and 6.66 µM, respectively. The antiapoptotic-protein Bcl-2 was downregulated, and the proapoptotic protein Bax was upregulated following treatment with the oleanolic acid derivative for 48 h. The oleanolic acid derivative induced the cleavage of caspase-9 and caspase-3 as well as promoted annexin V-FITC/PI uptake in SMMC-7721 cells. Furthermore, treatment of SMMC-7721 cells with the oleanolic acid derivative induced a reduction of the intracellular ATP expression level, loss of ΔΨm and Cyt-C release from the mitochondria. The oleanolic acid derivative induced apoptosis in SMMC-7721 human cells. Mitochondrial dysfunction was involved in the anticancer effects of this derivative on SMMC-7721 human cells.

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

    Directory of Open Access Journals (Sweden)

    Kai-Uwe Jarr

    2014-01-01

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

  8. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Science.gov (United States)

    Shen, Bo; He, Pei-Jie; Shao, Chun-Lin

    2013-01-01

    Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.

  9. Nitric oxide-induced cell death in developing oligodendrocytes is associated with mitochondrial dysfunction and apoptosis-inducing factor translocation.

    Science.gov (United States)

    Baud, Olivier; Li, Jianrong; Zhang, Yumin; Neve, Rachael L; Volpe, Joseph J; Rosenberg, Paul A

    2004-10-01

    Reactive nitrogen species are thought to be involved in both hypoxic-ischemic and cytokine-induced brain injury, including periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in premature infants. PVL appears to be the result of perinatal inflammatory events and hypoxic-ischemic injury to the cerebral white matter. The chronic disturbance of myelination resulting from PVL suggests that developing oligodendrocytes (OLs) are involved in its pathogenesis. We hypothesized that nitric oxide (NO) could participate in the pathogenesis of PVL through a toxic effect on developing OLs. Using primary cultures of highly enriched OLs we found that NO is toxic to developing OLs (O4+, O1-, MBP-), with an EC50 value of 236 +/- 125 microm of DETANOnoate. Peroxynitrite formation does not appear to be involved in NO toxicity in developing OLs, as determined by the failure of peroxynitrite scavengers as well as superoxide dismutase overexpression to prevent NO-induced toxicity. Similarly, several pathways involving PARP, excitotoxicity, guanylyl cyclase and caspase activation were not related to NO toxicity to developing OLs. NO toxicity to OLs resulted in ATP depletion and loss of mitochondrial membrane potential (DeltaPsi) in developing OLs. Apoptosis-inducing factor (AIF) has been shown to be involved in caspase-independent cell death, and we found that AIF translocated from mitochondria into the nucleus upon NO exposure. In conclusion, we suggest that the vulnerability of developing OLs to NO involves mitochondrial dysfunction and translocation of AIF from mitochondria to nuclei.

  10. Mitochondrial Dysfunction Causes Oxidative Stress and Tapetal Apoptosis in Chemical Hybridization Reagent-Induced Male Sterility in Wheat

    Directory of Open Access Journals (Sweden)

    Shuping Wang

    2018-01-01

    Full Text Available Male sterility in plants has been strongly linked to mitochondrial dysfunction. Chemical hybridization agent (CHA-induced male sterility is an important tool in crop heterosis. Therefore, it is important to better understand the relationship between mitochondria and CHA-induced male sterility in wheat. This study reports on the impairment of mitochondrial function duo to CHA-SQ-1, which occurs by decreasing cytochrome oxidase and adenosine triphosphate synthase protein levels and theirs activities, respiratory rate, and in turn results in the inhibition of the mitochondrial electron transport chain (ETC, excessive production of reactive oxygen species (ROS and disruption of the alternative oxidase pathway. Subsequently, excessive ROS combined with MnSOD defects results in damage to the mitochondrial membrane, followed by ROS release into the cytoplasm. The microspores underwent severe oxidative stress during pollen development. Furthermore, chronic oxidative stress, together with the overexpression of type II metacaspase, triggered premature tapetal apoptosis, which resulted in pollen abortion. Accordingly, we propose a metabolic pathway for mitochondrial-mediated male sterility in wheat, which provides information on the molecular events underlying CHA-SQ-1-induced abortion of anthers and may serve as an additional guide to the practical application of hybrid breeding.

  11. Selected aspects of apoptosis in psoriasis

    Directory of Open Access Journals (Sweden)

    Hanna Myśliwiec

    2017-03-01

    Full Text Available Apoptosis is a physiological mechanism of programmed cell death, in contrast to necrosis, without eliciting an inflammatory response. It plays the key role in the functioning of different tissues and organs. The balance between proliferation and apoptosis of keratinocytes is important for epidermal maintenance of homeostasis. Dysfunctional apoptosis plays an important role in the development of several skin disorders. Diseases with an increase of apoptosis are usually acute, while those with inhibited apoptosis tend to be chronic. Psoriasis is an immune-mediated chronic inflammatory skin disease. It is characterized by keratinocyte hyperproliferation and abnormal differentiation. Psoriatic keratinocytes are resistant to apoptosis and this phenomenon can be the key event in psoriatic hyperplasia. Apoptosis disturbances can also affect immune cells involved in the pathogenesis of psoriasis. In this review, we describe the basic concept of apoptosis and its relevance in psoriatic pathogenesis.

  12. The prevention of endothelial dysfunction through endothelial cell apoptosis inhibition in a hypercholesterolemic rabbit model: the effect of L-arginine supplementation

    Directory of Open Access Journals (Sweden)

    Haghjooyjavanmard Shaghayegh

    2008-08-01

    Full Text Available Abstract Background The impact of L-arginine on atherogenesis and its ability to prevent endothelial dysfunction have been studied extensively during the past years. L-arginine is a substance for nitric oxide synthesis which involves in apoptosis. Hypercholesterolemia promotes endothelial dysfunction, and it is hypothesized that L-arginine prevents endothelial dysfunction through endothelial cells apoptosis inhibition. To test this hypothesis, thirty rabbits were assigned into two groups. The control group received 1% cholesterol diet for 4 weeks, and the L-arginine group received same diets plus 3% L-arginine in drinking water. Results No significant differences were observed in cholesterol level between two groups, but the nitrite concentration in L-arginine group was significantly higher than other group (control group: 11.8 ± 1; L-arginine group: 14.7 ± 0.5 μmol/l; (p p p Conclusion The inhibition of endothelial cells apoptosis by L-arginine restores endothelial function in a model of hypercholesterolemia.

  13. Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Li; Wang, Jing; Xiao, Haifang; Xiao, Chunxia; Wang, Yutang; Liu, Xuebo, E-mail: xueboliu@yahoo.com.cn

    2012-11-15

    Isoorientin (ISO) is a flavonoid compound that can be extracted from several plant species, such as Phyllostachys pubescens, Patrinia, and Drosophyllum lusitanicum; however, its biological activity remains poorly understood. The present study investigated the effects and putative mechanism of apoptosis induced by ISO in human hepatoblastoma cancer (HepG2) cells. The results showed that ISO induced cell death in a dose-dependent manner in HepG2 cells, but no toxicity in human liver cells (HL-7702) and buffalo rat liver cells (BRL-3A) treated with ISO at the indicated concentrations. ISO-induced cell death included apoptosis which characterized by the appearance of nuclear shrinkage, the cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. ISO significantly (p < 0.01) increased the Bax/Bcl-2 ratio, disrupted the mitochondrial membrane potential (MMP), increased the release of cytochrome c, activated caspase-3, and enhanced intracellular levels of reactive oxygen species (ROS) and nitric oxide (NO). In addition, ISO effectively inhibited the phosphorylation of Akt and increased FoxO4 expression. The PI3K/Akt inhibitor LY294002 enhanced the apoptosis-inducing effect of ISO. However, LY294002 markedly quenched ROS and NO generation and diminished the protein expression of heme peroxidase enzyme (HO-1) and inducible nitric oxide synthase (iNOS). Furthermore, the addition of a ROS inhibitor (N-acetyl cysteine, NAC) or iNOS inhibitor (N-[3-(aminomethyl) benzyl] acetamidine, dihydrochloride, 1400W) significantly diminished the apoptosis induced by ISO and also blocked the phosphorylation of Akt. These results demonstrated for the first time that ISO induces apoptosis in HepG2 cells and indicate that this apoptosis might be mediated through mitochondrial dysfunction and PI3K/Akt signaling pathway, and has no toxicity in normal liver cells, suggesting that ISO may have good potential as a therapeutic and chemopreventive agent for liver cancer. Highlights:

  14. Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K/Akt signaling pathway in HepG2 cancer cells

    International Nuclear Information System (INIS)

    Yuan, Li; Wang, Jing; Xiao, Haifang; Xiao, Chunxia; Wang, Yutang; Liu, Xuebo

    2012-01-01

    Isoorientin (ISO) is a flavonoid compound that can be extracted from several plant species, such as Phyllostachys pubescens, Patrinia, and Drosophyllum lusitanicum; however, its biological activity remains poorly understood. The present study investigated the effects and putative mechanism of apoptosis induced by ISO in human hepatoblastoma cancer (HepG2) cells. The results showed that ISO induced cell death in a dose-dependent manner in HepG2 cells, but no toxicity in human liver cells (HL-7702) and buffalo rat liver cells (BRL-3A) treated with ISO at the indicated concentrations. ISO-induced cell death included apoptosis which characterized by the appearance of nuclear shrinkage, the cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. ISO significantly (p < 0.01) increased the Bax/Bcl-2 ratio, disrupted the mitochondrial membrane potential (MMP), increased the release of cytochrome c, activated caspase-3, and enhanced intracellular levels of reactive oxygen species (ROS) and nitric oxide (NO). In addition, ISO effectively inhibited the phosphorylation of Akt and increased FoxO4 expression. The PI3K/Akt inhibitor LY294002 enhanced the apoptosis-inducing effect of ISO. However, LY294002 markedly quenched ROS and NO generation and diminished the protein expression of heme peroxidase enzyme (HO-1) and inducible nitric oxide synthase (iNOS). Furthermore, the addition of a ROS inhibitor (N-acetyl cysteine, NAC) or iNOS inhibitor (N-[3-(aminomethyl) benzyl] acetamidine, dihydrochloride, 1400W) significantly diminished the apoptosis induced by ISO and also blocked the phosphorylation of Akt. These results demonstrated for the first time that ISO induces apoptosis in HepG2 cells and indicate that this apoptosis might be mediated through mitochondrial dysfunction and PI3K/Akt signaling pathway, and has no toxicity in normal liver cells, suggesting that ISO may have good potential as a therapeutic and chemopreventive agent for liver cancer. Highlights:

  15. SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia.

    Science.gov (United States)

    Ogura, Hiroshi; Gando, Satoshi; Iba, Toshiaki; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Murata, Atsuo; Ikeda, Toshiaki; Ishikura, Hiroyasu; Ueyama, Masashi; Kushimoto, Shigeki; Saitoh, Daizoh; Endo, Shigeatsu; Shimazaki, Shuji

    2007-10-01

    Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients. Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction. In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

  16. Cardio-protecteffect of qiliqiangxin capsule on left ventricular remodeling, dysfunction and apoptosis in heart failure rats after chronic myocardial infarction.

    Science.gov (United States)

    Liang, Tuo; Zhang, Yuhui; Yin, Shijie; Gan, Tianyi; An, Tao; Zhang, Rongcheng; Wang, Yunhong; Huang, Yan; Zhou, Qiong; Zhang, Jian

    2016-01-01

    Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear. Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor. QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability.

  17. The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy

    Directory of Open Access Journals (Sweden)

    Maurizio Cammalleri

    2017-12-01

    Full Text Available In a mouse model of oxygen induced retinopathy (OIR, beta adrenergic receptor (BAR blockade has been shown to recover hypoxia-associated retinal damages. Although the adrenergic signaling is an important regulator of apoptotic and autophagic processes, the role of BARs in retinal cell death remains to be elucidated. The present study was aimed at investigating whether ameliorative effects of BAR blockers may occur through their coordinated action on apoptosis and autophagy. To this aim, retinas from control and OIR mice untreated or treated with propranolol, a non-selective BAR1/2 blocker, were characterized in terms of expression and localization of apoptosis and autophagy markers. The effects of propranolol on autophagy signaling were also evaluated and specific autophagy modulators were used to get functional information on the autophagic effects of BAR antagonism. Finally, propranolol effects on neurodegenerative processes were associated to an electrophysiological investigation of retinal function by recording electroretinogram (ERG. We found that retinas of OIR mice are characterized by increased apoptosis and decreased autophagy, while propranolol reduces apoptosis and stimulates autophagy. In particular, propranolol triggers autophagosome formation in bipolar, amacrine and ganglion cells that are committed to die by apoptosis in response to hypoxia. Also our data argue that propranolol, through the inhibition of the Akt-mammalian target of rapamycin pathway, activates autophagy which decreases retinal cell death. At the functional level, propranolol recovers dysfunctional ERG by recovering the amplitude of a- and b-waves, and oscillatory potentials, thus indicating an efficient restoring of retinal transduction. Overall, our results demonstrate that BAR1/2 are key regulators of retinal apoptosis/autophagy, and that BAR1/2 blockade leads to autophagy-mediated neuroprotection. Reinstating the balance between apoptotic and autophagic

  18. Rons formation under restrictive reperfusion does not affect organ dysfunction early after hemorrhage and trauma.

    Science.gov (United States)

    Zifko, Clara; Kozlov, Andrey V; Postl, Astrid; Redl, Heinz; Bahrami, Soheyl

    2010-10-01

    Reactive oxygen species have been implicated in the pathophysiology of early reperfusion. We aimed to determine 1) reactive oxygen and nitrogen species (RONS) formation in organs of rats and 2) its pathophysiological relevance during a phase of restrictive reperfusion after hemorrhagic/traumatic shock (HTS). Fifty-seven male Sprague-Dawley rats were subjected to a clinically relevant HTS model, featuring laparotomy, bleeding, and a phase of restrictive reperfusion. The RONS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (continuous i.v. infusion) and electron paramagnetic resonance spectroscopy were applied for RONS (primarily superoxide and peroxynitrite) detection. Compared with sham-operated animals, the organ-specific distribution of RONS changed during restrictive reperfusion after HTS. Reactive oxygen and nitrogen species formation increased during restrictive reperfusion in red blood cells and ileum only but decreased in the kidney and remained unchanged in other organs. Hemorrhagic traumatic shock followed by restrictive reperfusion resulted in metabolic acidosis, dysfunction of liver and kidney, and increased oxidative burst capacity in circulating cells. Plasma RONS correlated with shock severity and organ dysfunction. However, RONS scavenging neither affected organ dysfunction nor oxidative burst capacity nor myeloperoxidase activity in lung when compared with the shock controls. In summary, a phase of restrictive reperfusion does not increase RONS formation in most organs except in intestine and red blood cells. Moreover, scavenging of RONS does not affect the early organ dysfunction manifested at the end of a phase of restrictive reperfusion.

  19. Detection of organ dysfunction by hypotension and/or hyperlactemia in septic patients

    DEFF Research Database (Denmark)

    Nissen, Janet Yde; Dynesen, Jens Jacob Østergaard; Pedersen, Marie Kristine Jessen

    BackgroundThe definitions of sepsis were updated February 2016[1] - organ dysfunctions remain the turning point between “simple infection” and sepsis (previously severe sepsis). Hypotension and hyperlactatemia define two of many organ dysfunctions presented in the most recent Surviving Sepsis Cam...... shock: 2012. Crit Care Med. 2013;41(2):580-637.2. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10....

  20. Background Noise Contributes to Organic Solvent Induced Brain Dysfunction.

    Science.gov (United States)

    Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

    2016-01-01

    Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures.

  1. The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

    Directory of Open Access Journals (Sweden)

    Luciano L. Paulo

    2018-05-01

    Conclusion: Acute treatment with the novel organic nitrate NDHP increases NO formation, which is associated with vasorelaxation and a significant reduction of blood pressure in hypertensive animals. Chronic NDHP treatment attenuates the progression of hypertension and endothelial dysfunction, suggesting a potential for therapeutic applications in cardiovascular disease.

  2. Prediction of peripartum hysterectomy and end organ dysfunction in major obstetric haemorrhage.

    LENUS (Irish Health Repository)

    O'Brien, D

    2010-12-01

    The aims of this study are to determine the incidence and aetiology of major obstetric haemorrhage (MOH) in our population, to examine the success rates of medical and surgical interventions and to identify risk factors for peripartum hysterectomy and end organ dysfunction (EOD).

  3. Improved survival of TNF-deficient mice during the zymosan-induced multiple organ dysfunction syndrome.

    NARCIS (Netherlands)

    Volman, T.J.H.; Hendriks, T.; Verhofstad, A.A.J.; Kullberg, B.J.; Goris, R.J.A.

    2002-01-01

    The purpose of the study was to investigate the course of the zymosan-induced multiple organ dysfunction syndrome (MODS) in the absence of tumor necrosis factor (TNF) in a murine model. Tumor Necrosis Factor-alpha-lymphotoxin-a knockout (TNF/LT-/-) mice (n = 36) and wild-type (TNF/LT+/+) mice (n =

  4. The induction of apoptosis in HepG-2 cells by ruthenium(II) complexes through an intrinsic ROS-mediated mitochondrial dysfunction pathway.

    Science.gov (United States)

    Zeng, Chuan-Chuan; Lai, Shang-Hai; Yao, Jun-Hua; Zhang, Cheng; Yin, Hui; Li, Wei; Han, Bing-Jie; Liu, Yun-Jun

    2016-10-21

    Four new ruthenium(II) polypyridyl complexes [Ru(N-N)2(dhbn)](ClO4)2 (N-N = dmb: 4,4'-dimethyl-2,2'-bipyridine 1; bpy = 2,2'-bipyridine 2; phen = 1,10-phenanthroline 3; dmp = 2,9-dimethyl-1,10-phenanthroline 4) were synthesized and characterized. The cytotoxicity in vitro of the ligand and complexes toward HepG-2, HeLa, MG-63 and A549 were assayed by MTT method. The IC50 values of the complexes against the above cells range from 17.7 ± 1.1 to 45.1 ± 2.8 μM. The cytotoxic activity of the complexes against HepG-2 cells follows the order of 4 > 2 > 3 > 1. Ligand shows no cytotoxic activity against the selected cell lines. Cellular uptake, apoptosis, comet assay, reactive oxygen species, mitochondrial membrane potential, cell cycle arrest, and the expression of proteins involved in apoptosis pathway induced by the complexes were investigated. The results indicate that complexes 1-4 induce apoptosis in HepG-2 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Dysfunctional Effects of a Conflict in a Healthcare Organization.

    Science.gov (United States)

    Raykova, Ekaterina L; Semerjieva, Mariya A; Yordanov, Georgi Y; Cherkezov, Todor D

    2015-01-01

    Conflicts in healthcare settings are quite common events because of the continuous changes and transformations today's healthcare organizations are undergoing and the vigorous interaction between the medical professionals working in them. To survey the opinions of medical professionals about the possible destructive effects of conflicts on them in the workplace. We conducted a direct individual survey of 279 medical employees at four general hospitals. We used a set of questions that reflect the negative effects and consequences of conflict on healthcare professionals as direct or indirect participants. All data were analysed using the descriptive statistics and non-parametric analysis at a significance level for the null hypothesis of p conflicts contribute a lot to the stress, psychological tension and emotional exhaustion medical professionals are exposed to. The confrontation the conflict brings the participants into acts as a catalyst of the conflict and enhances the manifestation of hostile actions. A conflict generates a situation which has an impact on the behaviour of all participants involved in it giving rise to emotional states such as anger, aggression and reproaches. The destructive consequences resulting from a conflict are seen in the reduced work satisfaction and demotivation to perform the work activity. The contradictions that arise as a result affect negatively the team cooperation and obstruct the collaborative efforts in solving the problems in the healthcare setting. A conflict in a healthcare setting exerts a considerable destructive effect on an employee, therefore it requires prompt identification and effective intervention to minimise its unfavourable outcomes.

  6. Organ Dysfunction and Failure Following Brain Death Do Not Preclude Successful Donation.

    Science.gov (United States)

    Essien, Eno-Obong I; Parimi, Nehu; Gutwald-Miller, Jennifer; Nutter, Tyree; Scalea, Thomas M; Stein, Deborah M

    2017-11-01

    Organ dysfunction is common after neurologic determination of death (NDD) but before organ collection. Reliable markers for graft success following transplant of these organs would be useful. We sought to determine the relationship between the donor after neurologic determination of death (DNDD) pathophysiology and successful organ donation. Donor information was obtained through the local organ procurement organization. Donor demographics and clinical data points for cardiovascular, renal, respiratory, hepatic, hematological and neuroendocrine systems were reviewed 12 h before and 12 h after neurologic determination of death was declared. The worst values were utilized for analysis and generation of the organ-specific Sequential Organ Failure Assessment (SOFA) scores. SOFA scores were calculated and used to quantify the degree of organ dysfunction. The NDD non-donors for a specific organ were used as a comparison control group. The control group refers to DNDD patients whose specific organs were not transplanted. Lack of use was mostly due to discard by the transplant team as a result of unsuitability of the organ caused by deterioration or possible donor-specific pathology. One hundred and five organ donors were analyzed. Mean age was 35.0 (± 13.6), 78.1% male, median GCS 3, interquartile range (IQR) 3-4 and median injury severity score 32 (IQR 25-43). Of the successful donors, organ-specific severe dysfunction (SOFA 3 or 4) occurred in 96, 27.5 and 3.3% of cardiac, lung and liver donors, respectively. There was no significant difference between the levels of organ dysfunction in donors versus non-donors except lung donors, in which the median lowest partial pressure of arterial oxygen-to-fraction of inspired oxygen (P/F) ratio in the non-donor was 194 (IQR 121.8-308.3) compared to the median lowest P/F ratio in the donor which was 287 (IQR 180-383.5), p = 0.02. In the recipients, graft failure 6 months after transplantation was reported in one kidney

  7. Oral and Fecal Campylobacter concisus Strains induce Barrier dysfunction by Apoptosis in HT-29/B6 Intestinal Epithelial Cells

    DEFF Research Database (Denmark)

    Nielsen, Hans Linde; Nielsen, Henrik Ib; Ejlertsen, Tove

    in Ussing chambers. Tight junction (TJ) protein expression was determined by Western blotting, and subcellular TJ distribution was analyzed by confocal laser-scanning microscopy. Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3 activation. All strains invaded confluent HT-29...

  8. Pivotal roles of p53 transcription-dependent and -independent pathways in manganese-induced mitochondrial dysfunction and neuronal apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Ma, Xa; Shi, Shangshi [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Zhao, Jianya; Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Han, Jingling; Xiao, Jing; Wang, Xiaoke [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Shengyang [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Junkang, E-mail: Jiang_junkang@163.com [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China)

    2014-12-15

    Chronic exposure to excessive manganese (Mn) has been known to lead to neuronal loss and a clinical syndrome resembling idiopathic Parkinson's disease (IPD). p53 plays an integral role in the development of various human diseases, including neurodegenerative disorders. However, the role of p53 in Mn-induced neuronal apoptosis and neurological deficits remains obscure. In the present study, we showed that p53 was critically involved in Mn-induced neuronal apoptosis in rat striatum through both transcription-dependent and -independent mechanisms. Western blot and immunohistochemistrical analyses revealed that p53 was remarkably upregulated in the striatum of rats following Mn exposure. Coincidentally, increased level of cleaved PARP, a hallmark of apoptosis, was observed. Furthermore, using nerve growth factor (NGF)-differentiated PC12 cells as a neuronal cell model, we showed that Mn exposure decreased cell viability and induced apparent apoptosis. Importantly, p53 was progressively upregulated, and accumulated in both the nucleus and the cytoplasm. The cytoplasmic p53 had a remarkable distribution in mitochondria, suggesting an involvement of p53 mitochondrial translocation in Mn-induced neuronal apoptosis. In addition, Mn-induced impairment of mitochondrial membrane potential (ΔΨm) could be partially rescued by pretreatment with inhibitors of p53 transcriptional activity and p53 mitochondrial translocation, Pifithrin-α (PFT-α) and Pifithrin-μ (PFT-μ), respectively. Moreover, blockage of p53 activities with PFT-α and PFT-μ significantly attenuated Mn-induced reactive oxidative stress (ROS) generation and mitochondrial H{sub 2}O{sub 2} production. Finally, we observed that pretreatment with PFT-α and PFT-μ ameliorated Mn-induced apoptosis in PC12 cells. Collectively, these findings implicate that p53 transcription-dependent and -independent pathways may play crucial roles in the regulation of Mn-induced neuronal death. - Highlights: • p53 is

  9. Room air versus carbon dioxide pneumoperitoneum: effects on oxidative state, apoptosis and histology of splanchnic organs.

    Science.gov (United States)

    Ypsilantis, Petros; Lambropoulou, Maria; Tentes, Ioannis; Chryssidou, Maria; Georgantas, Themistoklis; Simopoulos, Constantinos

    2016-04-01

    Although CO2 is the insufflation gas of choice in laparoscopic procedures, room air is usually used in natural orifice transluminal endoscopic surgery. The aim of the present study was to compare the safety of room air versus CO2 pneumoperitoneum in terms of their effect on the oxidative state, apoptosis and tissue injury of splanchnic organs. Eighteen Wistar rats were assigned to three groups (n = 6 per group) and were subjected to 8 mm Hg room air (group Pne-Air) or CO2 pneumoperitoneum (group Pne-CO2) or sham operation for 60 min. Forty-five minutes postdeflation, tissue samples were excised from the liver, stomach, ileum and kidneys for reduced glutathione-to-glutathione disulfide (GSH/GSSG) ratio, caspase-8 and caspase-3 and hypoxia-inducible factor-1α (HIF-1α) immunohistochemical assessment and histopathologic examination. GSH/GSSG ratio substantially declined in both pneumoperitoneum groups. No change was noted in HIF-1α expression. Mild upregulation of caspase-8 and caspase-3 was noted in both pneumoperitoneum groups being less pronounced in group Pne-Air. Histopathologic score was increased in all organs studied, but the stomach, in both pneumoperitoneum groups. Pneumoperitoneum established by either room air or CO2 induced substantial oxidative stress, mild apoptosis and mild tissue injury in splanchnic organs. While air pneumoperitoneum conferred a less pronounced apoptotic effect, the oxidative state and histopathologic profile of splanchnic organs did not differ between insufflation gases.

  10. Transcutaneous electrical nerve stimulation regulates organ blood flow and apoptosis during controlled hypotension in dogs.

    Directory of Open Access Journals (Sweden)

    Lele Zhang

    Full Text Available Transcutaneous electrical nerve stimulation (TENS is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP. The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05. Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA group (P<0.05. After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05. There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney.

  11. Mesenchymal Stem Cells in Sepsis and Associated Organ Dysfunction: A Promising Future or Blind Alley?

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    Jan Horák

    2017-01-01

    Full Text Available Sepsis, newly defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is the most common cause of death in ICUs and one of the principal causes of death worldwide. Although substantial progress has been made in the understanding of fundamental mechanisms of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. In this context, the immune-reprogramming properties of cell-based therapy using mesenchymal stem cells (MSC represent an emerging therapeutic strategy in sepsis and associated organ dysfunction. This article provides an update of the current knowledge regarding MSC in preclinical models of sepsis and sepsis-induced acute kidney injury. Recommendations for further translational research in this field are discussed.

  12. Elucidation of Molecular Mechanisms of Streptozotocin-Induced Oxidative Stress, Apoptosis, and Mitochondrial Dysfunction in Rin-5F Pancreatic β-Cells

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    Arwa M. T. Al Nahdi

    2017-01-01

    Full Text Available Streptozotocin is a pancreatic beta-cell-specific cytotoxin and is widely used to induce experimental type 1 diabetes in rodent models. The precise molecular mechanism of STZ cytotoxicity is however not clear. Studies have suggested that STZ is preferably absorbed by insulin-secreting β-cells and induces cytotoxicity by producing reactive oxygen species/reactive nitrogen species (ROS/RNS. In the present study, we have investigated the mechanism of cytotoxicity of STZ in insulin-secreting pancreatic cancer cells (Rin-5F at different doses and time intervals. Cell viability, apoptosis, oxidative stress, and mitochondrial bioenergetics were studied. Our results showed that STZ induces alterations in glutathione homeostasis and inhibited the activities of the respiratory enzymes, resulting in inhibition of ATP synthesis. Apoptosis was observed in a dose- and time-dependent manner. Western blot analysis has also confirmed altered expression of oxidative stress markers (e.g., NOS and Nrf2, cell signaling kinases, apoptotic protein-like caspase-3, PARP, and mitochondrial specific proteins. These results suggest that STZ-induced cytotoxicity in pancreatic cells is mediated by an increase in oxidative stress, alterations in cellular metabolism, and mitochondrial dysfunction. This study may be significant in better understanding the mechanism of STZ-induced β-cell toxicity/resistance and the etiology of type 1 diabetes induction.

  13. Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction

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    Yu-Feng Tian

    2013-01-01

    Full Text Available We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure, brain (or hypothalamic inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress, multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

  14. Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer's disease.

    Science.gov (United States)

    Justin Thenmozhi, Arokiasamy; William Raja, Tharsius Raja; Manivasagam, Thamilarasan; Janakiraman, Udaiyappan; Essa, Musthafa Mohamed

    2017-07-01

    Deregulation of metal ion homeostasis has been assumed as one of the key factors in the progression of neurodegenerative diseases. Aluminium (Al) has been believed as a major risk factor for the cause and progression of Alzheimer's disease (AD). In our lab, we have previously reported that hesperidin, a citrus bioflavonoid reversed memory loss caused by aluminium intoxication through attenuating acetylcholine esterase activity and the expression of Amyloid β biosynthesis related markers. Al has been reported to cause oxidative stress associated apoptotic neuronal loss in the brain. So in the present study, protective effect of hesperidin against aluminium chloride (AlCl 3 ) induced cognitive impairment, oxidative stress and apoptosis was studied. Male Wistar rats were divided into control, AlCl 3 treated (100 mg/kg., b.w.), AlCl 3 and hesperidin (100 mg/kg., b.w.) co-treated and hesperidin alone treated groups. In control and experimental rats, learning and memory impairment were measured by radial arm maze, elevated plus maze and passive avoidance tests. In addition, oxidative stress and expression of pro and anti-apoptotic markers were also evaluated. Intraperitoneal injection of AlCl 3 (100 mg/kg., b.w.) for 60 days significantly enhanced the learning and memory deficits, levels of thiobarbituric acid reactive substances and the expression of Bax and diminished the levels of reduced glutathione, activities of enzymatic antioxidants and the expression of B-cell lymphoma-2 (Bcl-2) as compared to control group in the hippocampus, cortex, and cerebellum. Coadministration of hesperidin (100 mg/kg., b.w. oral) for 60 days prevented the cognitive deficits, biochemical anomalies and apoptosis induced by AlCl 3 treatment. Results of the present study demonstrated that hesperidin could be a potential therapeutic agent in the treatment of oxidative stress and apoptosis associated neurodegenerative diseases including AD.

  15. Multiple organ dysfunction: a delayed envenomation syndrome caused by tentacle extract from the jellyfish Cyanea capillata.

    Science.gov (United States)

    Wang, Beilei; Zhang, Lin; Zheng, Jiemin; Wang, Qianqian; Wang, Tao; Lu, Jia; Wen, Xiaojuan; Zhang, Bo; Liu, Guoyan; Zhang, Wei; Xiao, Liang; Zhang, Liming

    2013-01-01

    The delayed jellyfish envenomation syndrome (DJES) with serious multiple organ dysfunction or systemic damages, generally developed 2 h after jellyfish stings, deserves special attention for it is very meaningful to the clinical interventions. To set up a DJES model as well as to obtain more details about its process, an integrative approach, including clinical chemistry, pathology and immunohistochemistry, was conducted to simultaneously monitor the effects of tentacle extract (TE) from the jellyfish Cyanea capillata on the vital target organs (heart, lung, liver and kidney). Our results showed that the TE from C. capillata could induce diverse toxic effects on these organs, among which the liver and kidney injuries seemed to be more serious than cardiopulmonary injuries and might be the leading causes of death in rats with DJES. In summary, we have established a DJES model with multiple organ dysfunction, which could facilitate the research on its underlying mechanism as well as the development of specific prevention or therapy strategies against jellyfish envenomation. The application of this model suggested that the possible mechanism of DJES might be attributed to the synergy of cytotoxicity, vasoconstriction effect and other specific target organ toxicities of jellyfish venom. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Osthole Attenuates Doxorubicin-Induced Apoptosis in PC12 Cells through Inhibition of Mitochondrial Dysfunction and ROS Production

    Directory of Open Access Journals (Sweden)

    Yalda Shokoohinia

    2014-01-01

    Full Text Available Doxorubicin (DOX is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated from Prangos ferulacea (L. Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP, the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.

  17. New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality

    NARCIS (Netherlands)

    Lin, J.C.; Spinella, P.C.; Fitzgerald, J.C.; Tucci, M.; Bush, J.L.; Nadkarni, V.M.; Thomas, N.J.; Weiss, S.L.; Lemson, J.; Sherring, C.; Bushell, T.

    2017-01-01

    OBJECTIVES: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. DESIGN: Secondary analysis of a prospective, cross-sectional, point prevalence study. SETTING: International, multicenter PICUs. PATIENTS:

  18. The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Flávio G. R. Freitas

    2008-01-01

    Full Text Available OBJECTIVES: This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. METHODS: Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. RESULTS: Fifty-six patients were enrolled. Mean age was 55.6 ± 20.7 years, mean APACHE II score was 20.6 ± 6.9, and mean SOFA score was 7.9 ± 3.7. Thirty-six patients (64.3% had septic shock. The mean duration of organ dysfunction was 1.9 ± 1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015, APACHE II (p=0.008, onset outside the intensive care unit (p=0.05, blood glucose control (p=0.05 and duration of organ dysfunction (p=0.0004. In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14, whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23. Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001. CONCLUSIONS: These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

  19. Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis.

    Science.gov (United States)

    Tozluoğlu, Melda; Karaca, Ezgi; Haliloglu, Turkan; Nussinov, Ruth

    2008-09-01

    We have compiled the p73-mediated cell cycle arrest and apoptosis pathways. p73 is a member of the p53 family, consisting of p53, p63 and p73. p73 exists in several isoforms, presenting different domain structures. p73 functions not only as a tumor suppressor in apoptosis but also as differentiator in embryo development. p53 mutations are responsible for half of the human cancers; p73 can partially substitute mutant p53 as tumor suppressor. The pathways we assembled create a p73-centered network consisting of 53 proteins and 176 interactions. We clustered our network into five functional categories: Upregulation, Activation, Suppression, Transcriptional Activity and Degradation. Our literature searches led to discovering proteins (c-Jun and pRb) with apparent opposing functional effects; these indicate either currently missing proteins and interactions or experimental misidentification or functional annotation. For convenience, here we present the p73 network using the molecular interaction map (MIM) notation. The p73 MIM is unique amongst MIMs, since it further implements detailed domain features. We highlight shared pathways between p53 and p73. We expect that the compiled and organized network would be useful to p53 family-based studies.

  20. Caution for anabolic androgenic steroid use: a case report of multiple organ dysfunction syndrome.

    Science.gov (United States)

    Unai, Shinya; Miessau, Joseph; Karbowski, Pawel; Baram, Michael; Cavarocchi, Nicholas C; Hirose, Hitoshi

    2013-12-01

    We report a 42-year-old male amateur body builder and user of anabolic androgenic steroids, who developed ARDS, acute kidney injury, and refractory supraventricular tachycardia. He required extracorporeal membrane oxygenation, continuous veno-venous hemodialysis, and catheter ablation. We believe that long-term anabolic androgenic steroid abuse predisposed the patient to multiple organ dysfunction syndrome, from its immunomodulatory effects in an otherwise healthy patient. Anabolic androgenic steroid use should be part of the history taking process, since it may complicate diagnosis, disease progression, and prognosis.

  1. Multiple cerebral infarctions with severe multi-organ dysfunction following multiple wasp stings

    Directory of Open Access Journals (Sweden)

    Mushtaq Wani

    2014-01-01

    Full Text Available Wasp and bee sting are commonly encountered worldwide. Local reactions are more common, generally are self-limiting and settle within a few hours. Multiple stings can lead to various clinical manifestations like vomiting, diarrhea, dyspnea, generalized edema, hypotension, syncope, acute renal failure, and even death. Rarely, they can cause vasculitis, serum sickness, neuritis, and encephalitis. We are reporting a case of 40-year-old male who presented with stroke, right hemiparesis with severe multi-organ dysfunction due to multiple wasp stings.

  2. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

    Science.gov (United States)

    Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-10-15

    Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Curcumin and hesperidin improve cognition by suppressing mitochondrial dysfunction and apoptosis induced by D-galactose in rat brain.

    Science.gov (United States)

    Banji, Otilia J F; Banji, David; Ch, Kalpana

    2014-12-01

    D-galactose, a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. Curcumin and hesperidin are antioxidants possessing multimodal functions; hence, their contribution in minimizing D-galactose induced ageing was assessed in the present study. A week prior to D-galactose treatment (150 mg/kg; s.c. for 56 days), animals were treated with curcumin alone, hesperidin alone and a combination of curcumin (50 and 100 mg/kg; orally) with hesperidin (10 and 25 mg/kg; orally) for 63 days. A naïve control was also maintained. Behavioural studies, tricarboxylic acid cycle enzymes, mitochondrial complexes, protein and lipid oxidation and glutathione levels were assessed in the brain mitochondrial fraction. Western blot analysis of caspase-3, cleaved caspase-3 and histological assessment of the CA1 region of the hippocampus were carried out. D-galactose induced significant cognitive deficits, biochemical changes and histological alterations. Individually, curcumin was more effective than hesperidin in reducing the levels of oxidized lipids, proteins, cleaved caspase-3 expression and mitochondrial enzymes. The combination reduced the expression of cleaved caspase-3, malondialdehyde, improved mitochondrial enzymes and glutathione levels. In combination, curcumin and hesperidin protect the morphological facets and improve biochemical functions of neurons thereby improving cognition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Mitochondrial dysfunction in obesity.

    Science.gov (United States)

    de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

    2018-01-01

    Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  6. A comparison of elderly and adult multiple organ dysfunction syndrome in the rat model.

    Science.gov (United States)

    Zhu, Qinglei; Qian, Xiaoshun; Wang, Shiwen; Yin, Tong; Yang, Jie; Xue, Qiao; Xu, Bin

    2006-08-01

    Multiple organ dysfunction syndrome (MODS) in the elderly is the most common cause of mortality in critically ill elderly patients, and it is different from MODS in the adult in clinic. Rare studies have been done on its pathogenesis and the comparison between adult and elderly MODS animal models. This work aimed at exploring the mechanisms mediating elderly MODS and compared this with adult MODS. Male Sprague-Dawley aged and adult rats were intraperitoneally injected with zymosan for incitement of MODS. Aged rats receiving zymosan showed severer pulmonary, cardiac and renal dysfunctions than adult rats. Likewise, the tissue lesions under light microscope in major organs of zymosan treated aged rats were much worse than those of zymosan treated adult rats. Moreover, zymosan treated aged rats showed 142% and 64% greater increase in pulmonary alveolar macrophages (AMs) apoptotic rate and serum TNF-alpha level, respectively, whereas 43% smaller increase in serum IL-10 level compared to zymosan treated adult rats. Furthermore, lung injury was much worse than that in other organs in zymosan treated aged rats. Overall, these results suggest that zymosan can be used in aged rats to incite MODS in the elderly. In the animal model of elderly MODS, there are (1) severer injury in lung, heart and kidney vs adult; (2) easier to develop severe systemic inflammatory response syndrome (SIRS) instead of compensatory anti-inflammatory response syndrome (CARS) compared to the adult; and (3) severer inflammation in lung than other organs indicative of the possible roles of lung in triggering MODS in the elderly.

  7. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

    Science.gov (United States)

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-11-03

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

  8. Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

    2008-02-10

    The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

  9. Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease

    Directory of Open Access Journals (Sweden)

    Speranza Rubattu

    2016-01-01

    Full Text Available Mechanisms underlying hypertensive target organ damage (TOD are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2 involved in OXPHOS complex I assembly and activity and the second one (UCP2 involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension.

  10. After the bomb drops: a new look at radiation-induced multiple organ dysfunction syndrome (MODS).

    Science.gov (United States)

    Williams, Jacqueline P; McBride, William H

    2011-08-01

    There is increasing concern that, since the Cold War era, there has been little progress regarding the availability of medical countermeasures in the event of either a radiological or nuclear incident. Fortunately, since much is known about the acute consequences that are likely to be experienced by an exposed population, the probability of survival from the immediate hematological crises after total body irradiation (TBI) has improved in recent years. Therefore focus has begun to shift towards later down-stream effects, seen in such organs as the gastrointestinal tract (GI), skin, and lung. However, the mechanisms underlying therapy-related normal tissue late effects, resulting from localised irradiation, have remained somewhat elusive and even less is known about the development of the delayed syndrome seen in the context of whole body exposures, when it is likely that systemic perturbations may alter tissue microenvironments and homeostasis. The sequence of organ failures observed after near-lethal TBI doses are similar in many ways to that of multiple organ dysfunction syndrome (MODS), leading to multiple organ failure (MOF). In this review, we compare the mechanistic pathways that underlie both MODS and delayed normal tissue effects since these may impact on strategies to identify radiation countermeasures.

  11. Multi-organic dysfunction syndrome caused by dengue 3 in children of Neiva Huila, Colombia

    International Nuclear Information System (INIS)

    Salgado, Doris; Vega, Martha R; Panqueva, Cesar A

    2006-01-01

    Dengue is the main arthropod -transmitted viral disease in the world with a growing number of cases in Neiva, Colombia. Clinical presentation of dengue hemorrhagic fever (DHF) is showing compromise of organs different from endothelium which could be associated to the circulating serotype and/or host immunological factors. Objective. To alert about the association of multiple organic dysfunction (MOD) and DHF. Results. MOD associated to DHF is described in three girls with an average of 16 months of age, two 7-month sold and 1 three year old. The evolution of fever at the beginning was 4 days; they had shock resistant to usual treatment with crystalloid and colloids with tachycardia,ventricular arrhythmia, increased CPK MB, AST and ALT,coagulopathy with prolonged PTT and PT but without severe thrombocytopenia, metabolic alteration with acidaemia and hypoglycemia in the three girls. Score for MOD was applied with an average of 23 and evidence of myocardial, hepatic and hematological major compromise. dengue 3 was showed by RT-PCR. Discussion. Similar reports are compared with these cases and probable pathophysiologic mechanisms are discussed. Conclusion. It has to be stressed that DHF might affect different organs, because of this definition of severity in dengue has to be reconsidered. An early thinking in different organs affected might help to introduce an opportune intervention or treatment.

  12. Unusual fatal multiple-organ dysfunction and pancreatitis induced by a single wasp sting

    Directory of Open Access Journals (Sweden)

    C Azad

    2011-01-01

    Full Text Available Acute onset of multiple organ dysfunction syndrome (MODS is a well-known complication following multiple wasp stings. However, MODS after a single wasp sting has been rarely reported in children and acute pancreatitis have probably never been observed before. Herein we describe the case of a 12-year-old boy who had urticaria and abdominal pain after a single wasp sting. The child gradually developed MODS while his abdominal complaints were worsening. Despite aggressive supportive management, the child did not survive. Afterward, the cause of the acute abdomen was finally diagnosed as acute pancreatitis. Both MODS and pancreatitis following a single wasp sting are very unusual. Thus, although pancreatitis is rarely manifested, it should be suspected after a wasp sting if there are predominant abdominal symptoms.

  13. Causes of Multiple Organ Dysfunction During Cardiosurgical Operations under Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    M. A. Babayev

    2010-01-01

    Full Text Available Objective: to reveal possible causes of postoperative multiple organ dysfunction syndrome (MODS in patients after surgery under extracorporeal circulation (EC, by measuring the level and balance of pro- and anti-inflammatory cytokines. Subjects and methods. The investigation enrolled 162 patients who had undergone operations on the heart and thoracic aorta. The levels of interleukins (IL-6, IL-8, and IL-10 were determined by ELISA. Results. At surgery under EC, MODS was encountered in 5.7%, mortality was 55.6%. The principal causes of MODS were prolonged EC concurrent with bleeding (23%, massive hemorrhage (16%, perioperative myocardial infarction and cardiogenic shock (15%, prolonged EC (12%, acute lung injury (12%, disseminated intravascular coagulation (10%, allergic and anaphylactic reactions (9%, and intravascular hemolysis (6%. The levels of pro- and anti-inflammatory cytokines were substantially increased in all the patients after surgery under EC irrespective of the presence of MODS in the postoperative period. The patients with MODS displayed pro- and anti-inflammatory cytokine imbalance due to a preponderance of the proinflammatory activity of a systemic response. During massive hemorrhage (more than 20 ml/kg, the patients with MODS exhibited a reduction in the two pools of cytokines. In the absence of MODS, there was a parallel increase in both pro- and anti-inflammatory cytokines. The magnitude of a change in the level of cytokines is related to the volume of blood loss. During prolonged EC (more than 170 min, the patients with MODS had a higher pro- and anti-inflammatory cytokine ratio due to the elevated levels of both pools, but the elevation of anti-inflammatory cytokines was more pronounced. In the patients without MODS, the values of both groups of interleukins were sigmficantly unchanged with longer duration of EC. Key words: multiple organ dysfunction syndrome, systemic inflammatory reaction, interleukins 6, 8, 10

  14. [Ulysses network: an approach to integral post-ICU treatment of patients with multiple organ dysfunction syndrome].

    Science.gov (United States)

    Nolla-Salas, M; Monmany-Roca, J; Vázquez-Mata, G

    2007-01-01

    The concept of continuity of care by intensivists as an element of quality control in the medical care of Intensive Care Unit (ICU) patients surviving multiple organ dysfunction syndrome has led to a rethinking of the ICU model in recent years. We discuss the rationale to design and implement a hospital-based, prospective, randomized, multicenter Intervention/Control study in order to estimate the impact of an interdisciplinary intervention during the post-ICU recovery phase on medium-term medical outcomes in ICU patients with multiple organ dysfunction.

  15. Mechanisms of endothelium and internal organs dysfunction associated with exposure to cobalt chloride (experimental study

    Directory of Open Access Journals (Sweden)

    L.V. Gigolaeva

    2016-09-01

    Full Text Available Cobalt administration in the human body is a risk factor for developing pulmonary and cardiovascular health problems. In this paper we report the results of functional studies and biochemical mechanisms of endothelial dysfunction and pathology of internal organs in cobalt intoxication in experiment. System-organ nature of the activation of oxidative processes is identified according to the increase of MDA secondary product in erythrocytes and homogenates of internal organs as well as the participation of AOC imbalance in the development of lipid peroxidation, the peculiarities of the violations of NO release endothelial function and participation in this process of L-arginine and an analogue of endogenous inhibitor of expression eNOS -L–NC - arginine methyl ester (L-NAME or L-nitro-arginine-methilester with cobalt intoxication in conditions of activation of oxidative processes. Chronic cobalt intoxication in rats leads to the activation of oxidative processes, thus there is inhibition of superoxide dismutase activity and the concentration of catalase and ceruloplasmin increased. Cholesterol metabolism is disturbed, as well as impaired nitric oxide production and its bioavailability, which is accompanied by the change of the microcirculatory hemodynamics of the visceral organs. The evaluation of the internal organs’ functional state according to the activity of the Na+,K+-ATPase in homogenates is performed, as well as due to the activity of organ-specific and excretory enzymes in blood serum on the background of cobalt toxicity. The role of changes of cholesterol metabolism is established – as a risk factor of atherogenesis in violation of the bioavailability of nitric oxide. For the pathogenetic correction of violations we applied the method using the endogenous antioxidant coenzyme Q10 and regulators of the expression eNOS L-arginine, L-NAME and their combination with coenzyme Q10.

  16. Apoptosis, proliferation and presence of estradiol receptors in the testes and Bidder's organ of the toad Rhinella arenarum (Amphibia, Anura).

    Science.gov (United States)

    Scaia, María Florencia; Czuchlej, Silvia Cristina; Cervino, Nadia; Ceballos, Nora Raquel

    2016-04-01

    The dynamic equilibrium between spermatogonial proliferation and testicular apoptosis determines the progression of spermatogenesis in amphibians. Estrogens and their receptors play a central role in regulating spermatogenesis in vertebrates, and in some species of anurans, estradiol (E2 ) is involved in the regulation of spermatogonial proliferation and apoptosis of germ cells. Bidder's organ (BO) is a structure characteristic of Bufonidae that has historically been compared to an undeveloped ovary. In adult Rhinella arenarum males, BO is one of the main sources of plasma E2 . The aim of this study was 1) to describe the seasonal variations in testicular apoptosis, spermatogonial proliferation, and cellular proliferation in BO; and 2) to analyze the presence and localization of estrogen receptor β (ERβ) in the testes and BO of R. arenarum. Testicular fragments and BOs from animals collected during the year were labeled with 5-bromo-2'-deoxyuridine (BrdU) and BrdU incorporation was determined using immunohistochemistry. Apoptosis in testicular sections was detected using the TUNEL method, and ERβ localization was assessed using immunohistochemistry in testes and BOs. The results indicate that spermatogonial proliferation is highest during the reproductive season and that cysts of spermatocytes and spermatids undergo apoptosis during the postreproductive season. Furthermore, the proliferation of follicular cells is highest during the reproductive and postreproductive seasons. ERβ was primarily detected by immunolocalization in Sertoli cells, follicular cells, and oocytes. Taken together, these results suggest that cysts that do not form spermatozoa are removed from testes by apoptosis and that estrogens regulate both spermatogenesis and oogenesis in adult males of R. arenarum. © 2015 Wiley Periodicals, Inc.

  17. Nonlinear analysis of sensory organization test for subjects with unilateral vestibular dysfunction.

    Directory of Open Access Journals (Sweden)

    Jia-Rong Yeh

    Full Text Available Vestibular disorder is the cause of approximately 50% of dizziness in older people. The vestibular system is a critical postural control mechanism, and posturography analysis is helpful for diagnosing vestibular disorder. In clinical practice, the sensory organization test (SOT is used to quantify postural control in an upright stance under different test conditions. However, both aging and vestibular disorder cause declines of postural control mechanisms. The aim of this study was to enhance the performance of the SOT using a nonlinear algorithm of empirical mode decomposition (EMD and to verify the differences of effects caused by aging and/or illnesses benefits to clinical diagnosis. A total of 51 subjects belonging to 3 groups--healthy-young, healthy-elderly and dizzy--were recruited for this study. New dynamic parameters of the SOT were derived from the center of pressure (COP signals. EMD served as an adaptive filter bank to derive the low- and high-frequency components of the COP. The effects on four ratios of sensory analysis caused by aging and vestibular disorder can be investigated for the specific frequency bands. According to our findings, new SOT parameters derived from the component with the specific frequency band more sensitively reflect the functional condition of vestibular dysfunction. Furthermore, both aging and vestibular dysfunction caused an increase in magnitude for the low-frequency component of the AP-direction COP time series. In summary, the low-frequency fluctuation reflects the stability of postural control, while the high-frequency fluctuation is sensitive to the functional condition of the sensory system. EMD successfully improved the accuracy of SOT measurements in this investigation.

  18. Effects of adenosine on the organ injury and dysfunction caused by hemorrhagic shock

    International Nuclear Information System (INIS)

    Soliman, M.M.

    2009-01-01

    Objectives: Adenosine has been shown in animal and human studies to decrease the post-ischemic myocardial injury by lowering the levels of tumor necrosis factor-a. The objectives of the study was to examine the protective effects of adenosine on the organ injury (liver, kidney, pancreas) associated with hemorrhagic shock in rats. Methodology: The study was conducted at Cardiovascular Physiology laboratory, King Saud University, Riyadh in 2007-2008. Anesthetized male Sprague- Dawley rats were assigned to hemorrhage and resuscitation treated with 20mM adenosine , untreated, or similar time matched control groups (n=6 per group). Rats were hemorrhaged for one hour using a reservoir model. Arterial blood pressure was monitored for one hour, and maintained at a mean arterial blood pressure of 40 mmHg. Adenosine 20mM was injected intra-arterially, before resuscitation in the adenosine treated group. Resuscitation was performed by re infusion of the sheded blood for 30 minutes. Arterial blood samples were analyzed for biochemical indicators of multiple organ injury: 1) liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), 2) renal function: urea and creatinine, 3) pancreatic function: amylase. Results: In the control group there was no significant rise in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. While in the adenosine treated group, resuscitation from one hour of hemorrhagic shock resulted in significant rises in the serum levels of (i) urea and creatinine, (ii) aspartate aminotransferase (AST) and alanine aminotransferase (ALT), (iii) amylase. Treatment of rats with 20mM adenosine before resuscitation following one hour of hemorrhagic shock decreased the multiple organ injury and dysfunction caused by hemorrhagic shock. Conclusion: Adenosine attenuated the renal, liver and pancreatic injury caused by hemorrhagic shock and resuscitation in rats. Thus

  19. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse

    DEFF Research Database (Denmark)

    Schäfer, Carolyn; Guldager, Helle Skov; Jørgensen, H L

    2011-01-01

    and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency...

  20. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse

    DEFF Research Database (Denmark)

    Schäfer, Carolyn; Guldager, Helle Skov; Jørgensen, H L

    2011-01-01

    , and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia....

  1. [Change in gene expression of inflammation-related genes induced in multiple organ dysfunction syndrome induced by infection of injuries in rat].

    Science.gov (United States)

    Ban, Yu; Shen, Hong; Li, Tan-shi

    2007-03-01

    To study the changes in inflammation-related gene expression in liver tissue during the course of multiple organ dysfunction syndrome (MODS) induced by infection of injuries and its implication. The rats model with MODS following trauma and infection was reproduced in rat. Liver tissue was harvested. The differences of gene expressions between the simple trauma group and MODS group were detected by means of cDNA microarray. Comparison between the two groups, differentially expressed genes included enhanced expression of genes related both of tissue damage and repair. There was also up-regulation of expression of both inflammation-related and anti-inflammation related genes. A few genes appeared down-regulated. The differences of expression extent were significant. There were up-regulation of some genes related to apoptosis and fibrosis. Differential expressions of genes in the liver tissue include both that related to the inflammation and anti-inflammation, with down-regulation and up-regulation at the same time. There is a difference in the intensity. There is also an expression of genes related to intrinsic protection, as manifested by co-existence of systemic inflammatory response syndrome (SIRS) and compensation anti-inflammatory response syndrome (CARS) under the condition of MODS. There is an imbalance in inflammatory reaction. The simultaneous up-regulation of the tissue damage and repair related genes suggests that cellular injury is accompanied by repair in the organs during the course of MODS.

  2. SHOCK VOLUME: A PATIENT-SPECIFIC INDEX THAT PREDICTS TRANSFUSION REQUIREMENTS AND ORGAN DYSFUNCTION IN MULTIPLY INJURED PATIENTS.

    Science.gov (United States)

    McKinley, Todd O; McCarroll, Tyler; Gaski, Greg E; Frantz, Travis L; Zarzaur, Ben L; Terry, Colin; Steenburg, Scott D

    2016-02-01

    Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt which causes organ dysfunction and can lead to death. We developed a noninvasive patient-specific index, Shock Volume (SV), to quantify the magnitude of hypoperfusion. SV integrates the magnitude and duration that incremental shock index values are elevated above known thresholds of hypoperfusion using serial individual vital sign data. SV can be monitored in real time to assess ongoing hypoperfusion. The goal of this study was to determine how SV corresponded to transfusion requirements and organ dysfunction in a retrospective cohort of 74 MIPs. We measured SV in 6-h increments for 48 h after injury in multiply injured adults (18-65; Injury Severity Score ≥18). Patients who had accumulated 40 units of SV within 6 h of injury and 100 units of SV within 12 h of injury were at high risk for requiring massive transfusion or multiple critical administration transfusions. SV measurements were equally sensitive and specific as compared with base deficit values in predicting transfusions. SV measurements at 6 h after injury stratified patients at risk for multiple organ failure determined by Denver scores. In addition, SV values corresponded to the magnitude of organ failure determined by Sequential Organ Failure Assessment scores. SV is a patient-specific index that can be quantified in real time in critically injured patients. It is a surrogate for cumulative hypoperfusion and it predicts high-volume transfusions and organ dysfunction.

  3. Exposure to volatile organic compounds and kidney dysfunction in thin film transistor liquid crystal display (TFT-LCD) workers.

    Science.gov (United States)

    Chang, Ta-Yuan; Huang, Kuei-Hung; Liu, Chiu-Shong; Shie, Ruei-Hao; Chao, Keh-Ping; Hsu, Wen-Hsin; Bao, Bo-Ying

    2010-06-15

    Many volatile organic compounds (VOCs) are emitted during the manufacturing of thin film transistor liquid crystal displays (TFT-LCDs), exposure to some of which has been reported to be associated with kidney dysfunction, but whether such an effect exists in TFT-LCD industry workers is unknown. This cross-sectional study aimed to investigate the association between exposure to VOCs and kidney dysfunction among TFT-LCD workers. The results showed that ethanol (1811.0+/-1740.4 ppb), acetone (669.0+/-561.0 ppb), isopropyl alcohol (187.0+/-205.3 ppb) and propylene glycol monomethyl ether acetate (PGMEA) (102.9+/-102.0 ppb) were the four dominant VOCs present in the workplace. The 63 array workers studied had a risk of kidney dysfunction 3.21-fold and 3.84-fold that of 61 cell workers and 18 module workers, respectively. Workers cumulatively exposed to a total level of isopropyl alcohol, PGMEA and propylene glycol monomethyl ether> or =324 ppb-year had a significantly higher risk of kidney dysfunction (adjusted OR=3.41, 95% CI=1.14-10.17) compared with those exposed to LCD industry, and cumulative exposure to specific VOCs might be associated with kidney dysfunction. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  4. Choice of an Infusion Agent for the Prevention of Multiple Organ Dysfunction in Acute Massive Blood Loss (Experimental Study

    Directory of Open Access Journals (Sweden)

    A. Yu. Yakovlev

    2010-01-01

    Full Text Available Objective: to perform an experimental study of the effect of sterofundin isotonic on the biochemical parameters characterizing the degree of organ injury after acute massive blood loss (AMBL. Material and methods. Experiments were carried out on 36 male Wistar rats weighing 230—250 g. Hemorrhagic stroke was simulated via AMBL in a volume of 2.5 ml/100 g at a rate of 2 ml/min. An hour after AMBL, there was hypovolemia compensation within 60 minutes in a volume of 200% of the blood loss: by Ringer’s solution in a control group and by sterofundin isotonic in an experimental group. Then blood reinfu-sion was made in a volume of 70% of blood loss. The biochemical parameters of multiple organ dysfunction (glucose, lactate, urea, creatinine, bilirubin, total protein, albumin, enzymemia (aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, lactate dehydrogenase, amylase, endotoxemia (low- and medium-molecular-weight substances in the plasma and erythrocytes, acid-base condition, electrolytes of venous blood, and animal survival were determined on days 1 and 3 following AMBL. Results. There was a reduction in the time and degree of posthemorrhagic metabolic, biochemical, and electrolyte disorders, enzymemia, and endotoxemia in the experimental animals. Conclusion. The experimental studies suggest that Ringer’s solution is inadequately effective in preventing multiple organ dysfunction due to AMBL. The malate-containing blood substitute sterofundin isotonic that is used during early therapy for AMBL exerts a marked preventive effect on the development of visceral organ injuries when multiple organ dysfunction occurs in the early and late posthemorrhagic period. The experimental findings make it possible to recommend that sterofundin isotonic should be used in intensive care of hypovolemic shock arising from AMBL. Key words: acute massive blood loss, malate, sterofun dinisotonic, lactate, endotoxemia, multiple organ

  5. Sensory organization test in elderly patients with and without vestibular dysfunction.

    Science.gov (United States)

    Pedalini, Maria Elisabete Bovino; Cruz, Oswaldo Laércio Mendonça; Bittar, Roseli Saraiva Moreira; Lorenzi, Maria Cecília; Grasel, Signe Schuster

    2009-09-01

    Elderly subjects without vestibular dysfunction had an overall worse performance as compared with the group of normal adults, confirming that age has a negative impact on balance. The group of elderly subjects with vestibular dysfunction had more important balance alterations than those without, confirming that vestibular dysfunction has a major impact on balance control in the elderly. The visual and vestibular systems presented more important functional changes with ageing than the somatosensory system. The main sensory input comes from the visual, vestibular and somatosensory systems; all of them may present changes due to ageing. This study aimed to investigate the performance of vestibular, visual and somatosensory systems in aged subjects with or without vestibular dysfunction, as compared to normal adults. Dynamic posturography was used in 60 elderly subjects without vestibular dysfunction (Gaa), 60 with vestibular dysfunction (Gas) and 58 normal adults (Gn). For condition 1 and 2 Gn performed significantly better than Gaa and Gas, with no difference between the latter. In conditions 4, 5 and 6 the performance of Gn was statistically superior to that of Gaa, which in turn, was better than that of Gas. The somatosensory responses showed no significant differences between the three groups. The performance of visual and vestibular systems showed progressive dysfunction: Gn did better than than Gaa, and Gaa did better than Gas.

  6. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  7. Depletion of end-binding protein 1 (EB1) promotes apoptosis of human non-small-cell lung cancer cells via reactive oxygen species and Bax-mediated mitochondrial dysfunction.

    Science.gov (United States)

    Kim, Min-Jung; Yun, Hong Shik; Hong, Eun-Hee; Lee, Su-Jae; Baek, Jeong-Hwa; Lee, Chang-Woo; Yim, Ji-Hye; Kim, Jae-Sung; Park, Jong Kuk; Um, Hong-Duck; Hwang, Sang-Gu

    2013-10-01

    Although end-binding protein 1 (EB1) is well known to regulate microtubule dynamics, the role of EB1 in apoptosis of non-small cell lung cancer (NSCLC) is poorly understood. Here, we investigated the molecular mechanism by which EB1 regulates apoptosis in H460, A549, and H1299 cells. Depletion of EB1 in A549 and H1299 cells, which express high levels of EB1, induced cell death in a p53-independent manner through over-production of reactive oxygen species (ROS) and Bax induction. This phenomenon was potentiated in radiation-treated EB1-knockdown cells and was largely blocked by N-acetyl-L-cysteine, a scavenger of ROS. ROS accelerated the activation of nuclear factor-kappa B (NF-κB) to promote transcriptional activity of Bax, an action that was accompanied by cytochrome c translocation and apoptosis-inducing factor (AIF) release. The NF-κB inhibitor, BAY 11-7082, potently inhibited the apoptosis induced by EB1 knockdown and radiation treatment, in association with diminished activity of the mitochondrial death pathway. Conversely, ectopic overexpression of EB1 in H460 cells, which express low levels of EB1, remarkably abrogated radiation-induced apoptosis and NF-κB-mediated mitochondrial dysfunction. Our data provide the first demonstration that down-regulation of EB1 promotes NSCLC cell death by inducing ROS-mediated, NF-κB-dependent Bax signaling cascades, a process in which cytochrome c and AIF play important roles, indicating a potential therapeutic benefit of EB1 in lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Penggunaan Skor Pediatric Logistic Organ Dysfunction Harian sebagai Prediktor Mortalitas Anak yang Dirawat di Unit Perawatan Intensif Anak

    OpenAIRE

    Hendra Salim; Suparyatha I B; Budi-Hartawan I Nym

    2016-01-01

    Latar belakang. Penggunaan sistem skoring Pediatric Logistic Organ Dysfunction (PELOD) sebagai prediktor mortalitas anak yang dirawat di Unit Perawatan Intensif Anak (UPIA) di Indonesia masih belum banyak diteliti. Tujuan. Mengetahui hubungan skor PELOD harian dalam memprediksi mortalitas anak yang dirawat di UPIA. Metode. Penelitian observasional analitik terhadap 49 anak yang dirawat di UPIA bulan Maret-Juli 2012. Skor PELOD harian dinilai selama satu minggu pertama perawatan dan diba...

  9. Influence of Obesity Diagnosis With Organ Dysfunction, Mortality, and Resource Use Among Children Hospitalized With Infection in the United States.

    Science.gov (United States)

    Maley, Nidhi; Gebremariam, Achamyeleh; Odetola, Folafoluwa; Singer, Kanakadurga

    2017-06-01

    Sepsis induces inflammation in response to infection and is a major cause of mortality and hospitalization in children. Obesity induces chronic inflammation leading to many clinical manifestations. Our understanding of the impact of obesity on diseases, such as infection and sepsis, is limited. The objective of this study was to evaluate the association of obesity with organ dysfunction, mortality, duration, and charges during among US children hospitalized with infection. Retrospective study of hospitalizations in children with infection aged 0 to 20 years, using the 2009 Kids' Inpatient Database. Of 3.4 million hospitalizations, 357 701 were for infection, 5685 of which were reported as obese children. Obese patients had higher rates of organ dysfunction (7.35% vs 5.5%, P obesity status (odds ratio: 0.56, 95% confidence interval: 0.23-1.34), however severity of illness modified the association between obesity status and the other outcomes. While there was no difference in in-hospital mortality by obesity diagnosis, variation in organ dysfunction, hospital stay, and hospital charges according to obesity status was mediated by illness severity. Findings from this study have significant implications for targeted approaches to mitigate the burden of obesity on infection and sepsis.

  10. Mitochondrial and endoplasmic reticulum dysfunction and related defense mechanisms in critical illness-induced multiple organ failure.

    Science.gov (United States)

    Thiessen, Steven E; Van den Berghe, Greet; Vanhorebeek, Ilse

    2017-10-01

    Patients with critical illness-induced multiple organ failure suffer from a very high morbidity and mortality, despite major progress in intensive care. The pathogenesis of this condition is complex and incompletely understood. Inadequate tissue perfusion and an overwhelming inflammatory response with pronounced cellular damage have been suggested to play an important role, but interventions targeting these disturbances largely failed to improve patient outcome. Hence, new therapeutic perspectives are urgently needed. Cellular dysfunction, hallmarked by mitochondrial dysfunction and endoplasmic reticulum stress, is increasingly recognized as an important contributor to the development of organ failure in critical illness. Several cellular defense mechanisms are normally activated when the cell is in distress, but may fail or respond insufficiently to critical illness. This insight may open new therapeutic options by stimulating these cellular defense mechanisms. This review summarizes the current understanding of the role of mitochondrial dysfunction and endoplasmic reticulum stress in critical illness-induced multiple organ failure and gives an overview of the corresponding cellular defense mechanisms. Therapeutic perspectives based on these cellular defense mechanisms are discussed. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients.

    Science.gov (United States)

    Toscano, V; Conti, F G; Anastasi, E; Mariani, P; Tiberti, C; Poggi, M; Montuori, M; Monti, S; Laureti, S; Cipolletta, E; Gemme, G; Caiola, S; Di Mario, U; Bonamico, M

    2000-07-01

    genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated group, respectively). DHA-S values were significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p hypothyroidism (thyroid-stimulating hormone > 6), and two patients showed preclinical hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19 untreated patients (52.6%) but only in five of 25 treated patients (20%), with a significantly different distribution (p gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

  12. 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-κB factors

    International Nuclear Information System (INIS)

    Tobón-Velasco, Julio C.; Limón-Pacheco, Jorge H.; Orozco-Ibarra, Marisol; Macías-Silva, Marina; Vázquez-Victorio, Genaro; Cuevas, Elvis; Ali, Syed F.

    2013-01-01

    6-Hydroxydopamine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson's disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways. The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration. The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum. Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-κB) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion. We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-κB-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway. Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-κB activation. In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage

  13. Concomitant Use of Sea Cucumber Organic Extract and Radiotherapy on Proliferation and Apoptosis of Cervical (HeLa Cell Line

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    Javad Baharara

    2016-04-01

    Full Text Available Background Cervical carcinoma is gynecologic malignancy with conventional treatment modality but drug resistance interferes with current therapeutic methods. Therefore, identification of novel new modality with low toxicity has uniquely favorable strategy. Objectives The aim of this study is evaluation of concomitant use of sea cucumber organic extract and radiotherapy on ovarian cancer. Materials and Methods In this in vitro experimental study, HeLa cancer cells were cultured and suspended in RPMI (Roswell Park Memorial Institute 1640 medium supplemented with 10 % FBS (Fetal Bovine Serum, 1 % antibiotic. Cells were treated with extract at different concentrations (0 to 100 μg/mL for 24 hours. After determination of suitable concentration, the cells were exposed to 2 Gray gamma radiation in presence of extract for 192 seconds and 66 hours were kept in incubator till anti-proliferative assay were evaluated. To assess apoptosis, flow cytometry with PI (Propodium Iodide and acridine orange staining were performed. Results Morphological analysis and results from cytotoxicity assay exhibited that 50 µg/mL of sea cucumber extract alone is considered IC50 and combination of gamma radiation became more valuable in growth inhibition. Also, flow cytometry histogram of treated cells indicated sub-G1 peak demonstrating disturbance in membrane integrity and apoptosis cell death. Fluorescence images have been confirmed apoptosis cell death in treatment groups. Conclusions These data indicate that sea cucumber extract as novel resource of aquatic natural products significantly can inhibit cervical cancer cell growth and synergistic effect of natural extract along with radiation therapy was more effective in anti-cervical cancer therapy.

  14. Injurious mechanical ventilation causes kidney apoptosis and dysfunction during sepsis but not after intra-tracheal acid instillation: an experimental study.

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    Kuiper, Jan Willem; Groeneveld, A B Johan; Haitsma, Jack J; Smeding, Lonneke; Begieneman, Mark P V; Jothy, Serge; Vaschetto, Rosanna; Plötz, Frans B

    2014-07-29

    Intratracheal aspiration and sepsis are leading causes of acute lung injury that frequently necessitate mechanical ventilation (MV), which may aggravate lung injury thereby potentially increasing the risk of acute kidney injury (AKI). We compared the effects of ventilation strategies and underlying conditions on the development of AKI. Spraque Dawley rats were challenged by intratracheal acid instillation or 24 h of abdominal sepsis, followed by MV with a low tidal volume (LVT) and 5 cm H2O positive end-expiratory pressure (PEEP) or a high tidal volume (HVT) and no PEEP, which is known to cause more lung injury after acid instillation than in sepsis. Rats were ventilated for 4 hrs and kidney function and plasma mediator levels were measured. Kidney injury was assessed by microscopy; apoptosis was quantified by TUNEL staining. During sepsis, but not after acid instillation, MV with HVT caused more renal apoptosis than MV with LVT. Increased plasma active plasminogen activator inhibitor-1 correlated to kidney apoptosis in the cortex and medulla. Increased apoptosis after HVT ventilation during sepsis was associated with a 40% decrease in creatinine clearance. AKI is more likely to develop after MV induced lung injury during an indirect (as in sepsis) than after a direct (as after intra-tracheal instillation) insult to the lungs, since it induces kidney apoptosis during sepsis but not after acid instillation, opposite to the lung injury it caused. Our findings thus suggest using protective ventilatory strategies in human sepsis, even in the absence of overt lung injury, to protect the kidney.

  15. Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases

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    O.T. Ranzani

    2011-11-01

    Full Text Available Our objective was to compare the pattern of organ dysfunctions and outcomes of critically ill patients with systemic lupus erythematosus (SLE with patients with other systemic rheumatic diseases (SRD. We studied 116 critically ill SRD patients, 59 SLE and 57 other-SRD patients. The SLE group was younger and included more women. Respiratory failure (61% and shock (39% were the most common causes of ICU admission for other-SRD and SLE groups, respectively. ICU length-of-stay was similar for the two groups. The 60-day survival adjusted for the groups’ baseline imbalances was not different (P = 0.792. Total SOFA scores were equal for the two groups at admission and during ICU stay, although respiratory function was worse in the other-SRD group at admission and renal and hematological functions were worse in the SLE group at admission. The incidence of severe respiratory dysfunction (respiratory SOFA >2 at admission was higher in the other-SRD group, whereas severe hematological dysfunction (hematological SOFA >2 during ICU stay was higher in the SLE group. SLE patients were younger and displayed a decreased incidence of respiratory failure compared to patients with other-SRDs. However, the incidences of renal and hematological failure and the presence of shock at admission were higher in the SLE group. The 60-day survival rates were similar.

  16. Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

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    Brisson, H; Arbelot, C; Monsel, A; Parisot, C; Girard, M; Savier, E; Vezinet, C; Lu, Q; Vaillant, J-C; Golmard, J-L; Gorochov, G; Langeron, O; Rouby, J-J

    2017-10-01

    During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure. Copyright © 2017. Published by Elsevier Masson SAS.

  17. Multiple organ dysfunction syndrome, an unusual complication of heroin intoxication: a case report and review of literature.

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    Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan

    2015-01-01

    Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.

  18. Clinical effects of pulse high-volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome.

    Science.gov (United States)

    Chu, La-Ping; Zhou, Jun-Jing; Yu, Ya-Fen; Huang, Yang; Dong, Wen-Xia

    2013-02-01

    To evaluate the effects of pulse high-volume hemofiltration (PHVHF) on severe acute pancreatitis (SAP) with multiple organ dysfunction syndrome (MODS). Thirty patients were divided into two groups: PHVHF group and continuous venovenous hemofiltration (CVVH) group. They were evaluated in terms of clinical symptoms, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, simplified acute physiology (SAPS) II score and biochemical changes. The levels of IL-6, IL-10 and TNF-α in plasma were assessed by ELISA before and after treatment. The doses of dopamine used in shock patients were also analyzed. In the two groups, symptoms were markedly improved after treatment. Body temperature (BT), breath rate (BR), heart rate (HR), APACHE II score, SOFA score, SAPS II score, serum amylase, white blood cell count and C-reactive protein were decreased after hemofiltration (P treatment of SAP with MODS. © 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

  19. Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

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    Chu, Yu-Feng; Meng, Mei; Zeng, Juan; Zhou, Hai-Yan; Jiang, Jin-Jiao; Ren, Hong-Sheng; Zhang, Ji-Cheng; Zhu, Wen-Ying; Wang, Chun-Ting

    2012-06-01

    Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  20. Combination of microRNA-21 and microRNA-146a Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction in Mice

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    Wei Huang

    2016-01-01

    Full Text Available Recent studies have revealed the cytoprotective roles of microRNAs (miRNAs miR-21 and miR-146a against ischemic cardiac injuries. While these studies investigated each of these miRNAs as an independent individual factor, our previous study has suggested the possible interaction between these two miRNAs. The present study was designed to investigate this possibility by evaluating the effects of miR-21 and miR-146a combination on cardiac ischemic injuries and the underlying mechanisms. MiR-21 and miR-146a synergistically decreased apoptosis under ischemia/hypoxic conditions in cardiomyocytes compared with either miR-21 or miR-146a alone. Mice coinjected with agomiR-21 and agomiR-146a had decreased infarct size, increased ejection fraction (EF, and fractional shortening (FS. These effects were greater than those induced by either of the two agomiRs. Furthermore, greater decreases in p38 mitogen-associated protein kinase phosphorylation (p-p38 MAPK were observed with miR-21: miR-146a combination as compared to application of either of the miRNAs. These data suggest that combination of miR-21 and miR-146a has a greater protective effect against cardiac ischemia/hypoxia-induced apoptosis as compared to these miRNAs applied individually. This synergistic action is mediated by enhanced potency of inhibition of cardiomyocyte apoptosis by the miR-21'PTEN/AKT'p-p38'caspase-3 and miR-146a'TRAF6'p-p38'caspase-3 signal pathways.

  1. Genetically Encoded Fluorescent Probe for Imaging Apoptosis in Vivo with Spontaneous GFP Complementation.

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    Nasu, Yusuke; Asaoka, Yoichi; Namae, Misako; Nishina, Hiroshi; Yoshimura, Hideaki; Ozawa, Takeaki

    2016-01-05

    Apoptosis plays a pivotal role in development and tissue homeostasis in multicellular organisms. Dysfunction of apoptosis is involved in many fatal diseases such as cancer. Visualization of apoptosis in living animals is necessary to understand the mechanism of apoptosis-related diseases. Here, we describe a genetically encoded fluorescent probe for imaging apoptosis in living multicellular organisms, based on spontaneous complementation of two fragments of a green fluorescent protein (GFP) variant (GFP OPT). The probe is designed for detection of mitochondria-mediated apoptosis during which a mitochondrial protein of Smac is released into cytosol. The Smac is connected with a carboxy-terminal fragment of GFP OPT (GFP11), whereas the remainder of GFP OPT (GFP(1-10)) is located in the cytosol. Under an apoptotic condition, the Smac is released from mitochondria into cytosol, allowing complementation of the GFP-OPT fragments and the emission of fluorescence. Live-cell imaging demonstrates that the probe enables detection of apoptosis in living cells with a high signal-to-background ratio. We applied the probe to living zebrafish, in which apoptotic cells were visualized with fluorescence. The technique provides a useful tool for the study of apoptosis in living animals, facilitating elucidation of the mechanisms of apoptosis-related diseases.

  2. Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis

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    Selvaraj Miltonprabu

    Full Text Available The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP against Cadmium (Cd induced hepatic inflammation, apoptosis and hepatic mitochondrial toxicity in rats. Male Wistar rats were distributed in four experimental groups: control, GSP, Cd and Cd + GSP. Exposure to a hepatotoxic dose of Cd (5 mg/kg BW caused liver damage, coupled with enhanced reactive oxygen species (ROS generation, increased inflammation and apoptosis in liver with increased DNA damage in hepatocytes of rats. Mitochondria were isolated from the hepatic tissues of rats from each group. Our results showed significant decrease in the tri-carboxylic acid cycle enzymes, increased mitochondrial swelling, inhibition of cytochrome c oxidase activity and complex I–III, II–III and IV mediated electron transfer, decreased mitochondrial ATPases, a reduction in calcium content and mitochondrial oxygen consumption in Cd treated rats. All these molecular changes caused by Cd were alleviated by the pre-supplementation with GSP (100 mg/kg BW. The ultra structural changes in the liver also support our findings. From our results, it is clearly indicated that the free radical scavenging, metal chelating and antioxidant potentials of GSP might be the possible reason, responsible for the rescue action against Cd induced mitochondrial damage in the liver of rats. Keywords: Cd, GSP, Mitochondria, Oxidative stress, Liver, Rats

  3. Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-L-carnitine.

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    Baghaei, Amir; Solgi, Reza; Jafari, Abbas; Abdolghaffari, Amir Hossein; Golaghaei, Alireza; Asghari, Mohammad Hossein; Baeeri, Maryam; Ostad, Seyed Nasser; Sharifzadeh, Mohammad; Abdollahi, Mohammad

    2016-03-01

    The aim of the present study was to investigate the efficacy of acetyl-L-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apoptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Sham that received almond oil only; the AlP that received oral LD50 dose of aluminum; the AC-100, AC-200, and AC-300 which received concurrent oral LD50 dose of AlP and single 100, 200, and 300 mg/kg of ALCAR by intraperitoneal injection. After 24 h, the rats were sacrificed; the heart and blood sample were taken for measurement of biochemical and mitochondrial factors. The results specified that ALCAR significantly attenuated the oxidative stress (elevated ROS and plasma iron levels) caused by AlP poisoning. ALCAR also increased the activity of cytochrome oxidase, which in turn amplified ATP production. Furthermore, flow cytometric assays and caspase activity indicated that ALCAR prohibited AlP-induced apoptosis in cardiomyocytes. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Insufficient autophagy contributes to mitochondrial dysfunction, organ failure, and adverse outcome in an animal model of critical illness.

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    Gunst, Jan; Derese, Inge; Aertgeerts, Annelies; Ververs, Eric-Jan; Wauters, Andy; Van den Berghe, Greet; Vanhorebeek, Ilse

    2013-01-01

    Increasing evidence implicates mitochondrial dysfunction as an early, important event in the pathogenesis of critical illness-induced multiple organ failure. We previously demonstrated that prevention of hyperglycemia limits damage to mitochondria in vital organs, thereby reducing morbidity and mortality. We now hypothesize that inadequate activation of mitochondrial repair processes (clearance of damaged mitochondria by autophagy, mitochondrial fusion/fission, and biogenesis) may contribute to accumulation of mitochondrial damage, persistence of organ failure, and adverse outcome of critical illness. Prospective, randomized studies in a critically ill rabbit model. University laboratory. Three-month-old male rabbits. We studied whether vital organ mitochondrial repair pathways are differentially affected in surviving and nonsurviving hyperglycemic critically ill animals in relation to mitochondrial and organ damage. Next, we investigated the impact of preventing hyperglycemia over time and of administering rapamycin as an autophagy activator. In both liver and kidney of hyperglycemic critically ill rabbits, we observed signs of insufficient autophagy, including accumulation of p62 and a concomitant decrease in the microtubule-associated protein light-chain-3-II/microtubule-associated protein light-chain-3-I ratio. The phenotype of insufficient autophagy was more pronounced in nonsurviving than in surviving animals. Molecular markers of insufficient autophagy correlated with impaired mitochondrial function and more severe organ damage. In contrast, key players in mitochondrial fusion/fission or biogenesis were not significantly different regarding survival status. Therefore, we focused on autophagy to study the impact of preventing hyperglycemia. Both after 3 and 7 days of illness, autophagy was better preserved in normoglycemic than in hyperglycemic rabbits, which correlated with improved mitochondrial function and less organ damage. Stimulation of autophagy in

  5. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.

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    Cassiano Felippe Gonçalves-de-Albuquerque

    Full Text Available Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA, a monounsaturated fatty acid (MUFA. We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP. OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A mRNA levels were increased, while uncoupling protein 2 (UCP2 liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA.

  6. The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

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    Luciano L. Paulo; Josiane Campos Cruz; Zhengbing Zhuge; Alynne Carvalho-Galvão; Maria C.R. Brandão; Thiago F. Diniz; Sarah McCann Haworth; Petrônio F. Athayde-Filho; Virginia S. Lemos; Jon O. Lundberg; Marcelo F. Montenegro; Valdir A. Braga; Mattias Carlström

    2018-01-01

    Rationale: Development and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance. In this study, we evaluated NO release capability and cardiovascular effects of the newly synthesized organic nitrate 1, 3-bis (hexyloxy) propan-2-y...

  7. Diabetes Mellitus as Dysfunction of Interactions among all Organs: “Ominous Orchestra of Organs”

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    Hiroyuki Koshiyama

    2008-01-01

    Full Text Available Epidemiological evidence has established a link among hyperlipidemia, visceral obesity, osteoporosis, and cardiovascular diseases. We have recently proposed a hypothesis that the associations of those disorders are based on interactions of the three organs, i.e. the bone, adipose, and vascular tissues, possibly through multiple actions of several humoral factors and/or transcription factors. We call this unified hypothesis “osteo-lipo-vascular interactions”, which may be explained by the common origin of the cells in each organ, such as mesenchymal stem cells or macrophages. Several groups proposed similar hypotheses. On the other hand, there have been accumulating evidences which indicate that there exist hitherto unknown various interactions between many organs, such as hypothalamus-liver, fat-liver, liver-muscle, intestine-pancreas, kidney-heart and so on. Therefore, it seems insufficient to consider only the interactions among several organs, and the standpoint of considering interactions among all organs may be warranted, especially in order to understand the pathogenesis of metabolic syndrome, insulin resistance and type 2 diabetes. We here propose a hypothesis that the abnormal interactions of all organs (“Ominous Orchestra of Organs” underlies the pathogenesis of type 2 diabetes. It is to be elucidated which of the “players” or the “conductor” may be mainly responsible for disharmony of the orchestra.

  8. [Chaotic dynamic process of multiple organs dysfunction syndrome and the regulatory function of shenqin liquid on it].

    Science.gov (United States)

    Liang, Jun-Xiong; Weng, Shu-He; Chen, Jing-He

    2008-07-01

    To explore the chaotic dynamic process of multiple organs dysfunction syndrome (MODS) and the regulatory effect of Shenqin Liquid (SQL), a Chinese herbal liquid preparation with the action of purging and qi-tonifying. Eighty SD rats were divided into 4 groups, and were given suspension of zymosan A and paraffine (1 mL/kg) by peritoneal injection except for those in the blank control group to set up the multiple organs dysfunction syndrome (MODS) model. Low and high doses SQL were administered twice at the doses of 30 and 60 g/kg of SQL respectively at an interval of 8 h per day before modeling. Serum concentration of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) in MODS model animals were tested diachronically, eg. 12, 6 h before modeling, during modeling, 6 and 12 h after modeling, and then the mathematic models were built up with compartment analysis. Lyapunov exponents (LE) of the mathematic models were calculated to evaluate their chaotic characteristics of movement and the degree of chaos was ascertained with the correlation dimension (CD). The serum levels of TNF-alpha and NO were significantly higher than those in the bland control group at modeling, 6, and 12 h after modeling (P SQL were significantly lower than the model group (P SQL was significantly lower than that in the low dose group (P 0 respectively; in the low dose and high dose SQL treated groups, CD was 0.517 and 0.653 respectively and LE >0. CD of NO movement in the blank control group was 0.670 and with LE 0; in the low dose SQL group, 0.574 and in the high dose SQL group 0.850, and LE SQL can intervene the movement of TNF-alpha and NO, decrease the complexity of their chaotic movement, and make them return back to a stable state.

  9. Suppression of Apoptosis by Basement Membrane Requires three-dimensional Tissue Organization and Withdrawal from the Cell Cycle

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    Boudreau, N.; Werb, Z.; Bissell, M.J.

    1995-12-28

    The basement membrane (BM) extracellular matrix induces differentiation and suppresses apoptosis in mammary epithelial cells, whereas cells lacking BM lose their differentiated phenotype and undergo apoptosis. Addition of purified BM components, which are known to induce {beta}-casein expression, did not prevent apoptosis, indicating that a more complex BM was necessary. A comparison of culture conditions where apoptosis would or would not occur allowed us to relate inhibition of apoptosis to a complete withdrawal from the cell cycle, which was observed only when cells acquired a three-dimensional alveolar structure in response to BM. In the absence of this morphology, both the G1 cyclin kinase inhibitor p21/WAF-I and positive proliferative signals including c-myc and cyclin Dl were expressed and the retinoblastoma protein (Rb) continued to be hyperphosphorylated. When we overexpressed either c-myc in quiescent cells or p21 when cells were still cycling, apoptosis was induced. In the absence of three-dimensional alveolar structures, mammary epithelial cells secrete a number of factors including transforming growth factor a and tenascin, which when added exogenously to quiescent cells induced expression of c-myc and interleukin-{beta}1-converting enzyme (ICE) mRNA and led to apoptosis. These experiments demonstrate that a correct tissue architecture is crucial for long-range homeostasis, suppression of apoptosis, and maintenance of differentiated phenotype.

  10. Nosography of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in internal medicine patients

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    Silvia Spoto

    2015-09-01

    Full Text Available Sepsis is defined by the presence of at least two systemic inflammatory response syndrome criteria associated with an infection microbiologically or clinically evidenced. In Italy sepsis is responsible for 80,000 hospital admissions per year and, in the last decades, severe sepsis and septic shock cases are increasing, in correlation with the increased prevalence of multi-drugresistant microbial strains. The predominant etiologic agents are Gram-positive and Gram-negative bacteria, but sepsis caused by fungi is increasing. The host response with both inflammatory and anti-inflammatory processes is responsible for organic failures, which complicate the syndrome, and for the susceptibility to secondary infections. The impairment of one or more organs or systems may be the onset clinical presentation. The organ dysfunctions complicating sepsis involve mainly cardiorespiratory system, kidneys, hemostatis and central nervous system. Fever or hypothermia, tachycardia, tachypnea, leukocytosis or leukopenia, elevated blood levels of lactate and procalcitonin, hypotension are diagnostically sensitive findings for sepsis. Definitive diagnosis requires isolation of the pathogen from blood sample or from the focus of infection. Therapeutic success against sepsis depends on the appropriate use of antibiotics, on the treatment of hemodynamic and respiratory disorder and on general supportive care. In some cases the use of activated protein C is to take in consideration.

  11. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.

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    Chi Zhang

    Full Text Available BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia. Increasing evidence suggests that fibroblast growth factor (FGF21 has a crucial role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. METHODS: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight or streptozotocin (150 mg/kg to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. CONCLUSION: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

  12. Psychological rejection of the transplanted organ and graft dysfunction in kidney transplant patients

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    Látos M

    2016-06-01

    Full Text Available Melinda Látos,1 György Lázár,1 Zoltán Horváth,1 Victoria Wittmann,1 Edit Szederkényi,1 Zoltán Hódi,1 Pál Szenohradszky,1 Márta Csabai2 1Department of Surgery, Faculty of Medicine, 2Psychology Institute, University of Szeged, Szeged, Hungary Abstract: Interdisciplinary studies suggest that the mental representations of the transplanted organ may have a significant effect on the healing process. The objective of this study was to examine the representations of the transplanted organ and their relationship with emotional and mood factors, illness perceptions, and the functioning of the transplanted organ. One hundred and sixty-four kidney transplant patients were assessed using the Spielberger Anxiety Inventory, the Beck’s Depression Scale, the Posttraumatic Growth Inventory, the Brief Illness Perception Questionnaire, and the Transplanted Organ Questionnaire. Medical parameters were collected from the routine clinical blood tests (serum creatinine and estimated glomerular filtration rate levels and biopsy results. Our most outstanding results suggest that kidney-transplanted patients’ illness representations are associated with health outcomes. The Transplanted Organ Questionnaire “psychological rejection” subscale was connected with higher serum creatinine and estimated glomerular filtration rate levels. Logistic regression analysis showed that psychological rejection subscale, Brief Illness Perception Questionnaire, and Posttraumatic Growth Questionnaire total scores were associated with graft rejection. These results may serve as a basis for the development of complex treatment interventions, which could help patients to cope with the bio-psycho-social challenges of integrating the new organ as part of their body and self. Keywords: anxiety, depression, illness representations, posttraumatic growth, psychological rejection, renal transplantation

  13. The potential dysfunction of otolith organs in patients after mumps infection.

    Science.gov (United States)

    Zhou, Yu-Juan; Yu, Jing; Wu, Yong-Zhen; Tian, Liang; Han, Zhao; Wang, Jing; Chi, Fang-Lu

    2017-01-01

    To investigate the relationship between mumps and the extent of hearing impairment and otolith organ damage. A total of 27 patients with unilateral hearing impairment following mumps were enrolled. The degrees of hearing loss and otolith organ damage were confirmed by audiometric and vestibular evoked myogenic potential [VEMP] tests. All the results were compared and analyzed using Stata 13.0 software for Windows. The VEMP thresholds of the affected ears were significantly higher than those of the unaffected ears in both tests (cervical VEMP [cVEMP] test and ocular VEMP [oVEMP] test; p = 0.000 and 0.001, respectively). The mean cVEMP and oVEMP threshold values of the affected ears with hearing impairment for ≤10 years were significantly lower than those of affected ears with hearing impairment for >10 years [p = 0.009 and 0.004, respectively]. Deafness resulting from mumps is usually profound and permanent, which indicates severe damage to the cochlea due to the disease. The functions of otolith organs in the vestibular system are also impaired. Over time, the function of the otolith organs or their neural pathway may suffer secondary damage.

  14. Delineation guidelines for organs at risk involved in radiation-induced salivary dysfunction and xerostomia

    NARCIS (Netherlands)

    van de Water, Tara A.; Bijl, Henk P.; Westerlaan, Henriette E.; Langendijk, Johannes A.

    2009-01-01

    Background and purpose It is believed that minimizing inconsistencies in OAR-volume definition will help to improve adequate reporting and interpreting of radial ion treatment results The aim of this paper is to introduce computed tomography (CT)-based delineation guidelines for organs at risk

  15. Sex, Symptom, and Premorbid Social Functioning Associated with Perceptual Organization Dysfunction in Schizophrenia

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    Jamie eJoseph

    2013-08-01

    Full Text Available Impairments in visual perceptual organization abilities are a repeatedly observed cognitive deficit in schizophrenia. These impairments have been found to be most prominent among patients with histories of poor premorbid social functioning, disorganized symptoms, and poor clinical outcomes. Despite the demonstration of significant sex differences for these clinical factors in schizophrenia, the extent of sex differences for visual perceptual organization in schizophrenia is unknown. Therefore, we investigated the extent to which previously known correlates (premorbid social sexual functioning and disorganized symptoms and a novel factor (participant sex accounted for performance on two perceptual organization tasks (contour integration and Ebbinghaus illusion that have previously demonstrated sensitivity to schizophrenia. We also determined the relative degree to which each of these factors predicted task scores over and above the others. Schizophrenia patients (N = 109, 43 female from different levels of care were ascertained. Female patients demonstrated higher contour integration scores, but lower performance on the context sensitivity index of the Ebbinghaus illusion, compared to males. Contour integration performance was significantly associated with poorer premorbid adolescent social sexual functioning and higher levels of disorganized symptoms, supporting past results that indicate a relationship among poor premorbid social sexual functioning, disorganized symptoms, and visual perceptual abnormalities in schizophrenia. However, analyses of Ebbinghaus illusion performance suggests there is a complex relationship among patient sex, clinical factors and perceptual abilities with relatively intact bottom-up grouping processes in females, but greater problems, compared to males with more top-down mediated context sensitivity. Therefore, sex differences may be an important consideration for future studies of visual perceptual organization in

  16. CMV-induced embryonic mouse organ of corti dysplasia: Network architecture of dysfunctional lateral inhibition.

    Science.gov (United States)

    Melnick, Michael; Jaskoll, Tina

    2015-07-01

    Congenital cytomegalovirus infection is the major nongenetic cause of sensorineural hearing loss at birth and beyond. Among other pathologies, there is a striking dysplasia/hyperplasia of organ of Corti hair and supporting cells. Using an in vitro embryonic mouse model of cytomegalovirus-induced cochlear teratogenesis that mimics the known human pathology, and functional signaling network modeling, we tested the hypothesis that cytomegalovirus disrupts the highly ordered organ of Corti hair and supporting cells pattern by dysregulating Notch and Fgfr3, their cognate ligands and downstream effectors. Several novel emergent properties of the critical lateral inhibition subnetwork became apparent. The subnetwork has classic small-world properties such as short paths between most gene pairs, few long-distance links, and considerable clustering. Concomitantly, the calculated probability that our specific gene expression dataset is from dysplastic organs of Corti is highly significant (p < 1 × 10(-12) ). Furthermore, we determined that the subnetwork has a highly heterogeneous scale-free topology in which the highly linked genes (hubs), Notch and Fgfr3, play a central role in mediating interactions among the less linked genes. This phenomenon has important biologic and therapeutic implications. © 2015 Wiley Periodicals, Inc.

  17. Pre-validation of the WHO organ dysfunction based criteria for identification of maternal near miss

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    Parpinelli Mary A

    2011-08-01

    Full Text Available Abstract Background To evaluate the performance of the WHO criteria for defining maternal near miss and identifying deaths among cases of severe maternal morbidity (SMM admitted for intensive care. Method Between October 2002 and September 2007, 673 women with SMM were admitted, and among them 18 died. Variables used for the definition of maternal near miss according to WHO criteria and for the SOFA score were retrospectively evaluated. The identification of at least one of the WHO criteria in women who did not die defined the case as a near miss. Organ failure was evaluated through the maximum SOFA score above 2 for each one of the six components of the score, being considered the gold standard for the diagnosis of maternal near miss. The aggregated score (Total Maximum SOFA score was calculated using the worst result of the maximum SOFA score. Sensitivity, specificity, positive and negative predictive values of these WHO criteria for predicting maternal death and also for identifying cases of organ failure were estimated. Results The WHO criteria identified 194 cases of maternal near miss and all the 18 deaths. The most prevalent criteria among cases of maternal deaths were the use of vasoactive drug and the use of mechanical ventilation (≥1 h. For the prediction of maternal deaths, sensitivity was 100% and specificity 70.4%. These criteria identified 119 of the 120 cases of organ failure by the maximum SOFA score (Sensitivity 99.2% among 194 case of maternal near miss (61.34%. There was disagreement in 76 cases, one organ failure without any WHO criteria and 75 cases with no failure but with WHO criteria. The Total Maximum SOFA score had a good performance (area under the curve of 0.897 for prediction of cases of maternal near miss according to the WHO criteria. Conclusions The WHO criteria for maternal near miss showed to be able to identify all cases of death and almost all cases of organ failure. Therefore they allow evaluation of the

  18. The occurrence of single and multiple organ dysfunction in pediatric electrical versus other thermal burns.

    Science.gov (United States)

    Hundeshagen, Gabriel; Wurzer, Paul; Forbes, Abigail A; Voigt, Charles D; Collins, Vanessa N; Cambiaso-Daniel, Janos; Finnerty, Celeste C; Herndon, David N; Branski, Ludwik K

    2017-05-01

    Multiple organ failure (MOF) is a major contributor to morbidity and mortality in burned children. While various complications induced by electrical injuries have been described, the incidence and severity of single organ failure (SOF) and MOF associated with this type of injury are unknown. The study was undertaken to compare the incidence and severity of SOF and MOF as well as other complications between electrically and thermally burned children. Between 2001 and 2016, 288 pediatric patients with electrical burns (EB; n = 96) or thermal burns (CTR; n = 192) were analyzed in this study. Demographic data; length of hospitalization; and number and type of operations, amputations, and complications were statistically analyzed. Incidence of SOF and MOF was assessed using the DENVER2 classification in an additive mixed model over time. Compound scores and organ-specific scores for lung, heart, kidney, and liver were analyzed. Serum cytokine expression profiles of both groups were also compared over time. Significance was accepted at p in age (CTR, 11 ± 5 years, vs EB, 11 ± 5 years), percent total body surface area burned (CTR, 33% ± 25%, vs EB, 32 ± 25%), and length of hospitalization (CTR, 18 ± 26 days, vs EB, 18 ± 21 days). The percentage of high-voltage injury in the EB group was 64%. The incidence of MOF was lower in the EB group (2 of 96 [2.1%]) than the CTR group (20 of 192 [10.4%]; p The incidence of single organ failure was comparable between groups. Incidence of pulmonary failure was comparable in both groups, but incidence of inhalation injury was significantly higher in the CTR group (p in the EB group had more amputations (p the groups. Serum cytokine expression profiles were also comparable between the groups. In pediatric patients, electrical injury is associated with a lower incidence of MOF than other thermal burns. Early and radical debridement of nonviable tissue is crucial to improve outcomes in the electrical burn patient population

  19. Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats.

    Science.gov (United States)

    Ozer, Erdem Kamil; Goktas, Mustafa Tugrul; Kilinc, Ibrahim; Toker, Aysun; Bariskaner, Hulagu; Ugurluoglu, Ceyhan; Iskit, Alper Bektas

    2017-07-01

    Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.

  20. [Reproducing and evaluating a rabbit model of multiple organ dysfunction syndrome after cardiopulmonary resuscitation resulted from asphyxia].

    Science.gov (United States)

    Zhang, Dong; Li, Nan; Chen, Ying; Wang, Yu-shan

    2013-02-01

    To evaluate the reproduction of a model of post resuscitation multiple organ dysfunction syndrome (PR-MODS) after cardiac arrest (CA) in rabbit, in order to provide new methods for post-CA treatment. Thirty-five rabbits were randomly divided into three groups, the sham group (n=5), the 7-minute asphyxia group (n=15), and the 8-minute asphyxia group (n=15). The asphyxia CA model was reproduced with tracheal occlusion. After cardiopulmonary resuscitation (CPR), the ratio of recovery of spontaneous circulation (ROSC), the mortality at different time points and the incidence of systemic inflammatory response syndrome (SIRS) were observed in two asphyxia groups. Creatine kinase isoenzyme (CK-MB), alanine aminotransferase (ALT), creatinine (Cr), glucose (Glu) and arterial partial pressure of oxygen (PaO2) levels in blood were measured in the two asphyxia groups before CPR and 12, 24 and 48 hours after ROSC. The survived rabbits were euthanized at 48 hours after ROSC, and heart, brain, lung, kidney, liver, and intestine were harvested for pathological examination using light microscope. PR-MODS after CA was defined based on the function of main organs and their pathological changes. (1) The incidence of ROSC was 100.0% in 7-minute asphyxia group and 86.7% in 8-minute asphyxia group respectively (P>0.05). The 6-hour mortality in 8-minute asphyxia group was significantly higher than that in 7-minute asphyxia group (46.7% vs. 6.7%, P0.05). (2) There was a variety of organ dysfunctions in survived rabbits after ROSC, including chemosis, respiratory distress, hypotension, abdominal distension, weakened or disappearance of bowel peristalsis and oliguria. (3) There was no SIRS or associated changes in major organ function in the sham group. SIRS was observed at 12 - 24 hours after ROSC in the two asphyxia groups. CK-MB was increased significantly at 12 hours after ROSC compared with that before asphyxia (7-minute asphyxia group: 786.88±211.84 U/L vs. 468.20±149.45 U/L, 8

  1. Dysfunctions in public psychiatric bureaucracies.

    Science.gov (United States)

    Marcos, L R

    1988-03-01

    The author describes common dysfunctions in public psychiatric organizations according to the model of bureaucracy articulated by Max Weber. Dysfunctions are divided into the categories of goal displacement, outside interference, unclear authority structure and hierarchy, and informal relations in the work place. The author emphasizes the bureaucratic nature of public psychiatry and the need for mental health professionals to understand the dysfunctions of the organizations in which they work, including the impact of these dysfunctions on the provision of quality care.

  2. Immunotherapeutical role of Flt3 ligand amplification of pulmonary dendritic cells in murine multiple organ dysfunction syndrome in vivo

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    Hong-wei WANG

    2012-08-01

    Full Text Available Objective To explore the therapeutic effect of Flt3 ligand (Flt3L on multiple organ dysfunction syndrome (MODS model via amplification of lung dendritic cells. Methods Animal model of MODS was replicated by injecting zymosan into the peritoneal cavity of BALB/c mice, and then the mice were randomly divided into Flt3L treatment group, MODS group, Flt3L group and control group. Mortality rate was observed. After 12 days, lung mononuclear cells were isolated by density gradient centrifugation and analyzed with flow cytometry. Blood AST, ALT, creatinine, lipase, amylase and glucose were determined by automatic biochemical analyzer. Pathological changes in lung tissue were observed under light microscope. Results Mortality in Flt3L treatment group decreased dramatically compared with MODS group. The proportions of myeloid, plasmacytoid and I-Ad+ DCs in Flt3L group were remarkably increased compared with control group, and the proportion of the three DC subsets in MODS group was much lower than that in control group. Howerver, Flt3L treatment dramatically increased the proportion of them in MODS group. In MODS group, the level of ALT, AST, lipase, amylase and creatinine remarkably increased and blood glucose decreased compared with that of Flt3L and control groups; but in Flt3L treatment group, the level of ALT, AST, lipase, amylase and creatinine decreased and blood glucose increased dramatically, and lung injury mitigated obviously compared with MODS group. Conclusion Flt3L could attenuate lung tissue injury in MODS model, improve organ function, and lower the mortality of experimental animals, thus exerting its immunotherapeutic effects by in vivo amplification of lung dendritic cells.

  3. Testosterone deficiency causes penile fibrosis and organic erectile dysfunction in aging men. Evaluating association among Age, TDS and ED

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    Iacono Fabrizio

    2012-11-01

    Full Text Available Abstract Introduction We studied the possible correlation between age, testosterone deficiency, cavernosal fibrosis and erectile dysfunction (ED. Methods 47 patients with ED were enrolled between September 2010 and October 2011. IIEF-EF score, NPTR test using the Rigiscan method, total and free testosterone levels, and cavernosum biopsy were carried out on all patients. Patients aged 65 or over were defined as Old Age (OA while patients under 65 were defined Young age (YA. The strength of the relationships found was estimated by Odds Ratio. Results 74% of patients with values of over 52% collagen fibers in the corpora cavernosa were found to have organic ED. A significant difference was found in age, percentage of collagen fibers, testosterone levels between patients with Positive Rigiscan (PR and Negative Rigiscan (NR. Hypotestosteronaemia increased the risk of ED with PR (OR: 21.4, 95% CI: 20.2-22.6 and in both young age patients (OR: 4.3, 95% CI: 2.4-6.2 and old age patients (OR: 15.5, 95% CI: 13.4-17.6. Moreover cavernosal fibrosis increased the risk of ED with PR in both young age patients (OR: 8.2, 95% CI: 6.4-10.0 and old age patients (OR: 24.6, 95% CI: 20.8-28.4. Conclusions This study demonstrates a strong association among age, testosterone deficiency, cavernosal fibrosis and ED with PR. Age, testosterone deficiency and cavernosal fibrosis are potentially correctable factors of cavernosal fibrosis and organic ED. Further, prospective studies are needed to evaluate if testosterone treatment, alone or in association with PDE5 inhibitors, may lower the risk of cavernosal fibrosis or decrease the severity the fibrosis in ED patients.

  4. Testosterone deficiency causes penile fibrosis and organic erectile dysfunction in aging men. Evaluating association among Age, TDS and ED.

    Science.gov (United States)

    Iacono, Fabrizio; Prezioso, Domenico; Ruffo, Antonio; Illiano, Ester; Romis, Leo; Di Lauro, G; Romeo, Giuseppe; Amato, Bruno

    2012-01-01

    We studied the possible correlation between age, testosterone deficiency, cavernosal fibrosis and erectile dysfunction (ED). 47 patients with ED were enrolled between September 2010 and October 2011. IIEF-EF score, NPTR test using the Rigiscan method, total and free testosterone levels, and cavernosum biopsy were carried out on all patients. Patients aged 65 or over were defined as Old Age (OA) while patients under 65 were defined Young age (YA). The strength of the relationships found was estimated by Odds Ratio. 74% of patients with values of over 52% collagen fibers in the corpora cavernosa were found to have organic ED. A significant difference was found in age, percentage of collagen fibers, testosterone levels between patients with Positive Rigiscan (PR) and Negative Rigiscan (NR). Hypotestosteronaemia increased the risk of ED with PR (OR: 21.4, 95% CI: 20.2-22.6) and in both young age patients (OR: 4.3, 95% CI: 2.4-6.2) and old age patients (OR: 15.5, 95% CI: 13.4-17.6). Moreover cavernosal fibrosis increased the risk of ED with PR in both young age patients (OR: 8.2, 95% CI: 6.4-10.0 and old age patients (OR: 24.6, 95% CI: 20.8-28.4). This study demonstrates a strong association among age, testosterone deficiency, cavernosal fibrosis and ED with PR. Age, testosterone deficiency and cavernosal fibrosis are potentially correctable factors of cavernosal fibrosis and organic ED. Further, prospective studies are needed to evaluate if testosterone treatment, alone or in association with PDE5 inhibitors, may lower the risk of cavernosal fibrosis or decrease the severity the fibrosis in ED patients.

  5. Effect of continuous blood purification in treatment of patients with severe acute pancreatitis and multiple organ dysfunction syndrome

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    ZHANG Yong

    2016-02-01

    Full Text Available ObjectiveTo observe the effect of continuous blood purification (CBP on serum inflammatory mediators in patients with severe acute pancreatitis (SAP and multiple organ dysfunction syndrome (MODS. MethodsSixty-five SAP patients with MODS who were treated in General Hospital of Chengdu Command Area of Chinese PLA from April 2008 to December 2013 were enrolled and divided into two groups. The 33 patients in the control group received comprehensive internal medicine treatment, and the 32 patients in the treatment group received comprehensive internal medicine treatment and CBP. Changes in APACHE II score, MODS score, and the serum levels of tumor necrosis factor α (TNFα, C-reactive protein (CRP, interleukin 6 (IL-6, IL-18, platelet-activating factor (PAF, and nitric oxide (NO after treatment were observed. Independent-samples t test was applied for comparison of continuous data between the two groups, and paired t test was applied for before-after comparison within the same group; chi-squared test was applied for comparison of categorical data between the two groups. ResultsIn both groups, APACHE II score, MODS score, and the serum levels of TNFα, CRP, IL-6, IL-18, PAF, and NO decreased significantly after treatment (all P<0.05, and the treatment group had significantly greater decreases in these values than the control group (all P<0.001; the survival rates in the treatment group and the control group were 90.6% (29/32 and 78.8% (26/33, respectively, with no significant difference between the two groups (χ2=1.749, P=0.186. ConclusionIn SAP patients with MODS, CBP can effectively clear the serum inflammatory mediators to block systemic inflammatory response and improve organ function, and, therefore, it is an effective method to treat SAP.

  6. Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells

    International Nuclear Information System (INIS)

    Shukla, Shatrunajay; Sharma, Ankita; Pandey, Vivek Kumar; Raisuddin, Sheikh; Kakkar, Poonam

    2016-01-01

    . - Highlights: • Berberine inhibits sirtuins at transcriptional as well as at translational level. • Sirtuins inhibition leads to acetylation of non-histone proteins, FoxO1/3a and p53. • Acetylated FoxO and p53 transcriptionally upregulate BH3-only proteins Bim and PUMA respectively. • BH3-only proteins trigger mitochondrial dysfunction culminating into apoptosis. • SRT-1720 (SIRT-1 activator) partially restores Bax/Bcl-2 ratio and reduces berberine induced cytotoxicity in HepG2 cells.

  7. Sepsis and myocardial dysfunction

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    Rafaela Deczka Morsch

    2006-12-01

    Full Text Available Sepsis and septic shock are prevalent in the intensive care setting,accounting for more than 40% of mortality in this scenario. Theappropriate management and recognition of sepsis-inducedmyocardial dysfunction are paramount for its proper treatmentand probably impact mortality rates. The objective of this articleis to review its definition, pathophysiologic mechanisms, possibletreatments and current research on the subject according to acritical view.Cellular signaling involved in myocardial depression is not fullyunderstood. Disturbances in calcium homeostasis,cardiodepressant circulating factors, inflammatory mediators,nitric oxide and apoptosis act as synergistic pathways that leadto severely depressed cardiac function. The diagnosis ofmyocardial dysfunction during sepsis carries a worse prognosisand increased mortality.Myocardial dysfunction plays an important role in morbidity andmortality rate of critically ill patients. Current research in thisarea will continue to evolve; we will, therefore, soon have moreinsights into potential novel therapies that can change its mortalityrates.

  8. Caspases: An apoptosis mediator

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    Tapan Kumar Palai

    2015-03-01

    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  9. Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

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    C. Zheyu

    2007-10-01

    Full Text Available The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5-triphosphate (IP3 in colon dysmotility induced by multiple organ dysfunction syndrome (MODS caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11 vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05. After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05. Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

  10. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

    Science.gov (United States)

    Schäfer, C N; Guldager, H; Jørgensen, H L

    2011-01-01

    A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Executive Dysfunction

    Science.gov (United States)

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  12. Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

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    Jon Hazeldine

    2017-07-01

    Full Text Available Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS.The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18-90 years, 75 males with a mean injury severity score (ISS of 24 (range 9-66, from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17-60 minutes. Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005 and CD14+HLA-DRlow/- monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05 and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function.Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune

  13. Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.

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    Claudia P Cabrera

    2017-07-01

    Full Text Available Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS. MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS.We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25 at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4. We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4% were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21% were differentially expressed compared to the hyperacute window. Only 202 (16% genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK cells, with underexpression of T- and B cell

  14. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo.

    Science.gov (United States)

    Gill, Sean E; Rohan, Marta; Mehta, Sanjay

    2015-09-16

    Sepsis remains a common and serious condition with significant morbidity and mortality due to multiple organ dysfunction, especially acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Sepsis-induced ALI is characterized by injury and dysfunction of the pulmonary microvasculature and pulmonary microvascular endothelial cells (PMVEC), resulting in enhanced pulmonary microvascular sequestration and pulmonary infiltration of polymorphonuclear leukocytes (PMN) as well as disruption of the normal alveolo-capillary permeability barrier with leak of albumin-rich edema fluid into pulmonary interstitium and alveoli. The role of PMVEC death and specifically apoptosis in septic pulmonary microvascular dysfunction in vivo has not been established. In a murine cecal ligation/perforation (CLP) model of sepsis, we quantified and correlated time-dependent changes in pulmonary microvascular Evans blue (EB)-labeled albumin permeability with (1) PMVEC death (propidium iodide [PI]-staining) by both fluorescent intravital videomicroscopy (IVVM) and histology, and (2) PMVEC apoptosis using histologic fluorescent microscopic assessment of a panel of 3 markers: cell surface phosphatidylserine (detected by Annexin V binding), caspase activation (detected by FLIVO labeling), and DNA fragmentation (TUNEL labeling). Compared to sham mice, CLP-sepsis resulted in pulmonary microvascular barrier dysfunction, quantified by increased EB-albumin leak, and PMVEC death (PI+ staining) as early as 2 h and more marked by 4 h after CLP. Septic PMVEC also exhibited increased presence of all 3 markers of apoptosis (Annexin V+, FLIVO+, TUNEL+) as early as 30 mins--1 h after CLP-sepsis, which all similarly increased markedly until 4 h. The time-dependent changes in septic pulmonary microvascular albumin-permeability barrier dysfunction were highly correlated with PMVEC death (PI+; r = 0.976, p pulmonary microvascular dysfunction, including both albumin-permeability barrier dysfunction and

  15. Physician Education: Apoptosis.

    Science.gov (United States)

    Kataoka; Tsuruo

    1996-01-01

    apoptosis include those that cause DNA damage such as radiation and anticancer drugs, those that are mediated by the TNF receptor and Fas receptor (the so-called "death signal receptors"), and the deprivation of cytokines that supply survival signals such as IL-3 and erythropoietin. The tumor suppressor gene p53 plays a very important role in apoptosis induced by damage to DNA. This has been demonstrated by studying resistance to apoptosis of cells derived from p53 knockout mice [2]. Other than the irritations that induce apoptosis, molecules that have been strongly implicated as major players in the drama of apoptosis include the Bcl-2 family proteins and the IL-1 converting enzyme (ICE) and its homolog proteases (caspase family). Both groups of proteins show homology with proteins that affect cell death in nematodes. It is believed that molecules that contribute to cell death have been well conserved in multicellular organisms all the way from the relatively primitive nematodes to mammals including humans. It was discovered that Bcl-2 suppressed apoptosis induced in IL-3 dependent cells by deprivation of IL-3 [3]. It has since become the gene around which apoptosis research revolves. Recently, it has become clear that cell death involving the Bcl-2 protein is under the control of similar proteins from the same family [4]. It is interesting that the phenomenon of cell death may be regulated by the balance of the molecules involved in it. APOPTOSIS ABNORMALITIES AND DISEASE: Physiological cell death plays a major role in the growth and permanent maintenance of the human body [5]. In the process of forming the nervous system, neurons that do not form proper connections die. Physiological cell death also accompanies the removal of virus-infected cells by cytotoxic T cells, the elimination of autoreactive immune cells, the formation of the gut, the reconstitution of cartilage and bone, etc. When physiological cell death that normally should occur is inhibited, inappropriate

  16. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida

    2016-01-01

    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also...

  17. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial.

    Science.gov (United States)

    Futier, Emmanuel; Lefrant, Jean-Yves; Guinot, Pierre-Gregoire; Godet, Thomas; Lorne, Emmanuel; Cuvillon, Philippe; Bertran, Sebastien; Leone, Marc; Pastene, Bruno; Piriou, Vincent; Molliex, Serge; Albanese, Jacques; Julia, Jean-Michel; Tavernier, Benoit; Imhoff, Etienne; Bazin, Jean-Etienne; Constantin, Jean-Michel; Pereira, Bruno; Jaber, Samir

    2017-10-10

    Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient's resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy

  18. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

    Science.gov (United States)

    Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

    2010-01-01

    Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer

  19. Expression of organic anion transporting polypeptide 1c1 and monocarboxylate transporter 8 in the rat placental barrier and the compensatory response to thyroid dysfunction.

    Directory of Open Access Journals (Sweden)

    Yi-na Sun

    Full Text Available Thyroid hormones (THs must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1 and monocarboxylate transporter 8 (Mct8 on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM; this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy.

  20. Bowel Dysfunction

    Science.gov (United States)

    ... to PCF? Featured Fundraise for PCF: Many vs Cancer Contact Us Bowel Dysfunction The broad term of bowel dysfunction includes ... immodium) can be used to help with loose bowel movements. Increasing fiber intake through whole grains, ... mission 82% Join the fight against prostate ...

  1. HIV and thyroid dysfunction.

    Science.gov (United States)

    Parsa, Alan A; Bhangoo, Amrit

    2013-06-01

    Human Immunodeficiency virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are associated with dysfunction of many endocrine organs and their axis. HIV infectivity leads to altered metabolism, poor oral intake and increased prevalence of weight loss and wasting which may have a role in thyroid dysfunction. Overt thyroid dysfunction occurs at similar rates as the general population while subclinical disease such as nonthyroidal illness (sick euthyroid syndrome), subclinical hypothyroidism and isolated low T4 levels are more frequent. Moreover, HAART therapy can complicate thyroid function further through drug interactions and the immune reconstitution inflammatory syndrome (IRIS). In this review we report the common thyroid dysfunctions associated with HIV before and after HAART therapy. We discuss presentation, diagnostic work up, treatment and follow up in each condition.

  2. Lysosomal dysfunction in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Klaudia Tomala

    2017-05-01

    Full Text Available Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

  3. Vacuole-mitochondrial cross-talk during apoptosis in yeast: a model for understanding lysosome-mitochondria-mediated apoptosis in mammals.

    Science.gov (United States)

    Sousa, Maria João; Azevedo, Flávio; Azevedo, Flávìa; Pedras, Andreia; Pedras, Ana; Marques, Carolina; Coutinho, Olga P; Preto, Ana; Gerós, Hernâni; Chaves, Susana R; Côrte-Real, Manuela

    2011-10-01

    The yeast apoptosis field emerged with the finding that key components of the apoptotic machinery are conserved in these simple eukaryotes. Thus it became possible to exploit these genetically tractable organisms to improve our understanding of the intricate mechanisms of cell death in higher eukaryotes and of severe human diseases associated with apoptosis dysfunctions. Early on, it was recognized that a mitochondria-mediated apoptotic pathway showing similarities to the mammalian intrinsic pathway was conserved in yeast. Recently, lysosomes have also emerged as central players in mammalian apoptosis. Following LMP (lysosomal membrane permeabilization), lysosomal proteases such as cathepsins B, D and L are released into the cytosol and can trigger a mitochondrial apoptotic cascade. CatD (cathepsin D) can also have anti-apoptotic effects in some cellular types and specific contexts. Nonetheless, the mechanisms underlying LMP and the specific role of cathepsins after their release into the cytosol remain poorly understood. We have recently shown that yeast vacuoles, membrane-bound acidic organelles, which share many similarities to plant vacuoles and mammalian lysosomes, are also involved in the regulation of apoptosis and that the vacuolar protease Pep4p, orthologue of the human CatD, is released from the vacuole into the cytosol in response to acetic acid. Here, we discuss how the conservation of cell-death regulation mechanisms in yeast by the lysosome-like organelle and mitochondria may provide new insights into the understanding of the complex interplay between the mitochondria and lysosome-mediated signalling routes during mammalian apoptosis.

  4. Erectile Dysfunction

    Science.gov (United States)

    ... rigid. Medications The oral medications for erectile dysfunction, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), relax the muscles ... to begin working; the erection helping effects of sildenafil and vardenafil last for about 8 hours and ...

  5. Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage.

    Science.gov (United States)

    Premkumar, Daniel R; Jane, Esther P; Agostino, Naomi R; DiDomenico, Joseph D; Pollack, Ian F

    2013-02-01

    Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. Copyright © 2011 Wiley Periodicals, Inc.

  6. Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Wang, Biao; Chen, Gang; Zhang, Jun; Xue, Jiping; Cao, Yifei; Wu, Yunfu

    2015-09-01

    This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P septic shock.

  7. Organizational Dysfunctions: Sources and Areas

    Directory of Open Access Journals (Sweden)

    Jacek Pasieczny

    2016-12-01

    Full Text Available Objective:The purpose of this article is to identify and describe various types and sources of organizational dysfunctions. Research Design & Methods: The findings are based on literature review and an ongoing empirical research project conducted in private sector organisations. The empirical study can be situated within interpretative approach. In this qualitative project open interviews and observations were used to collect data. Findings: The study indicates that various types and sources of organizational dysfunctions can be identified in organizations operating in Poland. The sources of dysfunctions may be found both within the organization and its environment. Regardless of its specific features, most of the dysfunctions may be interpreted as an undesirable goal displacement. Very often areas of these dysfunctions are strongly interconnected and create a system that hinders organizational performance. Yet, it is difficult to study these phenomena as respondents are unwilling, for various reasons, to disclose the problems faced by their organizations. Implications & Recommendations: The results imply that the issue of organisational dysfunctions requires open, long-lasting and comparative studies. Recommendations for further studies are formulated in the last section of the paper. Contribution & Value Added: The paper provides insight into "the dark side of organising" by identifying sources and areas of dysfunctions. It also reveals difficulties connected with conducting research on dysfunctions in the Polish context.

  8. Systemic response of Korean dark-striped field mice, Apodenmus agrarius coreae after high-dose- rate γ-irradiation: Organ weights, hemato-chemistry, apoptosis of splenocytes and sperm

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kwang Hee; Choi, Hoon; Joo, Hyun Jin; Kim, Hee Sun [Radiation Health Research Institute, KHNP, Gyeongju (Korea, Republic of); Keum, Dong Kwon [Nuclear Environment Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-11-15

    Since the territory of the radio-contaminated area is in homeogenous in radiation level and spectrum, investigation of the genetical mutation process in the natural animal populations inhabiting the radioontaminated areas will be provide a realistic picture of genetic effects for radiation exposure. However, little is known about the basic data such as systemic responses after ionizing radiation exposures in wild small rodents. Taking into account different radio-sensitivity of dark-striped field mice (A. a. coreae, THOMAS), the objective of the study is focus on investigate the level of systemic responses, included organ weights, hemato-chemistry and apoptosis in splenocytes and sperm of caudal epididymis after high-dose-rate irradiation especially as a potential biological dosimeter in radio-ecology. Figure 1 summarizes the results of the apoptotic events in spleen (data not shown at here) and in sperm of caudal epididymis at 24hrs after a single high-dose-rate γ-irradiation. The results of apoptosis in spleen and sperm caused by exposure to different doses of γ-irradiation are displayed. The data show that the field striped mice after irradiated with more than high dose of 0.5 Gy induces an significantly increased apoptosis. Results also shown that for exposure to 0.5 Gy, the apoptosis of both organs ware decreased compared to those of other γ-irradiated mice.

  9. Modern aspects of Drosophila melanogaster radiobiology. Apoptosis and aging

    International Nuclear Information System (INIS)

    Zajnulin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Taskaev, A.I.

    1999-01-01

    An attempt is made to explain the radioinduced change in life span of multicell organisms by deregulation of apoptosis processes. Radiation capacity to induce the apoptosis is shown in Drosophila as well. Assumption is made that radiation changes the rate of natural organism aging deregulating the control of apoptosis mechanisms [ru

  10. Erectile Dysfunction

    Science.gov (United States)

    ... cut out alcohol. Excess alcohol can contribute to erectile dysfunction. If you choose to drink alcohol, do so in moderation. For healthy adults, that means up to one drink a day for men older than age 65, and up to two drinks ...

  11. Endothelial dysfunction

    OpenAIRE

    Yaylalı, Yalın Tolga; Küçükaslan, Mete

    2011-01-01

    Endothelium is a multi-functional cluster of cells within the vascular system consisting of a single layer ofsquamous epithelium. Physiologically, endothelium performs various arrangement and protection functions.However, when these functions are disturbed toward derangement, endothelium also mediates pathologicalfunctions with negative effects on the body. Endothelial dysfunction is mediated by several mediators (nitricoxide, endothelins, prostaglandins, angiotensin 2, etc). Endothelial dysf...

  12. Association of Dioxin and Other Persistent Organic Pollutants (POPs) with Diabetes: Epidemiological Evidence and New Mechanisms of Beta Cell Dysfunction

    Science.gov (United States)

    De Tata, Vincenzo

    2014-01-01

    The worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet. For this reason, it has been recently proposed that other “nontraditional” risk factors could contribute to the diabetes epidemics. In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis. In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed. PMID:24802877

  13. Mitochondrial disfunction and apoptosis in leukemia cells

    Directory of Open Access Journals (Sweden)

    Annamaria PALLAG

    2008-05-01

    Full Text Available Apoptosis or programmed cell death is a process which involves the intentional degradation of the cell from the inside, the participation of the mitochondria to propagate the apoptotic signal, the alteration of the phospholipid cell membrane composition, the perturbation and alteration of the cell metabolism.The antineoplastic drugs is inducing the apoptotic process in the sensitive cells.It have been studied acute lymphoblastic leukemia cells. Using Annexin V-PE Apoptosis Detection Kit and flow cytometer, the amount of cells undergoing apoptosis, in various stages of the antineoplasic treatment, was detected. At the same time, were monitored, the serum level of malondialdehyde. The results obtained confirm the alteration of the mitochondrial metabolism. We can observed the mitochondrial dysfunction role in cell apoptosis.

  14. Hormonal and organ-specific dysfunction induced by the interaction between titanium dioxide nanoparticles and salicylic acid in male mice.

    Science.gov (United States)

    El-Shenawy, Nahla S; Al-Harbi, Mohammad S; Al Hamayani, Fatimah F E

    2016-06-01

    Nanomaterials coating gained much concern in orthopedic implants and cosmetics. Drug combination may be a promising strategy for treating multi-factorial diseases. Titanium dioxide (TDN) nanoparticles are being widely used in many industries as well as in medicine and pharmacology. Therefore, increased human and environmental exposure can be expected, which has put TDN under toxicological scrutiny, and it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. The toxicity of titanium oxide nanoparticles (TDN) and salicylic acid (SA) separately or in combination was studied for 21 days. The liver and kidney biomarker were determined, and hormones and oxidative stress levels were detected in mice. The intraperitoneal (i.p.) injection of TDN and SA in combination had a potential toxicological effect on major organs and hormonal homeostasis of mice. TDN and SA could antagonistically interact to affect the liver and kidney functions. No synergistic damage was observed in the liver function of mice that were treated with both TDN and SA as compared to the SA group. TDN acted as a synergistic agent to SA in the case of total cholesterol and total proteins levels. SA acted as antagonistic to the effect of TDN when injected together in mice because the effect on kidney functions is less than that predicted on the basis of the additive. The effect of co-administration of SA and TDN on the following hormones; triiodothyronine, thyroxine, estradiol II and insulin various among additive, potentiation, antagonistic and no effect, respectively as compared to TDN group. The interaction of TDN and SA was also found to induce oxidative stress as indicated by the increase in lipid peroxidation (LPO) levels. The decrease in the level of the reduced glutathione in the co-treated group indicated that there were no synergistic damages. SA and TDN co-administration could induce a potential increase in LPO levels in liver, kidney, and

  15. Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Shafia, Sakineh; Vafaei, Abbas Ali; Samaei, Seyed Afshin; Bandegi, Ahmad Reza; Rafiei, Alireza; Valadan, Reza; Hosseini-Khah, Zahra; Mohammadkhani, Raziyeh; Rashidy-Pour, Ali

    2017-03-01

    Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests

  16. Host-pathogen interactions during apoptosis

    Indian Academy of Sciences (India)

    Unknown

    rity and tissue homeostasis in multicellular organisms. (Vaux and Strasser 1996). Apoptosis characteristically occurs in isolated single cells. Inappropriate apoptosis is linked to a number of parasitic infections as well as the cause and progression of diseases such as neurodegenera- tive disorders, aging and cancer.

  17. Symptoms of epilepsy and organic brain dysfunctions in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

    Directory of Open Access Journals (Sweden)

    Linaker Olav M

    2009-09-01

    Full Text Available Abstract Background In psychiatric acute departments some patients present with brief depressive periods accompanied with fluctuating arrays of other psychiatric symptoms like psychosis, panic or mania. For the purpose of the present study we call this condition Acute Unstable Depressive Syndrome (AUDS. The aims of the present study were to compare clinical signs of organic brain dysfunctions and epilepsy in patients with AUDS and Major Depressive Episode (MDE. Methods Out of 1038 consecutive patients admitted to a psychiatric acute ward, 16 patients with AUDS and 16 age- and gender-matched MDE patients were included in the study. Using standardized instruments and methods we recorded clinical data, EEG and MRI. Results A history of epileptic seizures and pathologic EEG activity was more common in the AUDS group than in the MDE group (seizures, n = 6 vs. 0, p = 0.018; pathologic EEG activity, n = 8 vs. 1, p = 0.015. Five patients in the AUDS group were diagnosed as having epilepsy, whereas none of those with MDE had epilepsy (p = 0.043. There were no differences between the groups regarding pathological findings in neurological bedside examination and cerebral MRI investigation. Conclusion Compared to patients admitted with mood symptoms fulfilling DSM 4 criteria of a major depressive disorder, short-lasting atypical depressive symptoms seem to be associated with a high frequency of epileptic and pathologic EEG activity in patients admitted to psychiatric acute departments. Trial registration NCT00201474

  18. 4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients.

    Science.gov (United States)

    Huq, Muhammad Aminul; Takeyama, Naoshi; Harada, Makoto; Miki, Yasuo; Takeuchi, Akinori; Inoue, Sousuke; Nakagawa, Takashi; Kanou, Hideki; Hirakawa, Akihiko; Noguchi, Hiroshi

    2012-01-01

    Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit (ICU). Plasminogen activator inhibitor (PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism (rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean ± SD PAI-1 antigen level was 193.31 ± 167.93 ng/ml for the 4G/4G genotype, 100.67 ± 114.16 ng/ml for the 4G/5G genotype and 0.43 ± 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively. These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death. Copyright © 2011 S. Karger AG, Basel.

  19. Apoptosis-Inducing Factor (AIF in Physiology and Disease: The Tale of a Repented Natural Born Killer

    Directory of Open Access Journals (Sweden)

    Daniele Bano

    2018-04-01

    Full Text Available Apoptosis-inducing factor (AIF is a mitochondrial oxidoreductase that contributes to cell death programmes and participates in the assembly of the respiratory chain. Importantly, AIF deficiency leads to severe mitochondrial dysfunction, causing muscle atrophy and neurodegeneration in model organisms as well as in humans. The purpose of this review is to describe functions of AIF and AIF-interacting proteins as regulators of cell death and mitochondrial bioenergetics. We describe how AIF deficiency induces pathogenic processes that alter metabolism and ultimately compromise cellular homeostasis. We report the currently known AIFM1 mutations identified in humans and discuss the variability of AIFM1-related disorders in terms of onset, organ involvement and symptoms. Finally, we summarize how the study of AIFM1-linked pathologies may help to further expand our understanding of rare inherited forms of mitochondrial diseases. Keywords: Apoptosis-inducing factor (AIF, Cell death, Mitochondria, Mitochondrial diseases, Oxidative phosphorylation (OXPHOS

  20. [Characteristics and treatment of multiple organ dysfunction syndrome in patients with trauma in the Wenchuan earthquake on 12th May, 2008].

    Science.gov (United States)

    Pu, Hong; Jin, Xiao-dong; Deng, Yi-yun; Kang, Yan; Xie, Xiao-qi; Liao, Xue-lian; Yang, Ling; Wang, Lan; Wang, Cun-zhen

    2009-01-01

    To analyze the characteristics and treatment of the multiple organ dysfunction syndrome (MODS) in patients in the Wenchuan earthquake on 12th May, 2008, in order to provide theoretical reference for future care for such patients. Characteristics of MODS in these patients were analyzed, differences between survivors and non-survivors were compared, and therapeutic measures, and the time of the treatment for MODS in patients with earthquake related injury or illness who were admitted to West China Hospital from 12th May to 20th June, 2008, were retrospectively analyzed. A total of 42 MODS patients were admitted to intensive care unit (ICU). Both the acute physiology and chronic health evaluation II (APACHE II) score and predicted death risk were lowering during the course of therapy. Fractures of bones of extremities were predominant in the earthquake related diseases, with an incidence of 45.2%. The actual mortality of MODS (33.3%) was lower than the predicted death risk (41.5%). The age, the time of receiving the first treatment in ICU after the earthquake, the Glasgow score, the oxygen index, blood creatinine level, platelet count, and vasoactive agent pumping velocity were significantly different between survivors and non-survivors (all Pearthquake. Fracture of bones of extremities are predominant injury in the earthquake related diseases, and the cause of death is closely associated with multiple trauma and ARF, systemic infection of large wound surfaces. The central nervous system, respiratory system, circulatory system, renal function, circulatory system should be monitored during the treatment. Adequate preparedness is essential in order to cope with the peak period of occurrence of serious complications after a disaster.

  1. Validation of the Antiproliferative Effects of Organic Extracts from the Green Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of Apoptosis-Related Genes

    Directory of Open Access Journals (Sweden)

    Ali A. Alshatwi

    2012-01-01

    Full Text Available With the increased use of plant-based cancer chemotherapy, exploring the antiproliferative effects of phytochemicals for anticancer drug design has gained considerable attention worldwide. This study was undertaken to investigate the effect of walnut green husk extracts on cell proliferation and to determine the possible molecular mechanism of extract-induced cell death by quantifying the expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells. In this study, we found that green husk extracts suppressed proliferation and induced apoptosis in a dose- and time-dependent manner by modulating expression of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL assay and significant changes in levels of mRNA and the expression of corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53 genes and their corresponding proteins was detected using real-time PCR and western blot analysis in PC-3 cells treated with the green husk organic extracts. In contrast, Bcl2 expression was downregulated after exposure to the extracts. Our data suggest the presence of bioactive compound(s in walnut green husks that are capable of killing prostate carcinoma cells by inducing apoptosis and that the husks are a candidate source of anticancer drugs.

  2. Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin.

    Science.gov (United States)

    Yang, Fan; Li, Yuan; Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

    2017-05-09

    Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways.

  3. Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

    Science.gov (United States)

    Lonnemann, G; Floege, J; Kliem, V; Brunkhorst, R; Koch, K M

    2000-08-01

    In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent

  4. Laryngeal Dysfunction

    DEFF Research Database (Denmark)

    Hull, James H; Backer, Vibeke; Gibson, Peter G

    2016-01-01

    The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex, and highly evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing, and phonation...

  5. Suspecting Neurological Dysfunction From E Mail Messages ...

    African Journals Online (AJOL)

    A non medical person suspected and confirmed neurological dysfunction in an individual, based only on e mail messages sent by the individual. With email communication becoming rampant “peculiar” email messages may raise the suspicion of neurological dysfunction. Organic pathology explaining the abnormal email ...

  6. Effects of naringin on apoptosis and oxidative stress in type 2 diabetic rats

    Science.gov (United States)

    Adelani, Isaacson; Bankole, Esther; Rotimi, Oluwakemi; Rotimi, Solomon

    2018-04-01

    Oxidative stress and apoptosis have been reported to play major roles in the pathogenesis of Type 2 Diabetes Mellitus (T2DM) through insulin resistance and β-cell dysfunction. Naringin is a citrus derived flavonoid that has been reported for its antioxidant properties. Even though effects of naringin in T2DM related oxidative stress has been reported, varying dose concentration in oxidative stress and mechanism of action involving T2DM related apoptosis is far-fetched. This research studied the effects of naringin at varying dose concentration on apoptosis, biomarkers of organ function and oxidative stress in high fat diet/low-streptozotocin-induced T2DM in albino Wistar rats. Diabetic rats were treated with naringin at 50mg/kg, 100mg/kg and 200mg/kg body weight for 21 days. Some biomarkers of organ function and oxidative stress in the animals were assayed using spectrophotometric techniques. The levels of expression of caspases and apoptotic regulators were quantified using semi-quantitative reverse transcriptase polymerase chain reaction (RT PCR). Enzyme - linked immunosorbent assay was used to determine inducible nitric oxide synthase (iNOS) level. Naringin treatment shows a dose dependent significant (ptreatment also showed a significant (pdiabetic control. In addition, there was dose dependent decrease in plasma CO2 concentration and increase in the plasma iNOS concentration as compared to the diabetic control. This result highlights positive effect of naringin as an antioxidant, its role in apoptosis and also reverting the effects of organ damage in type 2 diabetes.

  7. Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Ryuji Sakakibara

    2011-01-01

    Full Text Available Bladder dysfunction (urinary urgency/frequency, bowel dysfunction (constipation, and sexual dysfunction (erectile dysfunction (also called “pelvic organ” dysfunctions are common nonmotor disorders in Parkinson's disease (PD. In contrast to motor disorders, pelvic organ 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, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus are responsible for the bowel dysfunction. In addition, 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 pelvic organ 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. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

  8. Female Sexual Dysfunction

    Science.gov (United States)

    ... medically as female sexual dysfunction. Many women experience problems with sexual function at some point. Female sexual dysfunction can occur at any stage of life. It can be lifelong or be acquired later in life. It can ...

  9. Apoptosis and Its Significance in Oral Diseases: An Update

    Directory of Open Access Journals (Sweden)

    Megha Jain

    2013-01-01

    Full Text Available Apoptosis is a well defined mode of cell death which plays an imperative role in the development, regulation, and maintenance of the cell populations in multicellular organisms. Apoptosis is implicated in both health and diseases. Errors in apoptotic mechanisms have been allied to a wide range of pathologies including oral diseases. This review presents an update focused on the role and significance of apoptosis in various oral diseases ranging from reactive to benign and malignant pathologies.

  10. Apoptosis of neutrophils

    NARCIS (Netherlands)

    Maianski, N. A.; Maianski, A. N.; Kuijpers, T. W.; Roos, D.

    2004-01-01

    Regulation of the neutrophil life span by apoptosis provides a fine balance between their function as effector cells of host defense and a safe turnover of these potentially harmful cells. Alterations of neutrophil apoptosis are associated with a number of diseases. As do other cell types,

  11. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.

    2014-01-01

    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  12. Hyperthermia-induced apoptosis

    NARCIS (Netherlands)

    Nijhuis, E.H.A.

    2008-01-01

    This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this

  13. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  14. Postanesthetic temporomandibular joint dysfunction.

    OpenAIRE

    Knibbe, M. A.; Carter, J. B.; Frokjer, G. M.

    1989-01-01

    Internal derangements, myofascial pain dysfunction, and chronic dislocation of the temporomandibular joint (TMJ) are three common sequelae resulting from mandibular trauma. Etiologic factors include prolonged dental and otolaryngologic procedures, and intraoperative use of the laryngoscope and bronchoscope. Three cases are reported to document postanesthetic TMJ dysfunction arising from normal preoperative joints. Four types of TMJ dysfunction are discussed: anterior meniscus dislocation with...

  15. Methane rescues retinal ganglion cells and limits retinal mitochondrial dysfunction following optic nerve crush.

    Science.gov (United States)

    Wang, Ruobing; Sun, Qinglei; Xia, Fangzhou; Chen, Zeli; Wu, Jiangchun; Zhang, Yuelu; Xu, Jiajun; Liu, Lin

    2017-06-01

    Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC. The retinal ganglion cells (RGCs) density was assessed by hematoxylin and eosin staining and Fluoro-Gold retrogradely labeling. Visual function was evaluated by flash visual evoked potentials (FVEP). The retinal apoptosis was measured by terminal-deoxy-transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of apoptosis-related factors, such as phosphorylated Bcl-2-associated death promoter (pBAD), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Bcl-2 associated X protein (Bax) and Bcl-2 extra large (Bcl-xL). Retinal mitochondrial function was assessed by the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), the mitochondrial DNA (mtDNA) copy number, citrate synthase activity and ATP content. Methane treatment significantly improved the RGC loss and visual dysfunction following ONC. As expected, methane also remarkably inhibited the retinal neural apoptosis, such as the fewer TUNEL-positive cells in ganglion cell layer, accompanied by the up-regulations of anti-apoptotic factors (pGSK-3β, pBAD, Bcl-xL) and the down-regulation of pro-apoptotic factor (Bax). Furthermore, methane treatment suppressed up-regulations of critical mitochondrial components (PGC-1α, NRF1 and TFAM) mRNA and mtDNA copy number, as well as improved the reduction of functional mitochondria markers, including citrate synthase

  16. Gene Expression Profiling of Apoptosis Regulators in Patients with Sepsis

    NARCIS (Netherlands)

    Hoogerwerf, Jacobien J.; van Zoelen, Marieke A.; Wiersinga, W. Joost; van 't Veer, Cornelis; de Vos, Alex F.; de Boer, Anita; Schultz, Marcus J.; Hooibrink, Berend; de Jonge, Evert; van der Poll, Tom

    2010-01-01

    Introduction: Sepsis is associated with a dysregulation of apoptosis in immune cells, which has been implicated in both immunosuppression and multiple organ failure. We describe the expression profiles of genes encoding key regulators of apoptosis in highly purified monocytes, granulocytes and CD4+

  17. Research Advances on Pathways of Nickel-Induced Apoptosis

    Science.gov (United States)

    Guo, Hongrui; Chen, Lian; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan

    2015-01-01

    High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity. PMID:26703593

  18. Roles of Apoptosis and Cellular Senescence in Cancer and Aging.

    Science.gov (United States)

    Cerella, Claudia; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc

    2016-01-01

    Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.

  19. Apoptosis in Pneumovirus Infection

    Directory of Open Access Journals (Sweden)

    Reinout A. Bem

    2013-01-01

    Full Text Available Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs.

  20. Reaper-Induced Apoptosis

    National Research Council Canada - National Science Library

    Perry, Jennifer

    2005-01-01

    Reaper is a central regulator of apoptosis in the fly, Drosophila melanogaster. At the start of this proposal our laboratory identified what was believed to be a pro-apoptotic human homolog of Reaper...

  1. Viruses and apoptosis.

    Science.gov (United States)

    Roulston, A; Marcellus, R C; Branton, P E

    1999-01-01

    Successful viral replication requires not only the efficient production and spread of progeny, but also evasion of host defense mechanisms that limit replication by killing infected cells. In addition to inducing immune and inflammatory responses, infection by most viruses triggers apoptosis or programmed cell death of the infected cell. This cell response often results as a compulsory or unavoidable by-product of the action of critical viral replicative functions. In addition, some viruses seem to use apoptosis as a mechanism of cell killing and virus spread. In both cases, successful replication relies on the ability of certain viral products to block or delay apoptosis until sufficient progeny have been produced. Such proteins target a variety of strategic points in the apoptotic pathway. In this review we summarize the great amount of recent information on viruses and apoptosis and offer insights into how this knowledge may be used for future research and novel therapies.

  2. Markers of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Kelvin P Davies

    2008-01-01

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

  3. Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

    Science.gov (United States)

    Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

    2017-10-01

    Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Apoptosis – is it good or bad?

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2012-08-01

    Full Text Available The most widely used classification of mammalian cell death recognizes two types: apoptosis and necrosis. Autophagy, which has been proposed as a third mode of cell death allows a starving cell, or in situations when cell is deprived of growth factors, to survive. Apoptosis, autophagy and necrosis, a particular mode of cell death may predominate, depending of the injury and the type of cell. [1] One very important characteristic of all multicellular organisms is apoptosis, the controlled death of cells. In necrosis, early loss of integrity of the plasma membrane resultant with swelling of the cell and its organelles. A key morphologic feature of apoptosis is collapses of cell and its subcellular components.[2] The distinction between apoptosis and necrosis is due in part to differences in how the plasma membrane participates in these processes. In apoptosis, plasma membrane integrity persists until late in the process. In necrosis, early loss of integrity of the plasma membrane allows an influx of extracellular ions and fluid, with resultant swelling of the cell and its organelles. During that time, on the inside of cell there occurs the cleavage of cytoskeletal proteins by aspartate specific proteases, which thereby collapses subcellular components. Other characteristic features are chromatin condensation, nuclear fragmentation and the formation of plasma membrane blebs. The type and intensity of noxious signals, ATP concentration, cell type, and other factors determine how cell death occurs. Acute myocardial ischemia induces necrosis (because the ischemia precipitates rapid and profound decreases of ATP, whereas chronic congestive heart failure induces apoptosis (with more modest and chronic decreases of ATP. The blockade of a particular pathway of cell death may not prevent the destruction of the cell but may instead recruit an alternative path: antiapoptotic caspase inhibitors cause hyperacute necrosis of hepatocytes and kidney tubular cells

  5. Autophagy and apoptosis in planarians.

    Science.gov (United States)

    González-Estévez, Cristina; Saló, Emili

    2010-03-01

    Adult planarians are capable of undergoing regeneration and body remodelling in order to adapt to physical damage or extreme environmental conditions. Moreover, most planarians can tolerate long periods of starvation and during this time, they shrink from an adult size to, and sometimes beyond, the initial size at hatching. Indeed, these properties have made them a classic model to study stem cells and regeneration. Under such stressful conditions, food reserves from the gastrodermis and parenchyma are first used up and later the testes, copulatory organs and ovaries are digested. More surprisingly, when food is again made available to shrunken individuals, they grow back to adult size and all their reproductive structures reappear. These cycles of growth and shrinkage may occur over long periods without any apparent impairment to the individual, or to its future maturation and breeding capacities. This plasticity resides in a mesoderm tissue known as the parenchyma, which is formed by several differentiated non-proliferating cell types and only one mitotically active cell type, the neoblasts, which represent approximately 20-30% of the cells in the parenchyma. Neoblasts are generally thought to be somatic stem-cells that participate in the normal continuous turnover of all cell types in planarians. Hence, planarians are organisms that continuously adapt their bodies (morphallaxis) to different environmental stresses (i.e.: injury or starvation). This adaptation involves a variety of processes including proliferation, differentiation, apoptosis and autophagy, all of which are perfectly orchestrated and tightly regulated to remodel or restore the body pattern. While neoblast biology and body re-patterning are currently the subject of intense research, apoptosis and autophagy remain much less studied. In this review we will summarize our current understanding and hypotheses regarding where and when apoptosis and autophagy occur and fulfil an essential role in

  6. Postanesthetic temporomandibular joint dysfunction.

    Science.gov (United States)

    Knibbe, M. A.; Carter, J. B.; Frokjer, G. M.

    1989-01-01

    Internal derangements, myofascial pain dysfunction, and chronic dislocation of the temporomandibular joint (TMJ) are three common sequelae resulting from mandibular trauma. Etiologic factors include prolonged dental and otolaryngologic procedures, and intraoperative use of the laryngoscope and bronchoscope. Three cases are reported to document postanesthetic TMJ dysfunction arising from normal preoperative joints. Four types of TMJ dysfunction are discussed: anterior meniscus dislocation with reduction, anterior meniscus dislocation without reduction, dislocation/subluxation of the mandibular condyle, and myofascial pain dysfunction syndrome. Preoperative screening of mandibular function is recommended in identifying patients as either normal or having potential TMJ dysfunction. Failure to recognize postoperative TMJ dysfunction can lead to long-term symptoms that are difficult to alleviate. Litigation is a common sequel in these cases. Images Figure 3 PMID:2604053

  7. Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells.

    Science.gov (United States)

    Wang, Tao; He, Qian; Xiao, Liang; Wang, Qianqian; Zhang, Bo; Wang, Beilei; Liu, Guoyan; Zheng, Jiemin; Yu, Bentong; Zhang, Liming

    2013-11-01

    Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E cells. The results showed that TE caused cell morphological change and decreased cell viability through induction of apoptosis and necrosis in NRK-52E cells. Meanwhile, ROS overproduction and mitochondrial membrane potential decrease were found before the cell death occurred. It was concluded that TE could induce cytotoxicity, especially apoptosis and necrosis, in NRK-52E cells, and mitochondrial dysfunction and ROS overproduction might play important roles in the process of cell injury and death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Burden of Sexual Dysfunction.

    Science.gov (United States)

    Balon, Richard

    2017-01-02

    Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

  9. Hepatitis C Virus-Induced Mitochondrial Dysfunctions

    Directory of Open Access Journals (Sweden)

    Birke Bartosch

    2013-03-01

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

  10. Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis.

    Science.gov (United States)

    Wang, Gui-Jun; Wang, Yue; Teng, Yong-Sheng; Sun, Fa-Lv; Xiang, Hong; Liu, Jian-Jun; Xia, Shi-Lin; Zhang, Gui-Xin; Chen, Hai-Long; Shang, Dong

    2016-01-01

    Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca 2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca 2+ -calpain 1-caspase 12-caspase 3 signaling pathway.

  11. Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury

    NARCIS (Netherlands)

    Brander, Lukas; Sinderby, Christer; Lecomte, François; Leong-Poi, Howard; Bell, David; Beck, Jennifer; Tsoporis, James N.; Vaschetto, Rosanna; Schultz, Marcus J.; Parker, Thomas G.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

    2009-01-01

    OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory

  12. Apoptosis signaling and radiation protection

    International Nuclear Information System (INIS)

    Morita, Akinori; Suzuki, Norio; Hosoi, Yoshio

    2005-01-01

    Radiation protection by apoptosis control is the suppression of cell death in highly radiosensitive tissues. This paper describes the outline of radiation-induced apoptosis framework, apoptosis-concerned target molecules possibly related to apoptosis by radiation and their inhibitors. Although there are intrinsic (via mitochondria) and extrinsic (via death receptor) pathways in apoptosis, this review mainly mentions the former which is more important in radiation-induced apoptosis. Those molecules known at present in the apoptosis are caspase, Bcl-2 family and p53. Caspase, a group of cystein proteases, initiates apoptosis but its inhibition is known not always to result in apoptosis suppression, suggesting the existence of caspase-independent pathways. Bcl-2 family involves apoptosis-suppressing (possessing BH domains) and -promoting (lacking BH domains or possessing BH3 domain alone/BH3-only protein) groups. Two p53-transcription-dependent and one -independent pathways in p53-induced apoptosis are known and p53 can be a most possible target molecule since it positions at the start of apoptosis. Authors have found a vanadate inactivates p53. Inhibitors affecting upstream molecules of apoptosis will be the most useful candidate for apoptosis suppression/radiation protection. (S.I.) 106 refs

  13. Death penalty for keratinocytes: apoptosis versus cornification.

    Science.gov (United States)

    Lippens, S; Denecker, G; Ovaere, P; Vandenabeele, P; Declercq, W

    2005-11-01

    Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

  14. Erectile Dysfunction (ED)

    Science.gov (United States)

    ... men older than 75 years of age. Is erectile dysfunction just a part of old age? ED doesn’t have to be a part of getting older. It’s true that as you get older, you may need more ... Symptoms of erectile dysfunction The primary symptom of ED is not ...

  15. Loneliness and Sexual Dysfunctions.

    Science.gov (United States)

    Mijuskovic, Ben

    1987-01-01

    Argues that sexual dysfunctions result from early childhood experiences which were originally nonsexual in nature. Contends that psychological difficulties centered around problems of loneliness tend to generate certain sexual dysfunctions. Extends and explores suggestion that genesis of sexual conflicts is in nonsexual infant separation anxiety…

  16. Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells

    Directory of Open Access Journals (Sweden)

    Keisuke Sato

    2015-01-01

    Full Text Available Schwann cell injury is caused by diabetic neuropathy. The apoptosis of Schwann cells plays a pivotal role in diabetic nerve dysfunction. Glycolaldehyde is a precursor of advanced glycation end products that contribute to the pathogenesis of diabetic neuropathy. In this study, we examined whether glycolaldehyde induces endoplasmic reticulum (ER stress and apoptosis in rat Schwann cells. Schwann cells treated with 500 μM glycolaldehyde showed morphological changes characteristic of apoptosis. Glycolaldehyde activated apoptotic signals, such as caspase-3 and caspase-8. Furthermore, it induced ER stress response involving RNA-dependent protein kinase-like ER kinase (PERK, inositol-requiring ER-to-nucleus signal kinase 1α (IRE1α, and eukaryotic initiation factor 2α (eIF2α. In addition, glycolaldehyde activated CCAAT/enhancer-binding homologous protein (CHOP, an ER stress response factor crucial to executing apoptosis. Knockdown of nuclear factor E2-related factor 2 (Nrf2, which is involved in the promotion of cell survival following ER stress, enhanced glycolaldehyde-induced cytotoxicity, indicating that Nrf2 plays a protective role in the cytotoxicity caused by glycolaldehyde. Taken together, these findings indicate that glycolaldehyde is capable of inducing apoptosis and ER stress in Schwann cells. The ER stress induced by glycolaldehyde may trigger the glycolaldehyde-induced apoptosis in Schwann cells. This study demonstrated for the first time that glycolaldehyde induced ER stress.

  17. Primary graft dysfunction.

    Science.gov (United States)

    Suzuki, Yoshikazu; Cantu, Edward; Christie, Jason D

    2013-06-01

    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 a 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 that may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review details recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers, and state-of-the-art technical developments affecting PGD. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Organic Nitrates and Nitrate Resistance in Diabetes: The Role of Vascular Dysfunction and Oxidative Stress with Emphasis on Antioxidant Properties of Pentaerithrityl Tetranitrate

    Directory of Open Access Journals (Sweden)

    Matthias Oelze

    2010-01-01

    Full Text Available Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.

  19. Spaceflight Associated Apoptosis

    Science.gov (United States)

    Ichiki, Albert T.; Gibson, Linda A.; Allebban, Zuhair

    1996-01-01

    Lymphoid tissues have been shown to atrophy in rats flown on Russian spaceflights. Histological examination indicated evidence for cell degradation. Lymphoid tissues from rats flown on Spacelab Life Sciences-2 mission were analyzed for apoptosis by evidence of fragmented lymphocytes, which could be engulfed by macrophages, or DNA strand breaks using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Apoptosis was not detected in the thymus and spleen collected inflight or from the synchronous ground rats but was detected in the thymus, spleen and inguinal lymph node of the flight animals on recovery. These results indicate that the apoptosis observed in the lymphatic tissues of the rats on recovery could have been induced by the gravitational stress of reentry, corroborating the findings from the early space-flight observations.

  20. [Urological dysfunction after sexual abuse and violence].

    Science.gov (United States)

    Berberich, H J; Neubauer, H

    2004-03-01

    Criminal statistics say that 300,000 children are sexually abused in the Federal Republic of Germany every year: 70-75% are abused by their own fathers or another psychological parent. Most victims are girls aged 7-12 years. Sexual abuse during childhood can lead to severe psychosomatic dysfunctions both in children and adults. Possible long-term results are depression, anxiety, emotional and cognitive problems, personal dysfunction, eating and sleeping disorders, alcohol or drug abuse, relationship problems, social maladaptation, and somatizations. Many urological dysfunctions without organic findings can be caused by sexual abuse. Among others, chronic pelvic pain (CPPS), enuresis, incontinence, and sexual dysfunction can occur. When children or adults see the urologist because of their symptoms there is always the danger of reproducing the abusive event by invasive diagnostic methods.Sometimes harming themselves the patients bring this situation about unconsciously. With the following article we want to heighten the awareness among urologists.

  1. Genetics Home Reference: surfactant dysfunction

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Surfactant dysfunction Surfactant dysfunction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Surfactant dysfunction is a lung disorder that causes breathing ...

  2. Diastolic dysfunction characterizes cirrhotic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Piyush O. Somani

    2014-11-01

    Conclusions: Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS.

  3. Cadmium toxicity induces ER stress and apoptosis via impairing energy homoeostasis in cardiomyocytes

    Science.gov (United States)

    Chen, Chun-yan; Zhang, Shao-li; Liu, Zhi-yong; Tian, Yong; Sun, Qian

    2015-01-01

    Cadmium, a highly toxic environmental pollutant, is reported to induce toxicity and apoptosis in multiple organs and cells, all possibly contributing to apoptosis in certain pathophysiologic situations. Previous studies have described that cadmium toxicity induces biochemical and physiological changes in the heart and finally leads to cardiac dysfunctions, such as decreasing contractile tension, rate of tension development, heart rate, coronary flow rate and atrioventricular node conductivity. Although many progresses have been made, the mechanism responsible for cadmium-induced cellular alternations and cardiac toxicity is still not fully understood. In the present study, we demonstrated that cadmium toxicity induced dramatic endoplasmic reticulum (ER) stress and impaired energy homoeostasis in cultured cardiomyocytes. Moreover, cadmium toxicity may inhibit protein kinase B (AKT)/mTOR (mammalian target of rapamycin) pathway to reduce energy productions, by either disrupting the glucose metabolism or inhibiting mitochondrial respiratory gene expressions. Our work will help to reveal a novel mechanism to clarify the role of cadmium toxicity to cardiomyocytes and provide new possibilities for the treatment of cardiovascular diseases related to cadmium toxicity. PMID:26182376

  4. Vocal cord dysfunction.

    Science.gov (United States)

    Deckert, James; Deckert, Linda

    2010-01-15

    Vocal cord dysfunction involves inappropriate vocal cord motion that produces partial airway obstruction. Patients may present with respiratory distress that is often mistakenly diagnosed as asthma. Exercise, psychological conditions, airborne irritants, rhinosinusitis, gastroesophageal reflux disease, or use of certain medications may trigger vocal cord dysfunction. The differential diagnosis includes asthma, angioedema, vocal cord tumors, and vocal cord paralysis. Pulmonary function testing with a flow-volume loop and flexible laryngoscopy are valuable diagnostic tests for confirming vocal cord dysfunction. Treatment of acute episodes includes reassurance, breathing instruction, and use of a helium and oxygen mixture (heliox). Long-term management strategies include treatment for symptom triggers and speech therapy.

  5. Mitochondria in neutrophil apoptosis

    NARCIS (Netherlands)

    van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

    2006-01-01

    Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

  6. Apoptosis and inflammation

    Directory of Open Access Journals (Sweden)

    C. Haanen

    1995-01-01

    Full Text Available During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972 introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

  7. Apoptosis and Necrosis in the Liver

    Science.gov (United States)

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  8. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

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

  9. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Sexual Dysfunction in Urogynaecology

    NARCIS (Netherlands)

    A.M.E. Roos (Anne-Marie)

    2014-01-01

    markdownabstract__abstract__ This thesis is dedicated to enhance understanding of sexual dysfunction in the field of urogynaecology, focussing on the prevalence of sexual problems in urogynaecology clinics, the clinical attention of the urogynaecologist to female sexual dyfunction, the impact

  11. Sequential Oxygenation Index and Organ Dysfunction Assessment within the First 3 Days of Mechanical Ventilation Predict the Outcome of Adult Patients with Severe Acute Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Hsu-Ching Kao

    2013-01-01

    Full Text Available Objective. To determine early predictors of outcomes of adult patients with severe acute respiratory failure. Method. 100 consecutive adult patients with severe acute respiratory failure were evaluated in this retrospective study. Data including comorbidities, Sequential Organ Failure Assessment (SOFA score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II score, PaO2, FiO2, PaO2/FiO2, PEEP, mean airway pressure (mPaw, and oxygenation index (OI on the 1st and the 3rd day of mechanical ventilation, and change in OI within 3 days were recorded. Primary outcome was hospital mortality; secondary outcome measure was ventilator weaning failure. Results. 38 out of 100 (38% patients died within the study period. 48 patients (48% failed to wean from ventilator. Multivariate analysis showed day 3 OI ( and SOFA ( score were independent predictors of hospital mortality. Preexisting cerebrovascular accident (CVA ( was the predictor of weaning failure. Results from Kaplan-Meier method demonstrated that higher day 3 OI was associated with shorter survival time (log-Rank test, . Conclusion. Early OI (within 3 days and SOFA score were predictors of mortality in severe acute respiratory failure. In the future, prospective studies measuring serial OIs in a larger scale of study cohort is required to further consolidate our findings.

  12. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  13. Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction?

    DEFF Research Database (Denmark)

    Olsen, Anne B.; Persiani, Marie; Boie, Sidsel

    2015-01-01

    OBJECTIVE: The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. MATERIALS AND METHODS: This prospective, randomized, blinded, placebo-controlled study included 112 ...... are needed. KEYWORDS: Erectile dysfunction; extracorporeal shockwave; penis...

  14. The effects of adjuvant immunoglobulin M-enriched immunoglobulin therapy on mortality rate and renal function in sepsis-induced multiple organ dysfunction syndrome: retrospective analysis of intensive care unit patients.

    Science.gov (United States)

    Yavuz, L; Aynali, G; Aynali, A; Alaca, A; Kutuk, S; Ceylan, B G

    2012-01-01

    To determine the effect of immunoglobulin (Ig)M-enriched Ig therapy on mortality rate and renal function in sepsis-induced multiple organ dysfunction syndrome (MODS), using the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Retrospective study of patients with sepsis-induced MODS treated with standard antibiotic plus supportive therapy (control group) or IgM-enriched Ig therapy adjuvant to control group therapy (IVIg group). Total length of stay in the intensive care unit (ICU), overall mortality rate and 28-day case fatality rate (CFR), as well as APACHE II scores and renal function parameters at day 1 and day 4 of therapy, were recorded. A total of 118 patients were included (control group, n = 62; IVIg group, n = 56). In both groups, day 4 APACHE II scores decreased significantly compared with day 1 scores; the effect of treatment on renal function was minimal. Length of ICU stay, overall mortality rate and 28-day CFR were significantly lower in the IVIg group compared with the control group. Adding IgM-enriched Ig therapy to standard therapy for MODS improved general clinical conditions and significantly reduced APACHE II scores, overall mortality rate and 28-day CFR, although effects on renal function were minimal.

  15. Organics.

    Science.gov (United States)

    Chian, Edward S. K.; DeWalle, Foppe B.

    1978-01-01

    Presents water analysis literature for 1978. This review is concerned with organics, and it covers: (1) detergents and surfactants; (2) aliphatic and aromatic hydrocarbons; (3) pesticides and chlorinated hydrocarbons; and (4) naturally occurring organics. A list of 208 references is also presented. (HM)

  16. Organizers.

    Science.gov (United States)

    Callison, Daniel

    2000-01-01

    Focuses on "organizers," tools or techniques that provide identification and classification along with possible relationships or connections among ideas, concepts, and issues. Discusses David Ausubel's research and ideas concerning advance organizers; the implications of Ausubel's theory to curriculum and teaching; "webbing," a…

  17. Sexual dysfunction during primiparous and multiparous women ...

    African Journals Online (AJOL)

    Normal sexual functioning comprises of sexual activity together with transition through the phases from arousal to relaxation with no problem. Delivery has different effects on body organs, especially, on genitalia the disorder of which can cause sexual dysfunctions. In this study, an attempt is made to compare postpartum ...

  18. Síndrome pulmonar por hantavírus com disfunção de múltiplos órgãos: relato de caso Hantavirus pulmonary syndrome with multiple organ dysfunctions: case report

    Directory of Open Access Journals (Sweden)

    Marcelo Spegiorin Moreno

    2007-12-01

    rates. The aim of this study is to report a case of HPS with multiple organ failure, managed with early goal-directed therapy guided by flow and tissue perfusion parameters. CASE REPORT: A 36 year-old male had fever with progressive dispnea, severe hypoxia and acute respiratory failure. Diffuse interstitial alveolar infiltrates were seen in the chest X-Ray. He developed multiple organ dysfunction syndromes (pulmonary, renal, coagulation, cardiovascular and metabolic. Treatment and invasive hemodynamic monitoring with pulmonary artery catheter was early instituted. The most important laboratory findings were thrombocytopenia, elevated hematocrit and hemoglobin concentrations, elevated liver enzymes, elevated lactate dehydrogenase and a positive sorology for Hantavirus (ELISA IgM positive. Organ dysfunctions reverted to normal and he was discharged after 21 days in hospital. CONCLUSIONS: An early and adequate resuscitation with goal-directed therapy enabled the reversion of the multiple organ failure syndromes and a favorable outcome, despite the severity of the disease.

  19. Fullerene and apoptosis

    Directory of Open Access Journals (Sweden)

    M. A. Orlova

    2013-01-01

    Full Text Available Fullerene derivatives superfamily attracts a serious attention as antiviral and anticancer agents and drug delivery carriers as well. A large number of such fullerene С60 derivatives obtained to date. However, there is an obvious deficit of information about causes and mechanisms of immediately and long-term consequences of their effects in vivo which is a true obstacle on the way leading to practical medical use of them. First, this concerns their impact on the proliferation, apoptosis and necrosis regulation. Fullerene nanoparticle functionalization type, their sizes and surface nanopathology are of great importance to further promoting of either cytoprotective or cytotoxic effects. This lecture provides modern concept analysis regarding fullerenes effects on apoptosis pathway in normal and tumor cells.

  20. Organizations

    DEFF Research Database (Denmark)

    Hatch, Mary Jo

    Most of us recognize that organizations are everywhere. You meet them on every street corner in the form of families and shops, study in them, work for them, buy from them, pay taxes to them. But have you given much thought to where they came from, what they are today, and what they might become...... and considers many more. Mary Jo Hatch introduces the concept of organizations by presenting definitions and ideas drawn from the a variety of subject areas including the physical sciences, economics, sociology, psychology, anthropology, literature, and the visual and performing arts. Drawing on examples from...... prehistory and everyday life, from the animal kingdom as well as from business, government, and other formal organizations, Hatch provides a lively and thought provoking introduction to the process of organization....

  1. Organizations

    DEFF Research Database (Denmark)

    Hatch, Mary Jo

    and considers many more. Mary Jo Hatch introduces the concept of organizations by presenting definitions and ideas drawn from the a variety of subject areas including the physical sciences, economics, sociology, psychology, anthropology, literature, and the visual and performing arts. Drawing on examples from......Most of us recognize that organizations are everywhere. You meet them on every street corner in the form of families and shops, study in them, work for them, buy from them, pay taxes to them. But have you given much thought to where they came from, what they are today, and what they might become...... prehistory and everyday life, from the animal kingdom as well as from business, government, and other formal organizations, Hatch provides a lively and thought provoking introduction to the process of organization....

  2. Voiding dysfunction - A review

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2005-01-01

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

  3. Endothelial dysfunction: a comprehensive appraisal

    Directory of Open Access Journals (Sweden)

    Vilariño Jorge O

    2006-02-01

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

  4. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat)

    Science.gov (United States)

    Lewis, M. L.; Reynolds, J. L.; Cubano, L. A.; Hatton, J. P.; Lawless, B. D.; Piepmeier, E. H.

    1998-01-01

    Alteration in cytoskeletal organization appears to underlie mechanisms of gravity sensitivity in space-flown cells. Human T lymphoblastoid cells (Jurkat) were flown on the Space Shuttle to test the hypothesis that growth responsiveness is associated with microtubule anomalies and mediated by apoptosis. Cell growth was stimulated in microgravity by increasing serum concentration. After 4 and 48 h, cells filtered from medium were fixed with formalin. Post-flight, confocal microscopy revealed diffuse, shortened microtubules extending from poorly defined microtubule organizing centers (MTOCs). In comparable ground controls, discrete microtubule filaments radiated from organized MTOCs and branched toward the cell membrane. At 4 h, 30% of flown, compared to 17% of ground, cells showed DNA condensation characteristic of apoptosis. Time-dependent increase of the apoptosis-associated Fas/ APO-1 protein in static flown, but not the in-flight 1 g centrifuged or ground controls, confirmed microgravity-associated apoptosis. By 48 h, ground cultures had increased by 40%. Flown populations did not increase, though some cells were cycling and actively metabolizing glucose. We conclude that cytoskeletal alteration, growth retardation, and metabolic changes in space-flown lymphocytes are concomitant with increased apoptosis and time-dependent elevation of Fas/APO-1 protein. We suggest that reduced growth response in lymphocytes during spaceflight is linked to apoptosis.

  5. The significance of intestinal apoptosis

    International Nuclear Information System (INIS)

    Potten, C.S.

    1997-01-01

    Apoptosis occurs at a low level spontaneously in the small intestine (SI). The levels can be raised by a variety of cytotoxic agents including radiation. The apoptosis induced by radiation, and some drugs and the spontaneous apoptosis, show some specificity for the stem cells in the small intestinal crypt. In the colon, these agents target transit cells in the mid crypt. p53 expression is elevated at the same time as apoptosis in the SI but not in the cells undergoing apoptosis. The expression of bcl-2, a survival gene, is largely absent in the SI, but is expressed, albeit weakly, in the stem cells in the colon. Spontaneous apoptosis is observed in p53 null mice which also develop normally suggesting that spontaneous and developmental apoptosis are p53 independent and that spontaneous apoptosis is part of the homeostatic mechanisms maintaining stem cell numbers. Radiation induced apoptosis is completely absent at these early times post-irradiation in p53 nulls. In bel-2 null mice, the levels of spontaneous and radiation induced apoptosis are elevated in the colon. Bax, a death gene, is expressed on the villus and inter-crypt table in the colon suggesting that cells at the end of their lifespan initiate apoptosis. It has been suggested that apoptosis in the SI is a protective mechanism against carcinogenesis in the stem cells of the SI which rarely develops cancer. Cells that possess genetic damage detected. In the large bowel, this mechanism is not effective due to the action of bcl-2. Thus stem cells may persist in this tissue with genetic damage resulting in a higher cancer risk. Furthermore, the lack of spontaneous apoptosis in the colon may result in a gradual increase of the stem cells with time resulting in more ells at risk. (author)

  6. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

    Science.gov (United States)

    Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

    2014-01-01

    Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. PMID:24563225

  7. Neurogenic voiding dysfunction.

    Science.gov (United States)

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

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

  8. Cadmium-induced apoptosis in primary rat cerebral cortical neurons culture is mediated by a calcium signaling pathway.

    Directory of Open Access Journals (Sweden)

    Yan Yuan

    Full Text Available Cadmium (Cd is an extremely toxic metal, capable of severely damaging several organs, including the brain. Studies have shown that Cd disrupts intracellular free calcium ([Ca(2+]i homeostasis, leading to apoptosis in a variety of cells including primary murine neurons. Calcium is a ubiquitous intracellular ion which acts as a signaling mediator in numerous cellular processes including cell proliferation, differentiation, and survival/death. However, little is known about the role of calcium signaling in Cd-induced apoptosis in neuronal cells. Thus we investigated the role of calcium signaling in Cd-induced apoptosis in primary rat cerebral cortical neurons. Consistent with known toxic properties of Cd, exposure of cerebral cortical neurons to Cd caused morphological changes indicative of apoptosis and cell death. It also induced elevation of [Ca(2+]i and inhibition of Na(+/K(+-ATPase and Ca(2+/Mg(2+-ATPase activities. This Cd-induced elevation of [Ca(2+]i was suppressed by an IP3R inhibitor, 2-APB, suggesting that ER-regulated Ca(2+ is involved. In addition, we observed elevation of reactive oxygen species (ROS levels, dysfunction of cytochrome oxidase subunits (COX-I/II/III, depletion of mitochondrial membrane potential (ΔΨm, and cleavage of caspase-9, caspase-3 and poly (ADP-ribose polymerase (PARP during Cd exposure. Z-VAD-fmk, a pan caspase inhibitor, partially prevented Cd-induced apoptosis and cell death. Interestingly, apoptosis, cell death and these cellular events induced by Cd were blocked by BAPTA-AM, a specific intracellular Ca(2+ chelator. Furthermore, western blot analysis revealed an up-regulated expression of Bcl-2 and down-regulated expression of Bax. However, these were not blocked by BAPTA-AM. Thus Cd toxicity is in part due to its disruption of intracellular Ca(2+ homeostasis, by compromising ATPases activities and ER-regulated Ca(2+, and this elevation in Ca(2+ triggers the activation of the Ca(2+-mitochondria apoptotic

  9. JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis

    DEFF Research Database (Denmark)

    Prause, Michala; Christensen, Dan Ploug; Billestrup, Nils

    2014-01-01

    Pancreatic β-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate β-cell dysfunction and apoptosis associated with increased c-Jun N-terminal Kinase (JNK) activity. Endoplas......Pancreatic β-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate β-cell dysfunction and apoptosis associated with increased c-Jun N-terminal Kinase (JNK) activity....... Endoplasmic reticulum (ER) and oxidative stress are elicited by palmitate and high glucose concentrations further potentiating JNK activity. Our aim was to determine the role of the JNK subtypes JNK1, JNK2 and JNK3 in palmitate and high glucose-induced β-cell apoptosis. We established insulin-producing INS1...... INS1 cells showed increased apoptosis and cleaved caspase 9 and 3 compared to non-sense shRNA expressing control INS1 cells when exposed to palmitate and high glucose associated with increased CHOP expression, ROS formation and Puma mRNA expression. JNK2 shRNA expressing INS1 cells did not affect...

  10. Inhibition of apoptosis in T cells expressing human T cell leukemia virus type I Tax

    NARCIS (Netherlands)

    Copeland, K. F.; Haaksma, A. G.; Goudsmit, J.; Krammer, P. H.; Heeney, J. L.

    1994-01-01

    This study set out to determine whether T cell dysfunction associated with HTLV-I led to increased sensitivity of infected cells to apoptosis or, owing to their potential to develop ATL, if infected cells would become resistant to this process. To test this hypothesis we utilized the monoclonal

  11. Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation

    NARCIS (Netherlands)

    Daemen, M. A.; van 't Veer, C.; Denecker, G.; Heemskerk, V. H.; Wolfs, T. G.; Clauss, M.; Vandenabeele, P.; Buurman, W. A.

    1999-01-01

    Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of tissue injury in organs subjected to ischemia. The mechanism that triggers inflammation and organ injury after ischemia remains to be elucidated, although

  12. Síndrome de disfunção de múltiplos órgãos induzida por sepse: estudo experimental em ratos Sepsis inducing syndrome of multiple organ dysfunction: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    João Batista de Area Lima

    2011-06-01

    Full Text Available RACIONAL: A principal causa de morte em pacientes com sepse em cirurgia é a síndrome de disfunção de múltiplos órgãos. Assim, modelos experimentais que simulem alterações orgânicas da sepse em humanos são necessários. OBJETIVO: Apresentar dois modelos que induzem a síndrome de disfunção de múltiplos órgãos e comparar as alterações induzidas por inoculação endovenosa de 36UE de lipopolissacarídeo ou célula viável de Escherichia coli, em relação à: mortalidade e sobrevivência; nível de lipopolissacarídeo; liberação de fator de necrose tumoral alfa; alterações hematológicas e das funções hepática e renal. MÉTODO: Este estudo teve duração de sete dias e utilizou-se nele 50 ratos Wistar machos, divididos em três grupos: controle, lipopolissacarídeo e Escherichia coli. Os grupos experimento eram inoculados e separados em dois subgrupos, com inoculação a cada 24 ou 48 horas. No sétimo dia eram procedidas coletas de sangue e análise histopatológica de fígado, rins e pulmões. RESULTADOS: Houve sobrevivência de dez animais no grupo controle; zero no bacteriano de 24 horas e seis no de 48 horas; dez no lipopolissacarídeo de 24 horas e seis no de 48 horas. Nos grupos experimentais, os níveis de lipopolissacarídeo, fator de necrose tumoral alfa, leucócitos, plaquetas, bastonetes e as alterações renais e hepáticas foram superiores ao grupo controle. Houve alterações histopatológicas no grupo bacteriano. CONCLUSÃO: Os dois modelos de sepse induziram síndrome de disfunção de múltiplos órgãos, contudo a administração de 36UE de endotoxina a cada 48 horas pode ser utilizada com vantagens sobre os demais por não induzir morte em número significativo durante o período de sete dias.BACKGROUND: The leading cause of death in patients with sepsis in surgery is syndrome of multiple organ dysfunction. Thus, experimental models that simulate organic changes of sepsis in humans are required. AIM: To

  13. CAPGRAS SYNDROME AND ORGANIC BRAIN DYSFUNCTION

    Science.gov (United States)

    Bhatia, M.S.; Agrwal, Pradeep; Malik, S.C.

    1996-01-01

    Capgras Syndrome was described in the late nineteenth century but its exact pathogenesis is still a source of controversy. Some believe its origin is due to psychodynamic factors whereas others have found the evidence of a generalized or localized brain lesion. We report three cases of Capgras Syndrome occurring in association with frontal lobe lesion. PMID:21584123

  14. CAPGRAS SYNDROME AND ORGANIC BRAIN DYSFUNCTION

    OpenAIRE

    Bhatia, M.S.; Agrwal, Pradeep; Malik, S.C.

    1996-01-01

    Capgras Syndrome was described in the late nineteenth century but its exact pathogenesis is still a source of controversy. Some believe its origin is due to psychodynamic factors whereas others have found the evidence of a generalized or localized brain lesion. We report three cases of Capgras Syndrome occurring in association with frontal lobe lesion.

  15. Female Sexual Dysfunctions and Urogynecological Disorders

    Directory of Open Access Journals (Sweden)

    Emillio Sacco

    2013-12-01

    Full Text Available Female sexual dysfunctions are a highly prevalent and often-underestimated health problem and include disorders of sexual desire, arousal, orgasm and sexual pain, associated with self-distress. Pathophysiology of female sexual dysfunctions is complex and still poorly understood, although it has been related to several biological, medical and psychological factors. Amongst women, urogynecological disorders such as urinary incontinence, overactive bladder syndrome, bladder pain syndrome and pelvic organ prolapse, have been found to be associated with sexual dysfunctions, although the biological and psychological bases of these associations are poorly investigated. Data on sexual function impact of these conditions come from several cross-sectional or community-based, epidemiological studies based on self-administered validated psychometric tools. This review focuses on the most relevant available evidence on the impact of urogynecological disorders and related surgical treatments on female sexual function.

  16. Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells.

    Science.gov (United States)

    Liu, Chuang; Sun, Yongkun; Song, Yutong; Saito, Takeshi; Kurasaki, Masaaki

    2016-11-01

    Nonylphenol and short-chain nonylphenol ethoxylates such as NP 2 EO are present in aquatic environment as wastewater contaminants, and their toxic effects on aquatic species have been reported. Apoptosis has been shown to be induced by serum deprivation or copper treatment. To understand the toxicity of nonylphenol diethoxylate, we investigated the effects of NP 2 EO on apoptosis induced by serum deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself showed no toxicity and recovered cell viability from apoptosis. In addition, nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12 cells. This phenomenon was confirmed after treating apoptotic PC12 cells with nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol decreased as compared to that in apoptotic cells not treated with nonylphenol diethoxylates. Furthermore, Bax contents in apoptotic cells were reduced after exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the opposite effect on apoptosis in PC12 cells compared to nonylphenol, which enhances apoptosis induced by serum deprivation. The difference in structure of the two compounds is hypothesized to be responsible for this phenomenon. These results indicated that nonylphenol diethoxylate has capability to affect cell differentiation and development and has potentially harmful effect on organisms because of its unexpected impact on apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1389-1398, 2016. © 2015 Wiley Periodicals, Inc.

  17. The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant.

    Science.gov (United States)

    Veenstra, David L; Guzauskas, Gregory F; Villa, Kathleen F; Boudreau, Denise M

    2017-05-01

    A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD). To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center. The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables. There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold. The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

  18. Korelasi Antara Kadar Laktat, Base Deficit Dan Saturasi Vena Sentral Dengan Skor Multiple Organ Dysfunction Hari Ke-3 Pada Pasien Pascabedah Dengan Hemodinamik Stabil Di Ruang Perawatan Intensif Rumah Sakit Dr. Hasan Sadikin Bandung

    Directory of Open Access Journals (Sweden)

    Ruby Satria Nugraha

    2013-04-01

    Full Text Available there is no precise indicator to evaluate adequate global perfussion yet. On haemodynamically stable patient is possible to experience change in lactate value, base deficit, and central vein saturation, which can be used to assess tissue hypoxia. The aim of this study is to find the best parameter among those three parameters toward day-third-MOD (Multiple organ dysfunction score on hemodinamically stable post surgery patients whose been hospitalized in ICU (Intensive care unit.This is a cross-sectional observational study. The subject of this study were 50 high-risk patients whose hospitalized in RPI, male and female between 18 – 65 years old who had been done explorative laparatomy procedures under general anesthesia. Blood lactate, arterial blood gas analysis and central vein blood gas analysis had been analysis on all subjects on admissions and on the 24th hours. On the third day, MOD score that covered neurologic, cardiovascular, respiration, renal, hematologic and liver function had been assessed. This study yielded rank Spearmen coeffisien correlation between blood lactate 1 and day-third-MOD score 0,572 (p<0,001, and base deficit 1 and day-third-MOD score was 0,811 (p<0,001. The value between central vein saturation 1 and day-third-MOD score, and central vein saturation 2 and day-third-MOD score were unsignificant, with rank Spearmen coeffisien correlation were 0,328 and 0,260. Good coeffisien correlation was found between blood lactate and base deficit with MOD score on third day, whilst central vein saturation had weak coeffisien correlation. Blood lactate level and base deficit can be used to evaluate early tissue perfusion disturbances on hemodinamically stable high risk post surgery patients.

  19. Apoptosis and DNA Methylation

    International Nuclear Information System (INIS)

    Meng, Huan X.; Hackett, James A.; Nestor, Colm; Dunican, Donncha S.; Madej, Monika; Reddington, James P.; Pennings, Sari; Harrison, David J.; Meehan, Richard R.

    2011-01-01

    Epigenetic mechanisms assist in maintaining gene expression patterns and cellular properties in developing and adult tissues. The molecular pathology of disease states frequently includes perturbation of DNA and histone methylation patterns, which can activate apoptotic pathways associated with maintenance of genome integrity. This perspective focuses on the pathways linking DNA methyltransferases and methyl-CpG binding proteins to apoptosis, and includes new bioinformatic analyses to characterize the evolutionary origin of two G/T mismatch-specific thymine DNA glycosylases, MBD4 and TDG

  20. Hypertension and sexual dysfunction

    African Journals Online (AJOL)

    Review Article: Hypertension and sexual dysfunction. 117. Vol 54 No 2. S Afr Fam Pract 2012. Introduction. Hypertension is a major independent cardiovascular risk factor, and also a marker of survival risk. Quality of life during the treatment of hypertension is an important health issue, as one in every five treated patients ...

  1. Temporomandibular Joint Dysfunction

    Science.gov (United States)

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

  2. Postirradiation cardiovascular dysfunction

    International Nuclear Information System (INIS)

    Hawkins, R.N.; Cockerham, L.G.

    1987-01-01

    Cardiovascular dysfunction may be defined as the inability of any element of the cardiovascular system to perform adequately upon demand, leading to inadequate performance and nutritive insufficiency of various parts of the body. Exposure to supralethal doses of radiation (accidental and therapeutic) has been show to induce significant alterations in cardiovascular function in man. These findings indicate that, after irradiation, cardiovascular function is a major determinant of continued performance and even survival. For the two persons who received massive radiation doses (45 and 88 Gy, respectively) in criticality accidents, the inability to maintain systematic arterial blood pressure (AP) was the immediate cause of death. In a study of cancer patients given partial-body irradiation, two acute lethalities were attributed to myocardial infarction after an acute hypotensive episode during the first few hours postexposure. Although radiation-induced cardiovascular dysfunction has been observed in many species, its severity, duration, and even etiology may vary with the species, level of exposure, and dose rate. For this reason, our consideration of the effects of radiation on cardiovascular performance is limited to the circulatory derangements that occur in rat, dog, and monkey after supralethal doses and lead to radiation-induced cardiovascular dysfunction in these experimental models. The authors consider other recent data as they pertain to the etiology of cardiovascular dysfunction in irradiated animals

  3. Female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Wåhlin-Jacobsen, Sarah

    2016-01-01

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

  4. Mitochondrial dysfunction in epilepsy

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Kunz, W.S.

    2012-01-01

    Roč. 12, č. 1 (2012), s. 35-40 ISSN 1567-7249 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : epilepsy * mitochondrial dysfunction * neurodegeneration Subject RIV: FH - Neurology Impact factor: 4.025, year: 2012

  5. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  6. Role of the nucleus in apoptosis: signaling and execution.

    Science.gov (United States)

    Prokhorova, Evgeniia A; Zamaraev, Alexey V; Kopeina, Gelina S; Zhivotovsky, Boris; Lavrik, Inna N

    2015-12-01

    Since their establishment in the early 1970s, the nuclear changes upon apoptosis induction, such as the condensation of chromatin, disassembly of nuclear scaffold proteins and degradation of DNA, were, and still are, considered as the essential steps and hallmarks of apoptosis. These are the characteristics of the execution phase of apoptotic cell death. In addition, accumulating data clearly show that some nuclear events can lead to the induction of apoptosis. In particular, if DNA lesions resulting from deregulation during the cell cycle or DNA damage induced by chemotherapeutic drugs or viral infection cannot be efficiently eliminated, apoptotic mechanisms, which enable cellular transformation to be avoided, are activated in the nucleus. The functional heterogeneity of the nuclear organization allows the tight regulation of these signaling events that involve the movement of various nuclear proteins to other intracellular compartments (and vice versa) to initiate and govern apoptosis. Here, we discuss how these events are coordinated to execute apoptotic cell death.

  7. Reassessing apoptosis in plants.

    Science.gov (United States)

    Dickman, Martin; Williams, Brett; Li, Yurong; de Figueiredo, Paul; Wolpert, Thomas

    2017-10-01

    Cell death can be driven by a genetically programmed signalling pathway known as programmed cell death (PCD). In plants, PCD occurs during development as well as in response to environmental and biotic stimuli. Our understanding of PCD regulation in plants has advanced significantly over the past two decades; however, the molecular machinery responsible for driving the system remains elusive. Thus, whether conserved PCD regulatory mechanisms include plant apoptosis remains enigmatic. Animal apoptotic regulators, including Bcl-2 family members, have not been identified in plants but expression of such regulators can trigger or suppress plant PCD. Moreover, plants exhibit nearly all of the biochemical and morphological features of apoptosis. One difference between plant and animal PCD is the absence of phagocytosis in plants. Evidence is emerging that the vacuole may be key to removal of unwanted plant cells, and may carry out functions that are analogous to animal phagocytosis. Here, we provide context for the argument that apoptotic-like cell death occurs in plants.

  8. Cardiovascular molecular imaging of apoptosis

    International Nuclear Information System (INIS)

    Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

    2007-01-01

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  9. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  10. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways.

    Science.gov (United States)

    Aoyama, Michiko; Kotani, Joji; Usami, Makoto

    2010-06-01

    Decreased neutrophil apoptosis is implicated in persistent inflammation resulting in systemic inflammatory response syndrome and multiple organ dysfunctions syndromes. Short-chain fatty acids (SCFAs) may be a candidate to control neutrophil apoptosis because SCFAs are normally produced in the gut and related products have been approved for human use. We investigated the effects of SCFAs on apoptosis of activated and non-activated neutrophils and their mechanisms. Purified neutrophils obtained from healthy volunteers were preincubated for 1 h with or without the G-protein receptor (GPR) inhibitor pertussis toxin (100 ng/mL) or U-73122 (50 ng/mL), extracellular signal-related protein kinase inhibitor PD98059 (10 microM), mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 (25 microM), Jun kinase inhibitor-I (2 microM), caspase-3 and -7 inhibitor Z-VAD-FMK (100 microM), caspase-8 inhibitor Z-IETD-FMK (50 microM), or caspase-9 inhibitor Z-LEHD-FMK (50 microM). The cells were then cultured with or without SCFAs or trichostatin A, a typical histone deacetylase inhibitor, in the presence or absence of lipopolysaccharide (1 microg/mL) or tumor necrosis factor-alpha (100 ng/mL). Neutrophil apoptosis was assessed by annexin V staining using flow cytometry. The GPR-41 and -43 and apoptosis-related proteins (bax, mcl-1, a1) mRNA were measured by quantitative real-time polymerase chain reaction and the expression of acetylated histone H3 was determined by western blot. The caspase inhibitors inhibited butyrate- and propionate-induced neutrophil apoptosis treated or untreated with lipopolysaccharide or tumor necrosis factor-alpha, whereas GPR and MAPK inhibitors had no effect. The mRNA expressions of GPR-43 and a1 protein were reduced by butyrate and propionate. The expressions of acetylated histone H3 were induced by butyrate and propionate. These results suggest that butyrate and propionate increase apoptosis of neutrophils irrespective of their activation state, by

  11. Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

    Directory of Open Access Journals (Sweden)

    E.P. Schmidt

    2010-01-01

    Full Text Available Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI and chronic obstructive pulmonary disease (COPD. Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. [Thyroid dysfunction and amiodarone].

    Science.gov (United States)

    Lima, Jandira; Carvalho, Patrícia; Molina, M Auxiliadora; Rebelo, Marta; Dias, Patrícia; Vieira, José Diniz; Costa, José M Nascimento

    2013-02-01

    Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

  14. Alcohol and Apoptosis: Friends or Foes?

    Science.gov (United States)

    Rodriguez, Ana; Chawla, Karan; Umoh, Nsini A; Cousins, Valerie M; Ketegou, Assama; Reddy, Madhumati G; AlRubaiee, Mustafa; Haddad, Georges E; Burke, Mark W

    2015-11-19

    Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

  15. Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury

    Directory of Open Access Journals (Sweden)

    Hao Zhou

    2017-10-01

    Full Text Available Ripk3-required necroptosis and mitochondria-mediated apoptosis are the predominant types of cell death that largely account for the development of cardiac ischemia reperfusion injury (IRI. Here, we explored the effect of Ripk3 on mitochondrial apoptosis. Compared with wild-type mice, the infarcted area in Ripk3-deficient (Ripk3-/- mice had a relatively low abundance of apoptotic cells. Moreover, the loss of Ripk3 protected the mitochondria against IRI and inhibited caspase9 apoptotic pathways. These protective effects of Ripk3 deficiency were relied on mitophagy activation. However, inhibition of mitophagy under Ripk3 deficiency enhanced cardiomyocyte and endothelia apoptosis, augmented infarcted area and induced microvascular dysfunction. Furthermore, ischemia activated mitophagy by modifying FUNDC1 dephosphorylation, which substantively engulfed mitochondria debris and cytochrome-c, thus blocking apoptosis signal. However, reperfusion injury elevated the expression of Ripk3 which disrupted FUNDC1 activation and abated mitophagy, increasing the likelihood of apoptosis. In summary, this study confirms the promotive effect of Ripk3 on mitochondria-mediated apoptosis via inhibition of FUNDC1-dependent mitophagy in cardiac IRI. These findings provide new insight into the roles of Ripk3-related necroptosis, mitochondria-mediated apoptosis and FUNDC1-required mitophagy in cardiac IRI.

  16. Mitochondria-derived superoxide links to tourniquet-induced apoptosis in mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Thai P Tran

    Full Text Available Our previous study has reported that superoxide mediates ischemia-reperfusion (IR-induced necrosis in mouse skeletal muscle. However, it remains poorly understood whether IR induces apoptosis and what factors are involved in IR-induced apoptosis in skeletal muscle. Using a murine model of tourniquet-induced hindlimb IR, we investigated the relationship between mitochondrial dysfunction and apoptosis in skeletal muscle. Hindlimbs of C57/BL6 mice were subjected to 3 h ischemia and 4 h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Compared to sham treatment, tourniquet-induced IR significantly elevated mitochondria-derived superoxide production, activated opening of mitochondrial permeability transition pore (mPTP, and caused apoptosis in the gastrocnemius muscles. Pretreatment with a superoxide dismutase mimetic (tempol, 50 mg/kg or a mitochondrial antioxidant (co-enzyme Q(10, 50 mg/kg not only decreased mitochondria-derived superoxide production, but also inhibited mPTP opening and apoptosis in the IR gastrocnemius muscles. Additionally, an inhibitor of mPTP (cyclosporine A, 50 mg/kg also inhibited both mPTP opening and apoptosis in the IR gastrocnemius muscles. These results suggest that mitochondria-derived superoxide overproduction triggers the mPTP opening and subsequently causes apoptosis in tourniquet-induced hindlimb IR.

  17. Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells.

    Science.gov (United States)

    Sordillo, Lorraine M; Weaver, James A; Cao, Yu-Zhang; Corl, Chris; Sylte, Matt J; Mullarky, Isis K

    2005-05-01

    Oxidant stress plays an important role in the etiology of vascular diseases by increasing rates of endothelial cell apoptosis, but few data exist on the mechanisms involved. Using a unique model of oxidative stress based on selenium deficiency (-Se), the effects of altered eicosanoid production on bovine aortic endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly increased the immediate oxygenation product of arachidonic acid metabolized by the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE). Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels of apoptosis, which was significantly reduced by the addition of a specific 15-lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA fragmentation, chromatin condensation, caspase-3 activation, and caspase-9 activation, which suggests mitochondrial dysfunction. The expression of Bcl-2 protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD-fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC, suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased apoptosis of BAEC as a result of oxidant stress and subsequent production of 15-HPETE may play a critical role in a variety of inflammatory based diseases.

  18. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    International Nuclear Information System (INIS)

    Rashid, Kahkashan; Sil, Parames C.

    2015-01-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  19. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  20. Sexual dysfunction in women with diabetes mellitus.

    Science.gov (United States)

    Giraldi, Annamaria; Kristensen, Ellids

    2010-03-01

    Diabetes mellitus (DM) is an increasing health concern throughout the world. DM is categorized as either type 1 (DM-1) or type 2 (DM-2), where DM-1 represents a lack of insulin production, and DM-2 is characterized by a relative lack of insulin (i.e., decreased sensitivity to the effect of insulin). DM has long been considered a risk factor for sexual dysfunction in men and women, although the evidence in women is less clear. This review attempts to give an overview of female sexual dysfunction in women with DM. Although women with DM are at higher risk of developing sexual dysfunction than women without DM, there is great variability in results across studies, with the incidence of sexual dysfunction in women with DM generally linked less to organic factors and more to psychological factors, especially coexisting depression. This review hypothesizes several presumed causes for such variation in findings across studies and uses these explanations as the basis for a discussion of differences between men's and women's sexuality.

  1. Diaphragm Dysfunction in Mechanically Ventilated Patients.

    Science.gov (United States)

    Dot, Irene; Pérez-Teran, Purificación; Samper, Manuel-Andrés; Masclans, Joan-Ramon

    2017-03-01

    Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure. Although the specific etiology of process is unknown, the muscle presents oxidative stress and mitochondrial changes. These cause changes in protein turnover, resulting in atrophy and impaired contractility, and leading to impaired functionality. The term 'ventilator-induced diaphragm dysfunction' was first coined by Vassilakopoulos et al. in 2004, and this phenomenon, along with injury cause by over-distention of the lung and barotrauma, represents a challenge in the daily life of ventilated patients. Diaphragmatic dysfunction affects prognosis by delaying extubation, prolonging hospital stay, and impairing the quality of life of these patients in the years following hospital discharge. Ultrasound, a non-invasive technique that is readily available in most ICUs, could be used to diagnose this condition promptly, thus preventing delays in starting rehabilitation and positively influencing prognosis in these patients. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Proliferation and apoptosis in infection with infectious bursal disease virus: a flow cytometric study.

    Science.gov (United States)

    Ojeda, F; Skardova, I; Guarda, M I; Ulloa, J; Folch, H

    1997-01-01

    Programmed cell death, or apoptosis, is involved in the normal physiology of many immunocompetent organs, including lymphocytes of the bursa of Fabricius in chickens. Involvement of apoptosis has also been described in some viral diseases such as AIDS. The purpose of this work was to study the potential role of apoptosis in the pathogenesis of Gumboro disease in the bursa of Fabricius. Our results show that 1-3 days after infection of young chickens with infectious bursal disease virus, the number of apoptotic cells increases and cellularity and proliferation decrease. Because of the dynamic nature of bursal lymphocyte populations and the involvement of apoptosis in lymphocyte cell physiology, the increased level of cells undergoing apoptosis may be due to an impairment in the withdrawal of apoptotic cells. A concomitant increase in macrophages in infected bursae and a dramatic decrease in cellularity suggest that an increase in apoptosis may be an important cause of cell depletion.

  3. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  4. Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin.

    Science.gov (United States)

    Prince, Lynne R; Bianchi, Stephen M; Vaughan, Kathryn M; Bewley, Martin A; Marriott, Helen M; Walmsley, Sarah R; Taylor, Graham W; Buttle, David J; Sabroe, Ian; Dockrell, David H; Whyte, Moira K B

    2008-03-01

    Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence. In this study, we investigated the mechanisms of pyocyanin-induced neutrophil apoptosis. Pyocyanin induced early lysosomal dysfunction, shown by altered lysosomal pH, within 15 min of exposure. Lysosomal disruption was followed by mitochondrial membrane permeabilization, caspase activation, and destabilization of Mcl-1. Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis, and translocation of CTSD to the cytosol followed pyocyanin treatment and lysosomal disruption. A stable analog of cAMP (dibutyryl cAMP) impeded the translocation of CTSD and prevented the destabilization of Mcl-1 by pyocyanin. Thus, pyocyanin activated a coordinated series of events dependent upon lysosomal dysfunction and protease release, the first description of a bacterial toxin using a lysosomal cell death pathway. This may be a pathological pathway of cell death to which neutrophils are particularly susceptible, and could be therapeutically targeted to limit neutrophil death and preserve host responses.

  5. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2007-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  6. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2005-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  7. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2006-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  8. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2004-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of PCa cells by methyl selenium (Se)/selenol...

  9. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2008-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  10. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan

    2003-01-01

    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of PCa cells by methyl selenium (Se...

  11. Recognition and Management of Nonrelaxing Pelvic Floor Dysfunction

    OpenAIRE

    Faubion, Stephanie S.; Shuster, Lynne T.; Bharucha, Adil E.

    2012-01-01

    Nonrelaxing pelvic floor dysfunction is not widely recognized. Unlike in pelvic floor disorders caused by relaxed muscles (eg, pelvic organ prolapse or urinary incontinence, both of which often are identified readily), women affected by nonrelaxing pelvic floor dysfunction may present with a broad range of nonspecific symptoms. These may include pain and problems with defecation, urination, and sexual function, which require relaxation and coordination of pelvic floor muscles and urinary and ...

  12. Managing female sexual dysfunction.

    Science.gov (United States)

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Intestinal bacterium-derived cyp27a1 prevents colon cancer cell apoptosis

    OpenAIRE

    Ji, Yan-Chao; Liu, Chang; Zhang, Xia; Zhang, Cheng-Sen; Wang, Dong; Zhang, Yan

    2016-01-01

    The pathogenesis of metastasis of colon cancer (Cca) is to be further investigated. The dysfunction of apoptotic mechanism plays a role in the cancer cell over growth. This study tests a hypothesis by which intestinal bacterium-derived cyp27a1 prevents apoptosis in colon cancer cells. In this study, the levels of cyp27a1 in human stool samples were assessed by enzyme-linked immunosorbent assay. The apoptosis of Cca cells was observed by flow cytometry. The expression of cyp27a1 was assessed b...

  14. Pelvic floor dysfunction and sensory impairment: Current evidence.

    Science.gov (United States)

    Mahoney, Charlotte; Smith, Anthony; Marshall, Andy; Reid, Fiona

    2017-03-01

    To explore the role of sensory nerve impairment in women with pelvic organ prolapse, painful bladder syndrome, urinary and fecal incontinence, and sexual dysfunction. Medline and Embase were searched for articles in which sensory testing, either quantitative sensory testing or current perception thresholds, had been used to evaluate women with pelvic organ prolapse, stress and urge urinary incontinence, fecal incontinence and female sexual dysfunction. All search terms were expanded within each database prior to searching. Research to date has included small numbers of participants, used poorly matched controls, lacked a systemic sensory examination and applied non-standardized sensory testing techniques. However, the evidence suggests women with pelvic organ prolapse demonstrate sensory dysfunction. The role of sensory impairment in stress urinary incontinence is inconclusive. In women with urge urinary incontinence there is some evidence to suggest it may be urethrally mediated. Women with painful bladder syndrome may have more sensitive nerve endings which are unable to ignore repeated stimuli. Sensory impairment is common in women with sexual dysfunction, typically involving larger nerve fibres. There were no studies evaluating sensory function in women with fecal incontinence. Current evidence suggests women with pelvic floor dysfunction demonstrate sensory impairment though the causes remain unclear. Further studies are needed to investigate the different conditions of pelvic floor dysfunction using standardized sensory testing techniques, as well as evaluate the timing and mechanism by which any sensory impairment develops. Neurourol. Urodynam. 36:550-556, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Investigating the evolution of apoptosis in malaria parasites: the importance of ecology

    Directory of Open Access Journals (Sweden)

    Pollitt Laura C

    2010-11-01

    Full Text Available Abstract Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention. However, it is important to understand when and why parasites employ an apoptosis strategy before the likely long- and short-term success of such an intervention can be evaluated. The occurrence of apoptosis in unicellular parasites provides a challenge for evolutionary theory to explain as organisms are expected to have evolved to maximise their own proliferation, not death. One possible explanation is that protozoan parasites undergo apoptosis in order to gain a group benefit from controlling their density as this prevents premature vector mortality. However, experimental manipulations to examine the ultimate causes behind apoptosis in parasites are lacking. In this review, we focus on malaria parasites to outline how an evolutionary framework can help make predictions about the ecological circumstances under which apoptosis could evolve. We then highlight the ecological considerations that should be taken into account when designing evolutionary experiments involving markers of cell death, and we call for collaboration between researchers in different fields to identify and develop appropriate markers in reference to parasite ecology and to resolve debates on terminology.

  16. Client attributions for sexual dysfunction.

    Science.gov (United States)

    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.

  17. Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

    Science.gov (United States)

    Possomato-Vieira, José S.; Khalil, Raouf A.

    2016-01-01

    Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia. PMID:27451103

  18. Prefrontal system dysfunction and credit card debt.

    Science.gov (United States)

    Spinella, Marcello; Yang, Bijou; Lester, David

    2004-10-01

    Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

  19. Sexual dysfunction in women partners of men with erectile dysfunction.

    Science.gov (United States)

    Greenstein, A; Abramov, L; Matzkin, H; Chen, J

    2006-01-01

    We evaluated 113 female partners of men with erectile dysfunction (ED) attending a sexual dysfunction clinic in order to define sexual dysfunction among these women. In all, 51 (45%) women denied having any sexual dysfunction. The other 62 (55%) responded to questions classifying their complaint(s) according to the international classification of female sexual dysfunction (FSD) in the following topics (40/62, 65%, reported having more than one problem): decreased sexual desire (n=35, 56%), sexual aversion (none), arousal (n=23, 37%) and orgasmic disorders (n=39, 63%), dyspareunia (n=19, 31%), vaginismus (n=3, 5%), and noncoital sexual pain (none). Many female partners of men with ED report having some form of sexual disorder, mostly orgasmic problems and decreased sexual desire. Therefore, for optimal outcome of ED treatment, evaluation and treatment of male and FSD should be addressed as one unit within the context of the couple, and be incorporated into one clinic of sexual medicine.

  20. Cycling and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Ina Šibli

    2015-01-01

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

  1. Progressive posterior cortical dysfunction

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

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

  2. Epilepsy and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Russell P. Saneto DO, PhD

    2017-10-01

    Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.

  3. Apoptosis-Like Cell Death Induction and Aberrant Fibroblast Properties in Human Incisional Hernia Fascia

    Science.gov (United States)

    Diaz, Ramon; Quiles, Maria T.; Guillem-Marti, Jordi; Lopez-Cano, Manuel; Huguet, Pere; Ramon-y-Cajal, Santiago; Reventos, Jaume; Armengol, Manel; Arbos, Maria A.

    2011-01-01

    Incisional hernia often occurs following laparotomy and can be a source of serious problems. Although there is evidence that a biological cause may underlie its development, the mechanistic link between the local tissue microenvironment and tissue rupture is lacking. In this study, we used matched tissue-based and in vitro primary cell culture systems to examine the possible involvement of fascia fibroblasts in incisional hernia pathogenesis. Fascia biopsies were collected at surgery from incisional hernia patients and non-incisional hernia controls. Tissue samples were analyzed by histology and immunoblotting methods. Fascia primary fibroblast cultures were assessed at morphological, ultrastructural, and functional levels. We document tissue and fibroblast loss coupled to caspase-3 activation and induction of apoptosis-like cell-death mechanisms in incisional hernia fascia. Alterations in cytoskeleton organization and solubility were also observed. Incisional hernia fibroblasts showed a consistent phenotype throughout early passages in vitro, which was characterized by significantly enhanced cell proliferation and migration, reduced adhesion, and altered cytoskeleton properties, as compared to non-incisional hernia fibroblasts. Moreover, incisional hernia fibroblasts displayed morphological and ultrastructural alterations compatible with autophagic processes or lysosomal dysfunction, together with enhanced sensitivity to proapoptotic challenges. Overall, these data suggest an ongoing complex interplay of cell death induction, aberrant fibroblast function, and tissue loss in incisional hernia fascia, which may significantly contribute to altered matrix maintenance and tissue rupture in vivo. PMID:21641387

  4. Activation of myocardial phosphoinositide-3-kinase p110α ameliorates cardiac dysfunction and improves survival in polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Chuanfu Li

    Full Text Available Phosphoinositide-3-kinase (PI3K/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction. Cardiac function and survival were evaluated in transgenic mice with cardiac myocyte specific expression of constitutively active PI3K isoform, p110α (caPI3K Tg. caPI3K Tg and wild type (WT mice were subjected to cecal ligation/puncture (CLP induced sepsis. Wild type CLP mice showed dramatic cardiac dysfunction at 6 hrs. Septic cardiomyopathy was significantly attenuated in caPI3K CLP mice. The time to 100% mortality was 46 hrs in WT CLP mice. In contrast, 80% of the caPI3K mice survived at 46 hrs after CLP (p30 days (p<0.01. Cardiac caPI3K expression prevented expression of an inflammatory phenotype in CLP sepsis. Organ neutrophil infiltration and lung apoptosis were also effectively inhibited by cardiac PI3k p110α expression. Cardiac high mobility group box-1 (HMGB-1 translocation was also inhibited by caPI3K p110α expression. We conclude that cardiac specific activation of PI3k/Akt dependent signaling can significantly modify the morbidity and mortality associated with sepsis. Our data also indicate that myocardial function/dysfunction plays a prominent role in the pathogenesis of sepsis and that maintenance of cardiac function during sepsis is essential. Finally, these data suggest that modulation of the PI3K/p110α signaling pathway may be beneficial in the prevention and/or management of septic cardiomyopathy and septic shock.

  5. Sexual dysfunction associated with infertility'

    African Journals Online (AJOL)

    1989-07-15

    Jul 15, 1989 ... In the present study 50% of women had a statistically increased incidence of sexual dysfunction during the fertile phase compared with the non-fertile phase. Loss of libido was found to be the most common dysfunction in 45% either alone or in combination with a decreased frequency of orgasm in.

  6. Bladder Dysfunction and Vesicoureteral Reflux

    Directory of Open Access Journals (Sweden)

    Ulla Sillén

    2008-01-01

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

  7. H2O2 INDUCES APOPTOSIS OF RABBIT CHONDROCYTES VIA BOTH THE EXTRINSIC AND THE CASPASE-INDEPENDENT INTRINSIC PATHWAYS

    Directory of Open Access Journals (Sweden)

    CAIPING ZHUANG

    2013-07-01

    Full Text Available Osteoarthritis (OA, one of the most common joint diseases with unknown etiology, is characterized by the progressive destruction of articular cartilage and the apoptosis of chondrocytes. The purpose of this study is to elucidate the molecular mechanisms of H2O2-mediated rabbit chondrocytes apoptosis. CCK-8 assay showed that H2O2 treatment induced a remarkable reduction of cell viability, which was further verified by the remarkable phosphatidylserine externalization after H2O2 treatment for 1 h, the typical characteristics of apoptosis. H2O2 treatment induced a significant dysfunction of mitochondrial membrane potential (ΔΨm, but did not induce casapse-9 activation, indicating that H2O2 treatment induced caspase-independent intrinsic apoptosis that was further verified by the fact that silencing of AIF but not inhibiting caspase-9 potently prevented H2O2-induced apoptosis. H2O2 treatment induced a significant increase of caspase-8 and -3 activation, and inhibition of caspase-8 or -3 significantly prevented H2O2-induced apoptosis, suggesting that the extrinsic pathway played an important role. Collectively, our findings demonstrate that H2O2 induces apoptosis via both the casapse-8-mediated extrinsic and the caspase-independent intrinsic apoptosis pathways in rabbit chondrocytes.

  8. Placental apoptosis in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Tarek A. Atia

    2017-09-01

    Full Text Available Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM. Placental tissue samples were collected from 40 women with RM (study group and 30 women with sporadic spontaneous abortion (control group. Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53 and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53 protein was significantly increased in the placental tissues of the RM group (p = 0.003. By contrast, the expression of anti-apoptotic (Bcl-2 antibodies was significantly increased in the placental tissues of the control group (p = 0.025. We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation.

  9. Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway.

    Science.gov (United States)

    Wu, Qian; Zhong, Zhao-Ming; Zhu, Si-Yuan; Liao, Cong-Rui; Pan, Ying; Zeng, Ji-Huan; Zheng, Shuai; Ding, Ruo-Ting; Lin, Qing-Song; Ye, Qing; Ye, Wen-Bin; Li, Wei; Chen, Jian-Ting

    2016-01-01

    Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

  10. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aibin; Liu, Jingyi [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Institute of Cardiovascular Disease, General Hospital of Beijing Command, PLA, Beijing (China); Liu, Peilin; Jia, Min; Wang, Han [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Tao, Ling, E-mail: lingtao2006@gmail.com [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China)

    2014-04-18

    Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H{sub 2}O{sub 2} led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H{sub 2}O{sub 2} and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the

  11. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

    International Nuclear Information System (INIS)

    Xu, Aibin; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

    2014-01-01

    Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H 2 O 2 led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H 2 O 2 and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the process

  12. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome.

    Science.gov (United States)

    Xu, Aibin; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

    2014-04-18

    Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H2O2 led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H2O2 and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the process. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Regeneration of the exocrine pancreas is delayed in telomere-dysfunctional mice.

    Directory of Open Access Journals (Sweden)

    Guido von Figura

    Full Text Available INTRODUCTION: Telomere shortening is a cell-intrinsic mechanism that limits cell proliferation by induction of DNA damage responses resulting either in apoptosis or cellular senescence. Shortening of telomeres has been shown to occur during human aging and in chronic diseases that accelerate cell turnover, such as chronic hepatitis. Telomere shortening can limit organ homeostasis and regeneration in response to injury. Whether the same holds true for pancreas regeneration in response to injury is not known. METHODS: In the present study, pancreatic regeneration after acute cerulein-induced pancreatitis was studied in late generation telomerase knockout mice with short telomeres compared to telomerase wild-type mice with long telomeres. RESULTS: Late generation telomerase knockout mice exhibited impaired exocrine pancreatic regeneration after acute pancreatitis as seen by persistence of metaplastic acinar cells and markedly reduced proliferation. The expression levels of p53 and p21 were not significantly increased in regenerating pancreas of late generation telomerase knockout mice compared to wild-type mice. CONCLUSION: Our results indicate that pancreatic regeneration is limited in the context of telomere dysfunction without evidence for p53 checkpoint activation.

  14. Nitric oxide contributes to cytokine-induced apoptosis in pancreatic beta cells via potentiation of JNK activity and inhibition of Akt

    DEFF Research Database (Denmark)

    Størling, J; Binzer, J; Andersson, Annica

    2005-01-01

    Pro-inflammatory cytokines cause beta cell secretory dysfunction and apoptosis--a process implicated in the pathogenesis of type 1 diabetes. Cytokines induce the expression of inducible nitric oxide (NO) synthase (iNOS) leading to NO production. NO contributes to cytokine-induced apoptosis......, but the underlying mechanisms are unclear. The aim of this study was to investigate whether NO modulates signalling via mitogen-activated protein kinases (MAPKs) and Akt....

  15. Mst1 inhibition rescues β1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather than myocyte apoptosis

    Science.gov (United States)

    Lee, Grace J.; Yan, Lin; Vatner, Dorothy E.

    2015-01-01

    It is generally held that inhibition of mammalian sterile 20-like kinase 1 (Mst1) protects the heart through reducing myocyte apoptosis. We determined whether inhibition with a dominant-negative Mst1 (DN-Mst1) would protect against the cardiomyopathy induced by chronic β1-adrenergic receptor (β1-AR) stimulation by preventing myocyte apoptosis. DN-Mst1 mice were mated with β1-AR transgenic (Tg) mice and followed for 20 months. β1-AR Tg mice developed cardiomyopathy as they aged, as reflected by premature mortality and depressed cardiac function, which were rescued in β1-AR × DN-Mst1 bigenic mice. Surprisingly, myocyte apoptosis did not significantly decrease with Mst1 inhibition. Instead, Mst1 inhibition predominantly reduced non-myocyte apoptosis, e.g., fibroblasts, macrophages, neutrophils and endothelial cells. Fibrosis in the hearts with cardiomyopathy increased fivefold and this increase was nearly abolished in the bigenic mice with Mst1 inhibition. Regression analysis showed no correlation between myocyte apoptosis and cardiac function or myocyte number, whereas the latter two correlated significantly, p myocyte necrosis, chronic β-AR stimulation with isoproterenol was induced for 24 h and myocyte necrosis was assessed by 1 % Evans blue dye. Compared to WT, DN-Mst1 mice showed significant inhibition, p myocyte necrosis. We confirmed this result in Mst1-knockout mice, which also showed significant protection, p myocyte necrosis compared to WT. These data indicate that Mst1 inhibition rescued cardiac fibrosis and myocardial dysfunction in β1-AR cardiomyopathy. However, this did not occur through Mst1 inhibition of myocyte apoptosis but rather by inhibition of cardiomyocyte necrosis and non-myocyte apoptosis, features of Mst1 not considered previously. PMID:25600225

  16. [Testosterone and erectile dysfunction].

    Science.gov (United States)

    Diemer, T

    2010-01-01

    Primary hypogonadism represents a classic but rare cause of erectile dysfunction (ED) in men. Therapy with testosterone as monotherapy is therefore unlikely to cure ED in the typical ED patient. However, recent developments indicate a much greater role of testosterone in erectile function than has been supposed in the past. Serum testosterone levels decline in men with increasing age. Aging men might develop late-onset hypogonadism (LOH) associated with characteristic symptoms. Typical symptoms of LOH are represented by decreased libido and sexual function, osteoporosis, altered distribution of body fat, overall reduction in physical strength, and alterations in the general mood. Experimental and clinical studies over the last few years have also pointed out that hypogonadism results in characteristic alterations of the erectile tissue of the penis. These alterations might be reversible in response to hormone therapy with testosterone. Particularly testosterone might be a helpful supportive therapy in cases where PDE-5 antagonists have tended to lose their effectiveness on the erectile tissue in the treatment of ED.

  17. [Thyroid dysfunction during pregnancy].

    Science.gov (United States)

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

    2015-10-21

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

  18. Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

    Science.gov (United States)

    Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

    2015-01-01

    Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

  19. Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy.

    Science.gov (United States)

    Son, Eun Suk; Kim, Se-Hee; Ryter, Stefan W; Yeo, Eui-Ju; Kyung, Sun Young; Kim, Yu Jin; Jeong, Sung Hwan; Lee, Chang Soo; Park, Jeong-Woong

    2018-04-01

    Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation.

    Science.gov (United States)

    Liu, Zhiyong; Shi, Qiao; Liu, Jiao; Abdel-Razek, Osama; Xu, Yongan; Cooney, Robert N; Wang, Guirong

    2015-12-04

    Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p < 0.05, vs septic WT mice), with lower Bcl-2 and higher caspase-3 levels in septic KO mice (p < 0.05). Molecular analysis revealed increased NF-κB-p65 and phosphorylated IκB-α levels along with higher serum levels of TNF-α and IL-6 in septic KO mice compared to septic WT mice (p < 0.01). Furthermore, in vitro islet cultures stimulated with LPS produced higher TNF-α and IL-6 (p < 0.05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-κB-mediated inflammation in CLP-induced API.

  1. Executive dysfunction, severity of traumatic brain injury, and IQ in workers with disabilities.

    Science.gov (United States)

    Matheson, Leonard

    2010-01-01

    To study whether severity of traumatic brain injury and the intelligence quotient are related to executive dysfunction. Sixty-two adults with brain injury who were referred for a work capacity evaluation. Retrospective review of severity of traumatic brain injury, intelligence quotient from a previously-conducted neuropsychological evaluation, determination of executive function status from the neuropsychological evaluation, and both self-report and informant-report executive dysfunction scores from the Behavior Rating Inventory of Executive Function. Executive dysfunction and the intelligence quotient are related to severity of traumatic brain injury, but executive dysfunction and the intelligence quotient are not related to each other. Executive dysfunction as determined by a neuropsychological evaluation was not consistent with clients' self-reports but was consistent with informant-reported executive dysfunction. Five types of executive dysfunction were reported by knowledgeable informants, with significant elevations on the Shift, Plan/Organize, Task Monitor, Organization of Materials, and Working Memory BRIEF clinical scales. The intelligence quotient is not a useful indicator of executive dysfunction. Informant-report executive dysfunction is a reliable and potentially useful adjunct to a neuropsychological evaluation. Working memory is the most severe type of executive dysfunction and may not be adequately measured by current neuropsychological evaluation methods.

  2. Apoptosis detection in histological sections

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Dubská, Lenka; Míšek, Ivan

    2003-01-01

    Roč. 72, č. 7 (2003), s. 18-19 ISSN 0001-7213. [Congress of the European Association of Veterinary Anatomists/24./. 21.07.2002-25.07.2002, Brno] R&D Projects: GA ČR GP204/02/P112 Institutional research plan: CEZ:AV0Z5045916 Keywords : apoptosis Subject RIV: FF - HEENT, Dentistry

  3. Iodine-induced thyroid dysfunction

    Science.gov (United States)

    Leung, Angela M.; Braverman, Lewis E.

    2017-01-01

    Purpose of review To summarize the mechanisms of iodine-induced hypothyroidism and hyperthyroidism, identify the risk factors for thyroid dysfunction following an iodine load, and summarize the major sources of excess iodine exposure. Recent findings Excess iodine is generally well tolerated, but individuals with underlying thyroid disease or other risk factors may be susceptible to iodine-induced thyroid dysfunction following acute or chronic exposure. Sources of increased iodine exposure include the global public health efforts of iodine supplementation, the escalating use of iodinated contrast radiologic studies, amiodarone administration in vulnerable patients, excess seaweed consumption, and various miscellaneous sources. Summary Iodine-induced thyroid dysfunction may be subclinical or overt. Recognition of the association between iodine excess and iodine-induced hypothyroidism or hyperthyroidism is important in the differential diagnosis of patients who present without a known cause of thyroid dysfunction. PMID:22820214

  4. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

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

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol......This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive...... neuropsychological test battery must be used to detect POCD and a well-matched control group is very useful for the analysis and interpretation of the test RESULTS: Cardiovascular surgery is associated with a high incidence of POCD. Cardiopulmonary bypass was thought to explain this difference, but randomized...

  5. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

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

    2014-01-01

    dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented......BACKGROUND: Muscle dysfunction is a prevalent phenomenon in the oncology setting where patients across a wide range of diagnoses are subject to impaired muscle function regardless of tumor stage and nutritional state. Here, we review the current evidence describing the degree, causes and clinical...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...

  6. Apoptosis in oral erythema multiforme.

    Science.gov (United States)

    Chrysomali, E; Lozada-Nur, F; Dekker, N P; Papanicolaou, S I; Regezi, J A

    1997-02-01

    Cell death was evaluated in oral erythema multiforme to test the hypothesis that apoptosis may be a mechanism by which keratinocytes die in this condition. Ten erythema multiforme and five control oral mucosa biopsy specimens were evaluated in immunohistochemically stained sections for apoptosis-regulating proteins Bcl-2, Bcl-x, Bax, p53, Fas, and Fas-ligand. Apoptotic keratinocytes, determined by a detection method for DNA fragmentation (TUNEL) and by conventional morphologic criteria were counted per high power field. Keratinocyte staining for Bcl-2 protein was comparable in erythema multiforme and controls. Bcl-x expression was reduced in five erythema multiforme cases. Staining for Bax protein differed in six erythema multiforme cases and showed variable intensity in layers under the parakeratin. Only slight differences in staining patterns of Fas and Fas-ligand proteins were noted between erythema multiforme and controls. The number of apoptotic keratinocytes evaluated by morphologic examination was significantly higher in erythema multiforme (mean per high power field, 0.90 +/- 0.2; controls, 0.06 +/- 0.04; p < 0.05, Mann-Whitney test) and was limited in significance by the TUNEL method (erythema multiforme, 0.43 +/- 0.1; controls, 0.02 +/- 0.02). Overexpression of p53 protein was seen in basal keratinocytes in five erythema multiforme specimens (mean, 17.5 +/- 4.03 per high power field; controls 1.2 +/- 0.3). There is evidence that cell death in erythema multiforme is at least in part due to apoptosis. The apoptotic mechanism may be related to an altered expression of apoptosis-regulating proteins. Although measurable alterations in the phenotypic expression of Fas and Fas-ligand proteins were not apparent, activation of Fas/Fas-ligand system could still be involved in the induction of apoptosis in erythema multiforme.

  7. Thyroid dysfunction and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Sima Nazarpour

    2015-07-01

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

  8. Psychological model of adolescent dysfunctionality

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    Cvetkov A. V.

    2016-05-01

    Full Text Available teenage dysfunctionality could be caused by a number of factors, which are an integral part of modern life. Particularly, in this work we considered such factors as uncertainty, frustration, and a mismatch of sexual behavior setting. The path analysis based on using structural equations. The results proved that teenage dysfunctionality is a consequence of the direct effect of the interconnection between moral reflection and moral and ethical responsibility on the perception level of social frustration, corporeality and sexual mismatch.

  9. Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer

    Directory of Open Access Journals (Sweden)

    Jiří Pokorný

    2015-09-01

    Full Text Available Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules’ ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells, and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts, disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition of pyruvate dehydrogenase kinases (phosphatases may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.

  10. Obesity, inflammation and endothelial dysfunction.

    Science.gov (United States)

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  11. Involvement of apoptosis in host-parasite interactions in the zebra mussel.

    Directory of Open Access Journals (Sweden)

    Laëtitia Minguez

    Full Text Available The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro- and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism.

  12. Involvement of Apoptosis in Host-Parasite Interactions in the Zebra Mussel

    Science.gov (United States)

    Minguez, Laëtitia; Brulé, Nelly; Sohm, Bénédicte; Devin, Simon; Giambérini, Laure

    2013-01-01

    The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro- and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp) can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism. PMID:23785455

  13. Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents.

    Science.gov (United States)

    Oropesa-Ávila, Manuel; de la Cruz-Ojeda, Patricia; Porcuna, Jesús; Villanueva-Paz, Marina; Fernández-Vega, Alejandro; de la Mata, Mario; de Lavera, Isabel; Rivero, Juan Miguel Suarez; Luzón-Hidalgo, Raquel; Álvarez-Córdoba, Mónica; Cotán, David; Zaderenko, Ana Paula; Cordero, Mario D; Sánchez-Alcázar, José A

    2017-03-01

    Cell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase activation and final apoptotic cell morphology. In the one referred as "slow" (~h) or round-shaped, apoptosis was characterized by a slow contraction of the actinomyosin ring and late caspase activation. In "slow" apoptosis the γ-tubulin complexes were not disorganized and microtubules were not depolymerized at early stages. In contrast, "fast" (~min) or irregular-shaped apoptosis was characterized by early caspase activation followed by full contraction of the actinomyosin ring. In fast apoptosis γ-tubulin complexes were disorganized and microtubules were initially depolymerized. However, after actinomyosin contraction, microtubules were reformed adopting a cortical but irregular disposition near plasma membrane. In addition to distinctive cytoskeleton reorganization kinetics, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocytes response. Our results suggest that the knowledge and modulation of the type of apoptosis promoted by genotoxic agents may be important for deciding a better therapeutic option and predicting the immune response in cancer treatment.

  14. Nitric oxide bioavailability dysfunction involves in atherosclerosis.

    Science.gov (United States)

    Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long

    2018-01-01

    The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

  15. Interference of Apoptosis by Hepatitis B Virus.

    Science.gov (United States)

    Lin, Shaoli; Zhang, Yan-Jin

    2017-08-18

    Hepatitis B virus (HBV) causes liver diseases that have been a consistent problem for human health, leading to more than one million deaths every year worldwide. A large proportion of hepatocellular carcinoma (HCC) cases across the world are closely associated with chronic HBV infection. Apoptosis is a programmed cell death and is frequently altered in cancer development. HBV infection interferes with the apoptosis signaling to promote HCC progression and viral proliferation. The HBV-mediated alteration of apoptosis is achieved via interference with cellular signaling pathways and regulation of epigenetics. HBV X protein (HBX) plays a major role in the interference of apoptosis. There are conflicting reports on the HBV interference of apoptosis with the majority showing inhibition of and the rest reporting induction of apoptosis. In this review, we described recent studies on the mechanisms of the HBV interference with the apoptosis signaling during the virus infection and provided perspective.

  16. Interference of Apoptosis by Hepatitis B Virus

    Science.gov (United States)

    2017-01-01

    Hepatitis B virus (HBV) causes liver diseases that have been a consistent problem for human health, leading to more than one million deaths every year worldwide. A large proportion of hepatocellular carcinoma (HCC) cases across the world are closely associated with chronic HBV infection. Apoptosis is a programmed cell death and is frequently altered in cancer development. HBV infection interferes with the apoptosis signaling to promote HCC progression and viral proliferation. The HBV-mediated alteration of apoptosis is achieved via interference with cellular signaling pathways and regulation of epigenetics. HBV X protein (HBX) plays a major role in the interference of apoptosis. There are conflicting reports on the HBV interference of apoptosis with the majority showing inhibition of and the rest reporting induction of apoptosis. In this review, we described recent studies on the mechanisms of the HBV interference with the apoptosis signaling during the virus infection and provided perspective. PMID:28820498

  17. Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

    Science.gov (United States)

    Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

    2012-11-01

    This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

  18. Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus.

    Science.gov (United States)

    Abdel-Mohsen, Mohamed Ahmed; El-Braky, Ahlam Abd-Allah; Ghazal, Abeer Abd El-Rahim; Shamseya, Mohammed Mohammed

    2018-03-01

    The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect.

  19. The cephalostatin way of apoptosis.

    Science.gov (United States)

    Rudy, Anita; López-Antón, Nancy; Dirsch, Verena M; Vollmar, Angelika M

    2008-03-01

    The cephalostatins, bis-steroidal natural products from the marine tube worm Cephalodiscus gilchristi, were isolated by Dr. G. R. Pettit and his group. These compounds show a unique cytotoxicity profile in the in vitro screen of the National Cancer Institute, suggesting a novel mechanism of action. Indeed, cephalostatin 1 ( 1) is an extremely powerful agent that acts via an unusual apoptosis pathway. It induces selective Smac/DIABLO, but no cytochrome c release from mitochondria. Nevertheless, caspase-9 is required for apoptosis induction. Interestingly, caspase-9 is activated without the participation of the apoptosome, leading to the question of its mechanism of activation. We found that endoplasmic reticulum stress-associated caspase-4 contributes to nonclassical cephalostatin-mediated caspase-9 activation, additionally pointing out the unusual pathway used by this substance. Cephalostatin 1 ( 1), therefore, provides a very good tool to discover novel apoptotic pathways, which might be important in the understanding and treatment of chemo-resistant cancer.

  20. Methylselenium and Prostate Cancer Apoptosis

    Science.gov (United States)

    2003-02-01

    miethylselenol generated in cell-culture medium by described previously [12,15]. All cell-culture workwas performed without antibiotics . L-methionine-cL-deamino...Thompson HJ. Effect of 16. Datta SR, Brunet A, Greenberg ME. Cellular survival: A play an aqueous extract of selenium enriched garlic on in vitro in three... garlic on in vitro markers and relationship to caspase-mediated apoptosis execution. The in vivo efficacy in cancer prevention. Carcinogenesis (Lond.), 17

  1. Shear Stress Inhibits Apoptosis of Ischemic Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiafeng Shen

    2013-01-01

    Full Text Available As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF is the most fundamental option. Laminar shear stress (LS, as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs. In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process.

  2. Senescence and apoptosis: dueling or complementary cell fates?

    Science.gov (United States)

    Childs, Bennett G; Baker, Darren J; Kirkland, James L; Campisi, Judith; van Deursen, Jan M

    2014-01-01

    In response to a variety of stresses, mammalian cells undergo a persistent proliferative arrest known as cellular senescence. Many senescence-inducing stressors are potentially oncogenic, strengthening the notion that senescence evolved alongside apoptosis to suppress tumorigenesis. In contrast to apoptosis, senescent cells are stably viable and have the potential to influence neighboring cells through secreted soluble factors, which are collectively known as the senescence-associated secretory phenotype (SASP). However, the SASP has been associated with structural and functional tissue and organ deterioration and may even have tumor-promoting effects, raising the interesting evolutionary question of why apoptosis failed to outcompete senescence as a superior cell fate option. Here, we discuss the advantages that the senescence program may have over apoptosis as a tumor protective mechanism, as well as non-neoplastic functions that may have contributed to its evolution. We also review emerging evidence for the idea that senescent cells are present transiently early in life and are largely beneficial for development, regeneration and homeostasis, and only in advanced age do senescent cells accumulate to an organism’s detriment. PMID:25312810

  3. Sexual Dysfunction in Interstitial Cystitis.

    Science.gov (United States)

    Tonyali, Senol; Yilmaz, Mehmet

    2017-11-01

    Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a debilitating disease characterized with urgency, frequency, and pelvic pain affecting especially women. Sexual dysfunction in female patients with IC/BPS consists of dyspareunia, altered sexual desire and orgasm frequency and insufficient lubrication is reported to negatively affect the patient's quality of life. In the present study, we aimed to determine the association between IC/BPS and sexual dysfunction and improvement in sexual dysfunction related to given treatments. A PubMed/Medline and EMBASE search was conducted using keywords: "interstitial cystitis", "sexual dysfunction", and "bladder pain syndrome". Several studies have been conducted to determine the relation between IC/BPS and sexual dysfunction. And also limited studies focusing on IC/BPS specific treatments reported significant improvements in sexual function after either oral or intravesical treatment. However, given the used different questionnaires, study protocols, patient characteristics, previous treatments and follow-up period, it is not possible to make a head-to-head comparison of the treatment effects on sexual function. Further, randomized controlled studies are needed to confirm these results and make a comparison between effects of various treatment modalities on sexual functioning in IC/BPS.

  4. Deltamethrin-induced testicular apoptosis in rats: the protective effect of nitric oxide synthase inhibitor.

    Science.gov (United States)

    El-Gohary, M; Awara, W M; Nassar, S; Hawas, S

    1999-01-01

    This study is the first to examine and characterize the testicular apoptosis which might be induced due to exposure of male rats to deltamethrin. Furthermore, the role which might be played by nitric oxide (NO), as well as the other reactive oxygen species (ROS) in controlling this testicular apoptosis was assessed. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis and cellular morphology on testicular tissue sections. It was found that administration of deltamethrin (1 mg/kg daily for 21 days) to animals resulted in characteristic DNA migration patterns (laddering), thereby providing evidence that apoptosis is the major mechanism of cell death in the testicular tissues. In addition, histopathological examination of testicular tissue sections showed that apoptosis was confined to the basal germ cells, primary and secondary spermatocytes. These changes, in addition to the appearance of Sertoli cell vacuoles in deltamethrin-intoxicated animals, indicates the suppression of spermatogenesis. At the same time, the plasma levels of both NO and lipid peroxides measured as malondialdehyde (MDA) were found to be significantly increased in deltamethrin-treated animals. Administration of NO synthase (NOS) inhibitors such as N(G)-nitro monomethyl L-arginine hydrochloride (L-NMMA, 1 mg/kg) to rats 2 h before exposure to deltamethrin was effective in the reduction of the typically testicular apoptotic DNA fragmentation pattern and the associated histopathological changes. These findings may suggest that deltamethrin-induced testicular apoptosis is mediated by NO. Therefore, the pharmacological manipulation of apoptosis by selective NOS inhibitors such as L-NMMA may offer new possibilities for the control of deltamethrin-induced testicular dysfunction and infertility in the future.

  5. New insights into the gut as the driver of critical illness and organ failure.

    Science.gov (United States)

    Meng, Mei; Klingensmith, Nathan J; Coopersmith, Craig M

    2017-04-01

    The gut has long been hypothesized to be the 'motor' of multiple organ dysfunction syndrome. This review serves as an update on new data elucidating the role of the gut as the propagator of organ failure in critical illness. Under basal conditions, the gut absorbs nutrients and serves as a barrier that prevents approximately 40 trillion intraluminal microbes and their products from causing host injury. However, in critical illness, gut integrity is disrupted with hyperpermeability and increased epithelial apoptosis, allowing contamination of extraluminal sites that are ordinarily sterile. These alterations in gut integrity are further exacerbated in the setting of preexisting comorbidities. The normally commensal microflora is also altered in critical illness, with increases in microbial virulence and decreases in diversity, which leads to further pathologic responses within the host. All components of the gut are adversely impacted by critical illness. Gut injury can not only propagate local damage, but can also cause distant injury and organ failure. Understanding how the multifaceted components of the gut interact and how these are perturbed in critical illness may play an important role in turning off the 'motor' of multiple organ dysfunction syndrome in the future.

  6. Brain-Derived Neurotrophic Factor Attenuates Septic Myocardial Dysfunction via eNOS/NO Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Ni Zeng

    2017-01-01

    Full Text Available Sepsis-induced myocardial dysfunction increases mortality in sepsis, yet the underlying mechanism is unclear. Brain-derived neurotrophic factor (BDNF has been found to enhance cardiomyocyte function, but whether BDNF has a beneficial effect against septic myocardial dysfunction is unknown. Septic shock was induced by cecal ligation and puncture (CLP. BDNF was expressed in primary cardiomyocytes, and its expression was significantly reduced after sepsis. In rats with sepsis, a sharp decline in survival was observed after CLP, with significantly reduced cardiac BDNF expression, enhanced myocardial fibrosis, elevated oxidative stress, increased myocardial apoptosis, and decreased endothelial nitric oxide (NO synthase (eNOS and NO. Supplementation with recombined BDNF protein (rhBDNF enhanced myocardial BDNF and increased survival rate with improved cardiac function, reduced oxidative stress, and myocardial apoptosis, which were associated with increased eNOS expression, NO production, and Trk-B, a BDNF receptor. Pretreatment with NOS inhibitor, N (omega-nitro-L-arginine methyl ester, abolished the abovementioned BDNF cardioprotective effects without affecting BDNF and Trk-B. It is concluded that BDNF protects the heart against septic cardiac dysfunction by reducing oxidative stress and apoptosis via Trk-B, and it does so through activation of eNOS/NO pathway. These findings provide a new treatment strategy for sepsis-induced myocardial dysfunction.

  7. Sexual dysfunctions in psoriatic patients

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2015-04-01

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

  8. Managing the workforce reduction: hospital CEO perceptions of organizational dysfunction.

    Science.gov (United States)

    Rondeau, Kent V; Wagar, Terry H

    2002-01-01

    Over the past few years many nations have undertaken activities aimed at restructuring and reengineering their health system as a means of achieving greater cost effectiveness and consumer responsiveness. Most efforts at reforming healthcare delivery have been accompanied by the downsizing of healthcare organizations. Organizations that are undergoing decline or significant workforce contractions are widely believed to experience a number of negative or dysfunctional attributes as a consequence of reductions in, or redeployments of, their labor force. For organizations undergoing planned workforce reductions, much speculation has been made in an attempt to identify a set of "best practices" that have the potential to mitigate the dysfunctional consequences associated with large permanent reductions in the workforce. This article explores the relationships among workforce-reduction practices and perceptions of organizational dysfunction in a large sample of Canadian hospitals. Results of the analysis suggest that the application of certain "progressive" workforce-reduction practices preceding, during, and subsequent to the downsizing process may play an important role in mitigating some of these dysfunctional organizational consequences. This research provides some evidence to suggest that how a workforce reduction is carried out may have a greater effect on organizational effectiveness than either the magnitude or severity of the overall workforce reduction.

  9. GASTROINTESTINAL MANIFESTATIONS OF MITOCHONDRIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    A. A. Ziganshina

    2016-01-01

    Full Text Available Objective: to highlight the current concepts of gastrointestinal manifestations of mitochondrial dysfunction. The data available in Russian and foreign literature on the gastrointestinal manifestations of mitochondrial dysfunction were analyzed. Functional digestive diseases are common in pediatric practice; however, their etiopathogenesis has not been adequately explored today. According to the literature, impaired cellular energy metabolism may underlie gastrointestinal motility disorders in cyclic vomiting syndrome, gastroesophageal reflux, gastric stasis, chronic diarrhea, constipation, intestinal pseudoobstruction, malabsorption syndrome, irritable bowel syndrome, as well as diseases of the liver and pancreas.

  10. Hormonal Changes and Sexual Dysfunction.

    Science.gov (United States)

    Zhou, Eric S; Frederick, Natasha N; Bober, Sharon L

    2017-11-01

    Sexual dysfunction is a common concern for many patients with cancer after treatment. Hormonal changes as a result of cancer-directed therapy can affect both male and female sexual health. This has the potential to significantly impact patients' quality of life, but is underreported and undertreated in the oncology setting. This review discusses commonly reported sexual issues and the role that hormonal changes play in this dysfunction. Although medical and psychosocial intervention strategies exist, there is a clear need for further research to formally develop programming that can assist people whose sexual health has been impacted by cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Bladder Dysfunction and Urinary Incontinence

    OpenAIRE

    F. faizi

    2009-01-01

      "nIn the name of God. Dear colleagues, ladies and gentlemen, it is a great honor to be here. Bladder dysfunction is serious enough to seek serious help. If you may know I am working in a private clinic which it is impossible to follow the patients so this lecture is based on unusual and rare cases who came to me. Bladder dysfunction (BD) is common among 30% of young and old people who are suffering from it, however it is more common in old ages. According to a research, women ...

  12. Endocrine dysfunction in patients of leprosy

    Directory of Open Access Journals (Sweden)

    Rohit Kumar Singh

    2015-01-01

    Full Text Available Background: Leprosy is a chronic granulomatous disease and affects many internal organs in addition to the skin and peripheral nerves. Endocrine dysfunction is often silent and is often missed in patients of leprosy leading to significant morbidity. We studied the presence of occult endocrine disorders in leprosy patients and compared the same with disease parameters. Materials and Methods: We evaluated 40 patients of leprosy (aged 18-70 years, any duration in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, gonadal function, and dynamic testing was done when deemed necessary. The participants were divided into two groups: Group 1 (Leprosy, n = 40 and Group 2 (Controls, n = 20 and the data were analyzed with appropriate statistical tests. Results: The study participants (35 males, 5 females had a mean age of 36.4 ± 11.3 years, and duration of the disease was 2.5 ± 5.5 years. Eleven out of 40 patients showed results consistent with an endocrine disorder, including subclinical hypothyroidism (n = 4, sick euthyroid syndrome (n = 3, growth hormone (GH deficiency (n = 2, primary hypogonadism (n = 2 and secondary hypogonadism in one patient. One patient had partial hypopituitarism (GH deficiency and secondary hypogonadism and none of the controls showed any hormonal dysfunction. Testosterone levels showed inverse correlation with the number of skin patches (P = 0.0006. Conclusion: Occult endocrine dysfunction is seen in a quarter of patients with leprosy. Thyroid and gonadal axes abnormalities are common, and the severity is more in lepromatous forms of the disease. Further large studies are required to confirm the findings observed in our study.

  13. RNAi screen reveals a role of SPHK2 in dengue virus-mediated apoptosis in hepatic cell lines.

    Directory of Open Access Journals (Sweden)

    Atthapan Morchang

    Full Text Available Hepatic dysfunction is a feature of dengue virus (DENV infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show apoptosis, which relates to the pathogenesis of DENV infection. However, how DENV induced liver injury is not fully understood. In this study, we aim to identify the factors that influence cell death by employing an apoptosis-related siRNA library screening. Our results show the effect of 558 gene silencing on caspase 3-mediated apoptosis in DENV-infected Huh7 cells. The majority of genes that contributed to apoptosis were the apoptosis-related kinase enzymes. Tumor necrosis factor superfamily member 12 (TNFSF12, and sphingosine kinase 2 (SPHK2, were selected as the candidate genes to further validate their influences on DENV-induced apoptosis. Transfection of siRNA targeting SPHK2 but not TNFSF12 genes reduced apoptosis determined by Annexin V/PI staining. Knockdown of SPHK2 did not reduce caspase 8 activity; however, did significantly reduce caspase 9 activity, suggesting its involvement of SPHK2 in the intrinsic pathway of apoptosis. Treatment of ABC294649, an inhibitor of SPHK2, reduced the caspase 3 activity, suggesting the involvement of its kinase activity in apoptosis. Knockdown of SPHK2 significantly reduced caspase 3 activity not only in DENV-infected Huh7 cells but also in DENV-infected HepG2 cells. Our results were consistent across all of the four serotypes of DENV infection, which supports the pro-apoptotic role of SPHK2 in DENV-infected liver cells.

  14. Recognition and Management of Nonrelaxing Pelvic Floor Dysfunction

    Science.gov (United States)

    Faubion, Stephanie S.; Shuster, Lynne T.; Bharucha, Adil E.

    2012-01-01

    Nonrelaxing pelvic floor dysfunction is not widely recognized. Unlike in pelvic floor disorders caused by relaxed muscles (eg, pelvic organ prolapse or urinary incontinence, both of which often are identified readily), women affected by nonrelaxing pelvic floor dysfunction may present with a broad range of nonspecific symptoms. These may include pain and problems with defecation, urination, and sexual function, which require relaxation and coordination of pelvic floor muscles and urinary and anal sphincters. These symptoms may adversely affect quality of life. Focus on the global symptom complex, rather than the individual symptoms, may help the clinician identify the condition. The primary care provider is in a position to intervene early, efficiently, and effectively by (1) recognizing the range of symptoms that might suggest nonrelaxing pelvic floor dysfunction, (2) educating patients, (3) performing selective tests when needed to confirm the diagnosis, and (4) providing early referral for physical therapy. PMID:22305030

  15. Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

    Directory of Open Access Journals (Sweden)

    Mihail V. Pokrovskiy

    2011-01-01

    Full Text Available This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction.

  16. Vasoactive substances in the circulatory dysfunction of cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens Henrik

    2001-01-01

    . Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions...... are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide...... and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction influencing the course of the disease, with reduction of organ...

  17. Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension.

    Science.gov (United States)

    Xu, Weiling; Erzurum, Serpil C

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary hemodynamics and excessive growth and dysfunction of the endothelial cells that line the arteries in PAH lungs. Establishment of methods for culture of pulmonary artery endothelial cells from PAH lungs has provided the groundwork for mechanistic translational studies that confirm and extend findings from model systems and spontaneous pulmonary hypertension in animals. Endothelial cell hyperproliferation, survival, and alterations of biochemical-metabolic pathways are the unifying endothelial pathobiology of the disease. The hyperproliferative and apoptosis-resistant phenotype of PAH endothelial cells is dependent upon the activation of signal transducer and activator of transcription (STAT) 3, a fundamental regulator of cell survival and angiogenesis. Animal models of PAH, patients with PAH, and human PAH endothelial cells produce low nitric oxide (NO). In association with the low level of NO, endothelial cells have reduced mitochondrial numbers and cellular respiration, which is associated with more than a threefold increase in glycolysis for energy production. The shift to glycolysis is related to low levels of NO and likely to the pathologic expression of the prosurvival and proangiogenic signal transducer, hypoxia-inducible factor (HIF)-1, and the reduced mitochondrial antioxidant manganese superoxide dismutase (MnSOD). In this article, we review the phenotypic changes of the endothelium in PAH and the biochemical mechanisms accounting for the proliferative, glycolytic, and strongly proangiogenic phenotype of these dysfunctional cells, which consequently foster the panvascular progressive pulmonary remodeling in PAH. © 2011 American Physiological Society.

  18. Laryngeal Dysfunction: Assessment and Management for the Clinician.

    Science.gov (United States)

    Hull, James H; Backer, Vibeke; Gibson, Peter G; Fowler, Stephen J

    2016-11-01

    The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex, and highly evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing, and phonation. In some situations the larynx appears to adopt a functional state that could be considered maladaptive or "dysfunctional." This laryngeal dysfunction can underpin and account for a number of respiratory symptoms that otherwise appear incongruous with a clinical disease state and/or contribute to the development of symptoms that appear "refractory" to treatment. These include conditions associated with a heightened tendency for inappropriate laryngeal closure (e.g., inducible laryngeal obstruction), voice disturbance, and chronic cough. Recognition of laryngeal dysfunction is important to deliver targeted treatment and failure to recognize the condition can lead to repeated use of inappropriate treatment. Diagnosis is not straightforward, however, and many patients appear to present with symptoms attributable to laryngeal dysfunction, but in whom the diagnosis has been overlooked in clinical work-up for some time. This review provides an overview of the current state of knowledge in the field of laryngeal dysfunction, with a focus on pragmatic clinical assessment and management.

  19. Relationship between female pelvic floor dysfunction and sexual dysfunction: an observational study.

    Science.gov (United States)

    Bortolami, Arianna; Vanti, Carla; Banchelli, Federico; Guccione, Andrew A; Pillastrini, Paolo

    2015-05-01

    The ability to express one's sexuality and engage in sexual activity requires multisystemic coordination involving many psychological functions as well as the integrity of the nervous, hormonal, vascular, immune, and neuromuscular body structures and functions. The purpose of this study was to investigate the associations among pelvic floor function, sexual function, and demographic and clinical characteristics in a population of women initiating physical therapy evaluation and treatment for pelvic floor-related dysfunctions (urinary incontinence, pelvic organ prolapse, vulvodynia, vaginismus, and constipation). We consented and collected completed demographic data and data related to symptoms and clinical condition on 85 consecutive patients in an outpatient physical therapy clinic. Clinical and anthropometric characteristics were analyzed descriptively. Analysis of variance and linear regression analyses were used to analyze Female Sexual Function Index (FSFI) scale ratings, whereas zero-inflated beta-binomial regression was applied to the pain subscale. Main outcome measure was FSFI score, whereas the secondary outcome measure was the FSFI subscale score related to pain. Women in our sample were 38 years old on average, 33% of whom had given birth and 82% of whom had high tone pelvic floor. Being in the middle-tercile age group and exhibiting low pelvic floor tone (Beta = 6.8; 95% confidence interval [CI] = [1.4; 12.0]) were significantly associated with lower levels of sexual dysfunction. Women with low tone pelvic floor also reported lower pain (odds ratio = 4.0; 95% CI = [1.6; 9.6]), whereas younger aged and physically unsatisfied subjects were more likely not to have sexual activity in the month prior to scale measurement. In female patients with pelvic floor muscle dysfunction undergoing physical therapy and rehabilitation, sexual dysfunction appears to be significantly correlated with age and high pelvic floor muscle tone. © 2015

  20. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  1. Pelvic floor and sexual male dysfunction

    Directory of Open Access Journals (Sweden)

    Antonella Pischedda

    2013-04-01

    Full Text Available The pelvic floor is a complex multifunctional structure that corresponds to the genito- urinary-anal area and consists of muscle and connective tissue. It supports the urinary, fecal, sexual and reproductive functions and pelvic statics. The symptoms caused by pelvic floor dysfunction often affect the quality of life of those who are afflicted, worsening significantly more aspects of daily life. In fact, in addition to providing support to the pelvic organs, the deep floor muscles support urinary continence and intestinal emptying whereas the superficial floor muscles are involved in the mechanism of erection and ejaculation. So, conditions of muscle hypotonia or hypertonicity may affect the efficiency of the pelvic floor, altering both the functionality of the deep and superficial floor muscles. In this evolution of knowledge it is possible imagine how the rehabilitation techniques of pelvic floor muscles, if altered and able to support a voiding or evacuative or sexual dysfunction, may have a role in improving the health and the quality of life.

  2. Thyroid dysfunction in the elderly

    African Journals Online (AJOL)

    1997-09-09

    thirds of the subjects in this study. The serum TSH concentration is a reliable screening test for thyroid dysfunction in the elderly, but is less useful if used to identify biochemical thyroid disease. An elevated TSH concentration is a ...

  3. Sweating dysfunction in Parkinson's disease

    NARCIS (Netherlands)

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

    2003-01-01

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

  4. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

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

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

  5. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

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

    2012-01-01

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

  6. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

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

    2012-01-01

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

  7. Medical therapy and smell dysfunction

    NARCIS (Netherlands)

    Hellings, P. W.; Rombaux, P.

    2009-01-01

    Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in different nasal inflammatory conditions like common cold, allergic rhinitis, and acute and chronic rhinosinusitis with and without nasal polyps (NP). The mechanism underlying olfactory impairment in

  8. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats

    International Nuclear Information System (INIS)

    Flora, Swaran J.S.; Bhatt, Kapil; Mehta, Ashish

    2009-01-01

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  9. MST1 is a novel regulator of apoptosis in pancreatic beta-cells

    Science.gov (United States)

    Ardestani, Amin; Khobragade, Vrushali; Yuan, Ting; Frogne, Thomas; Tao, Wufan; Oberholzer, Jose; Pattou, Francois; Conte, Julie Kerr; Maedler, Kathrin

    2014-01-01

    Apoptotic cell death is a hallmark of the loss of insulin producing beta-cells in all forms of diabetes mellitus. Current treatment fails to halt the decline in functional beta-cell mass. Strategies to prevent beta-cell apoptosis and dysfunction are urgently needed. Here, we identified Mammalian Sterile 20-like kinase 1 (MST1) as a critical regulator of apoptotic beta-cell death and function. MST1 was strongly activated in beta-cells under diabetogenic conditions and correlated with beta-cell apoptosis. MST1 specifically induced the mitochondrial-dependent pathway of apoptosis in beta-cells through up-regulation of the BH3-only protein Bim. MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion. Mst1 deficiency completely restored normoglycemia, beta-cell function and survival in vitro and in vivo. We show MST1 as novel pro-apoptotic kinase and key mediator of apoptotic signaling and beta-cell dysfunction, which may serve as target for the development of novel therapies for diabetes. PMID:24633305

  10. Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats.

    Science.gov (United States)

    Flora, Swaran J S; Bhatt, Kapil; Mehta, Ashish

    2009-10-15

    Gallium arsenide (GaAs), an intermetallic semiconductor finds widespread applications in high frequency microwave and millimeter wave, and ultra fast supercomputers. Extensive use of GaAs has led to increased exposure to humans working in semiconductor industry. GaAs has the ability to dissociate into its constitutive moieties at physiological pH and might be responsible for the oxidative stress. The present study was aimed at evaluating, the principle moiety (Ga or As) in GaAs to cause neurological dysfunction based on its ability to cause apoptosis, in vivo and in vitro and if this neuronal dysfunction translated to neurobehavioral changes in chronically exposed rats. Result indicated that arsenic moiety in GaAs was mainly responsible for causing oxidative stress via increased reactive oxygen species (ROS) and nitric oxide (NO) generation, both in vitro and in vivo. Increased ROS further caused apoptosis via mitochondrial driven pathway. Effects of oxidative stress were also confirmed based on alterations in antioxidant enzymes, GPx, GST and SOD in rat brain. We noted that ROS induced oxidative stress caused changes in the brain neurotransmitter levels, Acetylcholinesterase and nitric oxide synthase, leading to loss of memory and learning in rats. The study demonstrates for the first time that the slow release of arsenic moiety from GaAs is mainly responsible for oxidative stress induced apoptosis in neuronal cells causing behavioral changes.

  11. Mechanisms of Neuronal Apoptosis In Vivo

    National Research Council Canada - National Science Library

    Martin, Lee J

    2004-01-01

    .... Neuronal cell death in the form of apoptosis or necrosis occurs after exposure to neurotoxins, chemical warfare agents, radiation, viruses, and after seizures, trauma, limb amputation, and hypoxic...

  12. Apoptosis in cancer: from pathogenesis to treatment

    Directory of Open Access Journals (Sweden)

    Wong Rebecca SY

    2011-09-01

    Full Text Available Abstract Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

  13. Mitochondrial Dynamics: Functional Link with Apoptosis

    Directory of Open Access Journals (Sweden)

    Hidenori Otera

    2012-01-01

    Full Text Available Mitochondria participate in a variety of physiologic processes, such as ATP production, lipid metabolism, iron-sulfur cluster biogenesis, and calcium buffering. The morphology of mitochondria changes dynamically due to their frequent fusion and division in response to cellular conditions, and these dynamics are an important constituent of apoptosis. The discovery of large GTPase family proteins that regulate mitochondrial dynamics, together with novel insights into the role of mitochondrial fusion and fission in apoptosis, has provided important clues to understanding the molecular mechanisms of cellular apoptosis. In this paper, we briefly summarize current knowledge of the role of mitochondrial dynamics in apoptosis and cell pathophysiology in mammalian cells.

  14. Mitochondrial dynamics: functional link with apoptosis.

    Science.gov (United States)

    Otera, Hidenori; Mihara, Katsuyoshi

    2012-01-01

    Mitochondria participate in a variety of physiologic processes, such as ATP production, lipid metabolism, iron-sulfur cluster biogenesis, and calcium buffering. The morphology of mitochondria changes dynamically due to their frequent fusion and division in response to cellular conditions, and these dynamics are an important constituent of apoptosis. The discovery of large GTPase family proteins that regulate mitochondrial dynamics, together with novel insights into the role of mitochondrial fusion and fission in apoptosis, has provided important clues to understanding the molecular mechanisms of cellular apoptosis. In this paper, we briefly summarize current knowledge of the role of mitochondrial dynamics in apoptosis and cell pathophysiology in mammalian cells.

  15. Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

    Science.gov (United States)

    Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping

    2015-07-01

    Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control.

  16. Apoptosis and Molecular Targeting Therapy in Cancer

    Science.gov (United States)

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  17. Effects of low dose radiation on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2003-01-01

    Objective: To study the effect of low dose radiation (LDR) on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice. Methods: Kunming stain male mice were implanted with S180 sarcoma cells in the left inguen subcutaneously as an in situ experimental animal model. Seven days after implantation, the mice were given 75 mGy whole-body γ-irradiation. At 24 and 48 h after irradiation, all mice were sacrificed to measure the tumor volume, and tumor cell apoptosis, cell cycle progression were analyzed by flow cytometry. The expression of apoptosis-related protein bcl-2 and the apoptotic rate of tumor cells were observed by immunohistochemistry and electron microscopy. Results: Tumor growth was significantly slowed down after LDR (P 1 phase and the expression of bcl-2 protein decreased at 24 h. Apoptotic rate of tumor cells increased significantly at 48 h after LDR. Conclusion: LDR could cause a G 1 -phase arrest and increase the apoptosis of tumor cells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. The organized immune function and anti-tumor ability are markedly increased after LDR. The study provides practical evidence of clinical application to cancer treatment

  18. Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomal-mitochondrial axis.

    Science.gov (United States)

    Chang, Ye; Li, Yuan; Ye, Ning; Guo, Xiaofan; Li, Zhao; Sun, Guozhe; Sun, Yingxian

    2016-09-01

    This study was aimed to evaluate lysosomes-mitochondria cross-signaling in angiotensin II (Ang II)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and whether atorvastatin played a protective role via lysosomal-mitochondrial axis. Apoptosis was detected by flow cytometry, Hoechst 33342 and AO/EB assay. The temporal relationship of lysosomal and mitochondrial permeabilization was established. Activity of Cathepsin D (CTSD) was suppressed by pharmacological and genetic approaches. Proteins production were measured by western blotting. Our study showed that Ang II could induce the apoptosis of HUVECs in a dose-depended and time-depended manner. Exposure to 1 μM Ang II for 24 h resulted in mitochondrial depolarization, cytochrome c release, and increased ROS production. Lysosomal permeabilization and CTSD redistribution into the cytoplasm occurred several hours prior to mitochondrial dysfunction. These effects were all suppressed by atorvastatin. Either pharmacological or genetic inhibition of CTSD preserved mitochondrial function and decreased apoptosis in HUVECs. Most importantly, we found that the protective effect of atorvastatin was significantly greater than pharmacological or genetic inhibition of CTSD. Finally, overexpression of CTSD without exposure to Ang II had no effect on mitochondrial function and apoptosis. Our data strongly suggested that Ang II induced apoptosis through the lysosomal-mitochondrial axis in HUVECs. Furthermore, atorvastatin played an important role in the regulation of lysosomes and mitochondria stability, resulting in an antagonistic role against Ang II on HUVECs.

  19. miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Dong, Xiujuan; Yang, Long; Wang, Hui

    2017-04-01

    The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

  20. Nanoparticles of barium induce apoptosis in human phagocytes.

    Science.gov (United States)

    Mores, Luana; França, Eduardo Luzia; Silva, Núbia Andrade; Suchara, Eliane Aparecida; Honorio-França, Adenilda Cristina

    2015-01-01

    Nutrients and immunological factors of breast milk are essential for newborn growth and the development of their immune system, but this secretion can contain organic and inorganic toxins such as barium. Colostrum contamination with barium is an important issue to investigate because this naturally occurring element is also associated with human activity and industrial pollution. The study evaluated the administration of barium nanoparticles to colostrum, assessing the viability and functional activity of colostral mononuclear phagocytes. Colostrum was collected from 24 clinically healthy women (aged 18-35 years). Cell viability, superoxide release, intracellular Ca(2+) release, and phagocyte apoptosis were analyzed in the samples. Treatment with barium lowered mononuclear phagocyte viability, increased superoxide release, and reduced intracellular calcium release. In addition, barium increased cell death by apoptosis. These data suggest that nanoparticles of barium in colostrum are toxic to cells, showing the importance of avoiding exposure to this element.

  1. Prevalence of Sexual Dysfunction and Associations with Psychiatric Disorders Among Women Aged 50 and Older.

    Science.gov (United States)

    Park, Jee Eun; Sohn, Ji Hoon; Seong, Su Jeong; Cho, Maeng Je

    2015-06-01

    This study investigated the prevalence of sexual problems and associated factors, focusing particularly on comorbid psychiatric disorders, among older Korean women. A nationally representative sample of women aged 50-74 years (n=3828) responded to in-person interviews using the Korean version of the Composite International Diagnostic Interview to assess psychiatric disorders and four symptoms of sexual dysfunction: (1) lack of sexual interest/sexual aversion, (2) dyspareunia, (3) loss of pleasure, and (4) other organic dysfunction (e.g., inability of sexual arousal). We examined the likelihood of sexual dysfunction by sociodemographic and clinical variables, including specific psychiatric disorders, and compared the characteristics of sexual dysfunction among women with and without a comorbid psychiatric disorder. A total of 334 (8.7%) women reported one or more symptoms of sexual dysfunction during the year preceding the interview: lack of sexual interest/sexual aversion was most prevalent (7.7%), followed by loss of pleasure (4.2%), dyspareunia (2.4%), and other organic dysfunction (0.4%). Having a psychiatric disorder was associated with a 2.7-fold increase in the probability of sexual dysfunction. Among women with sexual dysfunction, having comorbid mental disorder was associated with being unmarried status, a symptom of loss of pleasure, and a history of sexual dysfunction before 50 years of age. The present study suggests a relatively lower prevalence of sexual dysfunction than previously reported, but supports its strong association with psychiatric disorders among postmenopausal women. We should evaluate comorbid mental disorder with sexual dysfunction, especially among those having some characteristics.

  2. Load dependent diastolic dysfunction in heart failure

    NARCIS (Netherlands)

    Gillebert, T. C.; Leite-Moreira, A. F.; de Hert, S. G.

    2000-01-01

    Congestive heart failure may result from cardiovascular overload, from systolic or from diastolic dysfunction. Diastolic left ventricular dysfunction may result from structural resistance to filling such as induced by pericardial constraint, right ventricular compression, increased chamber stiffness

  3. Apoptosis Gene Hunting Using Retroviral Expression Cloning: Identification of Vacuolar ATPase Subunit E

    Directory of Open Access Journals (Sweden)

    Claire L. Anderson

    2003-01-01

    Full Text Available Over the past 10-15 years there has been an explosion of interest in apoptosis. The delayed realisation that cell death is an essential part of life for any multicellular organism has meant that, despite the recent and rapid developments of the last decade, the precise biochemical pathways involved in apoptosis remain incomplete and potentially novel genes may, as yet, remain undiscovered. The hunt is therefore on to bridge the remaining gaps in our knowledge. Our contribution to this research effort utilises a functional cloning approach to isolate important regulatory genes involved in apoptosis. This mini-review focuses on the use and advantages of a retroviral expression cloning strategy and describes the isolation and identification of one such potential apoptosis regulatory gene, namely that encoding vacuolar ATPase subunit E.

  4. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  5. History of the Treatment of Female Sexual Dysfunction(s).

    Science.gov (United States)

    Kleinplatz, Peggy J

    2018-01-22

    This article reviews the history of the treatment of women's sexual problems from the Victorian era to the twenty-first century. The contextual nature of determining what constitutes female sexual psychopathology is highlighted. Conceptions of normal sexuality are subject to cultural vagaries, making it difficult to identify female sexual dysfunctions. A survey of the inclusion, removal, and collapsing of women's sexual diagnoses in the Diagnostic and Statistical Manual of Mental Disorders from 1952 to 2013 illuminates the biases in the various editions. Masters and Johnson's models of sexual response and dysfunction paved the way for the diagnosis and treatment of women's sexual dysfunctions. Their sex therapy paradigm is described. Conceptions of and treatments for anorgasmia, arousal difficulties, vaginismus, dyspareunia, and low desire are reviewed. The medicalization of human sexuality and the splintering of sex therapy are discussed, along with current trends and new directions in sexual health care for women. Expected final online publication date for the Annual Review of Clinical Psychology Volume 14 is May 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  6. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2012-09-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  7. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    International Nuclear Information System (INIS)

    Lee, Jeong Eun; Park, Jae Hyeon; Shin, In Chul; Koh, Hyun Chul

    2012-01-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  8. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    Science.gov (United States)

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic

  9. Inhibition of apoptosis in T cells expressing human T cell leukemia virus type I Tax.

    Science.gov (United States)

    Copeland, K F; Haaksma, A G; Goudsmit, J; Krammer, P H; Heeney, J L

    1994-10-01

    This study set out to determine whether T cell dysfunction associated with HTLV-I led to increased sensitivity of infected cells to apoptosis or, owing to their potential to develop ATL, if infected cells would become resistant to this process. To test this hypothesis we utilized the monoclonal antibody anti-APO-1, which has been demonstrated to induce apoptosis in human T cells. Human T cell lines expressing HTLV-I showed reduced susceptibility to anti-APO-1-induced apoptosis despite expression of high levels of cell surface APO-1. Cell-free supernatant of the Tax-expressing cell line C8166 and heat-inactivated supernatant of the HTLV-I-producing cell line MT2 transferred increased resistance to anti-APO-1 to susceptible Jurkat T cells. Susceptible T cells transfected with an HTLV-I Tax-expressing vector or treated with soluble Tax protein became less susceptible to anti-APO-1-induced cell death. Furthermore, primary human lymphocytes treated with soluble Tax were less susceptible to apoptosis induced by anti-APO-1. The protective effect of Tax in T cell lines and primary human lymphocytes was reversed by the addition of anti-Tax antibodies. Anti-APO-1-induced apoptosis was also found to be inhibited in Jurkat cells by the induction of protein kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate (TPA). Resistance to apoptosis conferred by HTLV-I Tax and an active PKC pathway may be factors contributing to the survival of dysregulated HTLV-I-infected T cells prone to the development of adult T cell leukemia.

  10. Erectile dysfunction among men attending surgical outpatients ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction is becoming a public health issue with high incidences reported in community studies. Objective: To evaluate the characteristics and outcome of treatment in men with erectile dysfunction in a tertiary center in Ibadan southwestern Nigeria. Methods: Data of men with erectile dysfunction was ...

  11. The treatment of autonomic dysfunction in tetanus

    African Journals Online (AJOL)

    may either be spontaneous or triggered by touch, visual, auditory or emotional stimuli.[7] Autonomic dysfunction may occur, and does not necessarily correlate with the severity of tetanus. Wassay et al.[8] reported autonomic dysfunction in a third of tetanus cases. Autonomic dysfunction presents as labile hypertension, ...

  12. CORRECTION OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC COR PULMONALE BY ANGIOTENSIN II RECEPTORS ANTAGONISTS

    Directory of Open Access Journals (Sweden)

    V. S. Zadionchenko

    2007-01-01

    Full Text Available Aim. To evaluate intensity of endothelial dysfunction, processes of apoptosis, state of central and peripheral hemodynamics and to evaluate how these characteristics are influenced by angiotensin II receptors antagonists (ARA II – candesartan (Atacand and losartan (Cosaar in patients with chronic cor pulmonale (CCP at different stages of disease.Material and methods. 100 patients with chronic obstructive pulmonary disease (COPD, complicated by CCP were included into the study. Caspase activity as apoptosis induction marker, von Willebrand factor, production of nitric oxide in blood plasma and condensate of breathing out air were assessed. 70 patients received ARA II (50 patients – candesartan 4-8 mg daily, 20 patients – losartan 50-100 mg daily, 30 patients received neither ARA II nor angiotensin converting enzyme inhibitors (ACEI.Results. Significant increase in intensity of endothelial dysfunction and activation of apoptosis processes were registered according to growth of CCP severity. After 6 months of therapy von Willebrand factor decreased by 25,2% and 27,7% in candesartan and losartan groups respectively (p<0.01 for both groups. In the control group only 13.2% of von Willebrand factor reduction was seen.Conclusion. ARA II added to common therapy of COPD complicated by CCP improves functional state of endothelium restricting hyperproduction of nitric oxide and its toxic effects and slowing down apoptotic cell death.

  13. CORRECTION OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHRONIC COR PULMONALE BY ANGIOTENSIN II RECEPTORS ANTAGONISTS

    Directory of Open Access Journals (Sweden)

    V. S. Zadionchenko

    2015-12-01

    Full Text Available Aim. To evaluate intensity of endothelial dysfunction, processes of apoptosis, state of central and peripheral hemodynamics and to evaluate how these characteristics are influenced by angiotensin II receptors antagonists (ARA II – candesartan (Atacand and losartan (Cosaar in patients with chronic cor pulmonale (CCP at different stages of disease.Material and methods. 100 patients with chronic obstructive pulmonary disease (COPD, complicated by CCP were included into the study. Caspase activity as apoptosis induction marker, von Willebrand factor, production of nitric oxide in blood plasma and condensate of breathing out air were assessed. 70 patients received ARA II (50 patients – candesartan 4-8 mg daily, 20 patients – losartan 50-100 mg daily, 30 patients received neither ARA II nor angiotensin converting enzyme inhibitors (ACEI.Results. Significant increase in intensity of endothelial dysfunction and activation of apoptosis processes were registered according to growth of CCP severity. After 6 months of therapy von Willebrand factor decreased by 25,2% and 27,7% in candesartan and losartan groups respectively (p<0.01 for both groups. In the control group only 13.2% of von Willebrand factor reduction was seen.Conclusion. ARA II added to common therapy of COPD complicated by CCP improves functional state of endothelium restricting hyperproduction of nitric oxide and its toxic effects and slowing down apoptotic cell death.

  14. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    Science.gov (United States)

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  15. Paraoxonases, mitochondrial dysfunction and non-communicable diseases.

    Science.gov (United States)

    Camps, Jordi; García-Heredia, Anabel; Hernández-Aguilera, Anna; Joven, Jorge

    2016-11-25

    The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, cancer, chronic respiratory diseases, and neurological diseases. Together, they constitute the commonest cause of death and disability worldwide. Mitochondrial alterations, oxidative stress and inflammation underpin NCD and are molecular mechanisms playing major roles in the disease onset and natural history. Interrelations between the mechanisms of oxidative stress, inflammation and metabolism are, in the broadest sense of energy transformations, being increasingly recognized as part of the problem in NCD. Whether or not oxidative stress and inflammation are the causes or the consequences of cellular disturbances, they do significantly contribute to NCD. Paraoxonases are associated with mitochondria and mitochondria-associated membranes. They modulate mitochondria-dependent superoxide production, and prevent apoptosis. Their overexpression protects mitochondria from endoplasmic reticulum stress and subsequent mitochondrial dysfunction; highlighting that the anti-inflammatory effects of paraoxonases may be mediated, at least in part, by their protective role in mitochondria and associated organelle function. Since oxidative stress is implicated in the development of NCD (as a result of mitochondrial dysfunction), these data suggest that understanding the role and the molecular targets of paraoxonases may provide novel strategies of intervention in the treatment of these important diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The apoptosis-inducing effect of ginsenoside F4 from steamed notoginseng on human lymphocytoma JK cells.

    Science.gov (United States)

    Chen, Bin; Shen, Yu-Ping; Zhang, Dong-Feng; Cheng, Jie; Jia, Xiao-Bin

    2013-01-01

    In this study, the inhibitory and apoptosis-inducing effect of ginsenoside F4 (GF4) from steamed notoginseng was investigated by using human lymphocytoma Jurkat (JK) cell. Cell Counting Kit-8 method was then used to assess the anti-proliferative effect of GF4, and Western blotting was run to detect the expression level of two apoptosis-related proteins including Bax and the Bcl-2. The results suggested that GF4 can effectively inhibit the proliferation of the cells, and Bax expression increased gradually, but Bcl-2 expression reduced with the increase of GF4 concentration. In conclusion, GF4 has inhibitory effect on human lymphocytoma JK cell by inducing its apoptosis. The mechanism of action could be related to the mitochondrial dysfunction and the increase of Bax expression and decrease of Bcl-2 expression by GF4.

  17. Prevention of Trauma/Hemorrhagic Shock-Induced Mortality,Apoptosis, Inflammation and Mitochondrial Dysfunction

    Science.gov (United States)

    2013-12-01

    with absent surfactant protein D in bronchoalveolar lavage have more frequently 550 pneumonia. Pediatr Allergy Immunol. 2008 Nov;19(7):639-47. 551 28...susceptibility to bacterial infections. Importantly from a mechanistic standpoint, results using a pharmacological inhibitor of Stat3 and mice deficient in...70 in hepatic ischemia-reperfusion injury in mice . Am J Physiol Gastrointest Liver Physiol 292, G1141–9 (2007). 29. Gupta, S. et al. HSP72 protects

  18. Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction

    Science.gov (United States)

    2015-02-01

    through 5 would be performed in Years 1 through 3 as summarized in the Gantt chart below: TIMELINE ( GANTT CHART) YEAR 1 YEAR 2 YEAR 3 Specific Aim 1...Core Facility. Microarray analysis. We used GenespringGX (Agilent Technologies Inc., Santa Clara CA) software package for quality assessment...STATA statistical software package, version 10.0 (StataCorp, College Station, TX). Comparisons of continuous, independent variables were performed

  19. TRAIL promotes membrane blebbing, detachment and migration of cells displaying a dysfunctional intrinsic pathway of apoptosis

    Czech Academy of Sciences Publication Activity Database

    Somasekharan, S.P.; Koc, Michal; Morizot, A.; Micheau, O.; Sorensen, P.H.B.; Gaide, O.; Anděra, Ladislav; Martinou, J.C.

    2013-01-01

    Roč. 18, č. 3 (2013), s. 324-336 ISSN 1360-8185 Institutional support: RVO:68378050 Keywords : TRAIL * membrane blebbing * ROCK1 * HCT116 Bax−/− * cancer cell migration * drug resistance * bortezomib * proteasome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.614, year: 2013

  20. Crosstalk between apoptosis and inflammation in atherosclerosis

    NARCIS (Netherlands)

    Westra, Marijke Marianne

    2010-01-01

    In this thesis the role of several apoptosis regulating proteins in the development of atherosclerosis and atherosclerotic plaque stability is investigated. Apoptosis of different cell types in atherosclerotic plaques, such as macrophages and smooth muscle cells may inhibit or promote plaque

  1. Apoptosis in mammalian oocytes: a review.

    Science.gov (United States)

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

  2. Fas-induced apoptosis in malnourished infants

    African Journals Online (AJOL)

    EL-HAKIM

    deprivation in animals, including man11. Factor of apoptosis signal (Fas) induces apoptosis in activated T cells when they are repeatedly stimulated by antigen and functions to maintain T cell tolerance by deleting auto reactive cells12. The functional role of Fas (CD95) in the immune system has been examined in a variety ...

  3. Nano-Micelle of Moringa Oleifera Seed Oil Triggers Mitochondrial Cancer Cell Apoptosis

    Science.gov (United States)

    Abd-Rabou, Ahmed A; Zoheir, Khairy M A; Kishta, Mohamed S; Shalby, Aziza B; Ezzo, Mohamed I

    2016-01-01

    Cancer, a worldwide epidemic disease with diverse origins, involves abnormal cell growth with the potential to invade other parts of the body. Globally, it is the main cause of mortality and morbidity. To overcome the drawbacks of the commercially available chemotherapies, natural products-loaded nano-composites are recommended to improve cancer targetability and decrease the harmful impact on normal cells. This study aimed at exploring the anti-cancer impacts of Moringa oleifera seed oil in its free- (MO) and nano-formulations (MOn) through studying whether it mechanistically promotes mitochondrial apoptosis-mediating cell death. Mitochondrial-based cytotoxicity and flow cytometric-based apoptosis analyses were performed on cancer HepG2, MCF7, HCT 116, and Caco-2 cell lines against normal kidney BHK-21 cell line. The present study resulted that MOn triggered colorectal cancer Caco-2 and HCT 116 cytotoxicity via mitochondrial dysfunction more powerful than its free counterpart (MO). On the other side, MOn and MO remarkably induces HCT 116 mitochondrial apoptosis, while sparing normal BHK-21 cells with minimal cytotoxic effect. The present results concluded that nano-micelle of Moringa oleifera seed oil (MOn) can provide a novel therapeutic approach for colorectal and breast cancers via mitochondrial-mediated apoptosis, while sparing normal and even liver cancer cells a bit healthy or with minimal harmful effect. Intriguingly, MOn induced breast cancer not hepatocellular carcinoma cell death. PMID:28032498

  4. Cadmium-induced apoptosis of Siberian tiger fibroblasts via disrupted intracellular homeostasis

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available BACKGROUND: Heavy metals can cause great harm to Siberian tigers in the natural environment. Cadmium (Cd2+ is an environmental contaminant that affects multiple cellular processes, including cell proliferation, differentiation, and survival. It has been shown to induce apoptosis in a variety of cell types and tissues. RESULTS: We investigated the apoptotic effects of Cd2+ on Siberian tiger fibroblasts in vitro. Our research revealed the typical signs of apoptosis after Cd²+ exposure. Apoptosis was dose- (0-4.8 μΜ and duration-dependent (12-48 h, and proliferation was strongly inhibited. Cd²+ increased the activity of caspase-3, -8, and -9 and disrupted calcium homeostasis by causing oxidative stress and mitochondrial dysfunction. It also increased K+ efflux and altered the mRNA levels of Bax, Bcl-2, caspase-3, caspase-8, Fas, and p53. CONCLUSIONS: Our results suggest that Cd2+ triggers the apoptosis of Siberian tiger fibroblasts by disturbing intracellular homeostasis. These results will aid in our understanding of the effects of Cd2+ on Siberian tigers and in developing interventions to treat and prevent cadmium poisoning.

  5. Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro

    Directory of Open Access Journals (Sweden)

    Bassem Y. Sheikh

    2013-09-01

    Full Text Available There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

  6. Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex

    Directory of Open Access Journals (Sweden)

    Wang Lily

    2005-07-01

    Full Text Available Abstract There is evidence that the kynurenine pathway (KP and particularly one of its end products, quinolinic acid (QUIN play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC. We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1 apoptotic astrocytes have been observed in the brains of ADC patients, 2 ADC patients have elevated cerebrospinal fluid QUIN concentrations, and 3 QUIN can induce astrocyte death. Primary cultures of human fetal astrocytes were treated with three pathophysiological concentrations of QUIN. Numeration of apoptotic cells was assessed using double immunocytochemistry for expression of active caspase 3 and for nucleus condensation. We found that treatment of human astrocytes with QUIN induced morphological (cell body shrinking and biochemical changes (nucleus condensation and over-expression of active caspase 3 of apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM respectively 10 and 14% of astrocytes were undergoing apoptosis. This would be expected to lead to a relative lack of trophic support factors with consequent neuronal dysfunction and possibly death. Astroglial apoptosis induced by QUIN provides another potential mechanism for the neurotoxicity of QUIN during ADC.

  7. Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HL60 cells.

    Science.gov (United States)

    Matsumoto, Kenji; Akao, Yukihiro; Yi, Hong; Ohguchi, Kenji; Ito, Tetsuro; Tanaka, Toshiyuki; Kobayashi, Emi; Iinuma, Munekazu; Nozawa, Yoshinori

    2004-11-15

    Our previous study has shown that alpha-mangostin, a xanthone from the pericarps of mangosteen, induces caspase-3-dependent apoptosis in HL60 cells. In the current study, we investigated the mechanism of apoptosis induced by alpha-mangostin in HL60 cells. Alpha-mangostin-treated HL60 cells demonstrated caspase-9 and -3 activation but not -8, which leads us to assume that alpha-mangostin may mediate the mitochondrial pathway in the apoptosis. Parameters of mitochondrial dysfunction including swelling, loss of membrane potential (deltapsim), decrease in intracellular ATP, ROS accumulation, and cytochrome c/AIF release, were observed within 1 or 2 h after the treatment. On the other hand, alpha-mangostin-treatment did not affect expression of bcl-2 family proteins and activation of MAP kinases. These findings indicate that alpha-mangostin preferentially targets mitochondria in the early phase, resulting in indication of apoptosis in HL60 cells. Furthermore, we examined the structure-activity relationship between xanthone derivatives including alpha-mangostin and the potency of deltapsim-loss in HL60 cells. Interestingly, replacement of hydroxyl group by methoxy group remarkably decreased its potency. It was also shown that the cytotoxicity substantially correlated with deltapsim decrease. These results indicate that alpha-mangostin and its analogs would be candidates for preventive and therapeutic application for cancer treatment.

  8. Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos

    International Nuclear Information System (INIS)

    Gapter, Leslie; Wang, Zaisen; Glinski, Jan; Ng, Ka-yun

    2005-01-01

    Pachymic acid (PA) is a natural triterpenoid known to inhibit the phospholipase A2 (PLA 2 ) family of arachidonic acid (AA)-producing enzymes. PLA 2 is elevated in prostatic adenocarcinoma and conversion of AA to prostaglandins leads to AKT pro-survival activity. In this study, we investigated the effect of PA on the growth of human prostate cancer cells. PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway. We speculate that PA influenced apoptosis by reducing prostaglandin synthesis and AKT activity

  9. Intestinal bacterium-derived cyp27a1 prevents colon cancer cell apoptosis.

    Science.gov (United States)

    Ji, Yan-Chao; Liu, Chang; Zhang, Xia; Zhang, Cheng-Sen; Wang, Dong; Zhang, Yan

    2016-01-01

    The pathogenesis of metastasis of colon cancer (Cca) is to be further investigated. The dysfunction of apoptotic mechanism plays a role in the cancer cell over growth. This study tests a hypothesis by which intestinal bacterium-derived cyp27a1 prevents apoptosis in colon cancer cells. In this study, the levels of cyp27a1 in human stool samples were assessed by enzyme-linked immunosorbent assay. The apoptosis of Cca cells was observed by flow cytometry. The expression of cyp27a1 was assessed by real time RT-PCR and Western blotting. We observed higher levels of cyp27a1 in the stool samples of Cca patients than that from healthy subjects. Cca colon epithelial biopsy contained high levels of cyp27a1 protein, but not the cyp27a1 mRNA. Cyp27a1 prevented Cca cell apoptosis induced by vitamin D3. In conclusion, intestinal bacterium-derived cyp27a1 facilitates Cca survival by inhibiting Cca cell apoptosis.

  10. Oral health and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Vijendra P Singh

    2017-01-01

    Full Text Available Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP and erectile dysfunction (ED by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions.

  11. Cancer Therapy Due to Apoptosis: Galectin-9

    Directory of Open Access Journals (Sweden)

    Koji Fujita

    2017-01-01

    Full Text Available Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null, which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described.

  12. Apoptosis in inner ear sensory hair cells

    Directory of Open Access Journals (Sweden)

    Seth Morrill

    2017-12-01

    Full Text Available Apoptosis, or controlled cell death, is a normal part of cellular lifespan. Cell death of cochlear hair cells causes deafness; an apoptotic process that is not well understood. Worldwide, 1.3 billion humans suffer some form of hearing loss, while 360 million suffer debilitating hearing loss as a direct result of the absence of these cochlear hair cells (Worldwide Hearing, 2014. Much is known about apoptosis in other systems and in other cell types thanks to studies done since the mid-20th century. Here we review current literature on apoptosis in general, and causes of deafness and cochlear hair cells loss as a result of apoptosis. The family of B-cell lymphoma (Bcl proteins are among the most studied and characterized. We will review current literature on the Bcl2 and Bcl6 protein interactions in relation to apoptosis and their possible roles in vulnerability and survival of cochlear hair cells.

  13. Mitochondrial dysfunction and organophosphorus compounds

    International Nuclear Information System (INIS)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-01-01

    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

  14. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

  15. Thyroid Dysfunction from Antineoplastic Agents

    Science.gov (United States)

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

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

  16. Thyroid dysfunction in Down's syndrome.

    OpenAIRE

    Loudon, M M; Day, R E; Duke, E M

    1985-01-01

    One hundred and sixteen children with Down's syndrome, living in the community, were examined for clinical or laboratory evidence of thyroid dysfunction. Three were hypothyroid and one was hyperthyroid. Twenty eight (29%) had thyroid autoantibodies. Autoimmune conditions were present in first or second degree relatives of 35 (30%) of the children, and in 17 (15%) this was a thyroid disorder. The families of normal control children also showed a 30% incidence of overt autoimmune conditions, an...

  17. Amiodarone-induced thyroid dysfunction.

    Science.gov (United States)

    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. © The Author(s) 2013.

  18. Synthesis, Characterization, In Vitro Cytotoxicity, and Apoptosis-Inducing Properties of Ruthenium(II) Complexes

    Science.gov (United States)

    Xu, Li; Zhong, Nan-Jing; Xie, Yang-Yin; Huang, Hong-Liang; Jiang, Guang-Bin; Liu, Yun-Jun

    2014-01-01

    Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements. PMID:24804832

  19. Spirulina platensis prevents high glucose-induced oxidative stress mitochondrial damage mediated apoptosis in cardiomyoblasts.

    Science.gov (United States)

    Jadaun, Pratiksha; Yadav, Dhananjay; Bisen, Prakash Singh

    2018-04-01

    The current study was undertaken to study the effect of Spirulina platensis (Spirulina) extract on enhanced oxidative stress during high glucose induced cell death in H9c2 cells. H9c2 cultured under high glucose (33 mM) conditions resulted in a noteworthy increase in oxidative stress (free radical species) accompanied by loss of mitochondrial membrane potential, release of cytochrome c, increase in caspase activity and pro-apoptotic protein (Bax). Spirulina extract (1 μg/mL), considerably inhibited increased ROS and RNS levels, reduction in cytochrome c release, raise in mitochondrial membrane potential, decreased the over expression of proapoptotic protein Bax and suppressed the Bax/Bcl2 ratio with induced apoptosis without affecting cell viability. Overall results suggest that Spirulina extract plays preventing role against enhanced oxidative stress during high glucose induced apoptosis in cardiomyoblasts as well as related dysfunction in H9c2 cells.

  20. Toxoplasma gondii Infection Is Associated with Mitochondrial Dysfunction in-Vitro

    Directory of Open Access Journals (Sweden)

    Genevieve Syn

    2017-12-01

    Full Text Available Upon invasion of host cells, the ubiquitous pathogen Toxoplasma gondii manipulates several host processes, including re-organization of host organelles, to create a replicative niche. Host mitochondrial association to T. gondii parasitophorous vacuoles is rapid and has roles in modulating host immune responses. Here gene expression profiling of T. gondii infected cells reveals enrichment of genes involved in oxidative phosphorylation (OXPHOS and mitochondrial dysfunction 6 h post-infection. We identified 11 hub genes (HIF-1α, CASP8, FN1, POU5F1, CD44, ISG15, HNRNPA1, MDM2, RPL35, VHL, and NUPR1 and 10 predicted upstream regulators, including 4 endogenous regulators RICTOR, KDM5A, RB1, and D-glucose. We characterized a number of mitochondrial parameters in T. gondii infected human foreskin fibroblast cells over a 36 h time-course. In addition to the usual rapid recruitment and apparent enlargement of mitochondria around the parasitophorous vacuole we observed fragmented host mitochondria in infected cells, not linked to cellular apoptosis, from 24 h post-infection. An increase in mitochondrial superoxide levels in T. gondii infected cells was observed that required active parasite invasion and peaked at 30 h post-infection. Measurement of OXPHOS proteins showed decreased expression of Complex IV in infected cells at 24 h post-infection, followed by decreased expression of Complexes I and II at 36 h post-infection. No change occurred in Complex V. No difference in host mitochondrial membrane potential between infected and mock-infected cells was observed at any time. Our results show perturbation of host mitochondrial function following T. gondii infection that likely impacts on pathogenesis of disease.

  1. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

    Science.gov (United States)

    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-04-01

    Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (Ppreeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (Ppreeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

  2. Erectile dysfunction and amatorial cycling.

    Science.gov (United States)

    Colpi, Giovanni Maria; Contalbi, Gianfranco; Ciociola, E; Mihalca, Radu

    2008-09-01

    Today cycling is considered a useful form of exercise for reducing cardiovascular risk, but it may also represent a risk factor for erectile dysfunction and perineal-genital paresthesia. These disorders are attributed to the local reduction of oxygen in the perineal-genital area, secondary to the perineal compression. Numerous studies have been carried out measuring the penile oxygen pressure or penile blood flow by echo-colour-Doppler: a reduced inflow of blood and oxygen to the cavernous tissue was demonstrated. The attention of the specialist is therefore concentrated on the compression of the perineum on the bicycle saddle and how to reduce this through the position of the cyclist on the bicycle (i.e. height and tilt of the saddle), the different shapes of saddle available (i.e. noseless, grooved, wide, etc.) and the padding materials of the saddle. In order to reduce perineal compression, the posterior part of the saddle should be as wide as the distance between the two ischiatic tuberosities. In addition, the saddle should be studied on the basis of the biotype of the cyclist: ectomorphic, mesomorphic or endomorphic. However, in the genesis of the erectile dysfunction of the cyclist, apart from the above-mentioned factors, an "individual predisposition to developing erectile dysfunction" linked to the perineal-genital anatomy (i.e. type of insertion of the perineum into the root of the penis, number of layers of the tunica albuginea of the corpus cavernosum) cannot be excluded.

  3. Gut dysfunction in Parkinson's disease.

    Science.gov (United States)

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

    2016-07-07

    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.

  4. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

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

    2017-02-01

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

  5. Pelvic Floor Dysfunction in Aging Women

    Directory of Open Access Journals (Sweden)

    Gin-Den Chen

    2007-12-01

    Full Text Available The occurrence of pelvic floor dysfunction may increase steadily during the aging process in women. Pelvic floor dysfunction may be associated with dysfunctions of micturition, defecation, prolapse, and sex. The natural history and mechanism of pelvic floor dysfunction in aged women are not well understood or explored. In this article, we review the effect of age on the prevalence of pelvic floor dysfunction and on the structural and functional changes of the lower urinary tract, anorectum and pelvic floor. Altogether, the aging process has a negative impact on either the function or structure of the lower urinary tract, anorectum and pelvic floor in women.

  6. Epigenetics: The missing link to understanding β-cell dysfunction in the pathogenesis of type 2 diabetes

    OpenAIRE

    Gilbert, Elizabeth R.; Liu, Dongmin

    2012-01-01

    Type 2 diabetes (T2D) is a growing health problem worldwide. While peripheral insulin resistance is common during obesity and aging in both animals and people, progression to T2D is largely due to insulin secretory dysfunction and significant apoptosis of functional β-cells, leading to an inability to compensate for insulin resistance. It is recognized that environmental factors and nutrition play an important role in the pathogenesis of diabetes. However, our knowledge surrounding molecular ...

  7. Importance of histopathological examination of endometrium in Dysfunctional Uterine Bleeding.

    Directory of Open Access Journals (Sweden)

    Dr. Yaminee Rana

    2017-12-01

    Full Text Available Introduction: Abnormal uterine bleeding is a common condition affecting women of reproductive age that has significant social and economic impact. Dysfunctional uterine bleeding (DUB is defined as abnormal uterine bleeding in the absence of organic disease. Dysfunctional uterine bleeding is one of the most commonly encountered gynaecological problems. Objectives: This study is done to evaluate the histopathological pattern of the endometrial biopsies of patients with dysfunctional uterine bleeding and its correlation with clinical data. Methods: The present prospective study included evaluation of 208 cases of dysfunctional uterine bleeding in the Department of Pathology, B. J. Medical College, Ahmedabad over a period of 10 months, from January 2017 to October 2017. Women presenting with abnormal uterine bleeding were included in the study. Those women in which bleeding is secondary to systemic causes, organic causes and due to cervical and vaginal causes were excluded. The specimens were processed, embedded and cut into sections of 3-4 microns. The histopathological patterns were studied. Results: Age distribution varied from 18 years to 70 years, majority of the patients were between 21 to 30 years. Among the cases of DUB, proliferative phase accounted for 66.3% and secretory phase accounted for 21.3%. 18 cases (8.6% of atrophic endometrium, four cases (1.9% of irregular shedding and two cases of luteal phase insufficiency were received. Conclusion: Dysfunctional uterine bleeding is a common and debilitating condition in women of reproductive age. Endometrial biopsy could be effectively used as the first diagnostic step in DUB and thus ensures correct management.

  8. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress.

    Science.gov (United States)

    Nataraj, Jagatheesan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohammed

    2016-07-01

    Mitochondrial dysfunction and oxidative stress-mediated apoptosis plays an important role in various neurodegenerative diseases including Huntington's disease, Parkinson's disease (PD) and Alzheimer's disease (AD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the most widely used neurotoxin mimics the symptoms of PD by inhibiting mitochondrial complex I that stimulates excessive intracellular reactive oxygen species (ROS) and finally leads to mitochondrial-dependent apoptosis. Lutein, a carotenoid of xanthophyll family, is found abundantly in leafy green vegetables such as spinach, kale and in egg yolk, animal fat and human eye retinal macula. Increasing evidence indicates that lutein has offers benefits against neuronal damages during diabetic retinopathy, ischemia and AD by virtue of its mitochondrial protective, antioxidant and anti-apoptotic properties. Male C57BL/6 mice (23-26 g) were randomized and grouped in to Control, MPTP, and Lutein treated groups. Lutein significantly reversed the loss of nigral dopaminergic neurons by increasing the striatal dopamine level in mice. Moreover, lutein-ameliorated MPTP induced mitochondrial dysfunction, oxidative stress and motor abnormalities. In addition, lutein repressed the MPTP-induced neuronal damage/apoptosis by inhibiting the activation of pro-apoptotic markers (Bax, caspases-3, 8 and 9) and enhancing anti-apoptotic marker (Bcl-2) expressions. Our current results revealed that lutein possessed protection on dopaminergic neurons by enhancing antioxidant defense and diminishing mitochondrial dysfunction and apoptotic death, suggesting the potential benefits of lutein for PD treatment.

  9. Caspase-mediated apoptosis induction in zebrafish cerebellar Purkinje neurons.

    Science.gov (United States)

    Weber, Thomas; Namikawa, Kazuhiko; Winter, Barbara; Müller-Brown, Karina; Kühn, Ralf; Wurst, Wolfgang; Köster, Reinhard W

    2016-11-15

    The zebrafish is a well-established model organism in which to study in vivo mechanisms of cell communication, differentiation and function. Existing cell ablation methods are either invasive or they rely on the cellular expression of prokaryotic enzymes and the use of antibiotic drugs as cell death-inducing compounds. We have recently established a novel inducible genetic cell ablation system based on tamoxifen-inducible Caspase 8 activity, thereby exploiting mechanisms of cell death intrinsic to most cell types. Here, we prove its suitability in vivo by monitoring the ablation of cerebellar Purkinje cells (PCs) in transgenic zebrafish that co-express the inducible caspase and a fluorescent reporter. Incubation of larvae in tamoxifen for 8 h activated endogenous Caspase 3 and cell death, whereas incubation for 16 h led to the near-complete loss of PCs by apoptosis. We observed synchronous cell death autonomous to the PC population and phagocytosing microglia in the cerebellum, reminiscent of developmental apoptosis in the forebrain. Thus, induction of apoptosis through targeted activation of caspase by tamoxifen (ATTAC TM ) further expands the repertoire of genetic tools for conditional interrogation of cellular functions. © 2016. Published by The Company of Biologists Ltd.

  10. dysfunction

    African Journals Online (AJOL)

    care unit. Electrocardiography revealed extensive ischaemic changes with the suggestion of established anteroseptal infarction. Chest radiography revealed significant cardiomegaly and pulmonary oedema. Transthoracic echocardiography showed a grossly dilated, poorly contracting left ventricle. The septal and posterior ...

  11. Honey and Apoptosis in Human Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    Alireza Ostadrahimi

    2012-07-01

    Full Text Available Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apoptosis in human gastric mucosa.Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred totwo hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire(FFQ and apoptosis was detected by TUNEL technique. We tested polynomial curve tofind the best fit between honey consumption and apoptosis.Results: A positive relation between honey consumption and apoptosis was found (P=0.024.Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honeyamount - 0.533(honey amount2 +1.833×10-5(honey amount7.Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis ingastric mucosa.

  12. Evasion of apoptosis by DNA viruses.

    Science.gov (United States)

    Cuff, S; Ruby, J

    1996-12-01

    Apoptosis is a form of cell death distinct from necrosis which plays an important role in processes such as homoeostasis and the elimination of damaged cells. It can be triggered by a variety of stimuli including DNA damage and cytotoxic T lymphocyte activity, both of which may be induced in the course of a viral infection. Initially, induction of apoptosis may occur through pathways which have also been shown to be activated on disturbance of the cell cycle or damage to cellular DNA. At later time points during the course of infection, apoptosis can also be triggered by cytokines and immune effector cells. Apoptosis of the host cell before the completion of the viral replication cycle may limit the number of progeny and the spread of infection. The importance of apoptosis as an antiviral defence is illustrated by the presence of multiple pathways for apoptosis induction and inhibition in both the host and virus. In this review, the inhibition of apoptosis is described in adenovirus and poxvirus infection. These examples illustrate two of the divergent paths by which viruses may avoid the apoptotic response.

  13. Fas antigen (CD95) expression and apoptosis in hepatocytes of patients with chronic viral hepatitis.

    Science.gov (United States)

    Kiyici, Murat; Gurel, Selim; Budak, Ferah; Dolar, Enver; Gulten, Macit; Nak, Selim Giray; Memik, Faruk

    2003-10-01

    Apoptosis may be defined as programmed cell death. It is involved in the normal development and homeostasis of tissues in multicellular organisms. An increased or decreased rate of apoptosis may lead to a range of diseases. Fas antigen is a cell-surface receptor that induces apoptotic pathways when treated with Fas ligand or anti-Fas antibody. There is increasing evidence that apoptosis plays an important role in the immunopathogenesis of chronic viral hepatitis, in which the Fas antigen-Fas ligand pathway is particularly involved. Fas antigen expression and apoptosis (apoptotic index) were assayed using flow cytometry in the hepatocytes of 27 patients with chronic viral hepatitis. Histopathological activity, scored by Knodell's histological activity index, other histopathological parameters, serum transaminase values and patient age were then compared with apoptotic index and Fas antigen expression. Apoptosis and Fas antigen expression in hepatocytes were correlated closely with histological activity (grade) of chronic viral hepatitis, but there were no correlations with histological stage, patient age or serum transaminase levels. Apoptosis and its triggering molecule, Fas antigen, induce mechanisms that appear to be associated with the pathogenesis of chronic viral hepatitis.

  14. Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

    Science.gov (United States)

    Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

    2013-11-28

    To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

  15. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    Francois, S.

    2006-01-01

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  16. Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout

    Science.gov (United States)

    Balbo, Bruno E.; Amaral, Andressa G.; Fonseca, Jonathan M.; de Castro, Isac; Salemi, Vera M.; Souza, Leandro E.; dos Santos, Fernando; Irigoyen, Maria C.; Qian, Feng; Chammas, Roger; Onuchic, Luiz F.

    2016-01-01

    Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations, in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1cond/cond:Nestincre (CYG+) cystic mice exposed to increased blood pressure, at 5–6 and 20–24 weeks of age, and Pkd1+/− (HTG+) noncystic mice at 5–6 and 10–13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1cond/cond and Pkd1+/+ controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1cond/cond:Nestincre;Lgals3−/− (CYG−) and Pkd1+/−;Lgals3−/− (HTG−) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from their controls. CYG− and HTG− showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1V/V; VVG+) showed that Pkd1V/V;Lgals3−/− (VVG−) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG− and VVG− animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype. PMID:27475230

  17. Apoptosis-like yeast cell death in response to DNA damage and replication defects

    International Nuclear Information System (INIS)

    Burhans, William C.; Weinberger, Martin; Marchetti, Maria A.; Ramachandran, Lakshmi; D'Urso, Gennaro; Huberman, Joel A.

    2003-01-01

    In budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe) yeast and other unicellular organisms, DNA damage and other stimuli can induce cell death resembling apoptosis in metazoans, including the activation of a recently discovered caspase-like molecule in budding yeast. Induction of apoptotic-like cell death in yeasts requires homologues of cell cycle checkpoint proteins that are often required for apoptosis in metazoan cells. Here, we summarize these findings and our unpublished results which show that an important component of metazoan apoptosis recently detected in budding yeast - reactive oxygen species (ROS) - can also be detected in fission yeast undergoing an apoptotic-like cell death. ROS were detected in fission and budding yeast cells bearing conditional mutations in genes encoding DNA replication initiation proteins and in fission yeast cells with mutations that deregulate cyclin-dependent kinases (CDKs). These mutations may cause DNA damage by permitting entry of cells into S phase with a reduced number of replication forks and/or passage through mitosis with incompletely replicated chromosomes. This may be relevant to the frequent requirement for elevated CDK activity in mammalian apoptosis, and to the recent discovery that the initiation protein Cdc6 is destroyed during apoptosis in mammals and in budding yeast cells exposed to lethal levels of DNA damage. Our data indicate that connections between apoptosis-like cell death and DNA replication or CDK activity are complex. Some apoptosis-like pathways require checkpoint proteins, others are inhibited by them, and others are independent of them. This complexity resembles that of apoptotic pathways in mammalian cells, which are frequently deregulated in cancer. The greater genetic tractability of yeasts should help to delineate these complex pathways and their relationships to cancer and to the effects of apoptosis-inducing drugs that inhibit DNA replication

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

    Directory of Open Access Journals (Sweden)

    N.O.S. Câmara

    2009-03-01

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

  19. Erectile dysfunction in haemodialysis patients

    International Nuclear Information System (INIS)

    Mumtaz, A.; Hussain, S.; Nazir, M.

    2009-01-01

    There is a very high prevalence of Erectile Dysfunction (ED) in dialysis patients. There is no as such available data on ED and factors affecting it in our patients. Analytical, cross-sectional, hospital based study conducted from January to March 2008, Haemodialysis unit of Shalimar and Mayo Hospital, Lahore. All male patients of end stage renal disease (ESRD) on maintenance haemodialysis therapy, whose spouses are alive and able to perform intercourse, were included in the study. Patient with cognitive and communication deficits were excluded from study. International index of erectile function-5 (IIEF-5), adopted in Urdu was used for the determination of prevalence of erectile function. Categorization of erectile dysfunction was done as mild, moderate and severe. Demographic data were collected and certain laboratory parameters (haemoglobin, haematocrit, urea, HBsAg and Anti HCV) were sent. Total numbers of patient were fifty. Major cause of ESRD was diabetes mellitus 28 (56%). Most of the patients 33 (66%) have passed 10th grade or they were under 10th grade. Prevalence of ED was 86% with mean IIEF-5 score of 10.36+-7.13. Majority of patients 33 (64.7%) were suffering from severe degree of ED. Factors responsible for ED are diabetes mellitus, age more than 50 year, high pre dialysis urea and Anti HCV positive patients. In this study, smoking, duration of dialysis and monthly spending is not related with ED. Majority of the patients suffering from ESRD, on maintenance haemodialysis are having ED. None of the patients suffering from ED were taking any treatment for it. Haemodialysis does not improve sexual dysfunction. Major factors responsible for ED are diabetes mellitus, age more than 50 years, high pre dialysis urea and Anti HCV positive patients. (author)

  20. Endothelial dysfunction in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hadi AR Hadi

    2008-01-01

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

  1. Conservative management of voiding dysfunction

    Directory of Open Access Journals (Sweden)

    Anita Patel

    2007-01-01

    Full Text Available 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.

  2. Ageing with neurogenic bowel dysfunction

    DEFF Research Database (Denmark)

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

    2017-01-01

    at 18% in 1996 and 19% in 2015. During the 19-year period, there had been no significant change in the methods for bowel care, but 22 (20%) had undergone surgery for bowel dysfunction, including 11 (10%) who had some form of stoma. Conclusion: Self-assessed severity of constipation increased but quality...... of life remained stable in a cohort of people with SCI followed prospectively for 19 years. Methods for bowel care remained surprisingly stable but a large proportion had undergone stoma surgery....

  3. Vaccination-related shoulder dysfunction.

    Science.gov (United States)

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

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

  4. MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5).

    Science.gov (United States)

    Li, Dong; Liu, Yu; Li, Hua; Peng, Jing-Jing; Tan, Yan; Zou, Qiang; Song, Xiao-Feng; Du, Min; Yang, Zheng-Hui; Tan, Yong; Zhou, Jin-Jun; Xu, Tao; Fu, Zeng-Qiang; Feng, Jian-Qiong; Cheng, Peng; chen, Tao; Wei, Dong; Su, Xiao-Mei; Liu, Huan-Yi; Qi, Zhong-Chun; Tang, Li-Jun; Wang, Tao; Guo, Xin; Hu, Yong-He; Zhang, Tao

    2015-01-02

    Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway

    Directory of Open Access Journals (Sweden)

    Xin Tian

    2016-01-01

    Full Text Available Objectives. Elevated plasma homocysteine (Hcy could lead to endothelial dysfunction and is viewed as an independent risk factor for atherosclerosis. Heat shock protein 27 (HSP27, a small heat shock protein, is reported to exert protective effect against atherosclerosis. This study aims to investigate the protective effect of HSP27 against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs and to determine the underlying mechanisms. Methods. Apoptosis, reactive oxygen species (ROS, and mitochondrial membrane potential (MMP of normal or HSP27-overexpressing HUVECs in the presence of Hcy were analyzed by flow cytometry. The mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR and western blot. Results. We found that Hcy could induce cell apoptosis with corresponding decrease of nitric oxide (NO level, increase of endothelin-1 (ET-1, intracellular adhesion molecule-1 (ICAM-1, vascular cellular adhesion molecule-1 (VCAM-1, and monocyte chemoattractant protein-1 (MCP-1 levels, elevation of ROS, and dissipation of MMP. In addition, HSP27 could protect the cell against Hcy-induced apoptosis and inhibit the effect of Hcy on HUVECs. Furthermore, HSP27 could increase the ratio of Bcl-2/Bax and inhibit caspase-3 activity. Conclusions. Therefore, we concluded that HSP27 played a protective role against Hcy-induced endothelial apoptosis through modulation of ROS production and the mitochondrial caspase-dependent apoptotic pathway.

  6. SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

    Science.gov (United States)

    Jia, Zhuqing; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qin; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

    2016-02-01

    Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

  7. The induction of autophagy against mitochondria-mediated apoptosis in lung cancer cells by a ruthenium (II) imidazole complex

    Science.gov (United States)

    Peng, Fa; Jie, Xinming; Dongye, Guangzhi; Cai, Kangrong; Feng, Ruibing; Li, Baojun; Zeng, Qingwang; Lun, Kaiyi; Chen, Jincan; Xu, Bilian

    2016-01-01

    In the present study, it was found that the ruthenium (II) imidazole complex [Ru(Im)4(dppz)]2+ (Ru1) could induce significant growth inhibition and apoptosis in A549 and NCI-H460 cells. Apart from the induction of apoptosis, it was reported for the first time that Ru1 induced an autophagic response in A549 and NCI-H460 cells as evidenced by the formation of autophagosomes, acidic vesicular organelles (AVOs), and the up-regulation of LC3-II. Furthermore, scavenging of reactive oxygen species (ROS) by antioxidant NAC or Tiron inhibited the release of cytochrome c, caspase-3 activity, and eventually rescued cancer cells from Ru1-mediated apoptosis, suggesting that Ru1 inducing apoptosis was partially caspase 3-dependent by triggering ROS-mediated mitochondrial dysfunction in A549 and NCI-H460 cells. Further study indicated that the extracellular signal-regulated kinase (ERK) signaling pathway was involved in Ru1-induced autophagy in A549 and NCI-H460 cells. Moreover, blocking autophagy using pharmacological inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) enhanced Ru1-induced apoptosis, indicating the cytoprotective role of autophagy in Ru1-treated A549 and NCI-H460 cells. Finally, the in vivo mice bearing A549 xenografts, Ru1 dosed at 10 or 20 mg/kg significantly inhibited tumor growth. PMID:27811372

  8. Alzheimer's Proteins, Oxidative Stress, and Mitochondrial Dysfunction Interplay in a Neuronal Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Antonella Bobba

    2010-01-01

    Full Text Available In this paper, we discuss the interplay between beta-amyloid (A peptide, Tau fragments, oxidative stress, and mitochondria in the neuronal model of cerebellar granule neurons (CGNs in which the molecular events reminiscent of AD are activated. The identification of the death route and the cause/effect relationships between the events leading to death could be helpful to manage the progression of apoptosis in neurodegeneration and to define antiapoptotic treatments acting on precocious steps of the death process. Mitochondrial dysfunction is among the earliest events linked to AD and might play a causative role in disease onset and progression. Recent studies on CGNs have shown that adenine nucleotide translocator (ANT impairment, due to interaction with toxic N-ter Tau fragment, contributes in a significant manner to bioenergetic failure and mitochondrial dysfunction. These findings open a window for new therapeutic strategies aimed at preserving and/or improving mitochondrial function.

  9. Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Felipe A. Zuniga

    2014-01-01

    Full Text Available The bioavailability of nitric oxide (NO represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE. PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1, which induces endothelial dysfunction by increasing reactive oxygen species (ROS and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

  10. Molecular Analysis of Neurotoxin-Induced Apoptosis

    National Research Council Canada - National Science Library

    D'Mello, Santosh R

    2006-01-01

    Apoptosis is a cell-suicide process that is required for the normal development of the nervous system, but that can be aberrantly activated in neurodegenerative diseases and following exposure to neurotoxins...

  11. Apoptosis and Tumor Progressionin Prostate Cancer

    National Research Council Canada - National Science Library

    Tenniswood, Martin P

    2005-01-01

    ... (as measured by BrdU incorporation) and apoptosis as measured by TUNEL staining. We have standardized an efficient methodologies for isolating cells from primary tumors expressing REP by fluorescence activated cell sorting (FACS...

  12. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    International Nuclear Information System (INIS)

    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  13. Advanced oxidative protein products induced human keratinocyte apoptosis through the NOX-MAPK pathway.

    Science.gov (United States)

    Sun, Baihui; Ding, Ruoting; Yu, Wenlin; Wu, Yanhong; Wang, Bulin; Li, Qin

    2016-07-01

    Impaired wound healing is a major diabetes-related complication. Keratinocytes play an important role in wound healing. Multiple factors have been proposed that can induce dysfunction in keratinocytes. The focus of present research is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing human immortalized keratinocyte (HaCaT) cell apoptosis and the cellular mechanism underlying the proapoptotic effect of AOPPs. HaCaT cells were treated with increasing concentrations of AOPP-human serum albumin or for increasing time durations. The cell viability was measured using the thiazolyl blue tetrazolium bromide method, and flow cytometry was used to assess the rate of cell apoptosis. A loss of mitochondrial membrane potential (MMP) and an increase in intracellular reactive oxygen species (ROS) were observed through a confocal laser scanning microscope system, and the level of ROS generation was determined using a microplate reader. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)4, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and apoptosis-related downstream protein interactions were investigated using the Western blot analysis. We found that AOPPs triggered HaCaT cell apoptosis and MMP loss. After AOPP treatment, intracellular ROS generation increased in a time- and dose-dependent manner. Proapoptotic proteins, such as Bax, caspase 9/caspase 3, and poly(ADP-ribose) polymerase (PARP)-1 were activated, whereas anti-apoptotic Bcl-2 protein was downregulated. AOPPs also increased NOX4, ERK1/2, and p38 MAPK expression. Taken together, these findings suggest that extracellular AOPP accumulation triggered NOX-dependent ROS production, which activated ERK1/2 and p38 MAPK, and induced HaCaT cell apoptosis by activating caspase 3 and PARP-1.

  14. Role of CD137 signaling in dengue virus-mediated apoptosis

    International Nuclear Information System (INIS)

    Nagila, Amar; Netsawang, Janjuree; Srisawat, Chatchawan; Noisakran, Sansanee; Morchang, Atthapan; Yasamut, Umpa; Puttikhunt, Chunya; Kasinrerk, Watchara

    2011-01-01

    Highlights: → For the first time the role of CD137 in dengue virus (DENV) infection. → Induction of DENV-mediated apoptosis by CD137 signaling. → Sensitization to CD137-mediated apoptosis by dengue virus capsid protein (DENV C). → Nuclear localization of DENV C is required for CD137-mediated apoptosis. -- Abstract: Hepatic dysfunction is a well recognized feature of dengue virus (DENV) infection. However, molecular mechanisms of hepatic injury are still poorly understood. A complex interaction between DENV and the host immune response contributes to DENV-mediated tissue injury. DENV capsid protein (DENV C) physically interacts with the human death domain-associated protein Daxx. A double substitution mutation in DENV C (R85A/K86A) abrogates Daxx interaction, nuclear localization and apoptosis. Therefore we compared the expression of cell death genes between HepG2 cells expressing DENV C and DENV C (R85A/K86A) using a real-time PCR array. Expression of CD137, which is a member of the tumor necrosis factor receptor family, increased significantly in HepG2 cells expressing DENV C compared to HepG2 cells expressing DENV C (R85A/K86A). In addition, CD137-mediated apoptotic activity in HepG2 cells expressing DENV C was significantly increased by anti-CD137 antibody compared to that of HepG2 cells expressing DENV C (R85A/K86A). In DENV-infected HepG2 cells, CD137 mRNA and CD137 positive cells significantly increased and CD137-mediated apoptotic activity was increased by anti-CD137 antibody. This work is the first to demonstrate the contribution of CD137 signaling to DENV-mediated apoptosis.

  15. Role of CD137 signaling in dengue virus-mediated apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Nagila, Amar [Medical Molecular Biology Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok (Thailand); Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok (Thailand); Netsawang, Janjuree [Faculty of Medical Technology, Rangsit University, Bangkok (Thailand); Srisawat, Chatchawan [Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok (Thailand); Noisakran, Sansanee [Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok (Thailand); Morchang, Atthapan; Yasamut, Umpa [Medical Molecular Biology Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok (Thailand); Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok (Thailand); Puttikhunt, Chunya [Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok (Thailand); Kasinrerk, Watchara [Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai (Thailand); Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at Chiang Mai University, Chiang Mai (Thailand); and others

    2011-07-08

    Highlights: {yields} For the first time the role of CD137 in dengue virus (DENV) infection. {yields} Induction of DENV-mediated apoptosis by CD137 signaling. {yields} Sensitization to CD137-mediated apoptosis by dengue virus capsid protein (DENV C). {yields} Nuclear localization of DENV C is required for CD137-mediated apoptosis. -- Abstract: Hepatic dysfunction is a well recognized feature of dengue virus (DENV) infection. However, molecular mechanisms of hepatic injury are still poorly understood. A complex interaction between DENV and the host immune response contributes to DENV-mediated tissue injury. DENV capsid protein (DENV C) physically interacts with the human death domain-associated protein Daxx. A double substitution mutation in DENV C (R85A/K86A) abrogates Daxx interaction, nuclear localization and apoptosis. Therefore we compared the expression of cell death genes between HepG2 cells expressing DENV C and DENV C (R85A/K86A) using a real-time PCR array. Expression of CD137, which is a member of the tumor necrosis factor receptor family, increased significantly in HepG2 cells expressing DENV C compared to HepG2 cells expressing DENV C (R85A/K86A). In addition, CD137-mediated apoptotic activity in HepG2 cells expressing DENV C was significantly increased by anti-CD137 antibody compared to that of HepG2 cells expressing DENV C (R85A/K86A). In DENV-infected HepG2 cells, CD137 mRNA and CD137 positive cells significantly increased and CD137-mediated apoptotic activity was increased by anti-CD137 antibody. This work is the first to demonstrate the contribution of CD137 signaling to DENV-mediated apoptosis.

  16. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

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

  17. [Male sexual dysfunctions and homosexuality].

    Science.gov (United States)

    Leuillet, P; Cour, F; Droupy, S

    2013-07-01

    The homosexuality, which expresses itself through a varied and complex behavior that those whom are shared by the heterosexual majority, is not that a simple sexual behavior, obvious or not, but a whole set of attitudes, affects, preferences, values, lifestyle which concern profoundly the individual, as the heterosexuality. A review of the literature using PubMed database has been performed to select 38 articles. Among sexual difficulties met by the gays, erectile dysfunction and hypoactive sexual desire are the more frequent. Concerning the ejaculation disorders observed in the gay population, premature ejaculation is rather rare in comparison with heterosexual men; however delayed ejaculation or anejaculation are more frequent. Painful sexual disorders in particular anodyspareunia are also reported. Sexual disorder management must follows the classic rules but it is necessary to be aware how to approach the specific questions affecting the homosexual persons. Still the homosexual person has to find a competent therapist, "opened" to the sexual problem of the homosexuals, with the aim of a care privileging the efficiency to efficacy in the respect for the truth of the homosexual person. The homosexuality is the only one of the "unusual" sexual conducts to possibly concern the daily medical practice due to is prevalence. The management of sexual dysfunctions must privilege the "meeting" in a quest of sense in front of any sexual symptom, whatever the individual sexual orientation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Epithelial apoptosis: cause or consequence of ulcerative colitis?

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Nielsen, Ole Haagen

    2009-01-01

    OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial...... apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate...

  19. Sexual dysfunction in Obsessive-Compulsive disorder

    Directory of Open Access Journals (Sweden)

    Firoozeh Raisi

    2015-05-01

    Conclusion: High prevalence of sexual dysfunction in OCD women and significant correlation between male sexual dysfunction and OCD (r= -481.0 between total score of OCI-R with erectile dysfunction and r= -458.0 between total score of OCI-R and sexual satisfaction could confirm a relation between OCD and sexual disorders. So, evaluation of sexual function in all patients with OCD is recommended.

  20. The treatment of autonomic dysfunction in tetanus

    Directory of Open Access Journals (Sweden)

    T van den Heever

    2017-07-01

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

  1. An ELISA for detection of apoptosis.

    OpenAIRE

    Salgame, P; Varadhachary, A S; Primiano, L L; Fincke, J E; Muller, S; Monestier, M

    1997-01-01

    We describe a simple and convenient enzyme-linked immunosorbent assay (ELISA) for the detection of apoptosis in tissue culture. An early event in apoptosis is DNA fragmentation followed by release of nucleosomes into the cytoplasm. Our sandwich assay uses a pair of monoclonal antibodies specific for two nucleosomal epitopes to capture and detect cytoplasmic nucleosomes onto the ELISA plate. Our assay is about 500 times more sensitive than the detection of apoptotic DNA ladder by agarose elect...

  2. Inflammatory cytokine TNF-α promotes corneal endothelium apoptosis via upregulating TIPE2 transcription during corneal graft rejection.

    Science.gov (United States)

    Wang, Qun; Wei, Chao; Ma, Li; Wang, Xin; Li, Lin; Zhou, Qingjun; Shi, Weiyun

    2018-02-26

    Endothelial dysfunction accounts for 50% of total corneal transplantation failures, suggesting that corneal endothelial damage is the leading cause of graft failure. Tumor necrosis factor-α (TNF-α) is known to contribute to the negative regulation of corneal transplantation, but how it does so remains unclear. Here, we report a regulatory loop involving TNF-α, TNF-α-induced protein 8 like 2 (TNFAIP8L2 or TIPE2), and apoptosis during corneal graft rejection. We established mice models of penetrating keratoplasty to verify whether the quantification of TNF-α in allogeneic corneas is enhanced through ELISA assay and immunofluorescence staining. In cornea tissues, we obtained corneal endothelium and measured apoptosis of the removed cells. Meanwhile, quantitative real-time PCR and Western blotting were used to detect the mRNA and protein expression of TIPE2. In human corneal endothelial cells, we verified the conclusions through some experiments. By specifically knocking down TIPE2, we detected the importance of TIPE2 in TNF-α-triggered apoptosis. In mice models, TNF-α was higher in the cornea and aqueous humor in allograft group and TNF-α elevation increased the apoptosis of the corneal endothelium. In addition, high levels of TIPE2 were found in allograft rejection models following TNF-α elevation. In human corneal endothelial cells (HCECs), TNF-α clearly augments TIPE2 expression and promotes cell apoptosis through upregulating TIPE2 transcription. Knocking down markedly decreased cell apoptosis. Our study identifies the molecular mechanisms underlying the interplay of TNF-α, TIPE2, and apoptosis during allograft rejection, and it suggests that both TNF-α and TIPE2 might be potential targets for the successfully grafted corneal endothelium.

  3. A design for the control of apoptosis in genetically modified Saccharomyces cerevisiae.

    Science.gov (United States)

    Nishida, Nao; Noguchi, Misa; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2014-01-01

    We have engineered a system that holds potential for use as a safety switch in genetically modified yeasts. Human apoptotic factor BAX (no homolog in yeast), under the control of the FBP1 (gluconeogenesis enzyme) promoter, was conditionally expressed to induce yeast cell apoptosis after glucose depletion. Such systems might prove useful for the safe use of genetically modified organisms.

  4. Molecular Mechanism of Apoptosis and Necrosis

    Directory of Open Access Journals (Sweden)

    Gulfidan Coskun

    2011-06-01

    Full Text Available Organismal homeostasis depends on an intricate balance between cell death and renewal. Apoptosis is a process of programmed cell death that plays a critical role in some normal and pathologic conditions beginning from embryologic development and ends at death. Apoptosis is initiated by morphological changes at the cell membrane, surface organels and nucleus. Apoptosis starts with death signals coming from outside or inside of the cell and continue to activate the mechanisms of apoptosis via cell death receptor or mitochondrial pathways. During apoptosis a group proteases are activated which cause DNA fragmentation, cytoplasmic shrinkage and membrane blebbing. Apoptotic cells divide into apoptotic bodies and then these apoptotic bodies are removed from tissue by phagocytes and adjacent cells In contrast to the “programmed” nature of apoptosis, necrotic cell death has always been believed to be a random, uncontrolled process that leads to death of the cell. Also necrosis, which is an other type of cell death, came to be used to describe pathologic cell death which cause inflamation. [Archives Medical Review Journal 2011; 20(3.000: 145-158

  5. Effect of sevoflurane on human neutrophil apoptosis.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

  6. Apoptosis in chronic tonsillitis and tonsillar hypertrophy.

    Science.gov (United States)

    Önal, Merih; Yılmaz, Taner; Bilgiç, Elif; Müftüoğlu, Sevda Fatma; Kuşçu, Oğuz; Günaydın, Rıza Önder

    2015-02-01

    Chronic tonsillitis is the persistent inflammation of the tonsillar tissue that occurs due to recurrent, acute or subclinical infection. The recurrent and chronic inflammation of palatine tonsils sometimes results in hypertrophy. Apoptosis provides an important balance between lymphocytes in tonsillar lymphoid tissue. The aim of this study is to investigate the apoptosis in tonsillar diseases. 43 patients with chronic tonsilitis and tonsillar hypertrophy underwent tonsillectomy. The specimens were examined immunohistochemically for apoptosis. Tonsils were assembled into groups according to their size. Specimens were compared for their apoptotic cell count. The apoptosis difference between the tonsil size groups is not statistically significant (p>0.05). However, when the study group was divided into two at age 6, the difference was not statistically significant for patients at and below 6 years of age; but, the difference was statistically significant for patients above 6 years of age (phypertrophy groups revealed no statistical significance (p>0.05). There was a statistically significant positive correlation between intrafollicular and interfollicular, interfollicular and intraepithelial & subepithelial and intraepithelial areas (phypertrophy and atrophy. Apoptosis functioned to balance lymphocyte proliferation in tonsil tissue. The association of apoptosis with tonsillar hypertrophy seemed to be age-dependent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Sexual Dysfunction and Intimacy for Ostomates.

    Science.gov (United States)

    Albaugh, Jeffrey A; Tenfelde, Sandi; Hayden, Dana M

    2017-07-01

    Sex and intimacy presents special challenges for the ostomate. Since some colorectal surgery patients will require either temporary or permanent stomas, intimacy and sexuality is a common issue for ostomates. In addition to the stoma, nerve damage, radiotherapy, and chemotherapy are often used in conjunction with stoma creation for cancer patients, thereby adding physiological dysfunction to the personal psychological impact of the stoma, leading to sexual dysfunction. The purpose of this paper is to describe the prevalence, etiology, and the most common types of sexual dysfunction in men and women after colorectal surgery and particularly those patients with stomas. In addition, treatment strategies for sexual dysfunction will also be described.

  8. Imaging for evaluation of erectile dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Hyup [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2001-03-15

    Penile erection is a complex phenomenon that includes coordinated intraaction of the nervous, arterial, venous, and sinusoidal systems. A defect in any of these systems may result in erectile dysfunction. Erectile dysfunction is defined as the consistent inability to generate or maintain an erection of sufficient rigidity for sexual intercourse. Although the introduction of sildenafil citrate made the information from imaging studies less critical in the management of the patients with erectile dysfunction, still the imaging studies such as Doppler US, penile arteriography, and cavemosonetry/cavemosography remain the major modalities in the evaluation of erectile dysfunction.

  9. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

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

  10. A biophysical approach to menadione membrane interactions: relevance for menadione-induced mitochondria dysfunction and related deleterious/therapeutic effects.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Nunes, Cláudia; Morais, Catarina M; Lúcio, Marlene; Reis, Salette; Pinheiro, Teresa J T; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2013-08-01

    Menadione (MEN), a polycyclic aromatic ketone, was shown to promote cell injury by imposing massive oxidative stress and has been proposed as a promising chemotherapeutic agent for the treatment of cancer diseases. The mechanisms underlying MEN-induced mitochondrial dysfunction and cell death are not yet fully understood. In this work, a systematic study was performed to unveil the effects of MEN on membrane lipid organization, using models mimicking mitochondrial membranes and native mitochondrial membranes. MEN was found to readily incorporate in membrane systems composed of a single phospholipid (phosphatidylcholine) or the lipids dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and tetraoleoylcardiolipin at 1:1:1 molar ratio, as well as in mitochondrial membranes. Increased permeability in both membrane models, monitored by calcein release, seemed to correlate with the extent of MEN incorporation into membranes. MEN perturbed the physical properties of vesicles composed of dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylethanolamine plus tetraoleoylcardiolipin (at 7:3 molar ratio), as reflected by the downshift of the lipid phase transition temperature and the emergence of a new transition peak in the mixed lipid system, detected by DSC. (31)P NMR studies revealed that MEN favored the formation of non-lamellar structures. Also, quenching studies with the fluorescent probes DPH and TMA-DPH showed that MEN distributed across the bilayer thickness in both model and native mitochondrial membranes. MEN's ability to promote alterations of membrane lipid organization was related with its reported mitochondrial toxicity and promotion of apoptosis, predictably involved in its anti-carcinogenic activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases.

    Science.gov (United States)

    Erdöl, Şahin; Sağlam, Halil

    2016-09-01

    Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction.

  12. Protein disulfide isomerase ameliorates β-cell dysfunction in pancreatic islets overexpressing human islet amyloid polypeptide.

    Science.gov (United States)

    Montane, Joel; de Pablo, Sara; Obach, Mercè; Cadavez, Lisa; Castaño, Carlos; Alcarraz-Vizán, Gema; Visa, Montserrat; Rodríguez-Comas, Júlia; Parrizas, Marcelina; Servitja, Joan Marc; Novials, Anna

    2016-01-15

    Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits in islets of type 2 diabetic patients. hIAPP misfolding and aggregation is one of the factors that may lead to β-cell dysfunction and death. Endogenous chaperones are described to be important for the folding and functioning of proteins. Here, we examine the effect of the endoplasmic reticulum chaperone protein disulfide isomerase (PDI) on β-cell dysfunction. Among other chaperones, PDI was found to interact with hIAPP in human islet lysates. Furthermore, intrinsically recovered PDI levels were able to restore the effect of high glucose- and palmitate-induced β-cell dysfunction by increasing 3.9-fold the glucose-stimulated insulin secretion levels and restoring insulin content up to basal control values. Additionally, PDI transduction decreased induced apoptosis by glucolipotoxic conditions. This approach could reveal a new therapeutic target and aid in the development of strategies to improve β-cell dysfunction in type 2 diabetic patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Proteína C ativada no tratamento de recém-nascido com sepse, choque e disfunção de múltiplos órgãos e sistemas: relato de caso e revisão de literatura Activated C protein in the treatment of a newborn with sepsis, shock and multiple organ dysfunction systems: case report and literature review

    Directory of Open Access Journals (Sweden)

    Flávia Carolina Davini Georgetti

    2006-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A sepse grave representa a síndrome de resposta inflamatória sistêmica resultante de uma infecção, na presença de disfunção cardiovascular, síndrome do desconforto respiratório agudo ou duas ou mais disfunções orgânicas. Embora a mortalidade atribuída à sepse em crianças tenha sido reduzida de maneira significativa nas últimas décadas, a incidência de óbitos em recém-nascidos permanece elevada (20% a 40%, a despeito dos avanços em cuidados intensivos. O objetivo deste estudo foi descrever o caso de um recém-nascido com sepse, choque e disfunção de múltiplos órgãos e sistemas (DMOS que se beneficiou do uso da proteína C ativada. RELATO DO CASO: Recém-nascido prematuro, do sexo masculino, nascido de cesariana em decorrência de ruptura prematura de membranas e sofrimento fetal agudo. Internado na UTI-Neonatal por insuficiência respiratória aguda secundária à pneumonia intra-útero. Recebeu assistência ventilatória, surfactante pulmonar exógeno e antibioticoterapia precocemente, evoluindo, no entanto, com hipertensão pulmonar persistente e choque. Houve difícil controle do quadro infeccioso, a despeito de ajustes no esquema de antibioticoterapia, evoluindo com DMOS. No 28º dia, foi iniciado o uso da proteína C ativada. O paciente evoluiu favoravelmente à medicação, com resolução das disfunções orgânicas e ausência de sangramentos. CONCLUSÕES: A proteína C ativada não pode ser prescrita de maneira rotineira no tratamento de recém-nascidos com sepse grave. No caso relatado, no entanto, acredita-se que ela tenha contribuído para a resolução das disfunções orgânicas apresentadas pelo paciente.BACKGROUND AND OBJECTIVES: Severe sepsis represents the systemic inflammatory response resulting from an infection, associated with one of the following: cardiovascular organ dysfunction, acute respiratory distress syndrome or two or more organ dysfunctions. Although the

  14. Interleukin-12 (IL-12)/STAT4 Axis Is an Important Element for β-Cell Dysfunction Induced by Inflammatory Cytokines

    Science.gov (United States)

    Weaver, Jessica R.; Nadler, Jerry L.; Taylor-Fishwick, David A.

    2015-01-01

    Pathology driving β-cell loss in diabetes is poorly defined. Chronic subclinical inflammation is associated with β-cell dysfunction. Acute in vitro exposure of islets and β-cells to an inflammatory cytokine cocktail (IL-1β/TNF-α/IFN-γ) results in loss of cell function and viability. The contribution of each cytokine alone or in combination has been evaluated in homogeneous mouse β-cell lines and primary mouse islets. Cytokine cooperation is required for β-cell apoptosis with the most potent combinations including IL-1β. Single cytokine exposure did not induce β-cell apoptosis. Expression of endogenous interleukin-12 in β-cells correlated with inflammatory cytokine combinations that induced β-cell apoptosis. Uncoupling of the IL-12 axis by a block of IL-12 production, inhibition of IL-12 receptor/ligand interaction or disruption of IL-12 receptor signaling conferred protection to β-cells from apoptosis induced by inflammatory cytokine stimulation. Signaling through STAT4 is indicated since disruption of IL-12 concomitantly reduced inflammatory cytokine stimulation of endogenous IFN-γ expression. Primary mouse islets isolated from mice deficient in STAT4 show resistance to inflammatory-cytokine-induced cell death when compared to islets isolated from wild type mice. Collectively, the data identify IL-12 as an important mediator of inflammation induced β-cell apoptosis. Modulation of IL-12/STAT4 signaling may be a valuable therapeutic strategy to preserve islet/β-cell viability in established diabetes. PMID:26555476

  15. Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Ikeda, Yasutaka; Tsuji, Shinji; Satoh, Akira; Ishikura, Masaharu; Shirasawa, Takuji; Shimizu, Takahiko

    2008-12-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although understanding of the pathogenesis of PD remains incomplete, increasing evidence from human and animal studies has suggested that oxidative stress is an important mediator in its pathogenesis. Astaxanthin (Asx), a potent antioxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. This study examined the protective effects of Asx on 6-hydroxydopamine (6-OHDA)-induced apoptosis in the human neuroblastoma cell line SH-SY5Y. Pre-treatment of SH-SY5Y cells with Asx suppressed 6-OHDA-induced apoptosis in a dose-dependent manner. In addition, Asx strikingly inhibited 6-OHDA-induced mitochondrial dysfunctions, including lowered membrane potential and the cleavage of caspase 9, caspase 3, and poly(ADP-ribose) polymerase. In western blot analysis, 6-OHDA activated p38 MAPK, c-jun NH(2)-terminal kinase 1/2, and extracellular signal-regulated kinase 1/2, while Asx blocked the phosphorylation of p38 MAPK but not c-jun NH(2)-terminal kinase 1/2 and extracellular signal-regulated kinase 1/2. Pharmacological approaches showed that the activation of p38 MAPK has a critical role in 6-OHDA-induced mitochondrial dysfunctions and apoptosis. Furthermore, Asx markedly abolished 6-OHDA-induced reactive oxygen species generation, which resulted in the blockade of p38 MAPK activation and apoptosis induced by 6-OHDA treatment. Taken together, the present results indicated that the protective effects of Asx on apoptosis in SH-SY5Y cells may be, at least in part, attributable to the its potent antioxidative ability.

  16. The protective effects and genetic pathways of thorn grape seeds oil against high glucose-induced apoptosis in pancreatic β-cells.

    Science.gov (United States)

    Lai, Xihu; Kang, Xincong; Zeng, Luman; Li, Jian; Yang, Yan; Liu, Dongbo

    2014-01-09

    Excessive apoptosis of β-cell is closely related to diabetes mellitus. Chronic exposure to high glucose causes β-cell dysfunction and apoptosis in diabetes. Thorn grape (Vitis davidii Foex.) has been used to treat diabetes in Traditional Chinese medicine for many years. In our previous research, thorn grape seeds oil (TGSO) showed promising anti-diabetic effects in animal models. However, it is unknown whether TGSO played an anti-apoptotic role in the anti-diabetic effects and the mechanism regarding signal transduction pathway is unclear either. The rattus pancreatic β-cell line RIN-m5F was treated with/without TGSO which was extracted by supercritical carbon dioxide (CO2) fluid extraction and analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). Cell apoptosis was detected by fluorescence activated cell sorting (FACS), insulin secretion was assayed by Enzyme-Linked Immunosorbent Assay (ELISA), and the apoptosis-related genes expressions were evaluated by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). TGSO, containing 87.02% unsaturated fatty acids (UFAs), significantly reduced pancreatic β-cell apoptosis and protected the insulin secretion impaired by high glucose. The expressions of pro-apoptotic genes such as iNOS, Caspase-3, ATF-3, JNK, p38 and Fas were down-regulated while the anti-apoptotic genes Akt and Bcl-2/Bax were up-regulated. The results indicated that TGSO protected β-cells from high glucose-induced apoptosis and its protective activity may be linked to mitochondrial pathway, endoplasmic reticulum (ER) stress pathway and Fas signal pathway, which implied that TGSO might be an effective complementary or alternative medicine to reduce β-cell apoptosis and dysfunction.

  17. Diabetes and sexual dysfunction: current perspectives

    Directory of Open Access Journals (Sweden)

    Maiorino MI

    2014-03-01

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

  18. Re: Engineered Nanoparticles Induce Cell Apoptosis: Potential for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-09-01

    Full Text Available Engineered nanoparticles (ENPs have been widely applied in industry, biology and medicine recently (i.e. clothes, sunscreens, cosmetics, foods, diagnostic medicine, imaging and drug delivery. There are many kinds of manufactured nanomaterial products including TiO2, ZnO, CeO2, Fe2O3, and CuO (as metal oxide nanoparticles as well as gold, silver, platinum and palladium (as metal nanoparticles, and other carbon-based ENP’s such as carbon nanotububes and quantum dots. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs and cause toxic effects. In many researches, ENP effects on the cancer cells of different organs with related cell apoptosis were noted (AgNP, nano-Cr2O3, Au-Fe2O3 NPs, nano-TiO2, nano-HAP, nano-Se, MoO3 nanoplate, Realgar nanoparticles. ENPs, with their unique properties, such as surface charge, particle size, composition and surface modification with tissue recognition ligands or antibodies, has been increasingly explored as a tool to carry small molecular weight drugs as well as macromolecules for cancer therapy, thus generating the new concept “nanocarrier”. Direct induction of cell apoptosis by ENPs provides an opportunity for cancer treatment. In the century of nanomedicine that depends on development of the nanotechnology, ENPs have a great potential for application in cancer treatment with minimal side effects.

  19. Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Regulatory T cells (Treg play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25(+ T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD25(- T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2 playing a significant role in sustaining Treg viability. In addition, pro- and anti-apoptotic signals are transduced by cell-to-cell interactions: CD3 and CD28 protect CD25(+ T cells from apoptosis, and in parallel sensitize naïve effector cells to apoptosis. Treg viability is modulated both by other T cells and other subsets within mixed splenocyte cultures. Variations in sensitivity to apoptosis are often hindered by fast proliferation of viable cells, therefore cycling rates are mandatory to adequate interpretation of cell death assays. CONCLUSIONS: The sensitivity of purified Treg to apoptosis is dominated by cytokine deprivation and absence of cell-to-cell interactions, and deviate significantly from measurements in mixed populations. Balanced sensitivity of naïve/effector and regulatory T cells to apoptosis in NOD mice argues against the concept that differential susceptibility affects disease evolution and progression.

  20. Sleep Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Falup-Pecurariu, Cristian; Diaconu, Ştefania

    2017-01-01

    The spectrum of sleep problems in Parkinson's disease (PD) is broad. These symptoms are recognized as being clinically relevant by the PD patients and may seriously affect their quality of life. Some studies reveal the occurrence of sleep disorders in more than half of the PD patients. The etiology is multifactorial and it mainly involves the degeneration of the sleep-regulating structures. Sleep disorders in PD can be classified into: disturbances of sleep and disturbances of wakefulness. Generic and specific scales were designed to help the screening and evaluation of sleep dysfunction. Further assessment can be done using sleep recording techniques, like actigraphy or polysomnography. All types of sleep disturbances may be encountered in PD: insomnia, excessive daytime sleepiness, rapid eye movement sleep behavior disorders, and restless legs syndrome. This chapter will focus on reviewing the main characteristics, pathophysiology, assessment, and management of the most frequent sleep disturbances encountered in PD. © 2017 Elsevier Inc. All rights reserved.

  1. Psychopathy: cognitive and neural dysfunction

    Science.gov (United States)

    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

  2. Sleep Dysfunction and Gastrointestinal Diseases.

    Science.gov (United States)

    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.

  3. Radiation-induced neurobehavioral dysfunctions

    International Nuclear Information System (INIS)

    Manda, Kailash

    2013-01-01

    There is a lacuna between sparsely reported immediate effects and the well documented delayed effects on cognitive functions seen after ionizing radiation exposure. We reported the radiation-dose dependent incongruity in the early cognitive changes and its correlation with the structural aberration as reported by imaging study. The delayed effect of radiation was investigated to understand the role of hippocampal neurogenesis in the functional recovery of cognition. C57BL/6 mice were exposed to different doses of γ-radiation and 24 hrs after exposure, the stress and anxiety levels were examined in the Open Field Exploratory Paradigms (OFT). 48hrs after irradiation, the hippocampal dependent recognition memory was observed by the Novel Object Recognition Test (NORT) and the cognitive function related to memory processing and recall was tested using the Elevated Plus Maze (EPM). Visualization of damage to the brain was done by diffusion tensor imaging at 48 hours post-irradiation. Results indicate a complex dose independent effect on the cognitive functions immediately after exposure to gamma rays. Radiation exposure caused short term memory dysfunctions at lower doses which were seen to be abrogated at higher doses, but the long term memory processing was disrupted at higher doses. The Hippocampus emerged as one of the sensitive regions to be affected by whole body exposure to gamma rays, which led to profound immediate alterations in cognitive functions. Furthermore, the results indicate a cognitive recovery process, which might be dependent on the extent of damage to the hippocampal region. While evaluating the delayed effect of radiation on the hippocampal neurogenesis, we observed that higher doses groups showed comparatively more adaptive regenerative neurogenic potential which they could not sustain at later stages. Our studies reported an important hitherto uncovered phenomenon of neurobehavioral dysfunctions in relation to radiation dose. Nevertheless, a

  4. Thyroid dysfunction in infertile women

    International Nuclear Information System (INIS)

    Elahi, S.; Tanseem, A.; Nazir, I.; Nagra, S.A.

    2007-01-01

    To determine the frequency of thyroid dysfunction in infertile women referred for thyroid evaluation. Age matched infertile (n=140 each) and fertile women (n=152 each) referred to CENUM for thyroid evaluation were investigated for incidence of hyperthyroidism (TSH 20 IU/L). Serum free T4 (FT4), free T3 (FT3) and antithyroid peroxidase antibody (TPO-Ab) was determined by radioimmunoassay (RIA) and TSH by immunoradiometric assay (IRMA). Most of the infertile women (89.3%), like control women (93.4%), were euthyroid. The difference of overall thyroid dysfunction was not statistically significant in infertile and control women (10.7% vs. 7.9%; p=0.395). The same was true for incidence of hyperthyroidism (4.3% vs. 5.3%; p=0.701) as well as hypothyroidism (6.4% vs. 2.6%; p=0.104). In infertile women, the incidence of hypothyroidism (6.4%) was slightly higher as compared to hyperthyroidism (4.3%). In euthyroid women of both groups, mean FT4, FT3 and TSH levels were significantly higher (p 2.5 mIU/L compared to fertile women (31.2% vs. 15.6%; p 20 IU/L) than control women (7.2% vs. 1.4%; p<0.05). Increased incidence of high normal TSH and raised TPO-Ab titer indicate relatively more frequent occurrence of compensated thyroid function in infertile women than normal women of reproductive age. This necessitates considering them a subgroup of women in which all aspects of pituitary-thyroid axis should be thoroughly investigated than merely TSH testing. (author)

  5. Test Performance Related Dysfunctional Beliefs

    Directory of Open Access Journals (Sweden)

    Recep TÜTÜNCÜ

    2012-11-01

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

  6. [Depression and treatment. Apoptosis, neuroplasticity and antidepressants].

    Science.gov (United States)

    Arantes-Gonçalves, Filipe; Coelho, Rui

    2006-01-01

    Depression's neurobiology begins to be better understood. The last decade data considers neuroplasticity and stress as implicated factors on the pathophisiology of depression. Because antidepressants have a lag-time on their action it is possible that inhibition of neurotransmitters recaptation is not sufficient to explain long term changes. For that purpose, neurogenesis increase, nervous fibers sprouting, new synapses and stabilization of the old ones can be responsible for those changes. AMPc-MAPcinases-CREB-BDNF cellular cascade can play a significant role in the mechanisms of dendritic restructuration, hippocampal neurogenesis increase and nervous cells survival. The aim of this article is to discuss if apoptosis could play a key role as an ethiopathogenic factor on the patogenesis of depression. It was done a medline search for references with apoptosis, stress, neuroplasticity, depression and antidepressants key-words. It were found 101 original or review references about these subjects. Stress plays a key role in the etiopathogeny of depression. Its deletery effects on apoptosis and neuroplasticity can be changed by antidepressants. Neurogenesis' increase is necessary for their action. This increase is reached with chronic antidepressant treatment and not with other psychotropic drugs which means some pharmacological specificity of antidepressants. AMPc, CREB, BDNF and Bcl-2 can be considered as target genes in antidepressant synthesis. At the level of this neurotrophic factors apoptosis might be included in the neuroplastic model of depression and play a prominent role in etiopathogeny of depression. To confirm that, we need more research on the field to know which are the mechanisms that trigger apoptosis and its biological significance. In relation to the last one, we can say that is possible to be physiological apoptosis in deteriorated neurons death which cannot make strong connections and pathological apoptosis because of stress via, namely, HPA axis.

  7. Atrial electromechanical abnormalities in hypertensive patients with diastolic dysfunction