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Sample records for counteracts intestinal atrophy

  1. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib

    DEFF Research Database (Denmark)

    Hare, Kristine Juul; Hartmann, Bolette; Kissow, Hannelouise;

    2007-01-01

    PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been introduced as antitumor agents in the treatment of cancers overexpressing the receptor. The treatment has gastrointestinal side effects which may decrease patient compliance and limit the efficacy. Glucagon...... and cross-sectional area were decreased. The same parameters were increased by GLP-2 treatment alone, and when GLP-2 was combined with the gefitinib treatment, the parameters remained unchanged. CONCLUSIONS: Treatment with an EGFR tyrosine kinase inhibitor in mice results in small-intestinal growth...... inhibition that can be completely prevented by simultaneous treatment with GLP-2. This suggests that the gastrointestinal side effects elicited by treatment with EGFR tyrosine kinase inhibitors can be circumvented by GLP-2 treatment....

  2. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

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    Cláudio Martins

    2016-01-01

    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  3. Intestinal mucosal atrophy and adaptation

    Institute of Scientific and Technical Information of China (English)

    Darcy Shaw; Kartik Gohil; Marc D Basson

    2012-01-01

    Mucosal adaptation is an essential process in gut homeostasis.The intestinal mucosa adapts to a range of pathological conditions including starvation,short-gut syndrome,obesity,and bariatric surgery.Broadly,these adaptive functions can be grouped into proliferation and differentiation.These are influenced by diverse interactions with hormonal,immune,dietary,nervous,and mechanical stimuli.It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation.This review will summarize current understanding of the basic science surrounding adaptation,delineate the wide range of potential targets for therapeutic intervention,and discuss how these might be incorporated into an overall treatment plan.Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

  4. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    Science.gov (United States)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  5. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    Science.gov (United States)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  6. Effect of IR Laser on Myoblasts: Prospects of Application for Counteracting Microgravity-Induced Muscle Atrophy

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    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Corsetto, Paola Antonia; Rizzo, Angela Maria; Caselli, Anna; Ranaldi, Francesco

    2013-02-01

    Microgravity-induced muscle atrophy is a problem of utmost importance for the impact it may have on the health and performance of astronauts. Therefore, appropriate countermeasures are needed to prevent disuse atrophy and favour muscle recovery. Muscle atrophy is characterized by loss of muscle mass and strength, and a shift in substrate utilization from fat to glucose, that leads to a reduced metabolic efficiency and enhanced fatigability. Laser therapy is already used in physical medicine and rehabilitation to accelerate muscle recovery and in sports medicine to prevent damages produced by metabolic disturbances and inflammatory reactions after heavy exercise. The aim of the research we present was to get insights on possible benefits deriving from the application of an advanced infrared laser system to counteract deficits of muscle energy metabolism and stimulate the recovery of the hypotrophic tissue. The source used was a Multiwave Locked System (MLS) laser, which combines continuous and pulsed emissions at 808 nm and 905 nm, respectively. We studied the effect of MLS treatment on morphology and energy metabolism of C2C12 cells, a widely accepted myoblast model, previously exposed to microgravity conditions modelled by a Random Positioning Machine. The MLS laser treatment was able to restore basal levels of serine/threonine protein phosphatase activity and to counteract cytoskeletal alterations and increase in glycolytic enzymes activity that occurred following the exposure to modelled microgravity. In conclusion, the results provide interesting insights for the application of infrared laser in the treatment of muscle atrophy.

  7. Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading

    OpenAIRE

    ZHANG, Zong-Kang; Li, Jie; Liu, Jin; Baosheng GUO; Leung, Albert; Zhang, Ge; Zhang, Bao-Ting

    2016-01-01

    Counteracting muscle atrophy induced by mechanical unloading/inactivity is of great clinical need and challenge. A therapeutic agent that could counteract muscle atrophy following mechanical unloading in safety is desired. This study showed that natural product Icaritin (ICT) could increase the phosphorylation level of Phosphatidylinositol 3 kinase (PI3K) at p110 catalytic subunit and promote PI3K/Akt signaling markers in C2C12 cells. This study further showed that the high dose ICT treatment...

  8. Muscle cell atrophy induced by HSP gene silencing was counteracted by HSP overexpression

    Science.gov (United States)

    Choi, Inho; Lee, Joo-Hee; Nikawa, Takeshi; Gwag, Taesik; Park, Kyoungsook; Park, Junsoo

    Heat shock proteins (HSP), as molecular chaperones, are known to assist protein quality control under various stresses. Although overexpression of HSP70 was found to contribute to muscle size retention under an unloading condition, it remains largely unclarified whether muscle atrophy is induced by active suppression of HSP expression. In this study, we pre-treated Hsp70 siRNA to rat L6 cells for the HSP gene silencing, and determined myotube diameter, HSP72 expression and anabolic and catabolic signaling activities in the absence or presence of triterpene celastrol (CEL), the HSP70 inducer. Relative to a negative control (NC), muscle cell diameter was reduced 0.89-fold in the siRNA-treated group, increased 1.2-fold in the CEL-treated group and retained at the size of NC in the siRNA+CEL group. HSP72 expression was decreased 0.35-fold by siRNA whereas the level was increased 6- to 8-fold in the CEL and siRNA+CEL groups. Expression of FoxO3 and atrogin-1 was increased 1.8- to 4.8-fold by siRNA, which was abolished by CEL treatment. Finally, phosphorylation of Akt1, S6K and ERK1/2 was not affected by siRNA, but was elevated 2- to 6-fold in the CEL and siRNA+CEL groups. Taken together, HSP downregulation by Hsp gene silencing led to muscle cell atrophy principally via increases in catabolic activities and that such anti-atrophic effect was counteracted by HSP overexpression.

  9. MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy.

    Science.gov (United States)

    Pourshafie, Naemeh; Lee, Philip R; Chen, Ke-Lian; Harmison, George G; Bott, Laura C; Katsuno, Masahisa; Sobue, Gen; Burnett, Barrington G; Fischbeck, Kenneth H; Rinaldi, Carlo

    2016-05-01

    Spinal and bulbar muscular atrophy (SBMA) is a currently untreatable adult-onset neuromuscular disease caused by expansion of a polyglutamine repeat in the androgen receptor (AR). In SBMA, as in other polyglutamine diseases, a toxic gain of function in the mutant protein is an important factor in the disease mechanism; therefore, reducing the mutant protein holds promise as an effective treatment strategy. In this work, we evaluated a microRNA (miRNA) to reduce AR expression. From a list of predicted miRNAs that target human AR, we selected microRNA-298 (miR-298) for its ability to downregulate AR mRNA and protein levels when transfected in cells overexpressing wild-type and mutant AR and in SBMA patient-derived fibroblasts. We showed that miR-298 directly binds to the 3'-untranslated region of the human AR transcript, and counteracts AR toxicity in vitro. Intravenous delivery of miR-298 with adeno-associated virus serotype 9 vector resulted in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in SBMA mice. Our findings support the development of miRNAs as a therapeutic strategy for SBMA and other neurodegenerative disorders caused by toxic proteins.

  10. An approach to counteracting long-term microgravity-induced muscle atrophy

    Science.gov (United States)

    Tesch, P. A.; Buchanan, P.; Dudley, G. A.

    1990-01-01

    To find means of alleviating muscle atrophy induced by long-term microgravity, the effects of a 19-week-long heavy-resistance training regime (using either concentric muscle actions only or concentric and eccentric muscle actions) on the strengths of the exercised knee extensor muscle group were investigated in two groups of male human subjects performing two types of training exercises: supine leg press or/and seated knee extension. Results show that a training program in which both the concentric and the eccentric muscle action was performed led to substantially greater increases in maximal muscle strength than when only concentric exercises were performed.

  11. An approach to counteracting long-term microgravity-induced muscle atrophy

    Science.gov (United States)

    Tesch, P. A.; Buchanan, P.; Dudley, G. A.

    1990-01-01

    To find means of alleviating muscle atrophy induced by long-term microgravity, the effects of a 19-week-long heavy-resistance training regime (using either concentric muscle actions only or concentric and eccentric muscle actions) on the strengths of the exercised knee extensor muscle group were investigated in two groups of male human subjects performing two types of training exercises: supine leg press or/and seated knee extension. Results show that a training program in which both the concentric and the eccentric muscle action was performed led to substantially greater increases in maximal muscle strength than when only concentric exercises were performed.

  12. Candida utilis and Chlorella vulgaris counteract intestinal inflammation in Atlantic salmon (Salmo salar L..

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    Fabian Grammes

    Full Text Available Intestinal inflammation, caused by impaired intestinal homeostasis, is a serious condition in both animals and humans. The use of conventional extracted soybean meal (SBM in diets for Atlantic salmon and several other fish species is known to induce enteropathy in the distal intestine, a condition often referred to as SBM induced enteropathy (SBMIE. In the present study, we investigated the potential of different microbial ingredients to alleviate SBMIE in Atlantic salmon, as a model of feed-induced inflammation. The dietary treatments consisted of a negative control based on fish meal (FM, a positive control based on 20% SBM, and four experimental diets combining 20% SBM with either one of the three yeasts Candida utilis (CU, Kluyveromyces marxianus (KM, Saccharomyces cerevisiae (SC or the microalgae Chlorella vulgaris (CV. Histopathological examination of the distal intestine showed that all fish fed the SC or SBM diets developed characteristic signs of SBMIE, while those fed the FM, CV or CU diets showed a healthy intestine. Fish fed the KM diet showed intermediate signs of SBMIE. Corroborating results were obtained when measuring the relative length of PCNA positive cells in the crypts of the distal intestine. Gene set enrichment analysis revealed decreased expression of amino acid, fat and drug metabolism pathways as well as increased expression of the pathways for NOD-like receptor signalling and chemokine signalling in both the SC and SBM groups while CV and CU were similar to FM and KM was intermediate. Gene expression of antimicrobial peptides was reduced in the groups showing SBMIE. The characterisation of microbial communities using PCR-DGGE showed a relative increased abundance of Firmicutes bacteria in fish fed the SC or SBM diets. Overall, our results show that both CU and CV were highly effective to counteract SBMIE, while KM had less effect and SC had no functional effects.

  13. Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition

    DEFF Research Database (Denmark)

    Xiao, Weidong; Feng, Yongjia; Holst, Jens Juul

    2014-01-01

    Small intestine luminal nutrient sensing may be crucial for modulating physiological functions. However, its mechanism of action is incompletely understood. We used a model of enteral nutrient deprivation, or total parenteral nutrition (TPN), resulting in intestinal mucosal atrophy and decreased...... significantly changed the amount of T1Rs, GLM receptors, and transporters, and GLM prevented these changes. GLM significantly prevented TPN-associated intestinal atrophy (2.5-fold increase in IEC proliferation) and was dependent on up-regulation of the protein kinase pAkt, but independent of T1R3 and mGluR5...

  14. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets

    DEFF Research Database (Denmark)

    Niinikoski, Harri; Stoll, Barbara; Guan, Xinfu

    2004-01-01

    Our aim was to determine the speed of onset of total parenteral nutrition (TPN)-induced mucosal atrophy, and whether this is associated with changes in intestinal blood flow and tissue metabolism in neonatal piglets. Piglets were implanted with jugular venous and duodenal catheters and either...... 24 h of TPN, and protein mass was lower (P parenteral nutrition induced a rapid (

  15. Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study.

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    Yamada, Waka; Kaji, Tatsuru; Onishi, Shun; Nakame, Kazuhiko; Yamada, Koji; Kawano, Takafumi; Mukai, Motoi; Souda, Masakazu; Yoshioka, Takako; Tanimoto, Akihide; Ieiri, Satoshi

    2016-12-01

    Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 μg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration. Copyright © 2016. Published by Elsevier Inc.

  16. The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin

    DEFF Research Database (Denmark)

    Rasmussen, Andreas Rosén; Viby, Niels-Erik; Hare, Kristine Juul;

    2010-01-01

    Erlotinib, an epidermal-growth-factor receptor inhibitor, belongs to a new generation of targeted cancer therapeutics. Gastrointestinal side-effects are common and have been markedly aggravated when erlotinib is combined with cytostatics. We examined the effects of erlotinib alone and combined wi...... with the cytostatic, cisplatin, on the gastrointestinal tract and examined whether glucagon-like peptide-2 (GLP-2), an intestinal hormone with potent intestinotrophic properties, might counteract the possible damaging effects of the treatments....

  17. Association between anti-endomysial antibody and total intestinal villous atrophy in children with coeliac disease.

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    Ozgenc F

    2003-01-01

    Full Text Available BACKGROUND: There is growing evidence to suggest that detection of anti-gliadin antibody (AGA and anti-endomysial antibody (EmA can serve as sensitive markers of the degree of histological abnormalities in patients with coeliac disease. AIM: To evaluate the association between the presence of AGA and EmA and villous atrophy in intestinal biopsies of children with suspected coeliac disease. SETTINGS AND DESIGN: Intestinal samples of 46 children with failure to thrive, chronic diarrhoea, malabsorption and short stature with either AGA and/or EmA positivity were evaluated, retrospectively. The diagnosis of coeliac disease was based on ESPGHAN criteria. METHODS AND MATERIAL: Patients with total villous atrophy who fulfilled the ESPGHAN criteria for the diagnosis of coeliac disease were diagnosed to have coeliac disease. Nine patients without villous atrophy were taken as negative controls for this study. AGA-IgA was measured both by immunoflourescence (IF and ELISA and EmA-IgA by IF while patients were on normal diet. Relationship between autoantibody positivity and intestinal total villous atrophy was evaluated. RESULTS: Overall positivity for AGA IgA was 85% (39/46 by IF+ELISA and EmA positivity was 85% (39/46 by IF within the study group. Histological examination revealed total villous atrophy with lymphocyte infiltration and crypt hyperplasia in 37 (80% patients. AGA IgA was positive in 14 (38% and 31 (84% of these children by ELISA and IF, respectively. EmA positivity was detected in 35/37 (95% cases with atrophy and 4/9 (44% without atrophy (p=0.002. Thirty out of 37 (81% patients with villous atrophy had both AGA IgA (IF and EmA positivity (p=0.186. All of the sixteen patients that had both positive AGA IgA (ELISA+IF and EmA had total villous atrophy (p=0.037. CONCLUSION: A significant association between total villous atrophy and EmA positivity has been documented in this study.

  18. Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition.

    Science.gov (United States)

    Xiao, Weidong; Feng, Yongjia; Holst, Jens J; Hartmann, Bolette; Yang, Hua; Teitelbaum, Daniel H

    2014-05-01

    Small intestine luminal nutrient sensing may be crucial for modulating physiological functions. However, its mechanism of action is incompletely understood. We used a model of enteral nutrient deprivation, or total parenteral nutrition (TPN), resulting in intestinal mucosal atrophy and decreased epithelial barrier function (EBF). We examined how a single amino acid, glutamate (GLM), modulates intestinal epithelial cell (IEC) growth and EBF. Controls were chow-fed mice, T1 receptor-3 (T1R3)-knockout (KO) mice, and treatment with the metabotropic glutamate receptor (mGluR)-5 antagonist MTEP. TPN significantly changed the amount of T1Rs, GLM receptors, and transporters, and GLM prevented these changes. GLM significantly prevented TPN-associated intestinal atrophy (2.5-fold increase in IEC proliferation) and was dependent on up-regulation of the protein kinase pAkt, but independent of T1R3 and mGluR5 signaling. GLM led to a loss of EBF with TPN (60% increase in FITC-dextran permeability, 40% decline in transepithelial resistance); via T1R3, it protected EBF, whereas mGluR5 was associated with EBF loss. GLM led to a decline in circulating glucagon-like peptide 2 (GLP-2) during TPN. The decline was regulated by T1R3 and mGluR5, suggesting a novel negative regulator pathway for IEC proliferation not previously described. Loss of luminal nutrients with TPN administration may widely affect intestinal taste sensing. GLM has previously unrecognized actions on IEC growth and EBF. Restoring luminal sensing via GLM could be a strategy for patients on TPN.

  19. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

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    Protim Sarker

    Full Text Available BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18 in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB, a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR and release of the CAP-18 peptide/protein in stool (Western blot. PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from

  20. Regeneration Process Markers in Hyperregenerative Type of Small Intestinal Mucosal Atrophy

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    T. A. Kuznetsova

    2015-01-01

    Full Text Available Objective: Our aim was to objectify structural changes in small intestinal mucosa in patients with celiac disease, with defining criteria of regeneration process forecast.Methods: We conducted an observational, retrospective, analytical study of «case-control». The research presents results of histologic, histochemical, immunohistochemical and morphometric analyses of the small intestinal mucosa in children with proven cases of celiac disease before/after a gluten-free diet. The state of main cell types providing a structural mucosa homeostasis and their impact on the remodelling of hystoarchitecton type of atrophy was studied. Two clinical groups were formed: group I — with a complete recovery of the small intestinal mucosa (n = 10, and group II — with a permanent hystoarchitectonics disturbance (n = 7, which were put to a comparative morphometric test.Results: Installs: cytoarchitectonics recovery against the background of diet accompanied by a decrease of between epithelial lymphocytes to 12% (p = 0.002, eosinophilic granulocytes to 0.36 cells per mm2 (p = 0.003, plasma cells — up to 1.9 cells per mm2 (p = 0.003, increase in the number of fibroblasts to 1.64 cells per mm2 (p = 0.003, and leyomiotsitov — up to 6 cells on villi (p = 0.002. If persistent structural violations against the background of positive dynamics of the diet was to reduce the number of eosinophilic granulocytes to 0.41 cells per mm2 (p = 0.009 and plasma cells per 2.9 mm2 (p = 0.009.Conclusion: Persistent mismatch between the cell elements — epithelial, stromal cells and smooth muscle cells in the lining of the small intestine — initially hinders the successful course of the reparative process and prolongs recovery structure of small intestinal mucosa of celiac disease.

  1. Differential cloning of novel intestine-specific genes whose expression is altered under conditions of villus atrophy.

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    Hodin, R A; Meng, S; Shei, A

    1995-07-01

    Atrophy of the small intestinal villi occurs in a variety of disease states and is associated with diarrhea, malabsorption, and impaired barrier function. We have previously demonstrated that villus atrophy is associated with an increase in lactase and a decrease in intestinal alkaline phosphatase gene expression. Given these changes in enterocyte phenotype with villus atrophy, we speculated that there may be other intestine-specific genes whose expression is altered as a function of epithelial growth state. We have employed two molecular techniques in order to identify and clone complementary DNAs (cDNA) which are differentially expressed in atrophic compared to normal small intestinal mucosa. In differential cDNA library (+/-) screening, duplicate filters of a normal jejunal cDNA library are hybridized with radiolabeled cDNA probes from either atrophic or control tissues. Comparisons of the intensities of hybridized clones allows for the identification of differentially expressed gene products. In the mRNA differential display system, RT-PCR is used to randomly amplify mRNA species. Similar to cDNA library screening, comparisons of radiolabeled bands on a polyacrylamide sequencing gel allow for the identification of differentially expressed genes. Using these methods, we have identified a novel cDNA, called D9, which appears to be expressed exclusively in the intestinal mucosa. Northern analyses have confirmed that the expression of the D9 mRNA is dramatically decreased under conditions of villus atrophy, suggesting an underlying relationship with epithelial growth state. DNA sequence analysis (GenBank) reveals no identity to previously cloned genes.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. -765G>C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

    Institute of Scientific and Technical Information of China (English)

    Carina Pereira; Hugo Sousa; Paula Ferreira; Maria Fragoso; Luís Moreira-Dias; Carlos Lopes; Rui Medeiros; Mário Dinis-Ribeiro

    2006-01-01

    AIM: To investigate the relationship between the -765G> C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma.METHODS: A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method. RESULTS: -765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%).Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).CONCLUSION: -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

  3. Bifidobacteria upregulate expression of toll-like receptor negative regulators counteracting enterotoxigenic Escherichia coli mediated inflammation in bovine intestinal epitheliocytes

    OpenAIRE

    Murata, Kozue; Villena, Julio Cesar; Tomosada, Yohsuke; Risa, Hara; Chiba, Eriko; Shimazu, Tomoyuki; Aso, Hisashi; Suda, Yoshihito; Iwabuchi, Noriyuki; Xiao, Jin-zhong; Saito, Tadao; Kitazawa, Haruki

    2015-01-01

    We previously established a bovine intestinal epithelial cell line (BIE cells) and showed that BIE cells are useful in vitro model system for the study of interactions between pathogenic and beneficial microorganisms and bovine intestinal epithelial cells (IECs). In the present study we aimed to select potential immunomodulatory bifidobacteria that may be used to beneficially modulate the inflammatory response in bovine IECs. We also aimed to gain insight in the molecular mechanisms involved ...

  4. The human intestinal microbiome at extreme ages of life. Dietary intervention as a way to counteract alterations

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    Nuria eSalazar

    2014-11-01

    Full Text Available The intestinal microbiome is defined as the assembly of genomes from microorganisms inhabiting the gut. This microbial ecosystem regulates important functions of the host and its correct composition and functionality is essential for a healthy status. Metagenomic studies have highlighted variations of the intestinal microbiota as a function of age and diet. Colonization of the infant gut starts at birth and is influenced by feeding habits (formula vs. breast-feeding, birth mode and antibiotic exposure. The intestinal microbiota of full-term vaginally-delivered breast-fed infants is considered the gold-standard of a healthy infant microbiota, representing the reference for studies of alterations in other pediatric populations. At two to three years of age, the intestinal microbiota reaches a composition similar to adults, remaining without noticeable variations until senescence, when microbial instability and changes reappear. Here we summarize the current knowledge on intestinal microbiota alterations at extreme stages of life and tools for designing differentiated nutritional strategies by the use of probiotics, prebiotics and specific nutrients in order to restore a balanced microbiota and to improve immune and nutritional status.

  5. Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs

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    Hong Liu

    2017-04-01

    Full Text Available This study was conducted to explore whether exposure to bisphenol A (BPA during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON; control diet supplemented with BPA (50 mg/kg; control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid; and control diet with BPA and MET supplementation (BPA + MET. Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1 and DNA methyl transferase 3a (DNMT3a, and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05. Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT, DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR, and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05. However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05. Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation.

  6. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

    Directory of Open Access Journals (Sweden)

    Palittiya Sintusek

    Full Text Available Gastrointestinal (GI defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA. Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

  7. Propolis reduces bacterial translocation and intestinal villus atrophy in experimental obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of propolis on bacterial translocation and ultrastructure of intestinal morphology in experimental obstructive jaundice.METHODS: Thirty Wistar-Albino male rats were randomly divided into three groups, each including 10 animals: group I, sham-operated; group Ⅱ, ligation and division of the common bile duct (BDL); group Ⅲ, BDL followed by oral supplementation of propolis 100 mg/kg per day. Liver, blood, spleen, mesenteric lymph nodes,and ileal samples were taken for microbiological, light and transmission electron microscopic examination on postoperative 7th d after sacrification.RESULTS: The mean number of villi per centimeter and mean mucosal height of the propolis group were significantly different in the BDL group (P = 0.001 and 0.012, respectively). The electron microscopic changes were also different between these groups. Sham and BDL+propolis groups had similar incidence of bacterial translocation (BT). The BDL group had significantly higher rates of BT as compared with sham and BDL + propolis groups. BT was predominantly detected in MLNs and the most commonly isolated bacteria was Escherichia coli.CONCLUSION: Propolis showed a significant protective effect on ileal mucosa and reduced bacterial translocation in the experimental obstructive jaundice model. Further studies should be carried out to explain the mechanisms of these effects.

  8. Vaginal Atrophy

    Science.gov (United States)

    ... Body in Balance › Vaginal Atrophy Fact Sheet Vaginal Atrophy November, 2011 Download PDFs English Espanol Editors JoAnn ... MD Richard J. Santen, MD What is vaginal atrophy? Vaginal atrophy is a condition in which the ...

  9. Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan Zhang; Nobutaka Yamada; Yun-Lin Wu; Min Wen; Takeshi Matsuhisa; Norio Matsukura

    2005-01-01

    AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis,gastric ulcer.METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients.Giemsa staining, improved toluidine-blue staining, and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System.RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%,in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%,respectively; in patients with gastric erosion 52.4%, 61.5%,52.4%, respectively; in patients with gastric ulcer 52.4%,61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01);however, there was no significant difference compared with erosive gastritis. The grades

  10. Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis.

    Science.gov (United States)

    Villarreal-Calderon, Rodolfo; Luévano-González, Arturo; Aragón-Flores, Mariana; Zhu, Hongtu; Yuan, Ying; Xiang, Qun; Yan, Benjamin; Stoll, Kathryn Anne; Cross, Janet V; Iczkowski, Kenneth A; Mackinnon, Alexander Craig

    2014-06-01

    Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (Pgastritis. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Vaginal Atrophy

    Science.gov (United States)

    Vaginal atrophy Overview Vaginal atrophy (atrophic vaginitis) is thinning, drying and inflammation of the vaginal walls due to your body having less estrogen. Vaginal atrophy occurs most often after ...

  12. Intestine.

    Science.gov (United States)

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  13. Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs

    DEFF Research Database (Denmark)

    Jain, Ajay Kumar; Stoll, Barbara; Burrin, Douglas G

    2012-01-01

    Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly...

  14. Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs

    Science.gov (United States)

    Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly des...

  15. [Atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems].

    Science.gov (United States)

    Ramírez-Mendoza, Pablo; Hernández-Briseño, Liliana; Casarrubias-Ramírez, Moisés; Alvarado-Cabrero, Isabel; Ángeles-Garay, Ulises

    2015-01-01

    Introducción: el carcinoma gástrico ocasiona al año unas 700 000 muertes en el mundo. El objetivo de este artículo es evaluar la atrofia en la mucosa vecina al adenocarcinoma gástrico tipo intestinal comparando los sistemas Sídney y OLGA. Diferencias en el rendimiento diagnóstico impulsarían el empleo de alguno. Métodos: estudiamos 28 sujetos con adenocarcinoma gástrico tipo intestinal (Lauren), que comparamos con 32 casos sin neoplasia, ambos grupos con gastrectomía total. Dos patólogos evaluaron la atrofia en el epitelio de cuerpo y antro no neoplásico con los sistemas Sídney y OLGA. Se obtuvieron la media, mediana y distribución de frecuencias por escala de medición, así como la distribución de las variables del estudio. Se calculó la sensibilidad, especificidad y los valores predictivos para cáncer gástrico gracias a dicotomizar las escalas con resultado positivo y negativo para atrofia avanzada. Resultados: veinticuatro de 28 casos con adenocarcinoma gástrico tipo intestinal mostraron atrofia avanzada con OLGA con una sensibilidad y especificidad de 77 y 85 % respectivamente. Con el sistema Sídney, 4 de 28 mostraron atrofia avanzada con una sensibilidad y especificidad de 14 y 100 % respectivamente. Conclusiones: el sistema OLGA tiene elevada sensibilidad y especificidad (77 y 85 % respectivamente) para reconocer cambios preneoplásicos en la mucosa vecina al cáncer gástrico. Empero, OLGA no mostró atrofia avanzada en adenomas foveolares con displasia de alto grado, ni en adenocarcinomas en las porciones proximales del estómago.

  16. Muscle atrophy

    Science.gov (United States)

    ... atrophy. Exercises may include ones done in a swimming pool to reduce the muscle workload, and other types ... a physical examination and ask about your medical history and symptoms, including: When did the muscle atrophy ...

  17. Gastric atrophy, diagnosing and staging

    Institute of Scientific and Technical Information of China (English)

    Hala MT El-Zimaity

    2006-01-01

    H pylori is now accepted as the cause of gastritis and gastritis-associated diseases, such as duodenal ulcer,gastric ulcer, gastric carcinoma, and gastric MALT lymphoma. The natural history of H pylori gastritis includes inflammation progressing from the antrum into the adjacent corpus resulting in an atrophic front of advancing injury leading to a reduction in acid secretion and eventual loss of parietal cells and development of atrophy. Sub-typing intestinal metaplasia has no clinical value to the patient, the pathologist, or the endoscopist.The pattern, extent, and severity of atrophy, with or without intestinal metaplasia, is a far more important predictor than is intestinal metaplasia subtype. The challenge remains to identify a reliable marker that relates to pre-malignant potential.

  18. Atrophy of the intestinal villi in a post-gastrectomy patient with severe iron deficiency anemia Atrofia de las vellosidades intestinales en un paciente postgastrectomizado con anemia ferropénica grave

    Directory of Open Access Journals (Sweden)

    A. Lizarraga

    2009-10-01

    Full Text Available Background & aims: Iron deficiency anemia is a common complication of gastric surgery that in certain patients can be refractory to treatment with oral iron and needs to be treated parenterally. Methods: A 48-year woman underwent gastric surgery for a gastric ulcer. She was referred to the nutrition unit for the study and treatment of a 3-year iron deficiency anemia refractory to oral iron supplementation. Blood tests, endoscopy and jejunal biopsy were made to study the case. Results: Intestinal villi atrophy in the absence of celiac disease was the result. She was treated with intravenous iron, resolving the villous atrophy and thus oral iron supplementation could be effective. Conclusion: This case illustrates that iron deficiency may cause villous atrophy. In this setting, parenteral iron administration is necessary to correct the haematological and non-hematological alterations associated with this deficiency.Introducción y objetivos: La anemia ferropénica es una complicación frecuente tras la cirugía gástrica que en algunos pacientes puede ser refractaria al tratamiento con hierro oral, siendo necesaria su administración por vía parenteral. Métodos: Presentamos el caso de una mujer de 48 años intervenida de gastrectomía para tratamiento de una úlcera gástrica. Fue remitida a la unidad de nutrición para estudio y tratamiento de una anemia ferropénica de 3 años de evolución refractaria al tratamiento con hierro oral. Para el estudio del caso se realizó analítica y endoscopia digestiva alta con biopsia yeyunal. Resultados: En el estudio realizado la paciente presentaba atrofia de la mucosa yeyunal en ausencia de enfermedad celíaca. Fue tratada con hierro intravenoso desapareciendo la atrofia intestinal, tras lo cual continuamos con suplementos de hierro por vía oral. Conclusión: Este caso ilustra que la deficiencia de hierro puede producir atrofia intestinal. Si esto ocurre, es necesario la suplementación de este metal

  19. Learning about Spinal Muscular Atrophy

    Science.gov (United States)

    ... News Release Fischbeck Group Learning About Spinal Muscular Atrophy What is spinal muscular atrophy? What are the ... for Spinal Muscular Atrophy What is spinal muscular atrophy? Spinal muscular atrophy is a group of inherited ...

  20. Electrical stimulation counteracts muscle decline in seniors.

    Science.gov (United States)

    Kern, Helmut; Barberi, Laura; Löfler, Stefan; Sbardella, Simona; Burggraf, Samantha; Fruhmann, Hannah; Carraro, Ugo; Mosole, Simone; Sarabon, Nejc; Vogelauer, Michael; Mayr, Winfried; Krenn, Matthias; Cvecka, Jan; Romanello, Vanina; Pietrangelo, Laura; Protasi, Feliciano; Sandri, Marco; Zampieri, Sandra; Musaro, Antonio

    2014-01-01

    The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise. We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function. We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity. ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF-1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis. Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

  1. Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    ... Habits for TV, Video Games, and the Internet Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) Print ... treatment for the disease's most troubling symptoms. About SMA Normally, healthy nerve cells in the brain called ...

  2. Optic nerve atrophy

    Science.gov (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. The optic ...

  3. Multiple System Atrophy (MSA)

    Science.gov (United States)

    Diseases and Conditions Multiple system atrophy (MSA) By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare neurological disorder that impairs your body's involuntary (autonomic) functions, including blood ...

  4. Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) A A A What's in this article? ... Outlook en español Atrofia muscular espinal Spinal muscular atrophy, or SMA, is an inherited condition that causes ...

  5. The combined influence of stretch, mobility and electrical stimulation in the prevention of muscle fiber atrophy caused hypokinesia and hypodynamia

    Science.gov (United States)

    Goldspink, G.; Goldspink, D.; Loughna, P.

    1984-01-01

    The morphological and biochemical changes which occur in the hind limb muscles of the rat in response to hypokinesia and hypodynamia were investigated. Hind limb cast fixation and suspension techniques were employed to study the musclar atrophy after five days of hypokinesia and hypodynamia induced by suspension, appreciable muscular atrophy was apparent, particularly in the anti-gravity muscles. The effect of passive stretching and electrical stimulation on muscle atrophy was studied. Changes in muscle protein mass were assessed with spectrophotometric and radioactive techniques. Passive stretch is shown to counteract muscle disuse atrophy. The change in the numbers of specific muscle fibers in atrophied muscles is discussed.

  6. Does gastric atrophy exist in children?

    Institute of Scientific and Technical Information of China (English)

    Georges Dimitrov; Frédéric Gottrand

    2006-01-01

    Several clinical reports confirmed that gastric atrophy is a pathology not only limited to adult patients. In pediatrics, it is most often described in association with a Hpylori infection but this bacteria does not seem to be the only etiological factor of this preneoplastic state in children. The frequency of gastric atrophy and intestinal metaplasia in children are unknown because they are not systematically sought during upper gastrointestinal endoscopy. The lack of specific histological classification of children's gastropathies makes their diagnosis difficult for pathologists. Based on our knowledge to date, we think that it is necessary to describe, in detail, the natural course of this lesion during childhood. A close and prolonged clinical and endoscopic follow-up is important for children with gastric atrophy.

  7. Coeliac disease: more than villous atrophy.

    Science.gov (United States)

    Wahab, Peter J; Meijer, Jos W R; Dumitra, Daniela; Goerres, Marije S; Mulder, Chris J J

    2002-06-01

    A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of a new concept of pathophysiology and clinical approach of the coeliac condition. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6. Immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies, and in addition the understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs and the disease may present with less severe symptoms of malabsorption while screening studies suggest an overall prevalence of up to 1 in 200-300. In the present paper (an update on histopathology) we specifically describe the work of our group in Arnhem, concerning the identification and validation of the spectrum of intestinal histopathology in gluten sensitive enteropathy, i.e. lymphocytic enteritis (Marsh I lesion), lymphocytic enteritis with crypthyperplasia (Marsh II lesion), and villous atrophy, subdivided in partial villous atrophy (Marsh IIIA), subtotal villous atrophy (Marsh IIIB) and total villous atrophy (Marsh IIIC). Special attention is given to a subgroup of "refractory coeliacs", including the identification of (pre-) malignant aberrant T-cells in the intestinal mucosa of these patients. The new data on immunogenetics, epidemiology, histo-pathology and patient characteristics point to a significant change of views on coeliac disease.

  8. Progressive hemifacial atrophy

    Directory of Open Access Journals (Sweden)

    Abhijeet Sande

    2013-01-01

    Full Text Available Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy.

  9. Spinal muscular atrophy

    National Research Council Canada - National Science Library

    D'Amico, Adele; Mercuri, Eugenio; Tiziano, Francesco D; Bertini, Enrico

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis...

  10. Spinal Muscular Atrophy

    Science.gov (United States)

    Spinal muscular atrophy (SMA) is a genetic disease that attacks nerve cells, called motor neurons, in the spinal cord. These cells communicate with your voluntary muscles - the ones you can control, like in your ...

  11. Bed Rest Muscular Atrophy

    Science.gov (United States)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  12. Bed Rest Muscular Atrophy

    Science.gov (United States)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  13. Mycotoxins and the intestine

    Directory of Open Access Journals (Sweden)

    Leon Broom

    2015-12-01

    Full Text Available Fungal biochemical pathways can yield various compounds that are not considered to be necessary for their growth and are thus referred to as secondary metabolites. These compounds have been found to have wide ranging biological effects and include potent poisons (mycotoxins. Mycotoxins invariably contaminate crops and (thus animal feeds. The intestine is the key link between ingested mycotoxins and their detrimental effects on the animal. Effects on the intestine, or intestinal environment, and immune system have been reported with various mycotoxins. These effects are almost certainly occurring across species. Most, if not all, of the reported effects of mycotoxins are negative in terms of intestinal health, for example, decreased intestinal cell viability, reductions in short chain fatty acid (SCFA concentrations and elimination of beneficial bacteria, increased expression of genes involved in promoting inflammation and counteracting oxidative stress. This challenge to intestinal health will predispose the animal to intestinal (and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity.

  14. Research opportunities in muscle atrophy

    Science.gov (United States)

    Herbison, G. J. (Editor); Talbot, J. M. (Editor)

    1984-01-01

    Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

  15. Dominant optic atrophy

    DEFF Research Database (Denmark)

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile

    2012-01-01

    DEFINITION OF THE DISEASE: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC...

  16. Electrical stimulation (ES counteracts muscle decline in seniors

    Directory of Open Access Journals (Sweden)

    Helmut eKern

    2014-07-01

    Full Text Available The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are all marks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise.We addressed whether electrical stimulation (ES is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function.We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity.ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis.Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

  17. Intestinal Ischemia

    Science.gov (United States)

    ... some generally recognized patterns. Symptoms of acute intestinal ischemia Signs and symptoms of acute intestinal ischemia typically ... confusion in older adults Symptoms of chronic intestinal ischemia Signs and symptoms of chronic intestinal ischemia can ...

  18. [Posterior cortical atrophy].

    Science.gov (United States)

    Solyga, Volker Moræus; Western, Elin; Solheim, Hanne; Hassel, Bjørnar; Kerty, Emilia

    2015-06-02

    Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.

  19. Small bowel villous atrophy: celiac disease and beyond.

    Science.gov (United States)

    Elli, Luca; Branchi, Federica; Sidhu, Reena; Guandalini, Stefano; Assiri, Asaad; Rinawi, Firas; Shamir, Raanan; Das, Prasenjit; Makharia, Govind K

    2017-02-01

    Small bowel villous atrophy can represent a diagnostic challenge for gastroenterologists and pathologists. In Western countries small bowel atrophy and mild non-atrophic alterations are frequently caused by celiac disease. However, other pathology can mimic celiac disease microscopically, widening the differential diagnosis. The several novelties on this topic and the introduction of the device-assisted enteroscopy in the diagnostic flowchart make an update of the literature necessary. Areas covered: In this review, a description of the different clinical scenarios when facing with small bowel mucosal damage, particularly small bowel atrophy, is described. The published literature on this subject has been summarized and reviewed. Expert commentary: When an intestinal mucosal alteration is histologically demonstrated, the pathology report forms part of a more complex workup including serological data, clinical presentation and clinical history. A multidisciplinary team, including pathologists and enteroscopy-devoted endoscopists, is frequently required to manage patients with small bowel alterations, especially in cases of severe malabsorption syndrome.

  20. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini

    2015-01-01

    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  1. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2014-01-01

    Full Text Available Cisplatin (CisPt is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.

  2. Serological assessment of gastric mucosal atrophy in gastric cancer

    Directory of Open Access Journals (Sweden)

    Bornschein Jan

    2012-01-01

    Full Text Available Abstract Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1, pepsinogen 2 (PG2 and gastrin 17 (G17 offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation, degree of mucosal abnormalities (intestinal metaplasia, atrophy and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status. Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003. The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058. The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.

  3. Olmesartan-Induced Enteropathy: An Unusual Cause of Villous Atrophy

    Directory of Open Access Journals (Sweden)

    Marta Eusébio

    2016-03-01

    Olmesartan is an angiotensin receptor blocker commonly prescribed for the management of hypertension. Spruelike enteropathy associated with this drug is a recently described entity with few cases reported. It presents with chronic diarrhea and intestinal villous atrophy and should be included in its differential diagnosis. This case intends to alert clinicians for the possibility of this event in a patient on treatment with this drug.

  4. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  5. Genetics Home Reference: multiple system atrophy

    Science.gov (United States)

    ... Home Health Conditions multiple system atrophy multiple system atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Multiple system atrophy is a progressive brain disorder that affects movement ...

  6. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  7. Intestinal obstruction

    Science.gov (United States)

    Paralytic ileus; Intestinal volvulus; Bowel obstruction; Ileus; Pseudo-obstruction - intestinal; Colonic ileus ... objects that are swallowed and block the intestines) Gallstones (rare) Hernias Impacted stool Intussusception (telescoping of 1 ...

  8. The inheritance of peripapillary atrophy

    NARCIS (Netherlands)

    Healey, Paul R.; Mitchell, Paul; Gilbert, Clare E.; Lee, Anne J.; Ge, Dongliang; Snieder, Harold; Spector, Timothy D.; Hammond, Christopher J.

    2007-01-01

    PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS. Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from

  9. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  10. Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

    Science.gov (United States)

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2016-01-01

    AIM To quantify the presence of villous atrophy in endoscopic images for improved automation. METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape. RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished. CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients. PMID:27803772

  11. Discourse on corruption counteraction in network trade

    Directory of Open Access Journals (Sweden)

    Leonid A. Zhigun

    2015-12-01

    Full Text Available Objective to determine the specific forms of corruption and promising methods to counteract corruption in network trade. Methods the combination of inductive observations comparisons generalizations facts and trends of corruption in network trade with a logical analytical deduction of economic theories and the corruption concept are the basis of the study and provide an opportunity on the one hand to assess the level of compliance of theoretical concepts of corruption with the practice and on the other handnbsp to determine their applicability to organize opposition and create conditions to prevent its occurrence to summarize the features of corruption in the form of a kickback the discourse method was applied in this work. Results on the basis of theoretical provisions and facts of corruption in trade it is proved that it has typical characteristics of corruption in commercial and nonprofit organizations. The key reasons are identified why corruption occurs in trade. Among them supply of poor quality goods at inflated prices leading to bribery in the form of laquopersonal bonusraquo to administrator of the trading organization when selling goods by an unscrupulous supplier and also supply goods to the trade organizations which will not buy without kickback. Most of these corrupt deals are carried out by natural monopolies in the form of state and municipal procurement. In some cases the kickback is the argument stimulating the decision to introduce new and advanced technologies. The factors that lead to corruption in trade are listed and reasonable methods to counteract it are grounded allowing to create conditions for its eradication in other branches of business as well. Scientific novelty for the first time a generalization has been made about the deficit as the driving force in the mechanism when the bribegivers and bribetakers change places. Practical significance the main provisions and conclusions of the article can be used in the

  12. Multiple system atrophy.

    Science.gov (United States)

    Peeraully, Tasneem

    2014-04-01

    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies.

  13. ISG15 counteracts Listeria monocytogenes infection

    Science.gov (United States)

    Radoshevich, Lilliana; Impens, Francis; Ribet, David; Quereda, Juan J; Nam Tham, To; Nahori, Marie-Anne; Bierne, Hélène; Dussurget, Olivier; Pizarro-Cerdá, Javier; Knobeloch, Klaus-Peter; Cossart, Pascale

    2015-01-01

    ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response. DOI: http://dx.doi.org/10.7554/eLife.06848.001 PMID:26259872

  14. The bacterial metabolism of carbohydrates used in tests of intestinal permeability

    OpenAIRE

    Qureishy, Gulzar A.

    1984-01-01

    Carbohydrates have been used for tests of intestinal function for many years and the impaired absorption of carbohydrates in the intestinal lumen is either due to the damaged intestinal absorptive surface, as in coeliac disease etc., in some types of acute gastroenteritis , when the absorptive area is reduced by villous atrophy , or due to the bacterial overgrowth in the small intestinal lumen as in blind loop syndrome , some types of malabsorption , which possibly produce alteration in the m...

  15. Idiopathic atrophie blanche.

    Science.gov (United States)

    Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo

    2006-01-01

    clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

  16. Endometriosis intestinal Intestinal endometriosis

    Directory of Open Access Journals (Sweden)

    C.I. González

    2008-08-01

    Full Text Available La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada. En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo.Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation. In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment

  17. [Atrophy of the bone marrow].

    Science.gov (United States)

    Dziecioł, J; Kemona, A; Sulik, M; Sulkowski, S; Brykalska, A; Sobaniec-Lotowska, M; Ostapiuk, H

    1990-01-01

    The authors made a quantitative analysis of the active hematopoietic tissue of the bone marrow with particular consideration of its atrophy in the course of various diseases. The material consisted of 407 non-selected autopsy cases. For a morphometric analysis the bone marrow was sampled from the sternum, ala ossis illi and spine. In the quantitative analysis of the active hematopoietic tissue we took into account age groups as quantitative changes appear with age. Atrophy of the bone marrow was in 19.4% of the studied cases. The presence of bone marrow atrophy was found in the course of various diseases, most frequently neoplastic, particularly in patients aged from 50 to 59 years.

  18. Optic atrophy and glaucomatous cupping.

    Science.gov (United States)

    Radius, R L; Maumenee, A E

    1978-02-01

    We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.

  19. Types of SMA (Spinal Muscular Atrophy)

    Science.gov (United States)

    ... genes other than the SMN1 gene. Spinal Muscular Atrophy Respiratory Distress (SMARD) SMARD is a very rare ... and 50. It causes muscle weakness and wasting (atrophy) throughout the body, which is most noticeable in ...

  20. Genetics Home Reference: dentatorubral-pallidoluysian atrophy

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions DRPLA dentatorubral-pallidoluysian atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Dentatorubral-pallidoluysian atrophy , commonly known as DRPLA , is a progressive brain ...

  1. Mitochondrial signaling contributes to disuse muscle atrophy

    Science.gov (United States)

    Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent experiments have provided direct evidence connecting mitochondrial dysfunction to muscle atrophy. Numerous studies have described changes in mitochondria shape, number, and function in skeletal muscles exposed to prolonged periods of inactivity. Furthermore, recent evidence indicates that increased mitochondrial ROS production plays a key signaling role in both immobilization-induced limb muscle atrophy and diaphragmatic atrophy occurring during prolonged mechanical ventilation. Moreover, new evidence reveals that, during denervation-induced muscle atrophy, increased mitochondrial fragmentation due to fission is a required signaling event that activates the AMPK-FoxO3 signaling axis, which induces the expression of atrophy genes, protein breakdown, and ultimately muscle atrophy. Collectively, these findings highlight the importance of future research to better understand the mitochondrial signaling mechanisms that contribute to disuse muscle atrophy and to develop novel therapeutic interventions for prevention of inactivity-induced skeletal muscle atrophy. PMID:22395111

  2. The quasi-parallel lives of satellite cells and atrophying muscle

    Directory of Open Access Journals (Sweden)

    Stefano eBiressi

    2015-07-01

    Full Text Available Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells, have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking satellite cell function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in satellite cells in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within satellite cells that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass.

  3. Novel OPA1 mutation featuring spastic paraparesis and intestinal dysmotility

    Directory of Open Access Journals (Sweden)

    Mohamed Kazamel

    2014-01-01

    Full Text Available A 58-year-old man with optic atrophy, spastic paraparesis, axonal sensorimotor peripheral neuropathy and intestinal dysmotility harbors a novel heterozygous missense mutation in the mitochondrial import signal peptide of OPA1. The case underscores the role of OPA1 in the pathogenesis of spastic paraparesis, so far reported only in very few cases, and it adds intestinal dysmotility to the spectrum of adult-onset clinical manifestation of OPA1-associated disease.

  4. Neuronal involvement in muscular atrophy

    Directory of Open Access Journals (Sweden)

    Bruno Alejandro Cisterna

    2014-12-01

    Full Text Available The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels formed by connexins and other none selective channels, including P2X7 receptors, TRPV2 channels were demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically prevented in denervated muscles deficient in connexins 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned none selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., BDNF, agrin/Lrp4/MuSK and acetylcholine are among the possible perpetrators of repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  5. Progress in endoscopic diagnosis of gastric corpus atrophy%胃体萎缩的内镜诊断

    Institute of Scientific and Technical Information of China (English)

    孟欣颖; 王青

    2011-01-01

    胃体萎缩是较为少见的胃黏膜萎缩,多见于自身免疫性胃炎.胃体萎缩伴肠化生是胃癌的癌前病变.内镜是诊断胃体萎缩的重要手段.本文就胃体萎缩的内镜诊断进展作一综述.%Gastric corpus atrophy is an uncommon type of gastric atrophy, mostly seen in autoimmune gastritis. Gastric corpus atrophy with intestinal metaplasia is considered as premalignant lesion of gastric cancer. Endoscopy is an important method for diagnosis. We will review the advance in endoscopic diagnosis of gastric corpus atrophy.

  6. Mitochondrial signaling contributes to disuse muscle atrophy

    OpenAIRE

    Powers, Scott K.; Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent exp...

  7. Intestinal leiomyoma

    Science.gov (United States)

    ... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...

  8. Intestinal Lymphangiectasia

    Science.gov (United States)

    ... source and a camera through which a small clipper can be inserted). The tissue that is removed ... can help. Malabsorption Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal Lymphangiectasia Lactose Intolerance Short Bowel ...

  9. Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.

    Science.gov (United States)

    De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G

    2015-03-01

    Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes.

  10. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    or localization of atrophy and subsequent summing to an ROI measure of atrophy. ST and SF only offer whole ROI atrophy measures. JI and SF suffer from a lack of precision originating from respectively approximating a space and a time integral by a finite sum. VM suffers from a high computational burden and the ST......Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  11. Sustainability and Counteracting Factors to Profit Rate Decline

    DEFF Research Database (Denmark)

    Ougaard, Morten

    2014-01-01

    This paper discusses sustainability implications of barriers to growth as specified in the theory of the long-term falling rate of profit but focusing on the counteracting factors (CFs) specified by Marx. These depend much on political processes and are important in state theory for understanding...... policies of national and international institutions. Fourteen partly overlapping factors are identified and grouped in five categories: increased pressure on labor, geographical expansion, resource efficiency, technological progress, and destruction or devaluation of capital. It is suggested...... which implies a destruction of capital that will counteract the falling rate of profit. This will require sustained political intervention....

  12. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  13. Genetics Home Reference: spinal and bulbar muscular atrophy

    Science.gov (United States)

    ... Kennedy spinal and bulbar muscular atrophy Kennedy's disease SBMA X-linked spinal and bulbar muscular atrophy Related ... Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006 ...

  14. Counteracting Age Stereotypes: A Self-Awareness Manipulation

    Science.gov (United States)

    Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

    2010-01-01

    The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition,…

  15. To what extent can cirrus seeding counteract global warming?

    Science.gov (United States)

    Gasparini, Blaz; Lohmann, Ulrike

    2017-04-01

    The idea of modifying cirrus clouds to directly counteract greenhouse gas warming has gained a lot of momentum in recent years, despite large disputes over its physical feasibility. We use the ECHAM-HAM general circulation model to evaluate the temperature and precipitation responses to cirrus thinning by seeding with efficient ice nucleating particles and increasing ice crystal sedimentation velocities in a 1.5xCO2 world. The seeding scenario can counteract about 40% of the warming and precipitation increase induced by 1.5 x CO2 concentrations with respect to present day values. The idealized ice crystal sedimentation velocity increase scenario on the other hand fully restores the global annual temperature but counteracts only half of the precipitation increase. Moreover, we define a climate damage function, quadratic in temperature and precipitation anomalies to calculate the damage of the different scenarios in 21 selected land regions. Seeding can decrease about 55% of the CO2 induced damage, while the sedimentation velocity increase can counteract about 95% of the damage. A regional analysis shows the negative responses of seeding are minimal both in terms of precipitation and temperature, which makes cirrus seeding an attractive geoengineering method.

  16. Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

    DEFF Research Database (Denmark)

    Feng, Yongjia; Demehri, Farok R; Xiao, Weidong

    2017-01-01

    BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal...... deprived of enteral nutrition. METHODS: Adult C57BL/6J, IEC-Egfr(knock out (KO)) and IEC-pik3r1(KO) mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC...

  17. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy.

    Science.gov (United States)

    Lach-Trifilieff, Estelle; Minetti, Giulia C; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji; Glass, David J

    2014-02-01

    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.

  18. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    Science.gov (United States)

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  19. Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability.

    Science.gov (United States)

    Dell'Orco, James M; Wasserman, Aaron H; Chopra, Ravi; Ingram, Melissa A C; Hu, Yuan-Shih; Singh, Vikrant; Wulff, Heike; Opal, Puneet; Orr, Harry T; Shakkottai, Vikram G

    2015-08-12

    shrinkage. Purkinje neuron firing in these mice is initially normal, but is followed by abnormal membrane depolarization resulting from a reduction in potassium channels. Subsequently, these electrophysiological effects are counteracted by cell atrophy, which by restoring normal potassium channel membrane density, re-establishes pacemaker firing. Reversing the initial membrane depolarization improved motor function and Purkinje neuron morphology in the SCA1 mice. These results suggest that Purkinje neuron remodeling in ataxia is an active compensatory response that serves to normalize intrinsic membrane excitability. Copyright © 2015 the authors 0270-6474/15/3511293-16$15.00/0.

  20. Using Misperception to Counteract Noise in the Iterated Prisoner's Dilemma

    Science.gov (United States)

    Brumley, Lachlan; Korb, Kevin B.; Kopp, Carlo

    The Iterated Prisoner's Dilemma is a game-theoretical model which can be identified in many repeated real-world interactions between competing entities. The Tit for Tat strategy has been identified as a successful strategy which reinforces mutual cooperation, however, it is sensitive to environmental noise which disrupts continued cooperation between players to their detriment. This paper explores whether a population of Tit for Tat players may evolve specialised individual-based noise to counteract environmental noise. We have found that when the individual-based noise acts similarly to forgiveness it can counteract the environmental noise, although excessive forgiveness invites the evolution of exploitative individual-based noise, which is highly detrimental to the population when widespread.

  1. A concept of a space hazard counteraction system: Astronomical aspects

    Science.gov (United States)

    Shustov, B. M.; Rykhlova, L. V.; Kuleshov, Yu. P.; Dubov, Yu. N.; Elkin, K. S.; Veniaminov, S. S.; Borovin, G. K.; Molotov, I. E.; Naroenkov, S. A.; Barabanov, S. I.; Emel'yanenko, V. V.; Devyatkin, A. V.; Medvedev, Yu. D.; Shor, V. A.; Kholshevnikov, K. V.

    2013-07-01

    The basic science of astronomy and, primarily, its branch responsible for studying the Solar System, face the most important practical task posed by nature and the development of human civilization—to study space hazards and to seek methods of counteracting them. In pursuance of the joint Resolution of the Federal Space Agency (Roscosmos) and the RAS (Russian Academy of Sciences) Space Council of June 23, 2010, the RAS Institute of Astronomy in collaboration with other scientific and industrial organizations prepared a draft concept of the federal-level program targeted at creating a system of space hazard detection and counteraction. The main ideas and astronomical content of the concept are considered in this article.

  2. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Matsuoka, Yukihiko [Suzuka National Hospital, Suzuka, Mie (Japan); Konagaya, Yoko [JR Tokai General Hospital, Nagoya (Japan)

    2002-02-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  3. Infraspinatus muscle atrophy from suprascapular nerve compression.

    Science.gov (United States)

    Cordova, Christopher B; Owens, Brett D

    2014-02-01

    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness.

  4. Mitochondrial signaling contributes to disuse muscle atrophy

    National Research Council Canada - National Science Library

    Powers, Scott K; Wiggs, Michael P; Duarte, Jose A; Zergeroglu, A Murat; Demirel, Haydar A

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals...

  5. Hippocampal atrophy rates in Alzheimer disease

    Science.gov (United States)

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F

    2009-01-01

    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  6. Zika virus causes testicular atrophy

    Science.gov (United States)

    Uraki, Ryuta; Hwang, Jesse; Jurado, Kellie Ann; Householder, Sarah; Yockey, Laura J.; Hastings, Andrew K.; Homer, Robert J.; Iwasaki, Akiko; Fikrig, Erol

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1−/− mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males. PMID:28261663

  7. Can antioxidants protect against disuse muscle atrophy?

    Science.gov (United States)

    Powers, Scott K

    2014-11-01

    Long periods of skeletal muscle inactivity (e.g. prolonged bed rest or limb immobilization) results in a loss of muscle protein and fibre atrophy. This disuse-induced muscle atrophy is due to both a decrease in protein synthesis and increased protein breakdown. Although numerous factors contribute to the regulation of the rates of protein breakdown and synthesis in skeletal muscle, it has been established that prolonged muscle inactivity results in increased radical production in the inactive muscle fibres. Further, this increase in radical production plays an important role in the regulation of redox-sensitive signalling pathways that regulate both protein synthesis and proteolysis in skeletal muscle. Indeed, it was suggested over 20 years ago that antioxidant supplementation has the potential to protect skeletal muscles against inactivity-induced fibre atrophy. Since this original proposal, experimental evidence has implied that a few compounds with antioxidant properties are capable of delaying inactivity-induced muscle atrophy. The objective of this review is to discuss the role that radicals play in the regulation of inactivity-induced skeletal muscle atrophy and to provide an analysis of the recent literature indicating that specific antioxidants have the potential to defer disuse muscle atrophy.

  8. Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

    Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  9. Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

    Science.gov (United States)

    Bhat, M Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2007-03-01

    The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  10. Acupuncture plus low-frequency electrical stimulation (Acu-LFES) attenuates denervation-induced muscle atrophy.

    Science.gov (United States)

    Su, Zhen; Hu, Li; Cheng, Jinzhong; Klein, Janet D; Hassounah, Faten; Cai, Hui; Li, Min; Wang, Haidong; Wang, Xiaonan H

    2016-02-15

    Muscle wasting occurs in a variety of clinical situations, including denervation. There is no effective pharmacological treatment for muscle wasting. In this study, we used a tibial nerve denervation model to test acupuncture plus low-frequency electric stimulation (Acu-LFES) as a therapeutic strategy for muscle atrophy. Acupuncture needles were connected to an SDZ-II electronic acupuncture device delivering pulses at 20 Hz and 1 mA; the treatment was 15 min daily for 2 wk. Acu-LFES prevented soleus and plantaris muscle weight loss and increased muscle cross-sectional area in denervated mice. The abundances of Pax7, MyoD, myogenin, and embryonic myosin heavy chain were significantly increased by Acu-LFES in both normal and denervated muscle. The number of central nuclei was increased in Acu-LFES-treated muscle fibers. Phosphorylation of Akt was downregulated by denervation leading to a decline in muscle mass; however, Acu-LFES prevented the denervation-induced decline largely by upregulation of the IGF-1 signaling pathway. Acu-LFES reduced the abundance of muscle catabolic proteins forkhead O transcription factor and myostatin, contributing to the attenuated muscle atrophy. Acu-LFES stimulated the expression of macrophage markers (F4/80, IL-1b, and arginase-1) and inflammatory cytokines (IL-6, IFNγ, and TNFα) in normal and denervated muscle. Acu-LFES also stimulated production of the muscle-specific microRNAs miR-1 and miR-206. We conclude that Acu-LFES is effective in counteracting denervation-induced skeletal muscle atrophy and increasing muscle regeneration. Upregulation of IGF-1, downregulation of myostatin, and alteration of microRNAs contribute to the attenuation of muscle atrophy in denervated mice. Copyright © 2016 the American Physiological Society.

  11. Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

    Science.gov (United States)

    Straniero, S; Rosqvist, F; Edholm, D; Ahlström, H; Kullberg, J; Sundbom, M; Risérus, U; Rudling, M

    2017-05-01

    Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. Ten morbidly obese women (BMI 42 ± 2.6 kg m(-2) ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day(-1) ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies. © 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  12. Probiotics to counteract biofilm-associated infections:promising and conflicting data

    Institute of Scientific and Technical Information of China (English)

    Claudia Vuotto; Francesca Longo; Gianfranco Donelli

    2014-01-01

    Altered bowel flora is currently thought to play a role in a variety of disease conditions, and the use of Bifidobacterium spp. and Lactobacillus spp. as probiotics has been demonstrated to be health-promoting, even if the success of their administration depends on the applied bacterial strain(s) and the targeted disease. In the last few decades, specific probiotics have been shown to be effective in the treatment or the prevention of acute viral gastroenteritis, pediatric post-antibiotic-associated diarrhea, some pediatric allergic disorders, necrotizing enterocolitis in preterm infants, inflammatory bowel diseases and postsurgical pouchitis. The potential application of probiotics is continuously widening, with new evidence accumulating to support their effect on the prevention and treatment of other disease conditions, including several oral diseases, such as dental caries, periodontal diseases and oral malodor, as well as genitourinary and wound infections. Considering the increasingly widespread ability of pathogens to generate persistent biofilm-related infections, an even more attractive proposal is to administer probiotics to prevent or counteract biofilm development. The response of biofilm-based oral, intestinal, vaginal and wound infections to probiotics treatment will be reviewed here in light of the most recent results obtained in this field.

  13. Determination of Intestine Inflammation Markers in Diagnostic Search in Children with Intestinal Diseases

    Directory of Open Access Journals (Sweden)

    N.V. Pavlenko

    2016-10-01

    Full Text Available Introduction. Prevalence of bowel diseases in children is the second, trailing only the diseases of gastroduodenal zone and growing in recent years. Actual one is the problem of differential diagnosis of functional and inflammatory intestinal diseases using non-invasive methods on the prehospital stage and as a screening. Objective. Comparative analysis of fecal markers of the bowel inflammation (lactoferrine and calprotectine with endoscopy and morphology of intestinal mucosa in children. Matherials and methods. 49 children aged 6–18 years were examined. All patients underwent endoscopic and morphological study of the intestine, coprotest, determination of fecal markers of bowel inflammation (lactoferrin and calprotectine. Results. It is shown that in young children, the intestinal mucosa mainly hadn’t endoscopic changes, coprotest and morphological examination didn’t reveal the signs of inflammation, fecal intestinal inflammation markers were negative (p < 0.05. In the group of older children, moderate or marked catarrhal changes were found endoscopically, coprotest results were typical of inflammation in the intestines, it was morphologically proved the presence of chronic inflammation of the mucous membrane of the colon with signs of atrophy, the results of lactoferrin and calprotectine determination were positive (p < 0.05. Conclusion. The findings suggest that the evaluation of calprotectine and lactoferrin can be used in pediatric patients because of its non-invasiveness as diagnostic screening for the selection of patients for the further endoscopic examination and diagnostic search.

  14. Intestinal Coccidia

    Directory of Open Access Journals (Sweden)

    MJ Ggaravi

    2007-06-01

    Full Text Available Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycle that has 20% thin layer and 80% thick layer. Oocyst with thick layer is able to live a long time in nature. They are the third or forth of gastroentritis disease that have digestive disorder like anorexia, nausea, persistent diarrhoea, malabsorption and leanness. The disease forms choronic and acute stages and it is able to kill the immunodeficiency cases. Sometimes it has HIV symptoms similar to pneumonia and respiratory track infection. Laboratory diagnosis is based on Oocyst finding in stool exam and that shitter floatation and Cr (KOH2 are the best methods. Modified zyh-lnelson and fleocroum are the best staining methods too. This parasite is transmitted by zoonotic and Antroponotic origin. Molecular studies have shown two Genotypes (I&II. Genotype I is aquatic and II is zoonotic. The prevalence rate is 3% in infants and 10% in calves. Cyclospora: This parasite is novel and is bigger than cryptosporidium.It isn't known a clear life cycle but is transmitted by water, vegetables and fruits as raspberries. and mulberries. Human is a specific host. When a parasite is in the intestine it causes inflammatory reaction in Entrocyte.The patient shows watery diarrhoea with nausea, vomitting, pain, Stomach cramp, anorexia, malabsorption and cachexia. The disease period is 3 monthes in immunodeficiency cases but it is selflimited in normal cases. Autofluorescence characteristic is differential diagnosis, prevalence rate of disease is unknown. Isospora: This

  15. Spatial warping by oriented line detectors can counteract neural delays

    Directory of Open Access Journals (Sweden)

    Don eVaughn

    2013-11-01

    Full Text Available The slow speed of neural transmission necessitates that cortical visual information from dynamic scenes will lag reality. The perceiving the present (PTP hypothesis suggests that the visual system can mitigate the effect of such delays by spatially warping scenes to look as they will in ~100 ms from now (Changizi, 2001. We here show that the Hering illusion, in which straight lines appear bowed, can be induced by a background of optic flow, consistent with the PTP hypothesis. However, importantly, the bowing direction is the same whether the flow is inward or outward. This suggests that if the warping is meant to counteract latencies, it is accomplished by a simple strategy that is insensitive to motion direction, and that works only under typical (forward-moving circumstances. We also find that the illusion strengthens with longer pulses of optic flow, demonstrating motion integration over ~80 ms. The illusion is identical whether optic flow precedes or follows the flashing of bars, exposing the spatial warping to be equally postdictive and predictive, i.e., peri-dictive. Additionally, the illusion is diminished by cues which suggest the bars are independent of the background movement. Collectively, our findings are consistent with a role for networks of visual orientation-tuned neurons (e.g., simple cells in primary visual cortex in spatial warping. We conclude that under the common condition of forward ego-motion, spatial warping counteracts the disadvantage of neural latencies. It is not possible to prove that this is the purpose of spatial warping, but our findings at minimum place constraints on the PTP hypothesis, demonstrating that any spatial warping for the purpose of counteracting neural delays is not a precise, on-the-fly computation, but instead a heuristic achieved by a simple mechanism that succeeds under normal circumstances.

  16. Global brain atrophy but not hippocampal atrophy is related to type 2 diabetes

    NARCIS (Netherlands)

    Wisse, L.E.; Bresser, J. de; Geerlings, M.I.; Reijmer, Y.D.; Portegies, M.L.; Brundel, M.; Kappelle, L.J.; Graaf, Y. van der; Biessels, G.J.; Kessels, R.P.C.

    2014-01-01

    AIMS: It has been suggested that in patients with type 2 diabetes mellitus (T2DM), brain atrophy is most pronounced in the hippocampus, but this has not been investigated systematically. The present pooled analysis of three studies examined if hippocampal atrophy is more prominent than global brain

  17. Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan.

    Science.gov (United States)

    Kono, Shin; Gotoda, Takuji; Yoshida, Shigeaki; Oda, Ichiro; Kondo, Hitoshi; Gatta, Luigi; Naylor, Greg; Dixon, Michael; Moriyasu, Fuminori; Axon, Anthony

    2015-12-14

    To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries.

  18. Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis.

    Science.gov (United States)

    Paz Soldán, M Mateo; Raman, Mekala R; Gamez, Jeffrey D; Lohrey, Anne K; Chen, Yi; Pirko, Istvan; Johnson, Aaron J

    2015-01-01

    Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability. Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 spinal cord cross-sectional area measurements were performed using Analyze 10. At 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post-infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross-sectional area was 25.6% reduced (P = .001) among cases. Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate. Copyright © 2015 by the American Society of Neuroimaging.

  19. Chronic idiopathic intestinal pseudo-obstruction in an English bulldog.

    Science.gov (United States)

    Dvir, E; Leisewitz, A L; Van der Lugt, J J

    2001-05-01

    A case of chronic idiopathic intestinal pseudo-obstruction in an English bulldog is described. The dog was presented with chronic weight loss and vomiting. An intestinal obstruction was suspected based on clinical and radiological findings. A diagnosis of chronic idiopathic intestinal pseudo-obstruction was made on the basis of full thickness intestinal biopsies. The dog was refractory to any antiemetic therapy. Necropsy revealed marked atrophy and fibrosis of the tunica muscularis, together with a mononuclear cell infiltrate extending from the duodenum to the colon. This case was presented with clinical findings consistent with visceral myopathy in humans--namely, atony and dilatation of the whole gut--but the histological findings resembled sclerosis limited to the gastrointestinal tract.

  20. Intestinal myiasis

    Directory of Open Access Journals (Sweden)

    U S Udgaonkar

    2012-01-01

    Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.

  1. Intestinal microsporidiosis in African skink Mabuya perrotetii.

    Science.gov (United States)

    Koudela, B; Didier, E S; Rogers, L B; Modrý, D; Kucerová, S

    1998-01-01

    Intestinal microsporidiosis was documented by detecting abundant slightly curved spores (2.9 x 1.2 microns) in the faeces of five of twelve skinks Mabuya perrotetii Duméril et Bibron, 1839 that originated from Ghana. Clinically, the microsporidiosis was characterized by decreased appetite, diarrhea, and weight loss. Histopathological changes consisted of villous atrophy, blunting of mucosa and flattening of individual epithelial cells in the large intestine. The ultrastructure of microsporidian spores was consistent with an Encephalitozoon species. The PCR-RFLP assay and the heteroduplex mobility shift analyses were used to verify that the skink microsporidian is a species of the genus Encephalitozoon Levaditi, Nicolau et Schoen, 1923 and indicate that this microsporidian is not E. hellem, E. intestinalis or a strain of E. cuniculi. The microsporidia in African skink represent an Encephalitozoon species morphologically identical to Encephalitozoon lacertae Canning, 1981.

  2. No relevant midbrain atrophy in Parkinson's disease.

    Science.gov (United States)

    Mäkinen, E; Joutsa, J; Isotalo, J; Kaasinen, V

    2016-11-01

    To investigate whether significant midbrain atrophy is present in Parkinson's disease (PD), and if so, whether it can be used as a marker of striatal dopaminergic degeneration. In total, 150 PD patients and 155 controls were scanned with both brain dopamine transporter (DAT) [(123) I]FP-CIT SPECT and 1.5T MRI. Midbrain atrophy was measured from sagittal MRIs using the midbrain-to-pons ratios. Both striatal region-of-interest-based (Brass) and striatal and extrastriatal voxel-by-voxel-based DAT binding (SPM8) were investigated in relation to midbrain atrophy. The midbrain-to-pons ratios in PD patients were slightly lower than those in the controls (mean 0.59 vs 0.61, P atrophy is present in PD and can be detected with MRI. However, the midbrain atrophy in PD is not associated with the level of striatal dopaminergic dysfunction, and midbrain measurements therefore cannot be used as a clinically useful predictor of dopamine function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Hao eTan

    2016-03-01

    Full Text Available Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis (CF patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM.

  4. Counteractive effect of antacid suspensions on intrinsic dental erosion.

    Science.gov (United States)

    Turssi, Cecilia P; Vianna, Lídia M F F; Hara, Anderson T; do Amaral, Flávia L B; França, Fabiana M G; Basting, Roberta T

    2012-08-01

    This in vitro study aimed to investigate the anti-erosive effect of antacid suspensions applied to enamel after exposure to hydrochloric acid (HCl). Ninety bovine enamel slabs were embedded, flattened, and polished. Reference areas were created and specimens were divided into six groups. They were exposed to 0.01 M HCl (pH 2) for 2 min, followed by immersion for 1 min in one of the following test suspensions: magnesium hydroxide, aluminum hydroxide, magnesium hydroxide/aluminum hydroxide, sodium alginate/sodium bicarbonate/calcium carbonate, or hydrated magnesium aluminate. Artificial saliva was used as a negative control. Specimens were subjected to a total of five cycles of erosion/antacid treatment. Enamel surface loss was measured (in micrometers) by optical profilometry. In addition, baseline and final surface microhardness (SMH) values of enamel were obtained. It was found that antacid suspensions significantly reduced enamel loss, and that similar protection was afforded by all formulations. No differences were observed between the final enamel SMH values among groups. Antacid suspensions counteracted HCl-induced enamel loss, although they were not effective in reducing enamel softening. Mouth rinsing with antacid suspensions after vomiting can potentially represent a promising strategy to counteract enamel loss caused by erosion.

  5. Robo 4 Counteracts Angiogenesis in Herpetic Stromal Keratitis.

    Directory of Open Access Journals (Sweden)

    Fernanda Gimenez

    Full Text Available The cornea is a complex tissue that must preserve its transparency to maintain optimal vision. However, in some circumstances, damage to the eye can result in neovascularization that impairs vision. This outcome can occur when herpes simplex virus type 1 (HSV-1 causes the immunoinflammatory lesion stromal keratitis (SK. Potentially useful measures to control the severity of SK are to target angiogenesis which with herpetic SK invariably involves VEGF. One such way to control angiogenesis involves the endothelial receptor Robo4 (R4, which upon interaction with another protein activates an antiangiogenic pathway that counteracts VEGF downstream signaling. In this study we show that mice unable to produce R4 because of gene knockout developed significantly higher angiogenesis after HSV-1 ocular infection than did infected wild type (WT controls. Moreover, providing additional soluble R4 (sR4 protein by subconjunctival administration to R4 KO HSV-1 infected mice substantially rescued the WT phenotype. Finally, administration of sR4 to WT HSV-1 infected mice diminished the extent of corneal angiogenesis compared to WT control animals. Our results indicate that sR4 could represent a useful therapeutic tool to counteract corneal angiogenesis and help control the severity of SK.

  6. Topical legal aspects of corruption counteraction in public procurement

    Directory of Open Access Journals (Sweden)

    Aleksandr Igorevich Zemlin

    2015-03-01

    Full Text Available Objective to analyze the current developments in the Russian legislation on corruption counteraction and the legislation on public procurement system on this basis to study legal conflicts and gaps and to develop proposals under the provisions of the National AntiCorruption Plan for 2014ndash2015. Methods historical formallegal logical and systemicfunctional structural and contextual approach to the study of law and theoretical propositions concerning the definition nature and characteristics of legal relations arising in the process of and relating to the corruption counteraction in the public procurement system. Results аn aggregate of theoretical conclusions and proposals aimed at perfection of anticorruption legislation and legislation on the contractual public procurement system is presented. Scientific novelty the results of the author39s interpretation of changes in the Russian anticorruption legislation and legislation on the contractual public procurement system existing legal conflicts and gaps. Practical significance developing proposals for improving the standards of anticorruption legislation and legislation on public procurement system under the provisions of the National AntiCorruption Plan for 2014ndash2015. nbsp

  7. Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy

    Science.gov (United States)

    Boido, Marina; Vercelli, Alessandro

    2016-01-01

    Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs. PMID:26869891

  8. Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

    Science.gov (United States)

    Tuntiviriyapun, P; Panyakhamlerd, K; Triratanachat, S; Chatsuwan, T; Chaikittisilpa, S; Jaisamrarn, U; Taechakraichana, N

    2015-04-01

    The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. A cross-sectional descriptive study. Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p atrophy score (r = 0.230, p atrophy symptoms and the objective parameters. Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

  9. Cardiac Atrophy and Heart Failure In Cancer.

    Science.gov (United States)

    Sweeney, Mark; Yiu, Angela; Lyon, Alexander R

    2017-04-01

    Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer.

  10. Differential induction of muscle atrophy pathways in two mouse models of spinal muscular atrophy

    Science.gov (United States)

    Deguise, Marc-Olivier; Boyer, Justin G.; McFall, Emily R.; Yazdani, Armin; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Motor neuron loss and neurogenic atrophy are hallmarks of spinal muscular atrophy (SMA), a leading genetic cause of infant deaths. Previous studies have focused on deciphering disease pathogenesis in motor neurons. However, a systematic evaluation of atrophy pathways in muscles is lacking. Here, we show that these pathways are differentially activated depending on severity of disease in two different SMA model mice. Although proteasomal degradation is induced in skeletal muscle of both models, autophagosomal degradation is present only in Smn2B/− mice but not in the more severe Smn−/−; SMN2 mice. Expression of FoxO transcription factors, which regulate both proteasomal and autophagosomal degradation, is elevated in Smn2B/− muscle. Remarkably, administration of trichostatin A reversed all molecular changes associated with atrophy. Cardiac muscle also exhibits differential induction of atrophy between Smn2B/− and Smn−/−; SMN2 mice, albeit in the opposite direction to that of skeletal muscle. Altogether, our work highlights the importance of cautious analysis of different mouse models of SMA as distinct patterns of atrophy induction are at play depending on disease severity. We also revealed that one of the beneficial impacts of trichostatin A on SMA model mice is via attenuation of muscle atrophy through reduction of FoxO expression to normal levels. PMID:27349908

  11. Geographic atrophy phenotype identification by cluster analysis.

    Science.gov (United States)

    Monés, Jordi; Biarnés, Marc

    2017-07-20

    To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis. This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for ≥6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared. Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p≤0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm(2)/year, respectively, p=0.0005). Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Restless legs syndrome in multiple system atrophy.

    Science.gov (United States)

    Ghorayeb, Imad; Dupouy, Sandrine; Tison, François; Meissner, Wassilios G

    2014-12-01

    The purpose of the study was to evaluate the frequency of restless legs syndrome in 30 patients with multiple system atrophy. Eight patients complained from restless legs syndrome, their severity score was 19.4 ± 4.1. Pittsburgh Sleep Quality Index scores were significantly higher in patients with restless legs syndrome than those without (9.3 ± 3.7 vs. 4.8 ± 2.9, p = 0.00165). Periodic limb movements were found in 75% of patients with restless legs syndrome. Restless legs syndrome is more prevalent in multiple system atrophy as compared to the acknowledged prevalence in the general population.

  13. Progressive cerebral atrophy in neuromyelitis optica.

    Science.gov (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  14. Mirror movements in progressive hemifacial atrophy

    Science.gov (United States)

    Verma, Rajesh; Dixit, Puneet Kumar; Lalla, Rakesh; Singh, Babita

    2015-01-01

    Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand. PMID:26019431

  15. Mirror movements in progressive hemifacial atrophy

    Directory of Open Access Journals (Sweden)

    Rajesh Verma

    2015-01-01

    Full Text Available Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand.

  16. Posterior cortical atrophy: a brief review.

    Science.gov (United States)

    Kirshner, Howard S; Lavin, Patrick J M

    2006-11-01

    Posterior cortical atrophy is a striking clinical syndrome in which a dementing illness begins with visual symptoms. Initially, the problem may seem to be loss of elementary vision, but over time the patient develops features of visual agnosia, topographical difficulty, optic ataxia, simultanagnosia, ocular apraxia (Balint's syndrome), alexia, acalculia, right-left confusion, and agraphia (Gerstmann's syndrome), and later a more generalized dementia. Occasional patients have visual hallucinations and signs of Parkinson's disease or Lewy body dementia. A number of different neuropathologic disorders are associated with posterior cortical atrophy.

  17. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis.

    Directory of Open Access Journals (Sweden)

    Daniele De Filippis

    Full Text Available Enteric glial cells (EGC actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to

  18. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    Science.gov (United States)

    ... Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness ... muscle jerks (myoclonic epilepsy). In individuals with SMA-PME, spinal muscular atrophy results from a loss of ...

  19. Enteral obeticholic acid promotes intestinal growth in total parenteral nutrition fed neonatal pigs

    Science.gov (United States)

    Intestinal atrophy is an adverse outcome associated with prolonged total parenteral nutrition (PN) partly due to disruption of normal enterohepatic circulation of bile acids. Previously we showed that enteral treatment with chenodeoxycholic acid (CDCA), a dual agonist for the nuclear receptor, farne...

  20. Acidification counteracts negative effects of warming on diatom silicification

    KAUST Repository

    Coello-Camba, Alexandra

    2016-10-24

    Diatoms are a significant group contributing up to 40 % of annual primary production in the oceans. They have a special siliceous cell wall that, acting as a ballast, plays a key role in the sequestration of global carbon and silica. Diatoms dominate primary production in the Arctic Ocean, where global climate change is causing increases in water temperature and in the partial pressure of CO2 (pCO2). Here we show that as water temperature increases diatoms become stressed, grow to smaller sizes, and decrease their silicification rates. But at higher pCO2, as the pH of seawater decreases, silica incorporation rates are increased. In a future warmer Arctic ocean diatoms may have a competitive advantage under increased ocean acidification, as increased pCO2 counteracts the adverse effects of increasing temperature on silicification and buffers its consequences in the biogeochemical cycles of carbon and silica.

  1. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  2. [Non-indicated cesarean section--does the "Golem" counteract?].

    Science.gov (United States)

    Herman, Arie

    2011-11-01

    Cesarean section rate is steadily increasing and in Israel it has risen to 20%. MultipLe and different reasons have led to this phenomenon, among them are non-indicated cesarean sections. Although health care providers disagree whether this development is medically, ethically and publically justified, national associations allow it, while respecting those obstetricians who decline to do so. In Israel there are some hospitals which allow non-indicated cesarean sections, whereas others reject them. When discussing this issue with the patients, documentation is advised concerning the reasons for approval or rejection of the patients' request in order to avoid future complaints in the case of adverse outcome. Low risk vaginal delivery should be regarded as a natural process and not as a medical treatment and keeping balanced and reasonable decisions may help to contain the phenomenon and avoid a situation in which the "Golem" created by the medical system, counteracts.

  3. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    Science.gov (United States)

    Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem

    2016-01-01

    Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

  4. Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach.

    Science.gov (United States)

    Candela, Marco; Biagi, Elena; Brigidi, Patrizia; O'Toole, Paul W; De Vos, Willem M

    2014-01-01

    Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal microbiota-host mutualistic interaction, compromising the possibility to reach longevity. In this scenario, the NU-AGE project involves the development of dietary interventions specifically tailored to the maintenance of a healthy trajectory of the intestinal microbiome, counteracting all processes connected to the pathophysiology of the human aging. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Grey matter atrophy in patients suffering from multiple sclerosis.

    Science.gov (United States)

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László

    2014-09-30

    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  6. Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice.

    Science.gov (United States)

    Murphy, Kate T; Cobani, Vera; Ryall, James G; Ibebunjo, Chikwendu; Lynch, Gordon S

    2011-04-01

    Counteracting the atrophy of skeletal muscle associated with disuse has significant implications for minimizing the wasting and weakness in plaster casting, joint immobilization, and other forms of limb unloading, with relevance to orthopedics, sports medicine, and plastic and reconstructive surgery. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the loss of muscle mass and functional capacity in mice during 14 or 21 days of unilateral hindlimb casting. Twelve-week-old C57BL/10 mice were subjected to unilateral hindlimb plaster casting or served as controls. Mice received subcutaneous injections of saline or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n = 6-9) on days 0 and 7 and were tested for muscle function on day 14, or were treated on days 0, 7, and 14 and tested for muscle function on day 21. Hindlimb casting reduced muscle mass, fiber size, and function of isolated soleus and extensor digitorum longus (EDL) muscles (P casting, when wasting and weakness had plateaued (P casting with reductions in muscle size and strength being most apparent during the first 14 days of disuse. These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for disuse atrophy especially within the first 2 wk of disuse.

  7. An unusual cause of optic atrophy in a child

    Directory of Open Access Journals (Sweden)

    Nishant Kumar

    2014-01-01

    Full Text Available A 13-year-old child presenting with gross visual impairment was diagnosed as a case of optic atrophy. However, radiological investigations revealed osteopetrosis, which, though rare, can result in optic atrophy. The aim of this case report is to highlight this possibility while evaluating cases of optic atrophy in young patients.

  8. Redox control of skeletal muscle atrophy.

    Science.gov (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  9. Matrix metalloproteinase imbalance in muscle disuse atrophy.

    Science.gov (United States)

    Giannelli, G; De Marzo, A; Marinosci, F; Antonaci, S

    2005-01-01

    Muscle atrophy commonly occurs as a consequence of prolonged muscle inactivity, as observed after cast immobilization, bed rest or space flights. The molecular mechanisms responsible for muscle atrophy are still unknown, but a role has been proposed for altered permeability of the sarcolemma and of the surrounding connective tissue. Matrix metallo-proteinases (MMPs) are a family of enzymes with proteolytic activity toward a number of extracellular matrix (ECM) components; they are inhibited by tissue inhibitors of MMPs (TIMPs). In a rat tail-suspension experimental model, we show that after fourteen days of non-weight bearing there is increased expression of MMP-2 in the atrophic soleus and gastrocnemius and decreased expression of TIMP-2. In the same experimental model the expression of Collagen I and Collagen IV, two main ECM components present in the muscles, was reduced and unevenly distributed in unloaded animals. The difference was more evident in the soleus than in the gastrocnemius muscle. This suggests that muscle disuse induces a proteolytic imbalance, which could be responsible for the breakdown of basal lamina structures such as Collagen I and Collagen IV, and that this leads to an altered permeability with consequent atrophy. In conclusion, an MMP-2/TIMP-2 imbalance could have a role in the mechanism underlying muscle disuse atrophy; more studies are needed to expand our molecular knowledge on this issue and to explore the possibility of targeting the proteolytic imbalance with MMP inhibitors.

  10. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... and abdomen, weakness in the leg muscles, involuntary muscle contractions, tremors, and a protrusion of the abdomen thought to be related to muscle weakness. Some affected individuals experience difficulty swallowing and problems with bladder and ... Frequency Spinal muscular atrophy affects 1 in 6,000 to 1 ...

  11. Malacoplaquia intestinal

    Directory of Open Access Journals (Sweden)

    Jacinto José Frem Aun

    Full Text Available Malacoplakia is a chronic granulomatous disease of unknown origin. However immunodeficiency states (immunossuppressive medication, old people, renal transplantation, leukaemia, diabetes mellitus, malnutrition and others have been associated with patients with malacoplakia. An infectious cause of malakoplakia is suggested by the finding of coliform bacteria in the phagolysosomes of macrophages. The histologic study is characterized by a infiltrate of large macrophages (Hansenmann cells with pathognomonic inclusions containing siderocalcific structures (Michaelis-Gutmann bodies. Most of the cases reported in literature, involve the genitourinary tract, but other structures can be affected (brain, bone, adrenal glands, lymph nodes, intestine, and others. A 66-year-old man whith a abdominal mass, went to our hospital with a colonic tumour diagnosis. The patient was submitted to a surgery, with resection of the rigth colon. The disease was invading a portion of the retroperitoneal tissue that was removed. The histopatologic study showed the pathognomonic sign of malakoplakia (Hansenmann cells and Michaelis-Gutmann bodies. Norfloxacin have been used to the complementar treatment with total cure of the patient.

  12. Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Alessandra Costa

    2014-01-01

    Full Text Available Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

  13. [Mechanism of cardiac atrophy under weightlessness/simulated weightlessness].

    Science.gov (United States)

    Zhong, Guo-Hui; Ling, Shu-Kuan; Li, Ying-Xian

    2016-04-25

    Cardiac remodeling is the heart's response to external or internal stimuli. Weightlessness/simulated weightlessness leads to cardiac atrophy and heart function declining. Understanding the mechanism of cardiac atrophy under weightlessness is important to help astronaut recover from unloading-induced cardiovascular changes after spaceflight. Unloading-induced changes of hemodynamics, metabolic demands and neurohumoral regulation contribute to cardiac atrophy and function declining. During this process, Ca(2+)-related signaling, NF-κB signaling, ERK signaling, ubiquitin-proteasome pathway and autophagy are involved in weightlessness-induced cardiac atrophy. This article reviews the underlying mechanism of cardiac atrophy under weightlessness/simulated weightlessness.

  14. DMPD: An arms race: innate antiviral responses and counteracting viral strategies. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031256 An arms race: innate antiviral responses and counteracting viral strategie...s. Schroder M, Bowie AG. Biochem Soc Trans. 2007 Dec;35(Pt 6):1512-4. (.png) (.svg) (.html) (.csml) Show An arms race...: innate antiviral responses and counteracting viral strategies. PubmedID 18031256 Title An arms race

  15. Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

    Science.gov (United States)

    Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

    2015-10-14

    The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

  16. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Shreesh Ojha

    2016-01-01

    Full Text Available Cisplatin (CSP is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

  17. Molecular chaperones as therapeutic targets to counteract proteostasis defects.

    Science.gov (United States)

    Cattaneo, Monica; Dominici, Roberto; Cardano, Marina; Diaferia, Giuseppe; Rovida, Ermanna; Biunno, Ida

    2012-03-01

    The health of cells is preserved by the levels and correct folding states of the proteome, which is generated and maintained by the proteostasis network, an integrated biological system consisting of several cytoprotective and degradative pathways. Indeed, the health conditions of the proteostasis network is a fundamental prerequisite to life as the inability to cope with the mismanagement of protein folding arising from genetic, epigenetic, and micro-environment stress appears to trigger a whole spectrum of unrelated diseases. Here we describe the potential functional role of the proteostasis network in tumor biology and in conformational diseases debating on how the signaling branches of this biological system may be manipulated to develop more efficacious and selective therapeutic strategies. We discuss the dual strategy of these processes in modulating the folding activity of molecular chaperones in order to counteract the antithetic proteostasis deficiencies occurring in cancer and loss/gain of function diseases. Finally, we provide perspectives on how to improve the outcome of these disorders by taking advantage of proteostasis modeling.

  18. Subarray-based FDA radar to counteract deceptive ECM signals

    Science.gov (United States)

    Abdalla, Ahmed; Wang, Wen-Qin; Yuan, Zhao; Mohamed, Suhad; Bin, Tang

    2016-12-01

    In recent years, the frequency diverse array (FDA) radar concept has attracted extensive attention, as it may benefit from a small frequency increment, compared to the carrier frequency across the array elements and thereby achieve an array factor that is a function of the angle, the time, and the range which is superior to the conventional phase array radar (PAR). However, limited effort on the subject of FDA in electronic countermeasure scenarios, especially in the presence of mainbeam deceptive jamming, has been published. Basic FDA is not desirable for anti-jamming applications, due to the range-angle coupling response of targets. In this paper, a novel method based on subarrayed FDA signal processing is proposed to counteract deceptive ECM signals. We divide the FDA array into multiple subarrays, each of which employs a distinct frequency increment. As a result, in the subarray-based FDA, the desired target can be distinguished at subarray level in joint range-angle-Doppler domain by utilizing the fact that the jammer generates false targets with the same ranges to each subarray without reparations. The performance assessment shows that the proposed solution is effective for deceptive ECM targets suppression. The effectiveness is verified by simulation results.

  19. Sweet delusion. Glucose drinks fail to counteract ego depletion.

    Science.gov (United States)

    Lange, Florian; Eggert, Frank

    2014-04-01

    Initial acts of self-control have repeatedly been shown to reduce individuals' performance on a consecutive self-control task. In addition, sugar containing drinks have been demonstrated to counteract this so-called ego-depletion effect, both when being ingested and when merely being sensed in the oral cavity. However, since the underlying evidence is less compelling than suggested, replications are crucially required. In Experiment 1, 70 participants consumed a drink containing either sugar or a non-caloric sweetener between two administrations of delay-discounting tasks. Experiment 2 (N=115) was designed to unravel the psychological function of oral glucose sensing by manipulating the temporal delay between a glucose mouth rinse and the administration of the consecutive self-control task. Despite applying powerful research designs, no effect of sugar sensing or ingestion on ego depletion could be detected. These findings add to previous challenges of the glucose model of self-control and highlight the need for independent replications.

  20. The beneficial effects of taurine to counteract sarcopenia.

    Science.gov (United States)

    Scicchitano, Bianca M; Sica, Gigliola

    2016-11-22

    Aging is a multifactorial process characterized by several features including low-grade inflammation, increased oxidative stress and reduced regenerative capacity, which ultimately lead to alteration in morpho-functional properties of skeletal muscle, thus promoting sarcopenia. This condition is characterized by a gradual loss of muscle mass due to an unbalance between protein synthesis and degradation, finally conveying in functional decline and disability. The development of specific therapeutic approaches able to block or reverse this condition may represent an invaluable tool for the promotion of a healthy aging among elderly. It is well established that changes in the quantity and the quality of dietary proteins, as well as the intake of specific amino acids, are able to counteract some of the physiopathological processes related to the progression of the loss of muscle mass and may have beneficial effects in improving the anabolic response of muscle in the elderly. Taurine is a non-essential amino acid expressed in high concentration in several mammalian tissues and particularly in skeletal muscle where it is involved in the modulation of intracellular calcium concentration and ion channel regulation and where it also acts as an antioxidant and anti-inflammatory factor. The aim of this review is to summarize the pleiotropic effects of taurine on specific muscle targets and to discuss its role in regulating signaling pathways involved in the maintenance of muscle homeostasis. We also highlight the potential use of taurine as a therapeutic molecule for the amelioration of skeletal muscle function and performance severely compromised during aging.

  1. Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis.

    Science.gov (United States)

    Nikitenko, Natalia A; Speiseder, Thomas; Groitl, Peter; Spirin, Pavel V; Prokofjeva, Maria M; Lebedev, Timofey D; Rubtsov, Petr M; Lam, Elena; Riecken, Kristoffer; Fehse, Boris; Dobner, Thomas; Prassolov, Vladimir S

    2015-06-01

    Human adenoviruses are non-enveloped DNA viruses causing various infections; their pathogenicity varies dependent on virus species and type. Although acute infections can sometimes take severe courses, they are rarely fatal in immune-competent individuals. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are hyperacute and highly contagious infections of the eye caused by human adenovirus types within species D. Currently there is no causal treatment available to counteract these diseases effectively. The E2B region of the adenovirus genome encodes for the viral DNA polymerase, which is required for adenoviral DNA replication. Here we propose novel model systems to test this viral key factor, DNA polymerase, as a putative target for the development of efficient antiviral therapy based on RNA interference. Using our model cell lines we found that different small interfering RNAs mediate significant suppression (up to 90%) of expression levels of viral DNA polymerase upon transfection. Moreover, permanent expression of short hairpin RNA based on the most effective small interfering RNA led to a highly significant, more than tenfold reduction in replication for different human group D adenoviruses involved in ocular infections.

  2. Update on alternative therapies for vulvovaginal atrophy

    Directory of Open Access Journals (Sweden)

    Chollet J

    2011-10-01

    Full Text Available Janet A Chollet1,2 1Beth Israel Deaconess Medical Center, Boston, 2Pear Tree Pharmaceuticals, Waltham, MA, USA Abstract: Although systemic absorption of estrogen with local treatment for vulvovaginal atrophy (VVA is most likely to be negligible, it is unknown whether this minimal absorption will affect outcomes in women with breast cancer. Use of adjuvant therapy with aromatase inhibitors for breast cancer is associated with high incidence of VVA symptoms. Because of the impact of moderate to severe VVA symptoms on the quality of life in breast cancer survivors, there has been an intense search for alternative therapies. Further, the publicity that followed the publication of data from the Women’s Health Initiative Study has led to the suggestion by the medical community to use the lowest dose therapy possible for minimal time duration in order to avoid risks. This article will highlight the progress in alternative therapies for VVA. Keywords: vulvovaginal atrophy, hormone therapy, alternative therapy

  3. Research progress of posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Li-jun PENG

    2016-06-01

    Full Text Available Posterior cotical atrophy (PCA is a kind of progressive dementia with main clinical manifestations of visual dysfunction as the starting symptom and associated with progressive cognitive disorder. The histopathology and imaging of PCA show visual dysfunction, neuritic plaques (NPs and neurofibrillary tangles (NFTs, which are the same as those in Alzheimer's disease (AD. Researches also showed that mutation of presenilin-1 (PS-1 gene and apolipoprotein E (ApoE genotype may participate in the occurrence and development of PCA. Parieto-occipital lobe atrophy, hypoperfusion and/or glucose metabolism reduction in the right posterior cerebrum can be seen in PCA. Cholinesterase inhibitors (ChEIs may improve the symptoms and postpone the progression of illness. No unified diagnostic criteria will reduce the comparability between different studies. Reasonable usage of the diagnostic criteria of PCA will be helpful in classifying and differentiating this disease. DOI: 10.3969/j.issn.1672-6731.2016.06.011

  4. Very severe spinal muscular atrophy (Type 0).

    Science.gov (United States)

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

  5. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG

    2016-06-01

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

  6. Cerebellar and cerebral atrophy in trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye-Kyung; Sargent, Michael A.; Poskitt, Kenneth J. [British Columbia Children' s Hospital, Department of Radiology, Vancouver, BC (Canada); Prendiville, Julie S. [British Columbia Children' s Hospital, Division of Paediatric Dermatology, Department of Paediatrics, Vancouver, BC (Canada)

    2005-10-01

    Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy. (orig.)

  7. Sensorimotor gating deficits in multiple system atrophy

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki

    2014-01-01

    Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

  8. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  9. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... intestine . The digestive system removes and processes nutrients ( vitamins , minerals , carbohydrates , fats, proteins , and water) from foods ... a microscope to see whether they contain cancer. Bypass : Surgery to allow food in the small intestine ...

  10. Large intestine (colon) (image)

    Science.gov (United States)

    ... portion of the digestive system most responsible for absorption of water from the indigestible residue of food. The ileocecal valve of the ileum (small intestine) passes material into the large intestine at the ...

  11. Intestinal ischemia and infarction

    Science.gov (United States)

    ... medlineplus.gov/ency/article/001151.htm Small intestinal ischemia and infarction To use the sharing features on this page, please enable JavaScript. Intestinal ischemia and infarction occurs when there is a narrowing ...

  12. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G

    2013-11-01

    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  13. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  14. Cellular and molecular mechanisms of muscle atrophy

    Science.gov (United States)

    Bonaldo, Paolo; Sandri, Marco

    2013-01-01

    Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases. PMID:23268536

  15. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  16. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  17. Aerobic exercise training prevents heart failure-induced skeletal muscle atrophy by anti-catabolic, but not anabolic actions.

    Science.gov (United States)

    Souza, Rodrigo W A; Piedade, Warlen P; Soares, Luana C; Souza, Paula A T; Aguiar, Andreo F; Vechetti-Júnior, Ivan J; Campos, Dijon H S; Fernandes, Ana A H; Okoshi, Katashi; Carvalho, Robson F; Cicogna, Antonio C; Dal-Pai-Silva, Maeli

    2014-01-01

    Heart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. We employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state.

  18. Aerobic exercise training prevents heart failure-induced skeletal muscle atrophy by anti-catabolic, but not anabolic actions.

    Directory of Open Access Journals (Sweden)

    Rodrigo W A Souza

    Full Text Available BACKGROUND: Heart failure (HF is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. METHODS AND RESULTS: We employed ascending aortic stenosis (AS inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET or to an untrained group (AS-UN. At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65, MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. CONCLUSIONS: Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state.

  19. Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

    Science.gov (United States)

    Guazzi, M D; Campodonico, J; Celeste, F; Guazzi, M; Santambrogio, G; Rossi, M; Trabattoni, D; Alimento, M

    1998-01-01

    Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

  20. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation.

    Science.gov (United States)

    Lin, Juan; Kumari, Snehlata; Kim, Chun; Van, Trieu-My; Wachsmuth, Laurens; Polykratis, Apostolos; Pasparakis, Manolis

    2016-12-01

    Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions. RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis. In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers. The mechanism by which RIPK1 counteracts RIPK3-MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3-MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1(mRHIM)) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1(mRHIM) in keratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1(mRHIM), suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases.

  1. Vertebrate intestinal endoderm development.

    Science.gov (United States)

    Spence, Jason R; Lauf, Ryan; Shroyer, Noah F

    2011-03-01

    The endoderm gives rise to the lining of the esophagus, stomach and intestines, as well as associated organs. To generate a functional intestine, a series of highly orchestrated developmental processes must occur. In this review, we attempt to cover major events during intestinal development from gastrulation to birth, including endoderm formation, gut tube growth and patterning, intestinal morphogenesis, epithelial reorganization, villus emergence, as well as proliferation and cytodifferentiation. Our discussion includes morphological and anatomical changes during intestinal development as well as molecular mechanisms regulating these processes. Copyright © 2011 Wiley-Liss, Inc.

  2. Severe spinal muscular atrophy variant associated with congenital bone fractures.

    Science.gov (United States)

    Felderhoff-Mueser, Ursula; Grohmann, Katja; Harder, Anja; Stadelmann, Christine; Zerres, Klaus; Bührer, Christoph; Obladen, Michael

    2002-09-01

    Infantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMNI) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures.

  3. Network structure of brain atrophy in de novo Parkinson's disease.

    Science.gov (United States)

    Zeighami, Yashar; Ulla, Miguel; Iturria-Medina, Yasser; Dadar, Mahsa; Zhang, Yu; Larcher, Kevin Michel-Herve; Fonov, Vladimir; Evans, Alan C; Collins, D Louis; Dagher, Alain

    2015-09-07

    We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

  4. Circulating micrornas as potential biomarkers of muscle atrophy

    Science.gov (United States)

    Wang, Fei

    2016-07-01

    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  5. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

    Science.gov (United States)

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M

    2016-03-01

    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p atrophy (p = 0.001, p = 0.023), and ventricular expansion (p atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase.

  6. The Impact of Gastric Atrophy on the Incidence of Diabetes

    Science.gov (United States)

    Yu, Tse-Ya; Wei, Jung-Nan; Kuo, Chun-Heng; Liou, Jyh-Ming; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Hsein, Yenh-Chen; Hsu, Ya-Wen; Chuang, Lee-Ming; Lee, Mei-Kuei; Hsiao, Ching-Hsiang; Wu, Ming-Shiang; Li, Hung-Yuan

    2017-01-01

    Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies. PMID:28045079

  7. Forest management could counteract distribution retractions forced by climate change.

    Science.gov (United States)

    Mair, Louise; Harrison, Philip J; Räty, Minna; Bärring, Lars; Strandberg, Gustav; Snäll, Tord

    2017-03-28

    Climate change is expected to drive the distribution retraction of northern species. However, particularly in regions with a history of intensive exploitation, changes in habitat management could facilitate distribution expansions counter to expectations under climate change. Here, we test the potential for future forest management to facilitate the southwards expansion of an old-forest species from the boreal region into the boreo-nemoral region, contrary to expectations under climate change. We used an ensemble of species distribution models based on citizen science data to project the response of Phellinus ferrugineofuscus, a red-listed old-growth indicator, wood-decaying fungus, to six forest management and climate change scenarios. We projected change in habitat suitability across the boreal and boreo-nemoral regions of Sweden for the period 2020-2100. Scenarios varied in the proportion of forest set-aside from production, the level of timber extraction, and the magnitude of climate change. Habitat suitabilities for the study species were projected to show larger relative increases over time in the boreo-nemoral region compared to the boreal region, under all scenarios. By 2100, mean suitabilities in set-aside forest in the boreo-nemoral region were similar to the suitabilities projected for set-aside forest in the boreal region in 2020, suggesting that occurrence in the boreo-nemoral region could be increased. However, across all scenarios, consistently higher projected suitabilities in set-aside forest in the boreal region indicated that the boreal region remained the species stronghold. Furthermore, negative effects of climate change were evident in the boreal region, and projections suggested that climatic changes may eventually counteract the positive effects of forest management in the boreo-nemoral region. Our results suggest that the current rarity of this old-growth indicator species in the boreo-nemoral region may be due to the history of intensive

  8. CLADA: cortical longitudinal atrophy detection algorithm.

    Science.gov (United States)

    Nakamura, Kunio; Fox, Robert; Fisher, Elizabeth

    2011-01-01

    Measurement of changes in brain cortical thickness is useful for the assessment of regional gray matter atrophy in neurodegenerative conditions. A new longitudinal method, called CLADA (cortical longitudinal atrophy detection algorithm), has been developed for the measurement of changes in cortical thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a subject-specific cortical model which is longitudinally deformed to match images from individual time points. The algorithm was designed to work reliably for lower resolution images, such as the MRIs with 1×1×5 mm(3) voxels previously acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability was 0.45% for images with 1mm(3) isotropic voxels and 0.77% for images with 1×1×5 mm(3) voxels. The mean absolute accuracy error was 0.43 mm, as determined by comparison of CLADA measurements to cortical thickness measured directly in post-mortem tissue. CLADA's sensitivity for correctly detecting at least 0.1mm change was 86% in a simulation study. A comparison to FreeSurfer showed good agreement (Pearson correlation=0.73 for global mean thickness). CLADA was also applied to MRIs acquired over 18 months in secondary progressive MS patients who were imaged at two different resolutions. Cortical thinning was detected in this group in both the lower and higher resolution images. CLADA detected a higher rate of cortical thinning in MS patients compared to healthy controls over 2 years. These results show that CLADA can be used for reliable measurement of cortical atrophy in longitudinal studies, even in lower resolution images.

  9. Intestinal alkaline phosphatase contributes to the reduction of severe intestinal epithelial damage.

    Science.gov (United States)

    Bol-Schoenmakers, Marianne; Fiechter, Daniëlle; Raaben, Willem; Hassing, Ine; Bleumink, Rob; Kruijswijk, Daniëlle; Maijoor, Kelly; Tersteeg-Zijderveld, Monique; Brands, Ruud; Pieters, Raymond

    2010-05-10

    Inflammatory bowel disease is characterized by chronic inflammation of the intestine and is accompanied by damage of the epithelial lining and by undesired immune responses towards enteric bacteria. It has been demonstrated that intestinal alkaline phosphatase (iAP) protects against the induction of inflammation, possibly due to dephosphorylation of lipopolysaccharide (LPS). The present study investigated the therapeutic potential of iAP in intestinal inflammation and epithelial damage. Intestinal epithelial damage was induced in C57BL/6 mice using detran sulfate sodium (DSS) and iAP was administered 4days after initial DSS exposure. Loss in body weight was significantly less in iAP-treated mice and accompanied with reduced colon damage (determined by combination of crypt loss, loss of goblet cells, oedema and infiltrations of neutrophils). Treatment with iAP was more effective in case of severe inflammation compared to situations of mild to moderate inflammation. Rectal administration of LPS into a moderate inflamed colon did not aggravate inflammation. Furthermore, soluble iAP did not lower LPS-induced nuclear factor-kappaB activation in epithelial cells in vitro but induction of cellular AP expression by butyrate resulted in decreased LPS response. In conclusion, the present study shows that oral iAP administration has beneficial effects in situations of severe intestinal epithelial damage, whereas in moderate inflammation endogenous iAP may be sufficient to counteract disease-aggravating effects of LPS. An approach including iAP treatment holds a therapeutic promise in case of severe inflammatory bowel disease. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Cardiac atrophy after bed rest and spaceflight

    Science.gov (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  11. Cardiac atrophy after bed rest and spaceflight

    Science.gov (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  12. [Susceptibility gene in multiple system atrophy (MSA)].

    Science.gov (United States)

    Tsuji, Shoji

    2014-01-01

    To elucidate molecular bases of multiple system atrophy (MSA), we first focused on recently identified MSA multiplex families. Though linkage analyses followed by whole genome resequencing, we have identified a causative gene, COQ2, for MSA. We then conducted comprehensive nucleotide sequence analysis of COQ2 of sporadic MSA cases and controls, and found that functionally deleterious COQ2 variants confer a strong risk for developing MSA. COQ2 encodes an enzyme in the biosynthetic pathway of coenzyme Q10. Decreased synthesis of coenzyme Q10 is considered to be involved in the pathogenesis of MSA through decreased electron transport in mitochondria and increased vulnerability to oxidative stress.

  13. Definition of singularity due to Newton’s second law counteracting gravity

    National Research Council Canada - National Science Library

    Arezu Jahanshir; Hossein Javadi; Farshid forouzbakhsh

    2013-01-01

    .... Regarding on review of Newton's second law in this paper, we have been attempted toenter to the sub-quantum space by crossing the border of quantum mechanics thento survey of counteracting Newton's...

  14. Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

    Directory of Open Access Journals (Sweden)

    Nakao A

    2002-04-01

    Full Text Available Two kinds of surgical models of small intestinal transplantation (SITx in rats, namely heterotopic (HIT and orthotopic transplantion (OIT, have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

  15. FoxO3 induces reversible cardiac atrophy and autophagy in a transgenic mouse model.

    Science.gov (United States)

    Schips, Tobias G; Wietelmann, Astrid; Höhn, Katharina; Schimanski, Silvia; Walther, Paul; Braun, Thomas; Wirth, Thomas; Maier, Harald J

    2011-09-01

    The transcription factor FoxO3 contributes to anti-hypertrophic signalling in the heart presumably by regulating autophagic-lysosomal and ubiquitin-proteasomal pathways. We wanted to study FoxO3 function in the adult heart in vivo by expressing a constitutively active mutant of FoxO3 in transgenic mice. We generated transgenic mice in which a tetracycline-regulated constitutively active FoxO3 transgene (FoxO3-CA) is controlled by the heart-specific α-myosin heavy chain promoter. Cardiac-specific expression in adult mice resulted in a decrease in heart weight by 25% and a reduction in stroke volume and cardiac output. The decrease in heart size was due to a reduction in the size of individual cardiomyocytes, whereas there was no evidence for increased cell death. FoxO3 activation was accompanied by the initiation of a foetal gene programme with increased expression of β-myosin heavy chain and natriuretic peptides, and by the activation of AKT and mammalian target of rapamycin signalling. As shown by electron microscopy, FoxO3-CA massively stimulated destruction of sarcomeres and autophagy, and induced expression of LC3-II and BNIP3. When FoxO3-CA expression was shut off in affected mice, cardiac atrophy and dysfunction as well as molecular markers were normalized within 1 month. FoxO3-CA expression did not counteract hypertrophy induced by transverse aortic constriction. Heart-specific expression of constitutively active FoxO3 leads to reversible heart atrophy. The reversibility of the phenotype suggests a remarkable ability of the adult myocardium to respond to different regulatory cues.

  16. Oats induced villous atrophy in coeliac disease

    Science.gov (United States)

    Lundin, K E A; Nilsen, E M; Scott, H G; Løberg, E M; Gjøen, A; Bratlie, J; Skar, V; Mendez, E; Løvik, A; Kett, K

    2003-01-01

    The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon γ were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon γ mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs. PMID:14570737

  17. Geographic atrophy: Etiopathogenesis and current therapies.

    Science.gov (United States)

    Sastre-Ibáñez, M; Barreiro-González, A; Gallego-Pinazo, R; Dolz-Marco, R; García-Armendariz, B

    2017-09-05

    Geographic atrophy is characterized by severe visual deficit whose etiology and pathophysiology are yet to be elucidated. As a working hypothesis, oxidative damage could trigger a chronic inflammation in Bruch's membrane-RPE-choriocapillaris complex, mostly due to complement pathway overactivation. Some individuals with mutations in the complement system and other factors have diminished capacity in the modulation of the inflammatory response, which results in cell damage and waste accumulation. This accumulation of intracellular and extracellular waste products manifests as drusen and pigmentary changes that precede the atrophy of photoreceptors, RPE, choriocapillaris with an ischemic process with decreased choroid flow. All these processes can be detected as tomographic findings and autofluorescence signals that are useful in the evaluation of patients with atrophic AMD, which helps to establish an individualized prognosis. Anti-inflammatory, antioxidant and therapies that decrease the accumulation of toxins for the preservation of the RPE cells and photoreceptors are being investigated in order to slow down the progression of this disease. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Effects of muscle atrophy on motor control

    Science.gov (United States)

    Stuart, D. G.

    1985-01-01

    As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

  19. Jejunum ileal intestinal atresia.

    Directory of Open Access Journals (Sweden)

    Claudio J. Puente Fonseca

    2005-12-01

    Full Text Available The intestinal atresia is one of the most important causes of intestinal obstruction in newborn. They constitute aorund 95% of total intestinal obstructions in this age group. Most of intestinal atresias are jejunoieal atresia. Although it is not frequent their relationship with other congenital anomalies, has been described the association in some cases with defects of intestine rotation, meconium peritonitis, with meconium ileus and rarely with the Hirschsprung diseases. The hereditary character has also been described in certain multiple intestinal atresias. We presented the Good Clinical Practices Guideline for Jejunoileal atresia, approved by consensus in the 1st National Good Clinical Practices Workshop in Pediatric Surgery (Cienfuegos, Cuba, March 7 – 9, 2002.

  20. Intestinal M cells.

    Science.gov (United States)

    Ohno, Hiroshi

    2016-02-01

    We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer's patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions.

  1. Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

    Science.gov (United States)

    Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

    2015-04-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

  2. Salt Potentiates Methylamine Counteraction System to Offset the Deleterious Effects of Urea on Protein Stability and Function

    Science.gov (United States)

    Singh, Laishram R.; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali

    2015-01-01

    Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea’s harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea’s effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction. PMID:25793733

  3. Salt potentiates methylamine counteraction system to offset the deleterious effects of urea on protein stability and function.

    Directory of Open Access Journals (Sweden)

    Safikur Rahman

    Full Text Available Cellular methylamines are osmolytes (low molecular weight organic compounds believed to offset the urea's harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea's effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction.

  4. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold

    2011-01-01

    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain......, such as age-related white matter changes (ARWMC) and progression of the disease....

  5. Cerebral atrophy after acute traumatic subdural orextradural hematomas in adults

    Institute of Scientific and Technical Information of China (English)

    冯海龙; 谭海斌; 黄光富; 廖晓灵

    2002-01-01

    @@ Cerebral atrophy is one of the serious sequelae ofsevere head injury. 1 Neuropathologicalinvestigation has revealed that cerebral atrophy iscaused by either diffuse axonal injury or cerebralhypoxia and ischemia. Secondary ipsilateral cerebralatrophy caused by acute subdural hematomas in infantshas been reported recently, but this unilateral cerebralatrophy after head injury in adult patients has rarelybeen reported.

  6. A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, N.; Katayama, T.; Makita, Y.; Kuroda, K.; Aizawa, H.; Kikuchi, K. [First Dept. of Internal Medicine, Asahikawa Medical Coll. (Japan)

    1999-07-01

    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum. (orig.)

  7. Multifocal motor neuropathy and progressive atrophy : Pathophysiological similarities and differences

    NARCIS (Netherlands)

    Vlam, L.

    2015-01-01

    Progressive muscular atrophy (PMA) and multifocal motor neuropathy (MMN) share many clinical similarities. They are both characterized by progressive asymmetric muscle weakness with atrophy and fasciculations. Tendon reflexes are normally low or absent, although in some patients with MMN normal or e

  8. Intestinal mucosal adaptation

    Institute of Scientific and Technical Information of China (English)

    Laurie Drozdowski; Alan BR Thomson

    2006-01-01

    Intestinal failure is a condition characterized by malnutrition and/or dehydration as a result of the inadequate digestion and absorption of nutrients. The most common cause of intestinal failure is short bowel syndrome, which occurs when the functional gut mass is reduced below the level necessary for adequate nutrient and water absorption. This condition may be congenital, or may be acquired as a result of a massive resection of the small bowel. Following resection, the intestine is capable of adaptation in response to enteral nutrients as well as other trophic stimuli. Identifying factors that may enhance the process of intestinal adaptation is an exciting area of research with important potential clinical applications.

  9. Oxyntic gastric atrophy in Helicobacter pylori gastritis is distinct from autoimmune gastritis.

    Science.gov (United States)

    Venerito, Marino; Varbanova, Mariya; Röhl, Friedrich-Wilhelm; Reinhold, Dirk; Frauenschläger, Katrin; Jechorek, Doerthe; Weigt, Jochen; Link, Alexander; Malfertheiner, Peter

    2016-08-01

    To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection. Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology. Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively). H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Bone and muscle atrophy with suspension of the rat

    Science.gov (United States)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  11. Centrifugal intensity and duration as countermeasures to soleus muscle atrophy

    Science.gov (United States)

    D'Aunno, Dominick S.; Thomason, Donald B.; Booth, Frank W.

    1990-01-01

    The effects of artificially induced gravity on the atrophy process of slow-twitch soleus muscle are studied in order to determine whether centrifugation could be an effective countermeasure to nonweight bearing at 1 G. It is observed that the soleus muscle atrophied 32 percent during seven days of nonweight bearing without countermeasures, and centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Nonweight-bearing groups receiving treatments of 1, 1.5, or 2.6 G had 48, 56, and 65 percent, respectively, of the atrophy observed in a nonweight-bearing-only group compared with the precontrol group. It is concluded that, as a countermeasure to nonweight-bearing-induced atrophy of the soleus muscle, centrifugation at 2.6 G is no more effective than exposure to 1 or 1.5 G.

  12. Bone and muscle atrophy with suspension of the rat

    Science.gov (United States)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  13. Indices of Regional Brain Atrophy: Formulae and Nomenclature

    Science.gov (United States)

    Arias-Carrión, Oscar

    2015-01-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  14. Endoscopic gastric atrophy is strongly associated with gastric cancer development after Helicobacter pylori eradication.

    Science.gov (United States)

    Toyoshima, Osamu; Yamaji, Yutaka; Yoshida, Shuntaro; Matsumoto, Shuhei; Yamashita, Hiroharu; Kanazawa, Takamitsu; Hata, Keisuke

    2017-05-01

    Risk factors for gastric cancer during continuous infection with Helicobacter pylori have been well documented; however, little has been reported on the risk factors for primary gastric cancer after H. pylori eradication. We conducted a retrospective, endoscopy-based, long-term, large-cohort study to clarify the risk factors for gastric cancer following H. pylori eradication. Patients who achieved successful H. pylori eradication and periodically underwent esophagogastroduodenoscopy surveillance thereafter at Toyoshima Endoscopy Clinic were enrolled. The primary endpoint was the development of gastric cancer. Statistical analysis was performed using the Kaplan-Meier method and Cox's proportional hazards models. Gastric cancer developed in 15 of 1232 patients. The cumulative incidence rates were 1.0 % at 2 years, 2.6 % at 5 years, and 6.8 % at 10 years. Histology showed that all gastric cancers (17 lesions) in the 15 patients were of the intestinal type, within the mucosal layer, and pylori, and gastric ulcers were marginally associated. Multivariate analysis identified higher grade of gastric atrophy (hazard ratio 1.77; 95 % confidence interval 1.12-2.78; P = 0.01) as the only independently associated parameter. Endoscopic gastric atrophy is a major risk factor for gastric cancer development after H. pylori eradication. Further long-term studies are required to determine whether H. pylori eradication leads to regression of H. pylori-related gastritis and reduces the risk of gastric cancer.

  15. IPLEX administration improves motor neuron survival and ameliorates motor functions in a severe mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Murdocca, Michela; Malgieri, Arianna; Luchetti, Andrea; Saieva, Luciano; Dobrowolny, Gabriella; de Leonibus, Elvira; Filareto, Antonio; Quitadamo, Maria Chiara; Novelli, Giuseppe; Musarò, Antonio; Sangiuolo, Federica

    2012-09-25

    Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA.

  16. Cardiac atrophy in women following bed rest.

    Science.gov (United States)

    Dorfman, Todd A; Levine, Benjamin D; Tillery, Tommy; Peshock, Ronald M; Hastings, Jeff L; Schneider, Suzanne M; Macias, Brandon R; Biolo, Gianni; Hargens, Alan R

    2007-07-01

    Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a

  17. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge

    Science.gov (United States)

    Cash, David M.; Frost, Chris; Iheme, Leonardo O.; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B.; Pennec, Xavier; Pierson, Ronald K.; Gunter, Jeffrey L.; Senjem, Matthew L.; Jack, Clifford R.; Guizard, Nicolas; Fonov, Vladimir S.; Collins, D. Louis; Modat, Marc; Cardoso, M. Jorge; Leung, Kelvin K.; Wang, Hongzhi; Das, Sandhitsu R.; Yushkevich, Paul A.; Malone, Ian B.; Fox, Nick C.; Schott, Jonathan M.; Ourselin, Sebastien

    2015-01-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated “direct” measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  18. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

    Science.gov (United States)

    Cash, David M; Frost, Chris; Iheme, Leonardo O; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B; Pennec, Xavier; Pierson, Ronald K; Gunter, Jeffrey L; Senjem, Matthew L; Jack, Clifford R; Guizard, Nicolas; Fonov, Vladimir S; Collins, D Louis; Modat, Marc; Cardoso, M Jorge; Leung, Kelvin K; Wang, Hongzhi; Das, Sandhitsu R; Yushkevich, Paul A; Malone, Ian B; Fox, Nick C; Schott, Jonathan M; Ourselin, Sebastien

    2015-12-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  19. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  20. Molecular characterisation of non-absorptive and absorptive enterocytes in human small intestine

    DEFF Research Database (Denmark)

    Gassler, N; Newrzella, D; Böhm, C;

    2006-01-01

    BACKGROUND AND AIMS: Perturbation of differentiation of the crypt-villus axis of the human small intestine is associated with several intestinal disorders of clinical importance. At present, differentiation of small intestinal enterocytes in the crypt-villus axis is not well characterised. SUBJECTS...... genes, and vesicle/transport related genes was found. CONCLUSION: Two types of enterocytes were dissected at the molecular level, the non-absorptive enterocyte located in the upper part of crypts and the absorptive enterocyte found in the middle of villi. These data improve our knowledge about...... the physiology of the crypt-villus architecture in human small intestine and provide new insights into pathophysiological phenomena, such as villus atrophy, which is clinically important....

  1. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Millino Caterina

    2009-04-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.

  2. Visual Dysfunction in Posterior Cortical Atrophy

    Directory of Open Access Journals (Sweden)

    Mari N. Maia da Silva

    2017-08-01

    Full Text Available Posterior cortical atrophy (PCA is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions.

  3. Visual Dysfunction in Posterior Cortical Atrophy

    Science.gov (United States)

    da Silva, Mari N. Maia; Millington, Rebecca S.; Bridge, Holly; James-Galton, Merle; Plant, Gordon T.

    2017-01-01

    Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions. PMID:28861031

  4. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  5. Diagnosis and therapy of multiple system atrophy

    Directory of Open Access Journals (Sweden)

    GU Wei-hong

    2012-06-01

    Full Text Available Multiple system atrophy (MSA is a sporadic and rapidly progressive neurodegenerative disorder characterised clinically by any combination of autonomic, cerebellar ataxia, parkinsonian, and pyramidal signs. Over the past 10 years, substantial progress has been achieved to establish MSA as an α-synucleinopathy along with other neurodegenerative diseases. Although the diagnosis of this disorder is largely based on clinical expertise, some investigations have been proposed to assist in early differential diagnosis, especially neuroimaging examination, which have resulted in revised diagnostic criteria. The UMSARS is a reliable and valid scale for semiquantitative clinical assessments of MSA patients. An outline of the rationale for managing symptomatic deterioration in MSA is provided including novel neuroprotective therapeutic approaches, together with the treatment of traditional Chinese medicine.

  6. Neuromodulation of intestinal inflammation

    NARCIS (Netherlands)

    Costes, L.M.M.

    2015-01-01

    Interactions between the central nervous system and the immune system have been shown to exert a crucial role in the tight regulation of the immune response in the intestine. In particular, the vagus nerve was recently unraveled as an important player in this neuromodulation of intestinal inflammati

  7. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and/or pro...

  8. Molecular detection of chicken parvovirus in broilers with enteric disorders presenting curving of duodenal loop, pancreatic atrophy, and mesenteritis.

    Science.gov (United States)

    Nuñez, L F N; Sá, L R M; Parra, S H S; Astolfi-Ferreira, C S; Carranza, C; Ferreira, A J P

    2016-04-01

    Enteric disorders are an important cause of economic losses in broiler chickens worldwide. Several agents have been associated with enteric problems, such as viruses, bacteria, and parasites. In this study, broiler chickens showing signs of enteric disorders were subjected to molecular diagnosis for several viral agents and also for pathological examination for elucidating this problem. Thus, the chickens were screened for avian nephritis virus (ANV), chicken astrovirus (CAstV), avian rotavirus (ArtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), fowl adenovirus group I (FAdV-1), and chicken parvovirus (ChPV). Postmortem examinations revealed a curving of the duodenal loop (J-like appearance) and intestines filled with liquid and gaseous content. Histopathological analysis of the duodenal loop showed pancreatic atrophy, acute mesenteritis, and enteritis. PCR results showed that ChPV was the sole viral agent detected in samples with lesions such as the curved duodenal loop and pancreatic atrophy. Molecular characterization of the nucleotide and deduced amino acid sequences revealed a high similarity with other strains of ChPV from Brazil, Canada, United States, Europe, and Asia. These findings suggest an association between ChPV and the development of enteritis, pancreatitis, and pancreatic atrophy, which may lead to curling of the duodenal loop. Together, these alterations may disrupt the normal functioning of the digestive system, diminishing digestion and the absorption of dietary nutrients and consequently leading to reduced weight gain, flock impairment, dwarfism, and an elevated feed conversion rate.

  9. Congenital intestinal lymphangiectasia

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    Popović Dušan Đ.

    2011-01-01

    Full Text Available Background. Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. Case report. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and suportive therapy. Conclusion. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

  10. Reviewing the options for local estrogen treatment of vaginal atrophy

    Directory of Open Access Journals (Sweden)

    Lindahl SH

    2014-03-01

    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  11. Transcriptional profile of a myotube starvation model of atrophy

    Science.gov (United States)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

    2005-01-01

    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  12. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

    Science.gov (United States)

    Manning, Emily N.; Bartlett, Jonathan W.; Cash, David M.; Malone, Ian B.; Ridgway, Gerard R.; Lehmann, Manja; Leung, Kelvin K.; Sudre, Carole H.; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T.; Fox, Nick C.; Cardoso, M. Jorge; Barnes, Josephine

    2017-01-01

    ABSTRACT This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27933676

  13. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

    Science.gov (United States)

    Fiford, Cassidy M; Manning, Emily N; Bartlett, Jonathan W; Cash, David M; Malone, Ian B; Ridgway, Gerard R; Lehmann, Manja; Leung, Kelvin K; Sudre, Carole H; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T; Fox, Nick C; Cardoso, M Jorge; Barnes, Josephine

    2017-03-01

    This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  14. Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats

    Directory of Open Access Journals (Sweden)

    Yeh C

    2016-10-01

    Full Text Available Chun Yeh,1 Ching-Heng Ting,2 Ming-Luen Doong,3 Chin-Wen Chi,4,5 Shou-Dong Lee,1 Chih-Yen Chen6–8 1Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital, 2Department of Pathology, Mackay Memorial Hospital, 3Institute of Physiology, 4Institute of Pharmacology, National Yang-Ming University School of Medicine, 5Department of Medical Research, Taipei Veterans General Hospital, 6Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 7Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 8Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan Purpose: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated.Methods: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV catheters. The functional importance of corticotropin-releasing factor (CRF receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B.Results: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2

  15. Cerebellar Atrophy in Adult Survivors of Childhood Cerebellar Tumor.

    Science.gov (United States)

    Ailion, Alyssa S; King, Tricia Z; Wang, Liya; Fox, Michelle E; Mao, Hui; Morris, Robin M; Crosson, Bruce

    2016-05-01

    The cerebellum (CB) is known for its role in supporting processing speed (PS) and cognitive efficiencies. The CB often sustains damage from treatment and resection in pediatric patients with posterior fossa tumors. Limited research suggests that CB atrophy may be associated with the radiation treatment experienced during childhood. The purpose of the study was to measure cerebellar atrophy to determine its neurobehavioral correlates. Brain magnetic resonance images were collected from 25 adult survivors of CB tumors and age- and gender-matched controls (M age= 24 years (SD=5), 52% female). Average age at diagnosis was 9 years (SD=5) and average time since diagnosis was 15 years (SD=5). PS was measured by the Symbol Digit Modality Test. To quantify atrophy, an objective formula was developed based on prior literature, in which Atrophy=[(CB White+CB Gray Volume)/Intracranial Vault (ICV)]controls-[(CB White+CB Gray+Lesion Size Volume)/ICV]survivors. Regression analyses found that the interaction term (age at diagnosis*radiation) predicts CB atrophy; regression equations included the Neurological Predictor Scale, lesion size, atrophy, and the interaction term and accounted for 33% of the variance in oral PS and 48% of the variance in written PS. Both interactions suggest that individuals with smaller CB lesion size but a greater degree of CB atrophy had slower PS, whereas individuals with a larger CB lesion size and less CB atrophy were less affected. The results of the current study suggest that young age at diagnosis and radiation is associated with CB atrophy, which interacts with lesion size to impact both written and oral PS.

  16. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    Science.gov (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  17. Evaluation of large intestinal mucosa regeneration in ulcerative colitis using linear measurements

    Directory of Open Access Journals (Sweden)

    Đolai Matilda

    2005-01-01

    Full Text Available Ulcerative colitis is a chronic inflammatory condition characterized by three phases: active, regression and remission phase. The active phase is followed by atrophy of the large intestinal mucosa. Although its evaluation is sometimes difficult, quantification of ceratin mucosal parameters can be used as an accessory method. The aim of the study was to determine the parameters of linear micrometry in order to estimate the regeneration of the large intestinal mucosa in ulcerative colitis, and to evaluate the efficiency of this method in everyday work. The measurements were performed on routine bioptic samples after qualitative histologic analysis and determination of the type and stage of the disease. The measurements were carried out to determine: the number of crypts per unit length, the height of crypt epithelium, diameter of crypts, their lumen and interstices; also, the quotient between the diameters of crypts and interstices was calculated. The analysis of the measured parameters points to presence and degree of regeneration and/or atrophy of mucosa, particularly by following the parameters of crypt epithelium. Linear measurements can be used in estimation of regeneration and atrophy of large intestinal mucosa. .

  18. Intestinal invagination Invaginación intestinal.

    Directory of Open Access Journals (Sweden)

    Dayamnelys Aguilar Atanay

    Full Text Available Intestinal intussusceptions are the most frequent cause of acute surgical occlusive syndrome in infants; it is idiopathic in more than 90% of cases. Their treatment can be conservative, with reduction by means of imaging and hydrostatic procedures, or surgical. We presented the Good Clinical Practices Guideline for Intestinal intussusceptions, approved by consensus in the 3th National Good Clinical Practices Workshop in Pediatric Surgery (Camagüey, Cuba; February 23 – 26, 2004.
    La invaginación intestinal es la causa más frecuente del síndrome de abdomen agudo quirúrgico oclusivo en lactantes y es idiopática en más del 90 % de los casos. Su tratamiento puede ser conservador, con reducción mediante procedimientos hidrostáticos combinados con vigilancia imaginológica, o quirúrgico. Se presenta la Guía de Buenas Prácticas Clínicas para invaginación intestinal, aprobada por consenso en el 3er Taller Nacional de Buenas Prácticas Clínicas en Cirugía Pediátrica (Camagüey, 23 al 26 de febrero de 2004.

  19. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2016-03-01

    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  20. Posterior cortical atrophy: an atypical variant of Alzheimer disease.

    Science.gov (United States)

    Suárez-González, Aida; Henley, Susie M; Walton, Jill; Crutch, Sebastian J

    2015-06-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by striking progressive visual impairment and a pattern of atrophy mainly involving posterior cortices. PCA is the most frequent atypical presentation of Alzheimer disease. The purpose of this article is to provide a summary of PCA's neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed in the context of signal characteristic features of the PCA syndrome (the early onset, focal loss of visual perception, focal posterior brain atrophy) and the underlying cause of the disease. The authors' experience with psychotherapeutic intervention and PCA support groups is shared in detail.

  1. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  2. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  3. Counteraction between overshadowing and degraded contingency treatments: support for the extended comparator hypothesis.

    Science.gov (United States)

    Urcelay, Gonzalo P; Miller, Ralph R

    2006-01-01

    Four experiments using rats in a Pavlovian lick-suppression preparation investigated the effects of combining 2 treatments known for their response-decrementing effects, namely, overshadowing and degraded contingency. Contrary to most contemporary learning theories, the extended comparator hypothesis predicts that these 2 treatments will counteract each other, and therefore, less of a decrement in conditioned responding should be observed than with either treatment alone. Experiments 1 and 2 confirmed this prediction in first-order conditioning and sensory preconditioning preparations, respectively. Experiment 3 demonstrated that posttraining extinction of the training context resulted in a recovery from degraded contingency and reversed the counteractive effect on overshadowing. Finally, Experiment 4 demonstrated that posttraining extinction of the overshadowing stimulus resulted in recovery from simple overshadowing and also reversed the counteractive effect on degraded contingency. These results are consistent with the extended comparator hypothesis but not traditional or recent acquisition-focused models.

  4. Deletion of atrophy enhancing genes fails to ameliorate the phenotype in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Iyer, Chitra C; McGovern, Vicki L; Wise, Dawnne O; Glass, David J; Burghes, Arthur H M

    2014-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disease causing degeneration of lower motor neurons and muscle atrophy. One therapeutic avenue for SMA is targeting signaling pathways in muscle to ameliorate atrophy. Muscle Atrophy F-box, MAFbx, and Muscle RING Finger 1, MuRF1, are muscle-specific ubiquitin ligases upregulated in skeletal and cardiac muscle during atrophy. Homozygous knock-out of MAFbx or MuRF1 causes muscle sparing in adult mice subjected to atrophy by denervation. We wished to determine whether blockage of the major muscle atrophy pathways by deletion of MAFbx or MuRF1 in a mouse model of SMA would improve the phenotype. Deletion of MAFbx in the Δ7 SMA mouse model had no effect on the weight and the survival of the mice while deletion of MuRF1 was deleterious. MAFbx(-/-)-SMA mice showed a significant alteration in fiber size distribution tending towards larger fibers. In skeletal and cardiac tissue MAFbx and MuRF1 transcripts were upregulated whereas MuRF2 and MuRF3 levels were unchanged in Δ7 SMA mice. We conclude that deletion of the muscle ubiquitin ligases does not improve the phenotype of a Δ7 SMA mouse. Furthermore, it seems unlikely that the beneficial effect of HDAC inhibitors is mediated through inhibition of MAFbx and MuRF1. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Acquired causes of intestinal malabsorption

    NARCIS (Netherlands)

    van der Heide, F.

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane

  6. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  7. Muscle ring finger 1 mediates cardiac atrophy in vivo

    National Research Council Canada - National Science Library

    Monte S. Willis; Mauricio Rojas; Luge Li; Craig H. Selzman; Ru-Hang Tang; William E. Stansfield; Jessica E. Rodriguez; David J. Glass; Cam Patterson

    2009-01-01

    ...; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression...

  8. The pathogenesis and treatment of cardiac atrophy in cancer cachexia

    National Research Council Canada - National Science Library

    Murphy, Kate T

    2016-01-01

    .... In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia...

  9. Genetics Home Reference: gyrate atrophy of the choroid and retina

    Science.gov (United States)

    ... atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and ... Criteria for Links Data Files & API Site Map Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  10. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    Science.gov (United States)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  11. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal mus

  12. Mechanisms of muscle growth and atrophy in mammals and Drosophila

    National Research Council Canada - National Science Library

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L

    2014-01-01

    .... Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. Results...

  13. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    Science.gov (United States)

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  14. Reversible "brain atrophy" in patients with Cushing's disease

    OpenAIRE

    Gnjidić, Živko; Sajko, Tomislav; Kudelić, Nenad; Malenica, Maša; Vizner, Branka; Vrkljan, Milan; Hat, Josip; Rumboldt, Zoran

    2008-01-01

    During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing’s disease. Neuroradiological examination showed prominent volume loss of the brain parenchyma, unexpected for the patient’s age. This »brain atrophy« appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level. Observed difference between degree of »brain atrophy« in the Cushing’s disease group and in the control group was statistically sign...

  15. Steroid-induced Kager's fat pad atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, Atul K. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil); Musculoskeletal Imaging, Diagnostic Center, Hospital do Coracao (HCor) and Teleimagem, Sao Paulo, SP (Brazil); Santos, Durval C.B. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil)

    2014-08-15

    We report a rare case of Kager's fat pad atrophy and fibrosis in a 60-year-old woman 1 year after a steroid injection for Achilles tendinopathy. There are few published reports of steroid-induced atrophy affecting deeper layers of fat tissue. To our knowledge, this case report is the first to illustrate its features using magnetic resonance imaging. A review of the scientific literature is also presented. (orig.)

  16. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    OpenAIRE

    Julia Krämer; Meuth, Sven G.; Jan-Gerd Tenberge; Patrick Schiffler; Heinz Wiendl; Michael Deppe

    2015-01-01

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (IC...

  17. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-09-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  18. Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

    Science.gov (United States)

    Algahtani, Hussein A; Aldarmahi, Ahmed A; Al-Rabia, Mohammed W; Young, G Bryan

    2014-01-01

    Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

  19. Intestinal Pseudo-Obstruction

    Science.gov (United States)

    ... the small intestine during an upper GI endoscopy. Biopsy A gastroenterologist can obtain a biopsy of the ... Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Events Health Information Diabetes Digestive ...

  20. Intestinal failure in childhood

    African Journals Online (AJOL)

    citrulline levels are predictive of intestinal recovery, or not, remains to be confirmed. ... GI secretions, salivary Epidermal Growth Factor (EGF) release and gallbladder .... This cause of neonatal diarrhoea requires permanent PN. However,.

  1. Small intestine (image)

    Science.gov (United States)

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the bloodstream. The pyloric sphincter governs the passage of partly digested food ...

  2. The intestinal stem cell.

    NARCIS (Netherlands)

    Barker, N.; van de Wetering, M.L.; Clevers, H.

    2008-01-01

    The epithelium of the adult mammalian intestine is in a constant dialog with its underlying mesenchyme to direct progenitor proliferation, lineage commitment, terminal differentiation, and, ultimately, cell death. The epithelium is shaped into spatially distinct compartments that are dedicated to

  3. Intestinal barrier damage caused by trauma and lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Lian-An Ding; Jie-Shou Li; You-Sheng Li; Nian-Ting Zhu; Fang-Nan Liu; Li Tan

    2004-01-01

    AIM: To investigate the intestinal barrier function damage induced by trauma and infection in rats.METHODS: Experimental models of surgical trauma and infection were established in rats. Adult Sprague-Dawley rats were divided into 4 groups: control group (n = 8), EN group (n = 10), PN group (n = 9) and Sep group (n = 8).The rats in PN and Sep groups were made into PN models that received isonitrogenous, isocaloric and isovolumic TPN solution during the 7-d period. Rats in EN and Sep groups received laparotomy and cervical catheterization on day 1 and received lipopolysaccharide injection intraperitoneally on d 7. On the 7th day all the animals were gavaged with lactulose and mannitol to test the intestinal permeability.Twenty-four hours later samples were collected and examined.RESULTS: The inflammatory responses became gradually aggravated from EN group to Sep group. The mucosal structure of small intestine was markedly impaired in PN and Sep groups. There was a low response in IgA level in Sep group when compared with that of EN group.Lipopolysaccharide injection also increased the nitric oxide levels in the plasma of the rats. The intestinal permeability and bacterial translocation increased significantly in Sep group compared with that of control group.CONCLUSION: One wk of parenteral nutrition causes an atrophy of the intestinal mucosa and results in a moderate inflammatory reaction in the rats. Endotoxemia aggravats the inflammatory responses that caused by laparotomy plus TPN, increases the production of nitric oxide in the body, and damages the intestinal barrier function.

  4. "Apperceptive" alexia in posterior cortical atrophy.

    Science.gov (United States)

    Mendez, Mario F; Shapira, Jill S; Clark, David G

    2007-02-01

    The most common presenting complaint in posterior cortical atrophy (PCA) is reading difficulty. Although often described as an alexia without agraphia, alexia in PCA may have multiple causes, including a primary visuoperceptual etiology, attentional alexia, and central reading difficulty. This study evaluated 14 patients with early PCA and disturbances in reading ability in comparison to 14 normal controls. All 14 patients had a progressive disorder of complex visual functions and neuroimaging evidence of occipitoparietal dysfunction. They underwent a task requiring identification of single letters with and without flanking distractors. They also read single words consisting of regular English spelling or irregular grapheme-phoneme correspondence (irregular words) and pronounceable nonsense words (pseudowords). The PCA patients made errors in letter identification when letters were flanked by visually similar letters or numbers. They could read most single regular and irregular words but made visual errors and had particular trouble with pseudowords. They could not use a letter-by-letter reading strategy effectively. The PCA patients had similar difficulties on other visuoperceptual tests. These findings are consistent with an alexia manifested by perceptual and attentional difficulty on attempting serial visual processing of letters in the context of other letters. This "apperceptive alexia" results when the configuration of letters into words is impaired during letter-by-letter reading. Disproportionate difficulty reading pseudowords suggests an additional impairment in phonological processing. PCA patients have variable neuropathology and individual patients may have other contributions to their reading impairment.

  5. Spinal Muscular Atrophy: Current Therapeutic Strategies

    Science.gov (United States)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  6. Forced oscillation technique in spinal muscular atrophy.

    Science.gov (United States)

    Gauld, Leanne M; Keeling, Lucy A; Shackleton, Claire E; Sly, Peter D

    2014-09-01

    Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA. Children with SMA aged resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P change +0.51, P .05) was found between clinical characteristics and FOT values. FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

  7. Maldistribution in air-water heat pump evaporators. Part 2: Economic analysis of counteracting technologies

    DEFF Research Database (Denmark)

    Mader, Gunda; Palm, Björn; Elmegaard, Brian

    2015-01-01

    In this study a methodology is applied to quantify the effect of evaporator maldistributionon operating costs of airewater heat pumps. The approach is used to investigate the cost-effectivenessof two technologies enabling to counteract maldistribution: a flash gasbypass setup and the individual...

  8. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis

    NARCIS (Netherlands)

    Schothorst, van E.M.; Franssen-Hal, van N.L.W.; Schaap, M.M.; Pennings, J.; Hoebee, B.; Keijer, J.

    2005-01-01

    VAN SCHOTHORST, EVERT M., NICOLE FRANSSEN-VAN HAL, MIRJAM M. SCHAAP, JEROEN PENNINGS, BARBARA HOEBEE, AND JAAP KEIJER. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis. Obes Res. 2005;13:1031-1041. Objective: To identify early molecular changes in weigh

  9. Allured or alarmed: Counteractive control responses to food temptations in the brain

    NARCIS (Netherlands)

    Smeets, P.A.M.; Kroese, F.M.; Evers, C.; Ridder, de D.T.D.

    2013-01-01

    Typically, it is believed that palatable, high caloric foods signal reward and trigger indulgent responses. However, Counteractive Control Theory suggests that, to the extent that people are concerned about their weight, a confrontation with palatable foods should also trigger ‘alarm bell responses’

  10. Calculation of brain atrophy using computed tomography and a new atrophy measurement tool

    Science.gov (United States)

    Bin Zahid, Abdullah; Mikheev, Artem; Yang, Andrew Il; Samadani, Uzma; Rusinek, Henry

    2015-03-01

    Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality. Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25-95yrs; (Mean 67+/-17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, patrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient.

  11. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  12. The intestine is a blender

    Science.gov (United States)

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  13. Visual neglect in posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Andrade Katia

    2010-08-01

    Full Text Available Abstract Background In posterior cortical atrophy (PCA, there is a progressive impairment of high-level visual functions and parietal damage, which might predict the occurrence of visual neglect. However, neglect may pass undetected if not assessed with specific tests, and might therefore be underestimated in PCA. In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of PCA patients. Methods Twenty-four right-handed PCA patients underwent a standardized battery of neglect tests. Visual fields were examined clinically by the confrontation method. Results Sixteen of the 24 patients (66% had signs of visual neglect on at least one test, and fourteen (58% also had visual extinction or hemianopia. Five patients (21% had neither neglect nor visual field defects. As expected, left-sided neglect was more severe than right-sided neglect. However, right-sided neglect resulted more frequently in this population (29% than in previous studies on focal brain lesions. Conclusion When assessed with specific visuospatial tests, visual neglect is frequent in patients with PCA. Diagnosis of neglect is important because of its negative impact on daily activities. Clinicians should consider the routine use of neglect tests to screen patients with high-level visual deficits. The relatively high frequency of right-sided neglect in neurodegenerative patients supports the hypothesis that bilateral brain damage is necessary for right-sided neglect signs to occur, perhaps because of the presence in the right hemisphere of crucial structures whose damage contributes to neglect.

  14. In vivo models of multiple system atrophy.

    Science.gov (United States)

    Fernagut, Pierre-Olivier; Ghorayeb, Imad; Diguet, Elsa; Tison, François

    2005-08-01

    Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

  15. Possible role of polyamines in gyrate atrophy.

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    Sulochana Konerirajapuram

    2000-01-01

    Full Text Available PURPOSE: Gyrate atrophy (GA is marked by hyperornithinemia and lowered ornithine amino transferase (OAT. However there are patients of GA without hyperornithinemia and those with hyperornithinemia without GA. Some cases of GA have been reported to have low lysine. The purpose of the study was to determine if polyamines, the metabolites of ornithine, and lysine have any diagnostic role in GA. METHODS: Ornithine in plasma was estimated by two-dimensional paper chromatography, with elution of the coloured spot, and the absorbance measured using a spectrophotometer at 560 nm. OAT assay in lymphocytes was done spectrophotometrically using ornithine as substrate. Blood and urinary polyamines were extracted with n-butanol, benzoylated and analysed with HPLC; putrescine, spermine, spermidine, and cadaverine were assayed individually at 254 nm with the UV detector using ODS, G18 column with 63% methanol as solvent. RESULTS: Of the 7 patients investigated, 6 had features typical of GA. One was diagnosed to have atypical retinitis pigmentosa (case 3. The first five cases had elevated ornithine and diminished OAT, but cases 6 and 7 had near-normal ornithine and case 7 had near-normal OAT. However, all 7 patients had increased levels of total polyamines in urine compared to normals. Five had increased putrescine and three had increased spermine. All the 7 had decreased cadaverine in urine. Thus, though there were inconsistencies with ornithine and OAT, all the 7 patients had elevated polyamines from ornithine and decreased cadaverine. CONCLUSION: In addition to estimating ornithine and OAT in GA, it is suggested that urinary polyamines may be analysed as the latter appears to correlate better with the clinical condition and help in the diagnosis to a greater extent. Moreover, while ornithine is an innocuous amino acid, polyamines are known to damage DNA and proteins.

  16. Neural correlates of cognitive impairment in posterior cortical atrophy.

    Science.gov (United States)

    Kas, Aurélie; de Souza, Leonardo Cruz; Samri, Dalila; Bartolomeo, Paolo; Lacomblez, Lucette; Kalafat, Michel; Migliaccio, Raffaella; Thiebaut de Schotten, Michel; Cohen, Laurent; Dubois, Bruno; Habert, Marie-Odile; Sarazin, Marie

    2011-05-01

    With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in B

  17. Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

    Science.gov (United States)

    Sei, Hirofumi; Taguchi, Aki; Nishida, Naoya; Hato, Naohito; Gyo, Kiyofumi

    2015-01-01

    We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

  18. Chronic intestinal pseudoobstruction syndrome

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    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)

    1992-03-15

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.

  19. Pediatric intestinal leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Chaudhary Amit

    2007-01-01

    Full Text Available The paper reports an infant presenting with leiomyosarcoma of the small intestine. The patient presented with intermittent abdominal pain. Examination revealed a hard and mobile intraperitoneal mass. The tumor arose from the mid-ileum with regional lymphadenopathy. Excision of the tumor along with the involved bowel was performed followed by three cycles of chemotherapy. Histological diagnosis was that of a low-grade malignant leiomyosarcoma of the small intestine. Surgical excision was followed by three cycles of chemotherapy. After surgery and three cycles of chemotherapy, the patient was followed up for four years with no evidence of recurrence or metastasis. Surgery followed by chemotherapy was curative for leiomyosarcoma in our patient. Intestinal leiomyosarcoma should be kept as a differential diagnosis for mobile solid intraabdominal tumors in childhood.

  20. Intestinal anisakidosis (anisakiosis).

    Science.gov (United States)

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  1. Gallstones: an intestinal disease?

    Science.gov (United States)

    Van Erpecum, K J; Van Berge-Henegouwen, G P

    1999-03-01

    Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world.

  2. Early and Degressive Putamen Atrophy in Multiple Sclerosis.

    Science.gov (United States)

    Krämer, Julia; Meuth, Sven G; Tenberge, Jan-Gerd; Schiffler, Patrick; Wiendl, Heinz; Deppe, Michael

    2015-09-25

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV). Patient's relative putamen volume (RPV), expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV) from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  3. Congenital segmental spinal muscular atrophy: a case report.

    Science.gov (United States)

    Savaş, Tülin; Erol, Ilknur; Özkale, Yasemin; Saygi, Semra

    2015-03-01

    Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

  4. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julia Krämer

    2015-09-01

    Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  5. Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats.

    Science.gov (United States)

    Shibaguchi, Tsubasa; Yamaguchi, Yusuke; Miyaji, Nobuyuki; Yoshihara, Toshinori; Naito, Hisashi; Goto, Katsumasa; Ohmori, Daijiro; Yoshioka, Toshitada; Sugiura, Takao

    2016-08-01

    Astaxanthin is a carotenoid pigment and has been shown to be an effective inhibitor of oxidative damage. We tested the hypothesis that astaxanthin intake would attenuate immobilization-induced muscle atrophy in rats. Male Wistar rats (14-week old) were fed for 24 days with either astaxanthin or placebo diet. After 14 days of each experimental diet intake, the hindlimb muscles of one leg were immobilized in plantar flexion position using a plaster cast. Following 10 days of immobilization, both the atrophic and the contralateral plantaris muscles were removed and analyzed to determine the level of muscle atrophy along with measurement of the protein levels of CuZn-superoxide dismutase (CuZn-SOD) and selected proteases. Compared with placebo diet animals, the degree of muscle atrophy in response to immobilization was significantly reduced in astaxanthin diet animals. Further, astaxanthin supplementation significantly prevented the immobilization-induced increase in the expression of CuZn-SOD, cathepsin L, calpain, and ubiquitin in the atrophied muscle. These results support the postulate that dietary astaxanthin intake attenuates the rate of disuse muscle atrophy by inhibiting oxidative stress and proteolysis via three major proteolytic pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy.

    Science.gov (United States)

    Fanin, Marina; Nascimbeni, Anna C; Angelini, Corrado

    2014-09-01

    Muscle fiber atrophy and the molecular pathways underlying this process have not been investigated in dysferlinopathy patients. In 22 muscles from dysferlinopathy patients we investigated fiber atrophy by morphometry and ubiquitin-proteasome and autophagic pathways using protein and/or transcriptional analysis of atrophy- and autophagy-related genes (MuRF1, atrogin1, LC3, p62, Bnip3). Dysferlinopathy showed significant fiber atrophy and higher MuRF-1 protein and mRNA levels, which correlated with fiber size, suggesting activation of the atrophy program by proteasome induction. Some of the MuRF-1 upregulation and proteasome induction may be attributed to the prominent regeneration found. A potential role of impaired autophagy was suggested by p62-positive protein aggregates in atrophic fibers and significantly higher levels of LC3-II and p62 proteins and overexpression of p62 and Bnip3 mRNA. Damaged muscle fibers and prominent inflammatory changes may also enhance autophagy due to the insufficient level of proteasomal degradation of mutant dysferlin. Copyright © 2014 Wiley Periodicals, Inc.

  7. [Intestinal microbiocenosis in children with intestinal enzymopathy].

    Science.gov (United States)

    Kamilova, A T; Akhmedov, N N; Pulatova, D B; Nurmatov, B A

    2001-01-01

    141 children with different kinds of intestinal enzymopathy were examined; of these, 33 had celiac disease, 39--the syndrome of celiac disease, 12--congenital lactase deficiency and 57--the syndrome of disaccharidase insufficiency. In these patients a significant decrease in the average characteristics of the main protective flora and the growth of hemolytic and lactose-negative enterobacteria were established. In all groups of patients increased amounts of Proteus were detected, which was indicative of profound dysbiosis. The content of bifidobacteria was found to be decreased in 89.5-97% of the patients and the content of lactic acid bacteria, in 15.8-33.3%. The decreased content of Escherichia coli with normal enzymatic activity (less than 10(7) colony-forming units) was noted in one-third of the patients with the syndrome of celiac disease and congenital lactase deficiency, in about a half of the patients with the syndrome of disaccharidase insufficiency and least of all in patients with celiac disease (9.1%). The association of opportunistic microbes was detected in 15.6% of the patients, more often in those with celiac disease, the syndrome of celiac disease and congenital lactase deficiency. The severity of disturbances in intestinal eubiosis was found to depend on the gravity of the patients' state.

  8. MiR-206 Attenuates Denervation-Induced Skeletal Muscle Atrophy in Rats Through Regulation of Satellite Cell Differentiation via TGF-β1, Smad3, and HDAC4 Signaling.

    Science.gov (United States)

    Huang, Qiang Kai; Qiao, Hu-Yuan; Fu, Ming-Huan; Li, Gang; Li, Wen-Bin; Chen, Zhi; Wei, Jian; Liang, Bing-Sheng

    2016-04-07

    BACKGROUND Denervation-induced skeletal muscle atrophy results in significant biochemical and physiological changes potentially leading to devastating outcomes including increased mortality. Effective treatments for skeletal muscle diseases are currently not available. Muscle-specific miRNAs, such as miR-206, play an important role in the regulation of muscle regeneration. The aim of the present study was to examine the beneficial effects of miR-206 treatment during the early changes in skeletal muscle atrophy, and to study the underlying signaling pathways in a rat skeletal muscle atrophy model. MATERIAL AND METHODS The rat denervation-induced skeletal muscle atrophy model was established. miRNA-206 was overexpressed with or without TGF-β1 inhibitor in the rats. The mRNA and protein expression of HDAC4, TGF-β1, and Smad3 was determined by real-time PCR and western blot. The gastrocnemius muscle cross-sectional area and relative muscle mass were measured. MyoD1, TGF-β1, and Pax7 were determined by immunohistochemical staining. RESULTS After sciatic nerve surgical transection, basic muscle characteristics, such as relative muscle weight, deteriorated continuously during a 2-week period. Injection of miR-206 (30 μg/rat) attenuated morphological and physiological deterioration of muscle characteristics, prevented fibrosis effectively, and inhibited the expression of TGF-β1 and HDAC4 as assessed 2 weeks after denervation. Moreover, miR-206 treatment increased the number of differentiating (MyoD1+/Pax7+) satellite cells, thereby protecting denervated muscles from atrophy. Interestingly, the ability of miR-206 to govern HDAC4 expression and to attenuate muscle atrophy was weakened after pharmacological blockage of the TGF-b1/Smad3 axis. CONCLUSIONS TGF-β1/Smad3 signaling pathway is one of the crucial signaling pathways by which miR-206 counteracts skeletal muscle atrophy by affecting proliferation and differentiation of satellite cells. miR-206 may be a potential

  9. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... intestine . The digestive system removes and processes nutrients ( vitamins , minerals , carbohydrates , fats, proteins , and water) from foods ... a microscope to see whether they contain cancer. Bypass : Surgery to allow food in the small intestine ...

  10. Small intestine contrast injection (image)

    Science.gov (United States)

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  11. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  12. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  13. Small intestinal bacterial overgrowth syndrome

    Institute of Scientific and Technical Information of China (English)

    Jan; Bures; Jiri; Cyrany; Darina; Kohoutova; Miroslav; Frstl; Stanislav; Rejchrt; Jaroslav; Kvetina; Viktor; Vorisek; Marcela; Kopacova

    2010-01-01

    Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There...

  14. Nature gives us strength: exposure to nature counteracts ego-depletion.

    Science.gov (United States)

    Chow, Jason T; Lau, Shun

    2015-01-01

    Previous research rarely investigated the role of physical environment in counteracting ego-depletion. In the present research, we hypothesized that exposure to natural environment counteracts ego-depletion. Three experiments were conducted to test this hypothesis. In Experiment 1, initially depleted participants who viewed pictures of nature scenes showed greater persistence on a subsequent anagram task than those who were given a rest period. Experiment 2 expanded upon this finding by showing that natural environment enhanced logical reasoning performance after ego-depleting task. Experiment 3 adopted a two- (depletion vs. no-depletion) -by-two (nature exposure vs. urban exposure) factorial design. We found that nature exposure moderated the effect of depletion on anagram task performance. Taken together, the present studies offer a viable and novel strategy to mitigate the negative impacts of ego-depletion.

  15. Apoptosis in skeletal muscle and its relevance to atrophy

    Institute of Scientific and Technical Information of China (English)

    Esther E Dupont-Versteegden

    2006-01-01

    Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

  16. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    Directory of Open Access Journals (Sweden)

    Michael P Wiggs

    2015-03-01

    Full Text Available Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase, the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning.

  17. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K.; Yamadori, A. [Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575 Sendai (Japan); Constans, J.M.; Courtheoux, P.; Theron, J. [MR Unit, University of Caen School of Medicine, Caen (France); Viader, F. [Department of Neuroradiology, University of Caen School of Medicine, Caen (France)

    2000-06-01

    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  18. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sluimer, Jasper D. [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Diagnostic Radiology and Alzheimer Centre, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); Karas, Giorgos B.; Barkhof, Frederik [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); Schijndel, Ronald van [VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Informatics, Amsterdam (Netherlands); Barnes, Josephine; Boyes, Richard G. [UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Cover, Keith S. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands); Olabarriaga, Silvia D. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam (Netherlands); Fox, Nick C. [VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Vrenken, Hugo [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2009-12-15

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 {+-} 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  19. The University of the Third Age as an institution counteracting marginalization of older people

    Directory of Open Access Journals (Sweden)

    Aleksandra Marcinkiewicz

    2011-12-01

    Full Text Available The article presents the role of the University of the Third Age in counteracting the effects of marginalization of the elderly. The history of the University of the Third Age is presented and also different models of this institution are characterized. The paper presents new trends in research conducted by participants of the U3A and shown their relation to marginalization

  20. More reflectivity for the soil to counteract the global-warming of the Earth

    OpenAIRE

    Tejedor, A; Pacheco, A. F.

    2009-01-01

    It is argued that a dedicated effort to increase the reflectivity of the surface of our planet by means of, for example, metallic plates would induce an increase in the global albedo which would counteract in part the present global-warming process of the Earth. This could alleviate the urgency of reducing the CO2 emissions. The City of Zaragoza (Spain) is chosen to illustrate the likelihood of our arguments.

  1. Muscle ring finger 1 mediates cardiac atrophy in vivo.

    Science.gov (United States)

    Willis, Monte S; Rojas, Mauricio; Li, Luge; Selzman, Craig H; Tang, Ru-Hang; Stansfield, William E; Rodriguez, Jessica E; Glass, David J; Patterson, Cam

    2009-04-01

    Pathological cardiac hypertrophy, induced by various etiologies such as high blood pressure and aortic stenosis, develops in response to increased afterload and represents a common intermediary in the development of heart failure. Understandably then, the reversal of pathological cardiac hypertrophy is associated with a significant reduction in cardiovascular event risk and represents an important, yet underdeveloped, target of therapeutic research. Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific protein, inhibits the development of experimentally induced pathological; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression. This prompted us to investigate the role of MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy regression after reversal of transaortic constriction (TAC) reversal and 2) dexamethasone-induced atrophy. Using echocardiographic, histological, and gene expression analyses, we found that upon TAC release, cardiac mass and cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately 70% less than in wild type mice in the 4 wk after release. This was in striking contrast to wild-type mice, who returned to baseline cardiac mass and cardiomyocyte size within 4 days of TAC release. Despite these differences in atrophic remodeling, the transcriptional activation of cardiac hypertrophy measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to dexamethasone-induced cardiac atrophy, as determined by echocardiographic analysis. This study demonstrates, for the first time, that MuRF1 is essential for cardiac atrophy in vivo, both in the setting of therapeutic

  2. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

    Directory of Open Access Journals (Sweden)

    Charlotte Hiroux

    2016-06-01

    Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

  3. In COS cells Vpu can both stabilize tetherin expression and counteract its antiviral activity.

    Science.gov (United States)

    Waheed, Abdul A; Kuruppu, Nishani D; Felton, Kathryn L; D'Souza, Darren; Freed, Eric O

    2014-01-01

    The interferon-inducible cellular protein tetherin (CD317/BST-2) inhibits the release of a broad range of enveloped viruses. The HIV-1 accessory protein Vpu enhances virus particle release by counteracting this host restriction factor. While the antagonism of human tetherin by Vpu has been associated with both proteasomal and lysosomal degradation, the link between Vpu-mediated tetherin degradation and the ability of Vpu to counteract the antiviral activity of tetherin remains poorly understood. Here, we show that human tetherin is expressed at low levels in African green monkey kidney (COS) cells. However, Vpu markedly increases tetherin expression in this cell line, apparently by sequestering it in an internal compartment that bears lysosomal markers. This stabilization of tetherin by Vpu requires the transmembrane sequence of human tetherin. Although Vpu stabilizes human tetherin in COS cells, it still counteracts the ability of tetherin to suppress virus release. The enhancement of virus release by Vpu in COS cells is associated with a modest reduction in cell-surface tetherin expression, even though the overall expression of tetherin is higher in the presence of Vpu. This study demonstrates that COS cells provide a model system in which Vpu-mediated enhancement of HIV-1 release is uncoupled from Vpu-mediated tetherin degradation.

  4. Aging and the intestine

    Institute of Scientific and Technical Information of China (English)

    Laurie Drozdowski; Alan BR Thomson

    2006-01-01

    Over the lifetime of the animal, there are many changes in the function of the body's organ systems. In the gastrointestinal tract there is a general modest decline in the function of the esophagus, stomach, colon,pancreas and liver. In the small intestine, there may be subtle alterations in the intestinal morphology, as well as a decline in the uptake of fatty acids and sugars.The malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2) or dexamethasone.Modifications in the type of lipids in the diet will influence the intestinal absorption of nutrients: for example, in mature rats a diet enriched with saturated as compared with polysaturated fatty acids will enhance lipid and sugar uptake, whereas in older animals the opposite effect is observed. Thus, the results of studies of the intestinal adaptation performed in mature rats does not necessarily apply in older animals. The age-associated malabsorption of nutrients that occurs with aging may be one of the several factors which contribute to the malnutrition that occurs with aging.

  5. Intestinal Complications of IBD

    Science.gov (United States)

    ... increases with the duration and severity of the disease. A link between colorectal cancer and Crohn’s disease is less strong, but it applies more to ... usually effective in the replacement of nutrients. BILE SALT DIARRHEA ... in Crohn’s disease. This is the principal area for intestinal absorption ...

  6. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian

    2010-01-01

    for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons...... dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help...

  7. Bilaterally impaired hand dexterity with posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Nages Nagaratnam, MD, FRACP, FRCPA, FACC

    2015-12-01

    Full Text Available A 79-year- old man presented with bilaterally impaired hand movements pertaining to handling of objects although hand movements without the use of objects were preserved, findings consistent with tactile apraxia. His hand and finger movements were slow and clumsy. He had an isolated optic ataxia, a component of Balint's syndrome. The computed tomography scan showed enlargement of the posterior horns of the lateral ventricles. He had recurrent falls probably owing to visual attentional deficits, which may be present in patients with posterior cortical atrophy. The findings can be deemed to fall within the posterior cortical atrophy spectrum. The underlying mechanisms are discussed.

  8. From alveolar diffuse atrophy to aggressive periodontitis: a brief history.

    Science.gov (United States)

    Guzeldemir, Esra; Toygar, Hilal Uslu

    2006-01-01

    Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end.

  9. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations.

    Science.gov (United States)

    Lev-Sagie, Ahinoam

    2015-09-01

    Vulvovaginal atrophy is a common condition associated with decreased estrogenization of the vaginal tissue. Symptoms include vaginal dryness, irritation, itching, soreness, burning, dyspareunia, discharge, urinary frequency, and urgency. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is approximately 50%. Despite the high prevalence and the substantial effect on quality of life, vulvovaginal atrophy often remains underreported and undertreated. This article aims to review the physiology, clinical presentation, assessment, and current recommendations for treatment, including aspects of effectiveness and safety of local vaginal estrogen therapies.

  10. Mechanisms of Muscle Growth and Atrophy in Mammals and Drosophila

    Science.gov (United States)

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L.

    2014-01-01

    The loss of skeletal muscle mass (atrophy) that accompanies disuse and systemic diseases is highly debilitating. Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. In this review, we highlight the outstanding unsolved questions that may benefit from a combination of studies in both flies and mammals. In particular, we discuss how different environmental stimuli and signaling pathways influence muscle mass and strength and how a variety of disease states can cause muscle wasting. PMID:24038488

  11. Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

    Science.gov (United States)

    Fernández-Rodríguez, Camino; González-Reimers, Emilio; Quintero-Platt, Geraldine; de la Vega-Prieto, María José; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

    2016-11-01

    Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis

  12. Brain atrophy and lesion load predict long term disability in multiple sclerosis

    DEFF Research Database (Denmark)

    Popescu, Veronica; Agosta, Federica; Hulst, Hanneke E

    2013-01-01

    To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).......To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS)....

  13. Genetics Home Reference: spinal muscular atrophy with respiratory distress type 1

    Science.gov (United States)

    ... Home Health Conditions SMARD1 spinal muscular atrophy with respiratory distress type 1 Enable Javascript to view the expand/ ... All Close All Description Spinal muscular atrophy with respiratory distress type 1 ( SMARD1 ) is an inherited condition that ...

  14. Interaction between food components, intestinal microbiota and intestinal mucosa as a function of intestinal health

    NARCIS (Netherlands)

    Venema, K.; Sandt, H. van de

    2003-01-01

    Interaction between food components, intestinal microbiota and intestinal mucosa was studied as a function of intestinal health. A microbiota was found to be important for the onset and progression of inflammatory diseases. Studies revealed a prominent effect of micro-organisms on the gene expressio

  15. Proteomic changes of the porcine small intestine in response to chronic heat stress.

    Science.gov (United States)

    Cui, Yanjun; Gu, Xianhong

    2015-12-01

    Acute heat stress (HS) negatively affects intestinal integrity and barrier function. In contrast, chronic mild HS poses a distinct challenge to animals. Therefore, this study integrates biochemical, histological and proteomic approaches to investigate the effects of chronic HS on the intestine in finishing pigs. Castrated male crossbreeds (79.00 ± 1.50 kg BW) were subjected to either thermal neutral (TN, 21 °C; 55% ± 5% humidity; n=8) or HS conditions (30 °C; 55% ± 5% humidity; n=8) for 3 weeks. The pigs were sacrificed after 3 weeks of high environmental exposure and the plasma hormones, the intestinal morphology, integrity, and protein profiles of the jejunum mucosa were determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS damaged intestinal morphology, increased plasma d-lactate concentrations and decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis of the jejunum mucosa was conducted by 2D gel electrophoresis and mass spectrometry. Fifty-three intestinal proteins were found to be differentially abundant, 18 of which were related to cell structure and motility, and their changes in abundance could comprise intestinal integrity and function. The down-regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron transport chain (ETC), and oxidative phosphorylation suggested that chronic HS impaired energy metabolism and thus induced oxidative stress. Moreover, the changes of ten proteins in abundance related to stress response and defense indicated pigs mediated long-term heat exposure and counteracted its negative effects of heat exposure. These findings have important implications for understanding the effect of chronic HS on intestines.

  16. Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies

    Directory of Open Access Journals (Sweden)

    Elijah Mak

    2015-01-01

    Conclusions: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.

  17. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    Science.gov (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  18. Is the Supraspinatus Muscle Atrophy Truly Irreversible after Surgical Repair of Rotator Cuff Tears?

    Science.gov (United States)

    Chung, Seok Won; Kim, Sae Hoon; Tae, Suk-Kee; Yoon, Jong Pil; Choi, Jung-Ah

    2013-01-01

    Background Atrophy of rotator cuff muscles has been considered an irreversible phenomenon. The purpose of this study is to evaluate whether atrophy is truly irreversible after rotator cuff repair. Methods We measured supraspinatus muscle atrophy of 191 patients with full-thickness rotator cuff tears on preoperative magnetic resonance imaging and postoperative multidetector computed tomography images, taken at least 1 year after operation. The occupation ratio was calculated using Photoshop CS3 software. We compared the change between pre- and postoperative occupation ratios after modifying the preoperative occupation ratio. In addition, possible relationship between various clinical factors and the change of atrophy, and between the change of atrophy and cuff integrity after surgical repair were evaluated. Results The mean occupation ratio was significantly increased postoperatively from 0.44 ± 0.17 to 0.52 ± 0.17 (p atrophy (more than a 10% increase in occupation ratio) and 33 (17.3%) worsening (more than a 10% decrease). Various clinical factors such as age tear size, or initial degree of atrophy did not affect the change of atrophy. However, the change of atrophy was related to repair integrity: cuff healing failure rate of 48.5% (16 of 33) in worsened atrophy; and 22.2% (18 of 81) in improved atrophy (p = 0.007). Conclusions The supraspinatus muscle atrophy as measured by occupation ratio could be improved postoperatively in case of successful cuff repair. PMID:23467404

  19. Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy*

    Science.gov (United States)

    Ebert, Scott M.; Dyle, Michael C.; Kunkel, Steven D.; Bullard, Steven A.; Bongers, Kale S.; Fox, Daniel K.; Dierdorff, Jason M.; Foster, Eric D.; Adams, Christopher M.

    2012-01-01

    Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the stress-inducible, pro-atrophy transcription factor ATF4. We show that Gadd45a is required for skeletal muscle atrophy induced by three distinct skeletal muscle stresses: fasting, muscle immobilization, and muscle denervation. Conversely, forced expression of Gadd45a in muscle or cultured myotubes induces atrophy in the absence of upstream stress. We show that muscle-specific ATF4 knock-out mice have a reduced capacity to induce Gadd45a mRNA in response to stress, and as a result, they undergo less atrophy in response to fasting or muscle immobilization. Interestingly, Gadd45a is a myonuclear protein that induces myonuclear remodeling and a comprehensive program for muscle atrophy. Gadd45a represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes. As a result, Gadd45a reduces multiple barriers to muscle atrophy (including PGC-1α, Akt activity, and protein synthesis) and stimulates pro-atrophy mechanisms (including autophagy and caspase-mediated proteolysis). These results elucidate a critical stress-induced pathway that reprograms muscle gene expression to cause atrophy. PMID:22692209

  20. Intestinal ascariasis in children.

    Science.gov (United States)

    Wani, Imtiaz; Rather, Muddasir; Naikoo, Ghulam; Amin, Abid; Mushtaq, Syed; Nazir, Mir

    2010-05-01

    Ascariasis is a staggering health problem commonly seen in children of endemic areas. In the abdomen, ascaris lumbricoides can cause a myriad of surgical complications. Intestinal obstruction by ascaris lumbricoides is commonly seen in children. Most cases are managed conservatively. The purpose was to study the clinical presentation and management of symptomatic intestinal ascariasis in children. A 3-year study was performed from April 2006 to April 2009 of pediatric-age patients who had symptomatic intestinal ascariasis. All patients had detailed clinical history, examination, plain X-ray of abdomen, and ultrasonography of abdomen. Peroperative findings were recorded in all patients who had surgical intervention. This prospective study had 360 patients. Male to female ratio was 1.37:1. 187 patients (52%) presented within 2-4 days of duration of illness. Mean +/- standard deviation (SD) age of patients was 6.35 +/- 2.25 years. Age group of 4-7 years (80%) was commonest group affected. Abdominal pain was a leading symptom in 357 patients (99%) with the pain in periumbilical area present in 215 patients (60%). In 227 patients (63%) abdominal distension was seen and was the commonest physical finding. Palpable worm masses were seen in 129 patients (36%); 81 patients (63%) had palpable worm masses in the umbilical quadrant. On X-ray of abdomen, visible worm masses were seen in 83 patients (23%). Abdominal sonography showed interloop fluid in 177 patients (49%) and free fluid in the pelvis of 97 patients (27%). The number of patients who were managed conservatively was 281 (78%), and 79 patients (22%) had surgical intervention. In patients who had surgical intervention, 39 patients (49%) had enterotomy and 7 patients (9%) had kneading of worms. Postoperative complications occurred in 33 patients, and an overall mortality of 1% (1 patient) was seen. Ascaridial intestinal obstruction is common in children in the Kashmir. Abdominal pain is the leading symptom in

  1. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    Science.gov (United States)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  2. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008; Mercur

  3. Pigmented paravenous chorioretinal atrophy with Coat′s like response

    Directory of Open Access Journals (Sweden)

    Manish Tandon

    2013-01-01

    Full Text Available Pigmented paravenous chorioretinal atrophy (PPCRA is an uncommon retinal disorder of unknown etiology that is neither well understood nor classified. We report an atypical case of PPCRA, associated with Coat′s like response (CLR in a 64-year-old man of Asian origin. Both the eyes were involved, though asymmetrically.

  4. Best practice guidelines for molecular analysis in spinal muscular atrophy

    NARCIS (Netherlands)

    Scheffer, H; Cobben, JM; Matthijs, G; Wirth, B

    With a prevalence of approximately 1/10 000, and a carrier frequency of 1/40-1/60 the proximal spinal muscular atrophies (SMAs) are among the most frequent autosomal recessive hereditary disorders. Patients can be classified clinically into four groups: acute, intermediate, mild, and adult (SMA

  5. Tubular atrophy in the pathogenesis of chronic kidney disease progression.

    Science.gov (United States)

    Schelling, Jeffrey R

    2016-05-01

    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  6. Brain atrophy at onset and physical disability in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2012-10-01

    Full Text Available The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003. DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

  7. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008;

  8. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.

    2011-01-01

    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  9. Atrophy of the Parietal Lobe in Preclinical Dementia

    Science.gov (United States)

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  10. Reversible Altered Consciousness and Brain Atrophy Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A 5-year-old female child with valproic acid (VPA-related alteration of consciousness and brain atrophy that progressed over a 3 day period and resolved within 12 hours of discontinuing VPA is reported from Dokkyo University School of Medicine and Shimotsuga General Hospital, Tochigi, Japan.

  11. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-06-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.

  12. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Science.gov (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  13. CT findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

    Energy Technology Data Exchange (ETDEWEB)

    Tokiguchi, Susumu; Kurashima, Akihiko; Tsuchiya, Toshiaki; Ito, Jusuke; Naito, Haruhiko; Nagai, Hiroko; Wakabayashi, Masatoshi; Morita, Masahiro

    1987-12-01

    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) has recently been recognized as a clinicopathological entity. It may be defined as a multisystem degenerative disease of dominant inheritance, and characterized clinically by a combination of epilepsy, myoclonus, ataxia, dementia, and choreo-athetosis. This paper reports on the CT findings of ten patients (in four families) with DRPLA. In two families, the diagnosis was established on the basis of the clinicopathological findings, while in the other two, the diagnosis was made clinically. Although the CT findings were not identical in all patients, some degree of atrophic change was always observed in the cerebellum, brainstem, and cerebral cortex. Cerebellar atrophy was always accompanied by a dilatation of the fourth ventricle. Midbrain atrophy was characterized by a prominent tegmental atrophy and aqueductal dilatation, such as is seen in progressive supranuclear palsy. Of the four patients over 40 years of age, three had a diffuse hypodensity of the cerebral white matter on CT. To our knowledge, there have been no previous reports on this hypodensity in patients with spino-cerebellar degeneration or Huntington's chorea. CT may be helpful in the differential diagnosis of progressive neuro-degenerative disorders.

  14. Epidural anaesthesia in a child with possible spinal muscular atrophy

    NARCIS (Netherlands)

    Veen, A; Molenbuur, B; Richardson, FJ

    2002-01-01

    Spinal muscular atrophy (SMA) is a rare lower motor neurone disease in which anaesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. Neuraxial anaesthesia is controversial in these patients; however, some cases have been reporte

  15. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J

    2014-01-01

    OBJECTIVE: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). METHODS: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  16. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    J. Raaphorst; M.J. van Tol; P.F.C. Groot; E. Altena; Y.D. van der Werf; C.B. Majoie; A.J. van der Kooi; L.H. van den Berg; B. Schmand; M. de Visser; D.J. Veltman

    2014-01-01

    Objective: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). Methods: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  17. Cardiac pathology in spinal muscular atrophy : a systematic review

    NARCIS (Netherlands)

    Wijngaarde, C A; Blank, A C; Stam, M; Wadman, R I; van den Berg, L H; van der Pol, W L

    2017-01-01

    BACKGROUND: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual

  18. Impact of diaphragm muscle fiber atrophy on neuromotor control.

    Science.gov (United States)

    Mantilla, Carlos B; Sieck, Gary C

    2013-11-01

    In skeletal muscles, motor units comprise a motoneuron and the group of muscle fibers innervated by it, which are usually classified based on myosin heavy chain isoform expression. Motor units displaying diverse contractile and fatigue properties are important in determining the range of motor behaviors that can be accomplished by a muscle. Muscle fiber atrophy and weakness may disproportionately affect specific fiber types across a variety of diseases or clinical conditions, thus impacting neuromotor control. In this regard, fiber atrophy that affects a specific fiber type will alter the relative contribution of different motor units to overall muscle structure and function. For example, in various diseases there is fairly selective atrophy of type IIx and/or IIb fibers comprising the strongest yet most fatigable motor units. As a result, there is muscle weakness (i.e., reductions in force per cross-sectional area) associated with an apparent improvement in resistance to fatiguing contractions. This review will examine neuromotor control of respiratory muscles such as the diaphragm muscle and the impact of muscle fiber atrophy on motor performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Epidural anaesthesia in a child with possible spinal muscular atrophy

    NARCIS (Netherlands)

    Veen, A; Molenbuur, B; Richardson, FJ

    2002-01-01

    Spinal muscular atrophy (SMA) is a rare lower motor neurone disease in which anaesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. Neuraxial anaesthesia is controversial in these patients; however, some cases have been reporte

  20. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.

    2011-01-01

    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  1. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect

    Directory of Open Access Journals (Sweden)

    Sue Ling Wan

    2015-01-01

    Full Text Available An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson’s syndrome.

  2. Benefits of Laser Therapy in Postmenopausal Vaginal Atrophy

    Science.gov (United States)

    Brînzan, Daniela; Pǎiuşan, Lucian; Daşcǎu, Voicu; Furǎu, Gheorghe

    2011-08-01

    Maybe the worst aspect of menopause is the decline of the quality of the sexual life. The aim of the study is to demonstrate the beneficial effects of laser therapy in comparison with topical application of estrogen preparations, for the treatment of vaginal atrophy and sexual dysfunctions induced by menopause. A total of 50 menopausal patients were examined during a one year period. The methods used for objectifying vaginal atrophy and sexual dysfunctions were history taking, local clinical exam and PAP smear. From this group, 40 patients had vaginal atrophy with sexual dysfunctions. They have been treated differently, being included in four groups: patients treated with local estrogens, patients treated with intravaginal laser therapy, patients treated with both laser therapy and estrogens, patients treated with estrogens and placebo laser therapy. Therapeutic benefit, improvement of vaginal atrophy and quality of sexual life, were objectified by anamnesis (questionnaire), local and general clinical examination and PAP smear. The best results have been obtained, by far, in the 3rd group, followed by the women treated only with laser. In conclusion, we can say that laser therapy is the best way for solving the sexual inconveniences of menopause.

  3. Skeletal muscle training for spinal muscular atrophy type 3

    NARCIS (Netherlands)

    Bartels, Bart; Montes, Jacqueline; van der Pol, W. Ludo; de Groot, Janke F.

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of skeletal muscle training on functional performance in people with spinal muscular atrophy (SMA) type 3 and to identify any adverse effects.

  4. Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

    Science.gov (United States)

    Al-Saqi, Shahla H; Uvnäs-Moberg, Kerstin; Jonasson, Aino F

    2015-09-01

    To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy. Double-blinded randomised controlled trial. Healthy post-menopausal women in Stockholm, Sweden. Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden. The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation. The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089). Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy. © The Author(s) 2015.

  5. Atrophy of the Parietal Lobe in Preclinical Dementia

    Science.gov (United States)

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  6. Intestinal Malakoplakia in Children

    Directory of Open Access Journals (Sweden)

    Fatemeh Mahjoub

    2008-04-01

    Full Text Available Objective: Malakoplakia is a rare inflammatory disease, related to enterobacterial infection in the context of a disorder of cell-mediated immunity. Malakoplakia is exceptional in children and usually involves the gastrointestinal tract. The diagnosis is exclusively based on histological analysis.Cases Presentation: In this paper we have reported 3 children with intestinal malakoplakia which were enrolled during a period of 6 years between 2001 to 2006 at Childrens Medical Center. Two were male, and one female. The main clinical manifestations were: chronic bloody and mucosal diarrhea, abdominal pain and polypoid masses detected by diagnostic colonoscopy. Histological diagnosis proved to be definite in these cases. The response to drug treatment with trimethoprim-sulfamthoxazole in all three patients was good. Conclusion: The presence of intestinal malakoplakia must be ruled out in every child having chronic bloody mucosal diarrhea.

  7. Intestinal sugar transport

    Institute of Scientific and Technical Information of China (English)

    Laurie A Drozdowski; Alan BR Thomson

    2006-01-01

    Carbohydrates are an important component of the diet.The carbohydrates that we ingest range from simple monosaccharides (glucose, fructose and galactose) to disaccharides (lactose, sucrose) to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane (BBM) of enterocytes. For example, lactase-phloridzin hydrolase and sucraseisomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.

  8. Small intestinal transplantation.

    LENUS (Irish Health Repository)

    Quigley, E M

    2012-02-03

    The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

  9. Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma.

    Science.gov (United States)

    Yamamoto, Takaya; Kadoya, Noriyuki; Takeda, Ken; Matsushita, Haruo; Umezawa, Rei; Sato, Kiyokazu; Kubozono, Masaki; Ito, Kengo; Ishikawa, Yojiro; Kozumi, Maiko; Takahashi, Noriyoshi; Katagiri, Yu; Onishi, Hiroshi; Jingu, Keiichi

    2016-05-26

    Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC). A total of 14 patients (11 males, 3 females) who received SBRT for RCC at Tohoku University Hospital between April 2010 and February 2014 were analyzed. The median serum creatinine level was 1.1 mg/dl and two patients had a single kidney. Nine patients were implanted with fiducial markers. The median tumor diameter was 30 mm. SBRT was delivered at 70 Gy in 10 fractions for 7 tumors, at 60 Gy in 10 fractions for 2 tumors, and at 50 Gy in 10 fractions for 5 tumors with 6 and/or 15 MV X-ray using 5 to 8 multi-static beams. Renal atrophy was assessed using post-SBRT CT images after 12-24 months intervals. Correlations were examined by Spearman rank correlation analysis. Differences between two groups were evaluated by the Mann-Whitney test, and pairwise comparisons were made by the Wilcoxon signed-rank test. The median tumor volume shrunk from 14.8 cc to 10.6 cc (p = 0.12), and the median irradiated kidney volume changed from 160.4 cc to 137.1 cc (p atrophy (p = 0.02). Significant renal atrophic change was observed. Dose distribution of SBRT at 20-30 Gy had a strong correlation with renal atrophy when irradiation was performed in 10 fractions.

  10. Pseudo-obstrucción intestinal por miopatía visceral esporádica Intestinal pseudo-obstruction due to sporadic visceral myopathy

    Directory of Open Access Journals (Sweden)

    Pedro Montalvo

    2004-12-01

    Full Text Available Se presenta el caso infrecuente de un paciente con miopatía visceral esporádica y afectación de la totalidad del tracto gastrointestinal y de la vía urinaria. La miopatía visceral es una forma de pseudo-obstrucción intestinal crónica idiopática caracterizada por degeneración vacuolar, atrofia y fibrosis de la capa muscular propia de la pared intestinal, sin células inflamatorias. Se puede presentar en niños y adolescentes afectando la musculatura visceral digestiva y urinaria. La manifestación familiar se encuentra en aproximadamente el 30% de los casos y se transmite de forma autosómica recesiva en la mayoría de las familias. Es fundamental descartar causas secundarias de pseudo-obstrucción intestinal crónica y la realización de biopsia de todo el espesor de la pared gastrointestinal para poder arribar al diagnóstico. El tratamiento quirúrgico sólo es eficaz en los que tienen afectación de porciones aisladas del tubo digestivo.We report an unusual case of a patient with sporadic visceral myopathy and involvement of the entire gastrointestinal and urinary tract. Visceral myopathy is a form of chronic idiophatic intestinal pseudo-obstruction characterized by vacuolar degeneration, atrophy and fibrosis of the intestinal propia muscle layer without inflammatory cells. It can be found in childhood and adolescence affecting the gastrointestinal and urinary visceral muscle. The familial occurrence can be found in about 30% of cases and the mode of transmission is autosomal recessive in most families. It is crucial to exclude secondary forms of chronic intestinal pseudo-obstruction and to obtain full thickness intestinal biopsy for the diagnosis. Surgical treatment is only beneficial in cases with isolated segmental involvement of the gastrointestinal tract.

  11. Osteoporosis in patients with intestinal insufficiency and intestinal failure

    DEFF Research Database (Denmark)

    Nygaard, Louis; Skallerup, Anders; Olesen, Søren Schou

    2017-01-01

    BACKGROUND & AIMS: Intestinal insufficiency and intestinal failure are associated with malabsorption of micro- and macronutrients that may negatively influence bone metabolism and increase the risk for developing osteoporosis. However, information regarding prevalence and contribution of individual...... risk factors is scarce. We investigated the prevalence of osteoporosis in patients with intestinal insufficiency and intestinal failure and identified associated risk factors. METHODS: This was a retrospective cross-sectional study including 167 clinically stable outpatients with intestinal...... insufficiency or intestinal failure. Bone mineral density (BMD) was measured by dual X-ray absorptiometry and the prevalence of osteoporosis was compared to a gender and age matched population. Several clinical and demographic parameters, including body mass index (BMI), vitamin-D, smoking habits...

  12. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Shuichi Segawa

    Full Text Available Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-µm filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P, a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 µg improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin β1-p38 MAPK.

  13. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

    Directory of Open Access Journals (Sweden)

    Takahiko Kawamura

    2016-02-01

    Full Text Available Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR, albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

  14. Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

    Science.gov (United States)

    Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

    2016-12-01

    Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain.

  15. Counteracting ammonia inhibition during anaerobic digestion by recovery using submersible microbial desalination cell

    DEFF Research Database (Denmark)

    Zhang, Yifeng; Angelidaki, Irini

    2015-01-01

    Ammonia inhibition is one of the most frequent and serious problems in biogas plants. In this study, a novel hybrid system consisting of a submersible microbial desalination cell (SMDC) and a continuous stirred tank reactor (CSTR) was developed for counteracting ammonia inhibition during anaerobic...... digestion (AD) with simultaneous in situ ammonia recovery and electricity production. The SMDC was powered by acetate in a buffer solution, while synthetic ammonia-rich wastewater was used as the feeding of the CSTR. Under continuous operation, ammonia recovery rate of 86 g-N/m2 /day and current density...

  16. Herpes simplex virus 1 counteracts viperin via its virion host shutoff protein UL41.

    Science.gov (United States)

    Shen, Guanghui; Wang, Kezhen; Wang, Shuai; Cai, Mingsheng; Li, Mei-li; Zheng, Chunfu

    2014-10-01

    The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.

  17. Semi-Supervised Learning Techniques in AO Applications: A Novel Approach To Drift Counteraction

    Science.gov (United States)

    De Vito, S.; Fattoruso, G.; Pardo, M.; Tortorella, F.; Di Francia, G.

    2011-11-01

    In this work we proposed and tested the use of SSL techniques in the AO domain. The SSL characteristics have been exploited to reduce the need for costly supervised samples and the effects of time dependant drift of state-of-the-art statistical learning approaches. For this purpose, an on-field recorded one year long atmospheric pollution dataset has been used. The semi-supervised approach benefitted from the use of updated unlabeled samples, adapting its knowledge to the slowly changing drift effects. We expect that semi-supervised learning can provide significant advantages to the performance of sensor fusion subsystems in artificial olfaction exhibiting an interesting drift counteraction effect.

  18. Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

    DEFF Research Database (Denmark)

    Fusi, Elenora; Rebucci, Raffaella; Pecorini, Chiara

    2010-01-01

    The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity....... Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that α...

  19. Microbes, intestinal inflammation and probiotics.

    Science.gov (United States)

    Khan, Mohammad W; Kale, Amod A; Bere, Praveen; Vajjala, Sriharsha; Gounaris, Elias; Pakanati, Krishna Chaitanya

    2012-02-01

    Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic balance among the intestinal immune compartment, epithelium and microbiota. Owing to the emergence of IBD as a major cause of morbidity and mortality, great efforts have been put into understanding the sequence of intestinal inflammatory events. Intestinal macrophages and dendritic cells act in a synergistic fashion with intestinal epithelial cells and microbiota to initiate the triad that governs the intestinal immune responses (whether inflammatory or regulatory). In this review, we will discuss the interplay of intestinal epithelial cells, bacteria and the innate immune component. Moreover, whether or not genetic intervention of probiotic bacteria is a valid approach for attenuating/mitigating exaggerated inflammation and IBD will also be discussed.

  20. Chronic intestinal pseudo-obstruction associated with enteric ganglionitis in a Persian cat

    Directory of Open Access Journals (Sweden)

    Jeremy Mortier

    2016-06-01

    Full Text Available Case summary A 7-year-old neutered male Persian cat was presented for acute vomiting and inappetence. Physical examination revealed severe abdominal distension. Radiographs demonstrated pneumoperitoneum, megaoesophagus and generalised gaseous distension of the digestive tract. Exploratory coeliotomy was performed, revealing markedly distended and thickened small and large intestines with no observable peristalsis. No intestinal perforation was present. Bacteriological and cytological analysis of abdominal fluid revealed a septic peritonitis involving Pasteurella multocida. Full-thickness intestinal biopsies demonstrated lymphocytic ganglioneuritis localised to the enteric nervous system, in association with glandular atrophy and muscular layer hypertrophy. Amoxicillin-clavulanate and analgesics were given. The cat’s general condition gradually improved after the addition of pyridostigmine bromide (0.5 mg/kg q12h PO, initiated 3 days postsurgery. Vomiting resolved and did not recur. Follow-up radiographs at 15 days, and 1 and 6 months showed persistent intestinal ileus, milder than on the pretreatment radiographs. Thirty months after presentation the cat is still alive, without clinical signs, and receives 1 mg/kg q12h pyridostigmine. Relevance and novel information To our knowledge, this is the first case of ganglioneuritis of the myenteric plexus described in cats, as well as the first one successfully treated with pyridostigmine. Chronic intestinal pseudo-obstruction is a very rare condition in cats but should be included in the differential diagnosis of generalised gastrointestinal ileus.

  1. Dynamic Foot Pressure as a Countermeasure to Muscle Atrophy

    Science.gov (United States)

    Kyparos, A.; Layne, C. S.; Martinez, D. A.; Clarke, M. S. F.; Feeback, D. L.

    2002-01-01

    Mechanical unloading of skeletal muscle (SKM) as a consequence of space flight or ground-based analogues, such as human bedrest and rodent hindlimb suspension (HLS) models, induces SKM atrophy particularly affecting the anti-gravity musculature of the lower limbs. In the context of manned space flight, the subsequent loss of muscle strength and functionality will pose operational implications jeopardizing mission success. Exercise, currently the primary muscle degradation countermeasure, has not proven completely effective in preventing muscle atrophy. It is therefore imperative that some other forms of in- flight countermeasure be also developed to supplement the prescribed exercise regimen the astronauts follow during spaceflight. Previous work in both humans and rats has shown that mechanical stimulation of the soles of the feet increases neuromuscular activation in the lower limb musculature and that such stimulation results in the limited prevention of atrophy in the soleus muscle of unloaded rats. This study was designed to investigate the effect of cutaneous mechanoreceptor stimulation on hindlimb unloading- induced SKM atrophy in rats. It was hypothesized that mechanical stimulation of the plantar surface of the rat foot during hindlimb suspension (HLS), utilizing a novel stimulation paradigm known as Dynamic Foot Pressure (DFP), would attenuate unloading-induced SKM atrophy. Mature adult male Wistar rats were randomly assigned to four groups of 10 rats each as follows: sedentary controls (Ctrl), hindlimb suspended only (HLS), hindlimb suspended wearing an inflatable boot (HLS-IFL) and hindlimb suspended rats wearing a non-inflatable boot (HLS-NIFL). The stimulation of mechanoreceptors was achieved by applying pressure to the plantar surface of the foot during the 10-day period of HLS using a custom-built boot. The anti-atrophic effects of DFP application was quantified directly by morphological (muscle wet weight, myofiber cross-sectional area

  2. Progressive Brain Atrophy in Super-refractory Status Epilepticus.

    Science.gov (United States)

    Hocker, Sara; Nagarajan, Elanagan; Rabinstein, Alejandro A; Hanson, Dennis; Britton, Jeffrey W

    2016-10-01

    Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking. To document and quantify the development of atrophy over time in SRSE. This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015. Change in VBR (ΔVBR) as a percentage of the starting measure. Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was

  3. Glucagon-like peptide 2 treatment may improve intestinal adaptation during weaning

    DEFF Research Database (Denmark)

    Thymann, Thomas; Le Huërou-Luron, I; Petersen, Y M;

    2014-01-01

    Transition from sow’s milk to solid feed is associated with intestinal atrophy and diarrhea. We hypothesized that the intestinotrophic hormone glucagon-like peptide 2 (GLP-2) would induce a dose- and health status-dependent effect on gut adaptation. In Exp. 1, weaned pigs (average BW at weaning 4......) were kept in a low-sanitary environment, leading to weaning diarrhea, and injected with saline or short-acting GLP-2 (200 µg/(kg BW·12 h); n = 11). Treatment with GLP-2 increased goblet cell density (P

  4. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  5. Autofrettage to Counteract Coefficient of Thermal Expansion Mismatch in Cryogenic Pressurized Pipes with Metallic Liners

    Science.gov (United States)

    Wen, Ed; Barbero, Ever; Tygielski, Phlip; Turner, James E. (Technical Monitor)

    2001-01-01

    Composite feedlines with metal liners have the potential to reduce weight/cost while providing the same level of permeation resistance and material compatibility of all-metal feedlines carrying cryogenic propellants in spacecraft. The major technical challenges are the large difference in Coefficient of Thermal Expansion between the liner and the composite, and the manufacturing method required to make a very thin liner with the required strength and dimensional tolerance. This study investigates the use of autofrettage (compressive preload) to counteract Coefficient of Thermal Expansion when pre-pressurization procedures cannot be used to solve this problem. Promising materials (aluminum 2219, Inconel 718, nickel, nickel alloy) and manufacturing techniques (chemical milling, electroplating) are evaluated to determine the best liner candidates. Robust, autofrettaged feedlines with a low Coefficient of Thermal Expansion liner (Inconel 718 or nickel alloy) are shown to successfully counteract mismatch at LOX temperature. A new concept, autofrettage by temperature, is introduced for high Coefficient of Thermal Expansion materials (aluminum and pure nickel) where pressure cannot be used to add compressive preload.

  6. Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.

    Science.gov (United States)

    Guignandon, Alain; Faure, Céline; Neutelings, Thibaut; Rattner, Aline; Mineur, Pierre; Linossier, Marie-Thérèse; Laroche, Norbert; Lambert, Charles; Deroanne, Christophe; Nusgens, Betty; Demets, René; Colige, Alain; Vico, Laurence

    2014-09-01

    Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects. © FASEB.

  7. Piracetam counteracts the effects of amitriptyline on inhibitory avoidance in CD1 mice.

    Science.gov (United States)

    Everss, Estrella; Arenas, M Carmen; Vinader-Caerols, Concepción; Monleón, Santiago; Parra, Andrés

    2005-04-30

    The purpose of the present work was to study the effects of amitriptyline on animal cognition in relation to some characteristics of its therapeutic effects. The modulation of acute and chronic effects of amitriptyline on inhibitory avoidance in male and female mice by piracetam was investigated. In Experiment 1, mice were subjected to the training phase of inhibitory avoidance conditioning 60 min after acute piracetam (100 mg/kg) or physiological saline administration. Immediately after the behavioural task, they received a single injection of the tricyclic antidepressant amitriptyline (30 mg/kg) or physiological saline. Twenty-four hours later, subjects were tested for avoidance. In Experiment 2, the same doses of amitriptyline and piracetam were chronically administered. Mice were subjected to the training phase of inhibitory avoidance on the 22nd day, and to the test phase 24 h later. Forty-five minutes after test, subjects explored the elevated plus-maze for 5 min in order to assess whether the effects of amitriptyline on avoidance performance may reflect general behavioural changes. Results obtained were that: (a) acute and chronic amitriptyline impaired inhibitory avoidance of male and female mice, (b) piracetam counteracted the effect of acutely administered amitriptyline on inhibitory avoidance, and (c) piracetam counteracted the effects of chronically administered amitriptyline in males but not females in the same learning task. These effects do not seem to be mediated by non-specific drug effects on spontaneous motor activity or anxiety.

  8. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  9. Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor.

    Science.gov (United States)

    Iwasaki, Yusaku; Dezaki, Katsuya; Kumari, Parmila; Kakei, Masafumi; Yada, Toshihiko

    2015-08-01

    Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism.

  10. Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

    Directory of Open Access Journals (Sweden)

    Natalia Cadaxo Rochael

    2013-09-01

    Full Text Available Leishmania parasites expose phosphatidylserine (PS on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.

  11. Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1

    Institute of Scientific and Technical Information of China (English)

    JIANG Hong-wei; ZHU Han-yu; WANG Jian-zhong; FU Bo; L(U) Yang; HONG Quan; XIE Yuan-sheng; CHEN Xiang-mei

    2011-01-01

    Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits matrix metalloproteinase (MMP) activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate (0.4 mmol/L),in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 (Pl-3) kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1's action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.

  12. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

    2015-03-06

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

  13. Elenoside increases intestinal motility

    Institute of Scientific and Technical Information of China (English)

    E Navarro; SJ Alonso; R Navarro; J Trujillo; E Jorge

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaphthalene lignan from Justicia hyssopifolia, on gastrointestinal motility in vivo and in vitro in rats.METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses,intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanolplant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg),cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2× 10-4, 6.4 × 10-4 and 1.2 × 10-3 mol/L, and cisapride at 10-6 mol/L were investigated.RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase.Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride.CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs.Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain.

  14. Neuro-Behcet's disease showing severe atrophy of the cerebrum.

    Science.gov (United States)

    Miyakawa, T; Murayama, E; Deshimaru, M; Shikai, I; Kozuma, S

    1976-03-15

    A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.

  15. Spinal muscular atrophy: development and implementation of potential treatments.

    Science.gov (United States)

    Arnold, W David; Burghes, Arthur H M

    2013-09-01

    In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

  16. Crustaceans as a model for microgravity-induced muscle atrophy

    Science.gov (United States)

    Mykles, D. L.

    1996-01-01

    Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein meatabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca2(+) -dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

  17. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

    DEFF Research Database (Denmark)

    Ipharraguerre, Ignacio R; Tedó, Gemma; Menoyo, David

    2013-01-01

    Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve.......05) but did not affect plasma GLP-1 and feed intake. The intestinal expression of glucagon-like peptide 2 receptor, sodium-dependent bile acid transporter, farnesoid X receptor, and guanosine protein-coupled bile acid receptor genes were not affected by CDC treatment. The intragastric administration of CDC...... did not alter the weight and length of the intestine, yet increased the activation of caspase-3 in ileal villi (P affect any of the variables that were measured. Our results show that the enteral...

  18. Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers.

    Science.gov (United States)

    Quiroz, Yakeel T; Stern, Chantal E; Reiman, Eric M; Brickhouse, Michael; Ruiz, Adriana; Sperling, Reisa A; Lopera, Francisco; Dickerson, Bradford C

    2013-05-01

    Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI. To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset. 40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions. Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe. Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD.

  19. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Martina Bocchetta

    2016-01-01

    Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

  20. [Association of post-radiation focal muscular atrophy and hypertrophy].

    Science.gov (United States)

    Serratrice, G; Sangla, I; Pouget, J; Azulay, J P

    1993-01-01

    We report a 48 year old woman who had radiotherapy for uterine carcinoma and who developed amyotrophy and muscle hypertrophy in one lower limb. Very few cases of post-radiation monomelic amyotrophy have been reported. On the other hand denervation hypertrophy was presumed to be well known. The seat of the lesions was presumed to be radicular and spinal. The mechanism of atrophy and hypertrophy is discussed.

  1. MR imaging of psychosurgery: rostral atrophy following stereotacic subcaudate tractotomy.

    Science.gov (United States)

    Cauley, K A; Waheed, W; Salmela, M; Filippi, C G

    2010-11-01

    There are few reports of MR imaging findings following psychosurgery. Here, we report the findings of 3T MR imaging of the sequelae of stereotactic subcaudate tractotomy (SST). Rostral atrophy is noted on conventional imaging. Diffusion tensor (DT) tractography demonstrated no communicating white matter tracts between the inferior frontal lobes, which appeared normally as thick fibre bundles in age-matched controls. DT tractography provides a unique tool for the evaluation of sequelae of ablative psychosurgical procedures.

  2. Phenytoin-induced cerebellar atrophy in an epileptic boy

    Directory of Open Access Journals (Sweden)

    Nithin Kumar

    2013-01-01

    Full Text Available Epilepsy is an important health problem due to its high prevalence and potential for causing long-term morbidity. It is commonly treated in children with phenytoin sodium. It has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity. Here, we report a case of phenytoin-induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the hospital with a viral infection.

  3. Optic atrophy and cerebral infarcts caused by methanol intoxication: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, H.H. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chen, C.Y. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chen, F.H. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Lee, C.C. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chou, T.Y. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Zimmerman, R.A. [Children`s Hospital of Philadelphia, PA (United States). Dept. of Radiology

    1997-03-01

    We present the MRI findings of cerebral and optic pathway damage in the acute and subacute stages of methanol intoxication. In the acute stage, CT and MRI showed bilateral haemorrhagic necrosis of the corpus striatum and infarcts in the anterior and middle cerebral arterial territories. MRI in the subacute stage demonstrated atrophy of the optic chiasm and prechiasmatic optic nerves in addition to the cerebral infarcts. The patient survived, with total blindness. (orig.)

  4. The treatment of postmenopausal vaginal atrophy with ovestin

    NARCIS (Netherlands)

    Kicovic, P.M.; Cortesprieto, J.; Milojevic, S.; Haspels, A.A.; Aljinovic, A.

    1980-01-01

    Seventy-four postmenopausal women presenting with vaginal atrophy were treated with either Ovestin® vaginal cream (Group A, 23 women: 1 mg/day E3; Group B, 30 women: 0.5 mg/day E3) or vaginal suppositories (Group C, 21 women: 0.5 mg/day E3), applied daily for 3 wk (A and B) or 2 wk (C) before

  5. Intermittent acceleration as a countermeasure to soleus muscle atrophy

    Science.gov (United States)

    D'Aunno, Dominick S.; Robinson, Ronald R.; Smith, Gregory S.; Thomason, Donald B.; Booth, Frank W.

    1992-01-01

    The effectiveness of using intermittent acceleration as a countermeasure to muscle atrophy was investigated in rats subjected to 7 days of hindlimb suspension interrupted by daily periods of 1.2 g acceleration, for 15-min periods evenly spaced over 12-hr interval. It was found that this regimen, when repeated for 7 days, failed to completely maintain the mass of soleus muscle, which was 84 percent of control.

  6. Interactive segmentation for geographic atrophy in retinal fundus images

    OpenAIRE

    Lee, Noah; SMITH, R. THEODORE; Laine, Andrew F.

    2008-01-01

    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12–21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of patho...

  7. Regulation of muscle atrophy in aging and disease.

    Science.gov (United States)

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  8. Liver Cirrhosis and Intestinal Bacterial Translocation

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

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

  9. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. Copyright © 2016 the American Physiological Society.

  10. Masticatory muscles of mouse do not undergo atrophy in space.

    Science.gov (United States)

    Philippou, Anastassios; Minozzo, Fabio C; Spinazzola, Janelle M; Smith, Lucas R; Lei, Hanqin; Rassier, Dilson E; Barton, Elisabeth R

    2015-07-01

    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50-90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.

  11. Hippocampal complex atrophy in poststroke and mild cognitive impairment.

    Science.gov (United States)

    Selnes, Per; Grambaite, Ramune; Rincon, Mariano; Bjørnerud, Atle; Gjerstad, Leif; Hessen, Erik; Auning, Eirik; Johansen, Krisztina; Almdahl, Ina S; Due-Tønnessen, Paulina; Vegge, Kjetil; Bjelke, Börje; Fladby, Tormod

    2015-11-01

    To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.

  12. Thymus atrophy and regeneration following dexamethasone administration to beef cattle.

    Science.gov (United States)

    Cannizzo, F T; Spada, F; Benevelli, R; Nebbia, C; Giorgi, P; Brina, N; Bollo, E; Biolatti, B

    2010-08-28

    Thymus atrophy and regeneration were studied in 13- to 22-month-old beef calves treated with dexamethasone (DMT), using anabolic dosages and implementing different withdrawal times. Two trials were conducted. In trial 1, group A (n=6) received 0.7 mg/day DMT orally for 40 days, group B (n=6) received 1.4 mg/day orally for 40 days and group C (n=6) was the control. In trial 2, group D (n=6) received 0.7 mg/day DMT orally for 40 days, group E (n=6) received 1.4 mg/day orally for 40 days and group K (n=6) was the control. DMT withdrawal times before slaughter were six days (groups A and B) and 26 days (groups D and E). At slaughter, thymus atrophy was severe and progressive in animals from groups A and B. In contrast, thymus weight and volume of the animals from groups D and E were almost normal. Slight atrophy was also detected in the calves in these groups. Histological changes and Ki67 immunostaining revealed a large number of positive lymphoid cells, mostly in the cortical area, associated with higher expression of apoptosis in the medulla compared with controls. This demonstrated that the thymus of beef cattle is still able to regenerate following DMT administration.

  13. Preprosthetic and implantological surgery in patients with severe maxillary atrophy.

    Science.gov (United States)

    González-García, Raúl; Naval-Gías, Luís; Muñoz-Guerra, Mario Fernando; Sastre-Pérez, Jesús; Rodríguez-Campo, Francisco José; Gil-Díez-Usandizaga, José Luís

    2005-01-01

    To evaluate the success of the osseointegration of dental implants in patients with severe maxillary atrophy after sinus lift augmentation and onlay graft surgery with autologous bone grafts. A descriptive and analytic study of 27 patients with severe maxillary atrophy and partial or total edentulism, after 4 years follow-up. All cases underwent to autologous bone graft sinus lift augmentation with or without onlay grafts in the anterior maxillae. After this, reconstruction with osseointegrated implants was performed. After the follow-up period, 89.1% of implants were osseointegrated and loaded. Anterior iliac crest bone graft provides good results with respect to implant osseointegration. The achievement of two surgical procedures for bone grafts surgery and implants surgery, separated 2 or more months, provides better results for osseointegration in comparison to a sole surgical procedure (p<0.01). Implants survival predictability is greater when a second surgical procedure is performed, once bone grafts have experimented an appropriate consolidation. The use of onlay graft and sinus lift augmentation techniques is useful in the resolution of complex problems such as the severe maxillary atrophy.

  14. Changes of Intestinal Permeability in Cholelithiasis Patients

    Institute of Scientific and Technical Information of China (English)

    Shao-long Sun; Shuo-dong Wu; Dong-xu Cui; Bao-lin Liu; Xian-wei Dai

    2009-01-01

    @@ In normal condition,intestine mucosa possesses barrier function.When the barrier function of intestine mucosa was damaged,intestinal bacteria,endotoxin,or other substances would enter blood.It is generally accepted that biliary bacteria origins from the intestine either via duodenal papilla or intestinal mucosa.In this study,we aimed to investigate the intestinal permeability changes of cholelithiasis patients to elucidate the possible pathogenesis of cholelithiasis.

  15. Insights into regulatory molecules of intestinal epithelial cell turnover during experimental infection by Heterophyes heterophyes.

    Science.gov (United States)

    Ashour, Dalia S; Othman, Ahmad A; Radi, Dina A

    2014-08-01

    Heterophyiasis is an intestinal disease that remains endemic in many parts of the world, particularly the Nile Delta of Egypt and Southeast Asia, yet the populations at risk of infection expand throughout the world. The main histopathological feature of infection is villous atrophy, but the underlying factors are not well understood. Apoptosis of the villous epithelial cells was previously reported to be enhanced during intestinal parasitic infections; however, the role of Heterophyes heterophyes on enterocyte apoptosis was to be explored. Therefore, intestinal sections from mice experimentally infected with H. heterophyes were studied histopathologically and immunohistochemically for caspase-3 and NF-κB and compared to non-infected control mice. Atrophic villi covered by poorly differentiated epithelial cells were observed in the 2nd week post-infection. Also, we noted marked hyperplasia of the intestinal crypts with abundant inflammatory cellular infiltrate in the lamina propria, as well as apoptosis of cells lining the intestinal villi. Both caspase-3 and NF-κB showed positive staining in the intestinal epithelial cells with varying grades of intensity over the length of infection. Caspase-3 expression rose at the 2nd week p.i. then decreased over time, whereas NF-κB expression showed progressive increase throughout the weeks of infection. In conclusion, caspase-3 activation may be an important factor in the apoptotic pathway in early heterophyiasis, and, on the other hand, NF-κB seems to play a role in protecting the intestinal cells from excessive apoptosis. These observations may help open new avenues for tissue protective therapies that avoid or control the deleterious processes of apoptosis in various inflammatory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Exercise, Intestinal Absorption, and Rehydration

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ KEYPOINTS 1. The proximal small intestine (duodenum & jejunum) is the primary site of fluid absorption. It absorbs about 50% to 60% of any given fluid load. The colon or large intestine absorbs approximately 80 to 90% of the fluid it receives, but accounts for only about 15% of the total fluid load.

  17. MDCT in blunt intestinal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy)]. E-mail: stefromano@libero.it; Scaglione, Mariano [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Tortora, Giovanni [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Martino, Antonio [Trauma Center, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Di Pietto, Francesco [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Romano, Luigia [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Grassi, Roberto [Department ' Magrassi-Lanzara' , Section of Radiology, Second University of Naples, 80138 Naples (Italy)

    2006-09-15

    Injuries to the small and large intestine from blunt trauma represent a defined clinical entity, often not easy to correctly diagnose in emergency but extremely important for the therapeutic assessment of patients. This article summarizes the MDCT spectrum of findings in intestinal blunt lesions, from functional disorders to hemorrhage and perforation.

  18. Intestinal failure in obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Stelios F. Assimakopoulos; Constantine E. Vagianos; Aristides Charonis; Vassiliki N. Nikolopoulou; Chrisoula D. Scopa

    2005-01-01

    @@ TO THE EDITOR We read with great interest the article by Ding LA and LiJS, which aimed to review the current knowledge on the physiology of normal intestinal barrier function and highlight the role of intestinal failure after various injurious insults in the development of septic complications or multiple organ failure with subsequent rapid clinical deterioration or even death.

  19. Feasibility of the Medial Temporal lobe Atrophy index (MTAi and derived methods for measuring atrophy of the medial temporal lobe

    Directory of Open Access Journals (Sweden)

    Francisco eConejo Bayón

    2014-11-01

    Full Text Available Introduction: the Medial Temporal-lobe Atrophy index (MTAi, 2D-Medial Temporal Atrophy (2D-MTA, yearly rate of MTA (yrRMTA and yearly rate of relative MTA (yrRMTA are simple protocols for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. Albeit preliminary studies showed interest of these methods in the diagnosis of AD, FTLD and correlation with cognitive impairment in PD, formal feasibility and validity studies remained pending. As a first step, we aimed to assess the feasibility. Mainly, we aimed to assess the reproducibility of measuring the areas needed to compute these indices. We also aimed to assess the efforts needed to start using these methods correctly. Methods: a series of 290 1.5T-MRI studies from 230 subjects ranging 65-85 years old who had been studied for cognitive impairment were used in this study. Six inexperienced tracers (IT plus one experienced tracer (ET traced the three areas needed to compute the indices. Finally, tracers underwent a short survey on their experience learning to compute the MTAi and experience of usage, including items relative to training time needed to understand and apply the MTAi, time to perform a study after training and overall satisfaction. Results: learning to trace the areas needed to compute the MTAi and derived methods is quick and easy. Results indicate very good intrarater ICC for the MTAi, good intrarater ICC for the 2D-MTA, yrMTA and yrRMTA and also good interrater ICC for the MTAi, 2D-MTA, yrMTA and yrRMTA.Conclusion: our data support that MTAi and derived methods (2D-MTA, yrMTA and yrRTMA have good to very good intrarater and interrater reproducibility and may be easily implemented in clinical practice even if new users have no experience tracing the area of regions of interest.

  20. Analysis of voxel-based rCBF in patients with olivopontocerebellar atrophy of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Sang Ho; Kim, Jae Woo [School of Medicine, Dong-A University, Busan (Korea, Republic of)

    2004-07-01

    Olivopontocerebellar Atrophy (OPCA) is one phenotype of multiple system atrophy (MSA) and is characterized neuropathologically by neuronal degeneration in the inferior olives, pons and cerebellar cortex. The diagnosis of OPCA requires clinical evaluation to exclude other diseases. And it's usually supported by atrophy of the cerebellum and brainstem visualized on CT or MRI. But there are some reports that the disease can occur without demonstrable atrophy in these anatomic studies. There are only a few reports about perfusion SPECT imaging in patients with OPCA. The aim of this study was to describe voxel-based rCBF of OPCA in comparison of healthy volunteers. We studied 5 patients with OPCA (1 men, 4 women: age 50.4{+-}9.6y) and age matched 13 healthy volunteers (4 men, 9 women: age 54.9{+-}6.6y). All subjects injected 20mCi of Tc-99m HMPAO and scanning was initiated 20 min after injection. Images were analyzed using SPM (SPM99) with Matlab 5.3. On visual analysis, in 3 patients with OPCA, SPECT image showed significant hypoperfusion in the cerebellum. In another 2 patients, diffuse hypoperfusion was found in the both cerebro-cerebellar hemispheres, untypical perfusion pattern in OPCA. So there is existed limitation to diagnosis by only visual analysis. On SPM analysis, in OPCA patients significantly decreased perfusion was present in culmen, tonsil, tuber in Lt. cerebellum and declive, tonsil, pyramid and inf. Semi-lunar lobule in Rt. cerebellum, Rt. inf. frontal gyrus and Rt. temporal lobe (p<0.001, uncorrected). We also performed individual analysis with SPM. Two of 5 patients have additional hypoperfusion brain lesions. In one patient, decreased perfusion found in Lt. temporal, both occipital lobe, Lt. parahippocampal gyrus. In another patient, decreased perfusion found in both frontal and parietal lobe. This study is one of a few trials analysis with SPM for OPCA. We defined the specific location of decreased perfusion in patients with OPCA.

  1. Testicular atrophy following paediatric primary orchidopexy: A prospective study.

    Science.gov (United States)

    Durell, J; Johal, N; Burge, D; Wheeler, R; Griffiths, M; Kitteringham, L; Stanton, M; Manoharan, S; Steinbrecher, H; Malone, P; Griffin, S J

    2016-08-01

    With the Nordic consensus statement advocating orchidopexy at an earlier age, the present study sought to investigate the outcomes of primary paediatric orchidopexy at a tertiary UK centre. To prospectively assess testicular atrophy following primary orchidopexy for undescended testes in a paediatric population. Secondary outcomes were complication rates and whether outcomes were dependent on grade of operating surgeon. Prospective data regarding age at operation, classification of the undescended testis, length of follow-up, and subjective comparison of intraoperative and postoperative testicular volumes compared with the contralateral testis were collected. Testicular atrophy was defined as >50% loss of testicular volume or a postoperative testicular volume atrophy occurred in 2.6% of cases. There was no reported testicular re-ascent. All secondary acquired cases underwent a previous ipsilateral hernia repair. There was no significant difference in outcomes comparing the grade of surgeon (consultant n = 8, trainee/staff-grade surgeon n = 7-8). There was a trend towards postoperative catch-up growth in approximately one fifth of cases. Previous studies have reported a testicular atrophy rate of 5%. The present study reported a similar rate of 2.6%. In agreement with a previous publication, it was also found that testicular atrophy was not dependent on the grade of operating surgeon. The mechanism for testicular catch-up growth is not well understood. Animal studies have supported the hypothesis that increased temperature has a detrimental effect on testicular volume. However, follow-up in the present cohort was short (median 6.9 months), making interpretation of this finding difficult. It is acknowledged that clinical palpation alone to determine testicular volume potentially introduces intra-observer and inter-observer error. However, prospective studies using ultrasound to determine testicular volumes following orchidopexy have reported catch-up growth. This

  2. Protein deficiency alters impact of intestinal nematode infection on intestinal, visceral and lymphoid organ histopathology in lactating mice.

    Science.gov (United States)

    Starr, Lisa M; Odiere, Maurice R; Koski, Kristine G; Scott, Marilyn E

    2014-05-01

    Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2 × 2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.

  3. Generalized megaviscera of lupus: Refractory intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus

    Institute of Scientific and Technical Information of China (English)

    Frederick D Park; Jeffrey K Lee; Ganga D Madduri; Pradipta Ghosh

    2009-01-01

    Dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus (SLE). Chronic intestinal pseudoobstruction (CIPO) resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation (megacholedochus). While the molecular pathogenesis is largely unknown, observed histopathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis. High dose immunosuppression usually results in resolution of symptoms with recovery of smooth muscle function, indicative of an autoimmune etiology. We report a patient with SLE who presented with intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus, and present images that illustrate megaviscera simultaneously involving all 3 visceral organs. Since the co-manifestation of all 3 is unusual and has been reported only once previously, we have termed this rare clinical syndrome generalized megaviscera of lupus (GML). Although the SLE disease-activity parameters responded to aggressive immunomodulative therapy in our patient, clinical evidence of peristaltic dysfunction persisted in all involved viscera. This is a variation from the favorable outcomes reported previously in SLE patients with GML and we attribute this poor clinical outcome to disease severity and, most importantly, delayed clinical presentation. Since inflammation followed by atrophy and fibrosis are key aspects in the pathogenesis and natural history of GML, the poor response in our patient who presented late in the clinical course irreversible end-stage fibrosis. Thus, early recognition and timely initiation of treatment may be the key to recover visceral peristaltic function in patients with GML.

  4. [Treatment of children with intestinal failure: intestinal rehabilitation, home parenteral nutrition or small intestine transplantation?

    NARCIS (Netherlands)

    Neelis, E.G.; Oers, H.A. van; Escher, J.C.; Damen, G.M.; Rings, E.H.; Tabbers, M.M.

    2014-01-01

    Intestinal failure is characterised by inadequate absorption of food or fluids, which is caused by insufficient bowel surface area or functioning. Children with chronic intestinal failure are dependent on parenteral nutrition (PN), which can be provided at home (HPN). In the Netherlands, HPN for chi

  5. Counteracting the climate effects of volcanic eruptions using short-lived greenhouse gases

    Science.gov (United States)

    Fuglestvedt, Jan S.; Samset, Bjørn H.; Shine, Keith P.

    2014-12-01

    A large volcanic eruption might constitute a climate emergency, significantly altering global temperature and precipitation for several years. Major future eruptions will occur, but their size or timing cannot be predicted. We show, for the first time, that it may be possible to counteract these climate effects through deliberate emissions of short-lived greenhouse gases, dampening the abrupt impact of an eruption. We estimate an emission pathway countering a hypothetical eruption 3 times the size of Mount Pinatubo in 1991. We use a global climate model to evaluate global and regional responses to the eruption, with and without counteremissions. We then raise practical, financial, and ethical questions related to such a strategy. Unlike the more commonly discussed geoengineering to mitigate warming from long-lived greenhouse gases, designed emissions to counter temporary cooling would not have the disadvantage of needing to be sustained over long periods. Nevertheless, implementation would still face significant challenges.

  6. In-vivo experimental demonstration that hyperhistaminism counteracts tumor-growth.

    Science.gov (United States)

    Dellarovere, F; Broccio, G; Granata, A; Fimiani, V

    1994-01-01

    Induction of hyperhistaminism in peritoneum of rats by daily intraperitoneal supply of 0.005 mu g of histamine, counteracts the growth of 10(3) Yoshida ascite sarcoma cells only if administration precedes inoculation of tumor cells and has a long duration. Treating animals for two weeks before tumor cell inoculation we observed significant 70% survival, that was increased to 80% continuing the supply for 20-days after the inoculation; treatment for 3 days before or 20 days after the inoculation did not show significant results. The condition created in rat peritoneum is similar to that in allergic people, and our data in animals confirm statistical data observed in allergic people showing decreased incidence of neoplastic disease due to histamine, that appears to be integrated in a highly potent immunoregulatory circuit.

  7. Malaysian adolescent students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience

    Science.gov (United States)

    Kuldas, Seffetullah; Hashim, Shahabuddin; Ismail, Hairul Nizam

    2015-01-01

    The adolescence period of life comes along with changes and challenges in terms of physical and cognitive development. In this hectic period, many adolescents may suffer more from various risk factors such as low socioeconomic status, substance abuse, sexual abuse and teenage pregnancy. Findings indicate that such disadvantaged backgrounds of Malaysian adolescent students lead to failure or underachievement in their academic performance. This narrative review scrutinises how some of these students are able to demonstrate academic resilience, which is satisfactory performance in cognitive or academic tasks in spite of their disadvantaged backgrounds. The review stresses the need for developing a caregiving relationship model for at-risk adolescent students in Malaysia. Such a model would allow educators to meet the students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience. PMID:25663734

  8. Malaysian adolescent students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience.

    Science.gov (United States)

    Kuldas, Seffetullah; Hashim, Shahabuddin; Ismail, Hairul Nizam

    2015-01-02

    The adolescence period of life comes along with changes and challenges in terms of physical and cognitive development. In this hectic period, many adolescents may suffer more from various risk factors such as low socioeconomic status, substance abuse, sexual abuse and teenage pregnancy. Findings indicate that such disadvantaged backgrounds of Malaysian adolescent students lead to failure or underachievement in their academic performance. This narrative review scrutinises how some of these students are able to demonstrate academic resilience, which is satisfactory performance in cognitive or academic tasks in spite of their disadvantaged backgrounds. The review stresses the need for developing a caregiving relationship model for at-risk adolescent students in Malaysia. Such a model would allow educators to meet the students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience.

  9. Desalted duck egg white peptides promote calcium uptake by counteracting the adverse effects of phytic acid.

    Science.gov (United States)

    Hou, Tao; Liu, Weiwei; Shi, Wen; Ma, Zhili; He, Hui

    2017-03-15

    The structure of the desalted duck egg white peptides-calcium chelate was characterized by fluorescence spectroscopy, fourier transform infrared spectroscopy, and dynamic light scattering. Characterization results showed structural folding and aggregation of amino acids or oligopeptides during the chelation process. Desalted duck egg white peptides enhanced the calcium uptake in the presence of oxalate, phosphate and zinc ions in Caco-2 monolayers. Animal model indicated that desalted duck egg white peptides effectively enhanced the mineral absorption and counteracted the deleterious effects of phytic acid. These findings suggested that desalted duck egg white peptides might promote calcium uptake in three pathways: 1) desalted duck egg white peptides bind with calcium to form soluble chelate and avoid precipitate; 2) the chelate is absorbed as small peptides by enterocyte; and 3) desalted duck egg white peptides regulate the proliferation and differentiation of enterocytes through the interaction with transient receptor potential vanilloid 6 calcium channel.

  10. Disentangling the counteracting effects of water content and carbon mass on zooplankton growth

    DEFF Research Database (Denmark)

    Mcconville, Kristian; Atkinson, Angus; Fileman, Elaine S.

    2017-01-01

    Zooplankton vary widely in carbon percentage (carbon mass as a percentage of wet mass), but are often described as either gelatinous or non-gelatinous. Here we update datasets of carbon percentage and growth rate to investigate whether carbon percentage is a continuous trait, and whether its...... time series at station L4 off Plymouth, UK. This showed separate biomass peaks for gelatinous and crustacean taxa, however, carbon percentage varied 8-fold within the gelatinous group. Species with high carbon mass had lower carbon percentage, allowing separation of the counteracting effects...... of these two variables on growth rate. Specific growth rates, g (d -1) were negatively related to carbon percentage and carbon mass, even in the gelatinous taxa alone, suggesting that the trend is not driven by a categorical difference between these groups. The addition of carbon percentage doubled...

  11. A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila.

    Science.gov (United States)

    Xu, Li; He, Jianzheng; Kaiser, Andrea; Gräber, Nikolas; Schläger, Laura; Ritze, Yvonne; Scholz, Henrike

    2016-01-01

    Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling-the serotonin transporter-in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.

  12. Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress.

    Science.gov (United States)

    Chylack, L T; Tung, W; Harding, R

    1986-01-01

    Heretofore, the intracellular accumulation of sorbitol has been associated exclusively with deleterious (cataractogenic) changes in the lens. This study demonstrates a beneficial role for the sorbitol pathway in the rabbit lens, namely that of counteracting extracellular, glucose-derived, osmotic stress with the intracellular production of osmotically active sorbitol. Large and sudden increases in the extracellular glucose concentration lead to dehydration of the lens, a response that can be diminished by intracellular sorbitol and fructose production. These results are discussed in light of the impact (beneficial/detrimental) of aldose reductase inhibitors on the lens. Sugar cataract formation appears to result from continuous, rather than cyclical, activity of a pathway which normally may have a protective function in the lens.

  13. Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.

    Science.gov (United States)

    Misgeld, Thomas; Kummer, Terrance T; Lichtman, Jeff W; Sanes, Joshua R

    2005-08-02

    Synaptic organizing molecules and neurotransmission regulate synapse development. Here, we use the skeletal neuromuscular junction to assess the interdependence of effects evoked by an essential synaptic organizing protein, agrin, and the neuromuscular transmitter, acetylcholine (ACh). Mice lacking agrin fail to maintain neuromuscular junctions, whereas neuromuscular synapses differentiate extensively in the absence of ACh. We now demonstrate that agrin's action in vivo depends critically on cholinergic neurotransmission. Using double-mutant mice, we show that synapses do form in the absence of agrin provided that ACh is also absent. We provide evidence that ACh destabilizes nascent postsynaptic sites, and that one major physiological role of agrin is to counteract this "antisynaptogenic" influence. Similar interactions between neurotransmitters and synaptic organizing molecules may operate at synapses in the central nervous system.

  14. Stevioside counteracts the alpha-cell hypersecretion caused by long-term palmitate exposure

    DEFF Research Database (Denmark)

    Hong, J; Chen, L; Jeppesen, P B;

    2006-01-01

    Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

  15. Voluntary exercise counteracts Aβ25-35-induced memory impairment in mice.

    Science.gov (United States)

    Wang, Qin; Xu, Zhiqiang; Tang, Jinrong; Sun, Jianguo; Gao, Junying; Wu, Ting; Xiao, Ming

    2013-11-01

    Exercise has been shown to enhance hippocampus-related cognition and slow the progression of Alzheimer's disease (AD). However, whether voluntary exercise directly decreases the neurotoxicity of amyloid peptide (Aβ) needs to be determined. In the present study, two-month old male C57bl/6 mice were intracerebroventricularly injected with Aβ25-35, and then allowed for voluntary exercise for 12 days. Y-maze test revealed that voluntary exercise mitigated spatial memory impairment induced by Aβ25-35. Consistently, Aβ25-35 treated mice with exercise showed reduced neuronal degeneration and synaptic protein loss in the hippocampus compared with sedentary controls. Moreover, voluntary exercise significantly ameliorated oxidative stress markers and increased vessel branches in the hippocampus of Aβ25-35 treated mice. Our results suggest that voluntary exercise counteracts the neurotoxicity of Aβ by reducing oxidative stress and increasing angiogenesis, which may underlie the beneficial effect of exercise on AD.

  16. Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

    Science.gov (United States)

    Ostadhadi, Sattar; Rahmatollahi, Mahdieh; Dehpour, Ahmad-Reza; Rahimian, Reza

    2015-03-01

    Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.

  17. Extending the GMR Current Measurement Range with a Counteracting Magnetic Field

    Directory of Open Access Journals (Sweden)

    Tin Yan Poon

    2013-06-01

    Full Text Available Traditionally, current transformers are often used for current measurement in low voltage (LV electrical networks. They have a large physical size and are not designed for use with power electronic circuits. Semiconductor-based current sensing devices such as the Hall sensor and Giant Magnetoresistive (GMR sensor are advantageous in terms of small size, high sensitivity, wide frequency range, low power consumption, and relatively low cost. Nevertheless, the operational characteristics of these devices limit their current measurement range. In this paper, a design based on using counteracting magnetic field is introduced for extending the GMR current measurement range from 9 A (unipolar to ±45 A. A prototype has been implemented to verify the design and the linear operation of the circuit is demonstrated by experimental results. A microcontroller unit (MCU is used to provide an automatic scaling function to optimize the performance of the proposed current sensor.

  18. Significance and usefulness of heart rate variability in patients with multiple system atrophy.

    Science.gov (United States)

    Furushima, Hiroshi; Shimohata, Takayoshi; Nakayama, Hideaki; Ozawa, Tetsutaro; Chinushi, Masaomi; Aizawa, Yoshifusa; Nishizawa, Masatoyo

    2012-04-01

    The purpose of this study was to investigate whether heart rate variability parameters can be useful for evaluating cardiac autonomic dysfunction in multiple system atrophy patients. Both the time and frequency domains of heart rate variability were investigated among 17 multiple system atrophy patients and 27 normal control subjects. All time- and frequency-domain measures, except the low- to high-frequency ratio, were significantly lower in multiple system atrophy patients than in controls. In multiple system atrophy patients, there were significant inverse correlations between heart rate variability parameters and disease duration, as well as disease severity, but heart rate variability parameters were not affected by other autonomic dysfunctions. The cardiac autonomic state of multiple system atrophy was characterized by decreases in both sympathetic and parasympathetic tones. Because heart rate variability parameters were not affected by other autonomic dysfunctions, this may be a useful method for evaluating cardiac autonomic dysfunction in multiple system atrophy. Copyright © 2012 Movement Disorder Society.

  19. β-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals.

    Science.gov (United States)

    Fletcher, Evan; Villeneuve, Sylvia; Maillard, Pauline; Harvey, Danielle; Reed, Bruce; Jagust, William; DeCarli, Charles

    2016-04-01

    Recent literature has examined baseline hippocampal volume and extent of brain amyloidosis to test potential synergistic effects on worsening cognition and extent of brain atrophy. Use of hippocampal volume in prior studies was based on the notion that limbic circuit degeneration is an early manifestation of the Alzheimer's Disease (AD) pathophysiology. To clarify these interactions early in the AD process, we tested the effects of amyloid and baseline normalized hippocampal volume on longitudinal brain atrophy rates in a group of cognitively normal individuals. Results showed that the combination of elevated β-amyloid and baseline hippocampal atrophy is associated with increased rates specific to the limbic circuit and splenium. Importantly, this atrophy pattern emerged from a voxelwise analysis, corroborated by regression models over region of interests in native space. The results are broadly consistent with previous studies of the effects of amyloid and baseline hippocampal atrophy in normals, while pointing to accelerated atrophy of AD-vulnerable regions detectable at the preclinical stage.

  20. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    Science.gov (United States)

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  1. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Scioli

    Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

  2. Impulse control in the dorsolateral prefrontal cortex counteracts post-diet weight regain in obesity.

    Science.gov (United States)

    Weygandt, Martin; Mai, Knut; Dommes, Esther; Ritter, Kerstin; Leupelt, Verena; Spranger, Joachim; Haynes, John-Dylan

    2015-04-01

    A variety of studies suggest that efficient treatments to induce short-term dietary success in obesity exist. However, sustained maintenance of reduced weight is rare as a large proportion of patients start to regain weight when treatment is discontinued. Thus, from a clinical perspective, it would be desirable to identify factors that counteract post-diet weight regain across longer time-scales. To address this question, we extended our previous work on neural impulse control mechanisms of short-term dietary success in obesity and now investigated the mechanisms counteracting long-term weight regain after a diet. Specifically, we measured neural impulse control during a delay discounting task with fMRI at two time points, i.e. the beginning ('T0') and the end ('T12') of a one-year follow-up interval after a 12-week diet. Then, we tested whether activity in the dorsolateral prefrontal cortex (DLPFC) at T0 and whether activity changes across the follow-up period (T0-T12) are linked to success in weight maintenance. The analyses conducted show that control-related DLPFC activity at T0 was coupled to the degree of success in weight maintenance. Consistently, also behavioral measures of control were linked to the degree of success in maintenance. A direct comparison of neural and behavioral control parameters for prognostic weight change modeling revealed that neural signals were more informative. Taken together, neural impulse control in the DLPFC measured with fMRI directly after a diet predicts real-world diet success in obese patients across extended time periods. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Postactivation potentiation can counteract declines in force and power that occur after stretching.

    Science.gov (United States)

    Kümmel, J; Kramer, A; Cronin, N J; Gruber, M

    2016-12-09

    Stretching can decrease a muscle's maximal force, whereas short but intense muscle contractions can increase it. We hypothesized that when combined, postactivation potentiation induced by reactive jumps would counteract stretch-induced decrements in drop jump (DJ) performance. Moreover, we measured changes in muscle twitch forces and ankle joint stiffness (KAnkle ) to examine underlying mechanisms. Twenty subjects completed three DJs and 10 electrically evoked muscle twitches of the triceps surae subsequent to four different conditioning activities and control. The conditioning activities were 10 hops, 20s of static stretching of the triceps surae muscle, 20s of stretching followed by 10 hops, and vice versa. After 10 hops, twitch peak torque (TPT) was 20% and jump height 5% higher compared with control with no differences in KAnkle . After stretching, TPT and jump height were both 9% and KAnkle 6% lower. When hops and stretching were combined as conditioning activities, jump height was not different compared with control but significantly higher (11% and 8%) compared with stretching. TPTs were 16% higher compared with control when the hops were performed after stretching and 9% higher compared with the reverse order. KAnkle was significantly lower when stretching was performed after the hops (6%) compared with control, but no significant difference was observed when hops were performed after stretching. These results demonstrate that conditioning hops can counteract stretch-related declines in DJ performance. Furthermore, the differences in TPTs and KAnkle between combined conditioning protocols indicate that the order of conditioning tasks might play an important role at the muscle-tendon level. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

    Science.gov (United States)

    Sinha, Dona; Roy, Madhumita; Siddiqi, Maqsood; Bhattacharya, Rathin K

    2005-01-01

    The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.

  5. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States); Lanni, Lydia; Jen, K.-L. Catherine [Department of Nutrition and Food Science, Wayne State University, Detroit MI (United States); McCabe, Michael J. [Department of Environmental Medicine, University of Rochester, Rochester NY (United States); Rosenspire, Allen, E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States)

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  6. INTESTINAL PARASITES IN IRAN

    Directory of Open Access Journals (Sweden)

    K. Mohammad

    1995-12-01

    Full Text Available The purpose of this study was to investigate the status and epidemiology of Intestinal Parasites in Iran. The information was driven from an extensive Health Survey which was done by the Ministry of Health and Medical Education, deputy of Research Affairs in 1990-92. Sampling fraction was 1 per 1000 of individuals aged between 2 and 69, the sampling method was cluster sampling and each cluster consisted of 7 families. Formal-ether was the method of finding parasites which included: Oxior, Ascariasis, Giardiasis, Entamoeba-histolytica, Tinea, Strongyloidiasis, Ancylostoma, and Trichocephaliasis. The highest prevalence rate belonged to Giardiasis with 14.4% and the lowest one belonged to Tinea and Ancylostoma with 0.2%. The prevalence rate in rural area was significantly lower than urban area (p<0.0001.

  7. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

    OpenAIRE

    Andrew D. Vigotsky; Bret Contreras; Chris Beardsley

    2015-01-01

    Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA) lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-secti...

  8. Associations of Cerebrovascular and Alzheimer’s Disease Pathology with Brain Atrophy

    Science.gov (United States)

    Crystal, Howard A.; Schneider, Julie A.; Bennett, David A.; Leurgans, Sue; Levine, Steven R.

    2015-01-01

    Cortical atrophy and brain vascular disease are both associated with dementia, but there are only limited pathological data on the association of brain vascular disease with cortical atrophy. We studied pathological material from the Rush Memory and Aging Project (MAP, N = 445). Cortical and hippocampal atrophy, and atherosclerosis at the circle of Willis (large vessel disease, LVD) and arteriolosclerosis (small vessel disease, SVD) were rated by neuropathologists unaware of this study’s hypothesis. Quantitative measures of Alzheimer’s disease (AD) pathology, specifically neuronal neurofibrillary tangles (NFT) and amyloid–beta (Aβ) burden, were also obtained. Chronic micro and macroscopic infarcts were noted. In ordinal logistic regression models that included age at death, sex, apoE genotype, statin-use, Aβ and NFT, more severe LVD was significantly associated with more severe cortical and hippocampal atrophy. The odds ratio for the association of the most severe LVD (compared to the least) with cortical atrophy was 2.7 (CI: 1.5–4.7) p = 0.001; for hippocampal atrophy the odds ratio was 2.8 (CI: 1.5–5.2), p = 0.001. The association of SVD with atrophy did not follow a consistent pattern. Neither macroscopic infarcts nor microscopic infarcts were associated with cortical or hippocampal atrophy (p’s > 0.15). Tangle density was associated with cortical (p = 0.014) and hippocampal atrophy (p atrophy. In this large autopsy study LVD was associated with cortical and hippocampal atrophy. The relationship between SVD and atrophy requires further study. PMID:24597507

  9. Intestinal flora, probiotics, and cirrhosis.

    Science.gov (United States)

    Guerrero Hernández, Ignacio; Torre Delgadillo, Aldo; Vargas Vorackova, Florencia; Uribe, Misael

    2008-01-01

    Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.

  10. Temperature modulates the effects of ocean acidification on intestinal ion transport in Atlantic cod, Gadus morhua

    Directory of Open Access Journals (Sweden)

    Marian Yong-An Hu

    2016-06-01

    Full Text Available CO2-driven seawater acidification has been demonstrated to enhance intestinal bicarbonate secretion rates in teleosts, leading to an increased release of CaCO3 under simulated ocean acidification scenarios. In this study, we investigated if increasing CO2 levels stimulate the intestinal acid–base regulatory machinery of Atlantic cod (Gadus morhua and whether temperatures at the upper limit of thermal tolerance stimulate or counteract ion regulatory capacities. Juvenile G. morhua were acclimated for four weeks to three CO2 levels (550, 1,200 and 2,200 μatm covering present and near-future natural variability, at optimum (10°C and summer maximum temperature (18°C, respectively. Immunohistochemical analyses revealed the subcellular localization of ion transporters, including Na+/K+-ATPase (NKA, Na+/H+-exchanger 3 (NHE3, Na+/HCO3- cotransporter (NBC1, pendrin-like Cl-/HCO3- exchanger (SLC26a6, V-type H+-ATPase subunit a (VHA and Cl- channel 3 (CLC3 in epithelial cells of the anterior intestine. At 10°C, proteins and mRNA were generally up-regulated for most transporters in the intestinal epithelium after acclimation to higher CO2 levels. This supports recent findings demonstrating increased intestinal HCO3- secretion rates in response to CO2 induced seawater acidification. At 18°C, mRNA expression and protein concentrations of most ion transporters remained unchanged or were even decreased, suggesting thermal compensation. This response may be energetically favorable to retain blood HCO3- levels to stabilize pHe, but may negatively affect intestinal salt and water resorption of marine teleosts in future oceans.

  11. Temperature Modulates the Effects of Ocean Acidification on Intestinal Ion Transport in Atlantic Cod, Gadus morhua

    Science.gov (United States)

    Hu, Marian Y.; Michael, Katharina; Kreiss, Cornelia M.; Stumpp, Meike; Dupont, Sam; Tseng, Yung-Che; Lucassen, Magnus

    2016-01-01

    CO2-driven seawater acidification has been demonstrated to enhance intestinal bicarbonate secretion rates in teleosts, leading to an increased release of CaCO3 under simulated ocean acidification scenarios. In this study, we investigated if increasing CO2 levels stimulate the intestinal acid–base regulatory machinery of Atlantic cod (Gadus morhua) and whether temperatures at the upper limit of thermal tolerance stimulate or counteract ion regulatory capacities. Juvenile G. morhua were acclimated for 4 weeks to three CO2 levels (550, 1200, and 2200 μatm) covering present and near-future natural variability, at optimum (10°C) and summer maximum temperature (18°C), respectively. Immunohistochemical analyses revealed the subcellular localization of ion transporters, including Na+/K+-ATPase (NKA), Na+/H+-exchanger 3 (NHE3), Na+/HCO3− cotransporter (NBC1), pendrin-like Cl−/HCO3− exchanger (SLC26a6), V-type H+-ATPase subunit a (VHA), and Cl− channel 3 (CLC3) in epithelial cells of the anterior intestine. At 10°C, proteins and mRNA were generally up-regulated for most transporters in the intestinal epithelium after acclimation to higher CO2 levels. This supports recent findings demonstrating increased intestinal HCO3− secretion rates in response to CO2 induced seawater acidification. At 18°C, mRNA expression and protein concentrations of most ion transporters remained unchanged or were even decreased, suggesting thermal compensation. This response may be energetically favorable to retain blood HCO3− levels to stabilize pHe, but may negatively affect intestinal salt and water resorption of marine teleosts in future oceans. PMID:27313538

  12. Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.

    Science.gov (United States)

    Kinnunen, Kirsi M; Cash, David M; Poole, Teresa; Frost, Chris; Benzinger, Tammie L S; Ahsan, R Laila; Leung, Kelvin K; Cardoso, M Jorge; Modat, Marc; Malone, Ian B; Morris, John C; Bateman, Randall J; Marcus, Daniel S; Goate, Alison; Salloway, Stephen P; Correia, Stephen; Sperling, Reisa A; Chhatwal, Jasmeer P; Mayeux, Richard P; Brickman, Adam M; Martins, Ralph N; Farlow, Martin R; Ghetti, Bernardino; Saykin, Andrew J; Jack, Clifford R; Schofield, Peter R; McDade, Eric; Weiner, Michael W; Ringman, John M; Thompson, Paul M; Masters, Colin L; Rowe, Christopher C; Rossor, Martin N; Ourselin, Sebastien; Fox, Nick C

    2017-07-22

    Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  13. Testicular atrophy secondary to a large long standing incarcerated inguinal hernia

    Directory of Open Access Journals (Sweden)

    Nikolaos S Salemis

    2011-09-01

    Full Text Available Testicular atrophy is a rare but distressing complication of inguinal hernia repair. Apart from the postsurgical etiology, ischemic orchitis and subsequent testicular atrophy may occur secondary to compression of the testicular vessels by chronically incarcerated hernias. We present a rare case of testicular atrophy secondary to a large long standing incarcerated inguinal hernia of 2-decade duration in a 79-year-old man. Testicular atrophy should be always considered in long standing incarcerated inguinal hernias and patients should be adequately informed of this possibility during the preoperative work-up. Preoperative scrotal ultrasonography can be used to determine testicular status in this specific group of patients.

  14. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-06-03

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy*

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-01-01

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. PMID:27129272

  16. miR-29b contributes to multiple types of muscle atrophy

    Science.gov (United States)

    Li, Jin; Chan, Mun Chun; Yu, Yan; Bei, Yihua; Chen, Ping; Zhou, Qiulian; Cheng, Liming; Chen, Lei; Ziegler, Olivia; Rowe, Glenn C.; Das, Saumya; Xiao, Junjie

    2017-01-01

    A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli. PMID:28541289

  17. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.

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    Emily N Manning

    Full Text Available OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD, mild cognitive impairment (MCI and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls were used. MCI subjects were divided into "progressors" (MCI-P if diagnosed with AD within 36 months or "stable" (MCI-S if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

  18. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

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    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  19. Intestinal spirochetosis and colon diverticulosis

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    Lima Marcus Aurelho de

    2005-01-01

    Full Text Available A case of intestinal spirochetosis in a 62-year-old white male is reported. The condition was characterized by chronic flatulence and episodes of intestinal hemorrhage, in addition to the evidence of hypotonic diverticular disease, with a large number of slender organisms in the colon epithelium and cryptae. Spirochetes were demonstrated by Whartin-Starry stain. The serologic tests for syphilis and HIV were positive. Spirochetosis was treated with penicillin G, and the patient remains free of intestinal complaints 20 months later.

  20. Intestinal nematodes: biology and control.

    Science.gov (United States)

    Epe, Christian

    2009-11-01

    A variety of nematodes occur in dogs and cats. Several nematode species inhabit the small and large intestines. Important species that live in the small intestine are roundworms of the genus Toxocara (T canis, T cati) and Toxascaris (ie, T leonina), and hookworms of the genus Ancylostoma (A caninum, A braziliense, A tubaeforme) or Uncinaria (U stenocephala). Parasites of the large intestine are nematodes of the genus Trichuris (ie, whipworms, T vulpis). After a comprehensive description of their life cycle and biology, which are indispensable for understanding and justifying their control, current recommendations for nematode control are presented and discussed thereafter.

  1. Recurrent gastric dilatation and intestinal dysmotility possibly resulting from autonomic neuropathy in a Great Dane.

    Science.gov (United States)

    Spoo, Joseph W; Shelton, G Diane

    2014-01-01

    A 5 yr old female spayed Great Dane was presented for recurrent episodes of gastric dilatation, intestinal dysmotility, and one episode of gastric rupture. Numerous hematologic, radiographic, and endocrine diagnostic tests were performed with no identifiable underlying cause. Many risk factors have been identified for gastric dilatation and most were present in this Great Dane. A number of symptomatic treatments, aimed primarily at altering the gastrointestinal tract flora and motility were tried, but failed to influence the clinical course of the disease. The dog continued to worsen, experienced more frequent episodes of gastric dilatation, and developed generalized muscle atrophy. Biopsies were collected from the biceps femoris and triceps brachii muscles. A pattern of denervation atrophy was evident in both muscles, consistent with polyneuropathy. The owners elected humane euthanasia and a necropsy was performed. A striking finding at necropsy was severe loss of myelinated fibers with extensive endoneurial fibrosis in the vagus nerve, consistent with an autonomic neuropathy. Autonomic neuropathy is a previously unexplored cause of gastric dilatation and intestinal dysmotility in dogs. These findings should open new directions for exploring pathogenic mechanisms for gastric dilatation in this species.

  2. A Model of Intestinal Anaphylaxis in Whey Sensitized Balb/c Mice

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    Kheroua Omar

    2009-01-01

    Full Text Available Problem statement: Cow’s Milk Allergy (CMA is a common disease in childhood. Pathophysiological mechanisms involved in gastrointestinal symptoms are relatively poorly understood. Approach: Therefore, an experimental model of intestinal anaphylaxis was needed to approach the problem. The aim of this study was to examine the effect of the parenteral sensitization to whey proteins through immune response and local intestine inflammation using a murine model of allergy. Sensitization of Balb/c mice with ß-lactoglobulin (ß-Lg or whey was performed in presence of Alum Al (OH3. Mice were analyzed for ß-Lg or whey specific serum antibodies by ELISA. Local anaphylactic responses were performed in vitro in using chamber by intestine challenge with ß-Lg or whey. Histological study was used to assess gut inflammation. Results: The sensitization induced the production of anti- ß-Lg or anti whey IgG, IgG1, IgG2a and IgE with a high IgG1/IgG2a ratio translating Th2 type response. The addition of ß-Lg or whey to the serosal side of the mouse intestinal epithelium in using chamber produced electrogenic chloride secretion as shown by Isc stimulation. Histological findings were mild with villi atrophy and lymphocyte hyperplasia. Conclusion: After sensitization, the mice became prone to developing anaphylactic response and may be useful experimental model for mechanistic studies of CMA or for hydrolyzed formulae.

  3. Effect of fasting in the digestive system: histological study of the small intestine in house sparrows.

    Science.gov (United States)

    Funes, Samanta Celeste; Filippa, Verónica Palmira; Cid, Fabricio Damián; Mohamed, Fabián; Caviedes-Vidal, Enrique; Chediack, Juan Gabriel

    2014-10-01

    In birds and mammals the metabolic response to fasting has been studied and can be characterized by three consecutive phases reflecting metabolic and physiological adjustments. An effective way to minimize energy expenditure during food scarcity is to decrease the mass of the organs. As the digestive system is metabolically expensive to maintain, the small intestine and the liver are the most affected organs. We evaluated the effects of phase III starvation on the mass of the different organs and histological parameters on house sparrows, a small non-migrant bird. In a short period of time (34 h) we observed a larger reduction in the digestive organ mass when compared to the mass of the body and non-alimentary tissues. Furthermore, the intestinal mass was proportionally more reduced than its length and nominal surface area. A reduction on the intestinal mucosal layer also resulted in a shortening of villus (length and thickness) and crypt depth. Moreover, the morphology of the enterocytes changed from cylindrical to cubical, suggesting that the surface exposed to the lumen was conserved. This may indicate an adaptive response to the moment of refeeding. The nominal surface area/body mass remained constant in both groups and several histological parameters were reduced, suggesting that starving induces the atrophy of the small intestine. However, the goblet cells were conserved after fasting indicating a protective tendency.

  4. Muscle wasting in collagen-induced arthritis and disuse atrophy.

    Science.gov (United States)

    de Oliveira Nunes Teixeira, Vivian; Filippin, Lidiane Isabel; Viacava, Paula Ramos; de Oliveira, Patrícia Gnieslaw; Xavier, Ricardo Machado

    2013-12-01

    The mechanisms of muscle wasting and decreased mobility have a major functional effect in rheumatoid arthritis, but they have been poorly studied. The objective of our study is to describe muscular involvement and the pathways in an experimental model of arthritis compared to the pathways in disuse atrophy. Female Wistar rats were separated into three groups: control (CO), collagen-induced arthritis (CIA), and immobilized (IM). Spontaneous locomotion and weight were evaluated weekly. The gastrocnemius muscle was evaluated by histology and immunoblotting to measure the expression of myostatin (a negative regulator), LC3 (autophagy), MuRF-1 (proteasome-mediated proteolysis), MyoD, and myogenin (satellite-cell activation). The significance level was set at P muscle weight, and relative muscle weight decreased 20%, 30%, and 20%, respectively, in the CIA rats. Inflammatory infiltration and swelling were present in the gastrocnemius muscles of the CIA rats. The mean cross-sectional area was reduced by 30% in the CIA group and by 60% in the IM group. The expressions of myostatin and LC3 between the groups were similar. There was increased expression of MuRF-1 in the IM (1.9-fold) and CIA (3.1-fold) groups and of myogenin in the muscles of the CIA animals (1.7-fold), while MyoD expression was decreased in the IM (20%) rats. This study demonstrated that the development of experimental arthritis is associated with decreased mobility, body weight, and muscle loss. Both IM and CIA animal models presented muscle atrophy, but while proteolysis and the regeneration pathways were activated in the CIA model, there was no activation of regeneration in the IM model. We can assume that muscle atrophy in experimental arthritis is associated with the disease itself and not simply with decreased mobility.

  5. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

    Science.gov (United States)

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei

    2014-11-01

    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  6. Axonal loss occurs early in dominant optic atrophy

    DEFF Research Database (Denmark)

    Milea, Dan; Sander, Birgit; Wegener, Marianne

    2010-01-01

    Purpose: This study set out to investigate retinal nerve fibre layer (RNFL) thickness and best corrected visual acuity (BCVA) in relation to age in healthy subjects and patients with OPA1 autosomal dominant optic atrophy (DOA). Methods: We carried out a cross-sectional investigation of RNFL...... thickness and ganglion cell layer density in 30 healthy subjects and 10 patients with OPA1 DOA using optical coherence tomography (OCT). We then performed a regression analysis of RNFL thickness and BCVA versus age. Results: Both healthy subjects and DOA patients demonstrated a gradual reduction in RNFL...

  7. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

    Science.gov (United States)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.

    1988-01-01

    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  8. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

    Directory of Open Access Journals (Sweden)

    K Abigail Andrews

    Full Text Available There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET, and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3 from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR, and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014. Twenty-two (1/3 were PiB-positive (SUVR>1.40, the remaining 44 PiB-negative (SUVR≤1.31. Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05 and more were APOE4 positive (63.6% vs. 19.2%, p<0.01 but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02, independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr change. Based on the observed effect size, recruiting 384 (95%CI 195-1080 amyloid-positive subjects/arm will provide 80% power to detect 25

  9. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  10. Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy

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    Haruhiko Banno

    2009-03-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR. The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA.

  11. Chorioretinal Atrophy after Spontaneous Resolution of Myopic Foveoschisis

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    Antonio García-Ben

    2014-01-01

    Full Text Available Myopic foveoschisis is one of the major complications of pathologic myopia, and it was most recently identified by new imaging modalities. During the natural evolution of this complication, anatomical and visual improvement without surgical intervention is an unusual course, and most of these eyes remain stable or progressively worsen. The authors report a case of a highly myopic eye that developed patchy chorioretinal atrophy after spontaneous resolution of myopic foveoschisis, which to the best of our knowledge has not been reported previously in the medical literature.

  12. Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.

    Science.gov (United States)

    Garas, Lydia C; Feltrin, Cristiano; Hamilton, M Kristina; Hagey, Jill V; Murray, James D; Bertolini, Luciana R; Bertolini, Marcelo; Raybould, Helen E; Maga, Elizabeth A

    2016-02-01

    Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.

  13. Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression.

    Science.gov (United States)

    Nilaweera, Kanishka N; Cabrera-Rubio, Raul; Speakman, John R; O'Connor, Paula M; McAuliffe, AnneMarie; Guinane, Caitriona M; Lawton, Elaine M; Crispie, Fiona; Aguilera, Mònica; Stanley, Maurice; Boscaini, Serena; Joyce, Susan; Melgar, Silvia; Cryan, John F; Cotter, Paul D

    2017-07-01

    We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2, and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated reduced energy absorption through the intestine. We propose that this mobilized energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway. Copyright © 2017 the American Physiological Society.

  14. Flow and active mixing have a strong impact on bacterial growth dynamics in the proximal large intestine

    Science.gov (United States)

    Cremer, Jonas; Segota, Igor; Yang, Chih-Yu; Arnoldini, Markus; Groisman, Alex; Hwa, Terence

    2016-11-01

    More than half of fecal dry weight is bacterial mass with bacterial densities reaching up to 1012 cells per gram. Mostly, these bacteria grow in the proximal large intestine where lateral flow along the intestine is strong: flow can in principal lead to a washout of bacteria from the proximal large intestine. Active mixing by contractions of the intestinal wall together with bacterial growth might counteract such a washout and allow high bacterial densities to occur. As a step towards understanding bacterial growth in the presence of mixing and flow, we constructed an in-vitro setup where controlled wall-deformations of a channel emulate contractions. We investigate growth along the channel under a steady nutrient inflow. Depending on mixing and flow, we observe varying spatial gradients in bacterial density along the channel. Active mixing by deformations of the channel wall is shown to be crucial in maintaining a steady-state bacterial population in the presence of flow. The growth-dynamics is quantitatively captured by a simple mathematical model, with the effect of mixing described by an effective diffusion term. Based on this model, we discuss bacterial growth dynamics in the human large intestine using flow- and mixing-behavior having been observed for humans.

  15. Small-molecule inhibitors at the PSD-95/nNOS interface protect against glutamate-induced neuronal atrophy in primary cortical neurons.

    Science.gov (United States)

    Doucet, M V; O'Toole, E; Connor, T; Harkin, A

    2015-08-20

    Glutamate and nitric oxide (NO) are important regulators of dendrite and axon development in the central nervous system. Excess glutamatergic stimulation is a feature of many pathological conditions and manifests in neuronal atrophy and shrinkage with eventual neurodegeneration and cell death. Here we demonstrate that treatment of cultured primary cortical rat neurons for 24h with glutamate (500μM) or N-methyl-d-aspartate (NMDA) (100-500μM) combined with glycine suppresses neurite outgrowth. A similar reduction of neurite outgrowth was observed with the NO precursor l-arginine and NO donor sodium nitroprusside (SNP) (100 and 300μM). The NMDA-receptor (NMDA-R) antagonists ketamine and MK-801 (10nM) counteracted the NMDA/glycine-induced reduction in neurite outgrowth and the neuronal NO synthase (nNOS) inhibitor 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) (100nM) counteracted both the NMDA/glycine and l-arginine-induced decreases in neurite outgrowth. Furthermore, targeting soluble guanylate cyclase (sGC), a downstream target of NO, with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10μM) also protected against l-arginine-induced decreases in neurite outgrowth. Since the NMDA-R is functionally coupled to nNOS via the postsynaptic protein 95kDa (PSD-95), inhibitors of the PSD-95/nNOS interaction were tested for their ability to protect against glutamate-induced suppression in neurite outgrowth. Treatment with the small-molecule inhibitors of the PSD-95/nNOS interface 2-((1H-benzo[d] [1,2,3]triazol-5-ylamino) methyl)-4,6-dichlorophenol (IC87201) (10 and 100nM) and 4-(3,5-dichloro-2-hydroxy-benzylamino)-2-hydroxybenzoic acid (ZL-006) (10 and 100nM) attenuated NMDA/glycine-induced decreases in neurite outgrowth. These data support the hypothesis that targeting the NMDA-R/PSD-95/nNOS interaction downstream of NMDA-R promotes neurotrophic effects by preventing neurite shrinkage in response to excess glutamatergic stimulation. The PSD-95/n

  16. Agent-based computational model investigates muscle-specific responses to disuse-induced atrophy

    Science.gov (United States)

    Martin, Kyle S.; Peirce, Shayn M.

    2015-01-01

    Skeletal muscle is highly responsive to use. In particular, muscle atrophy attributable to decreased activity is a common problem among the elderly and injured/immobile. However, each muscle does not respond the same way. We developed an agent-based model that generates a tissue-level skeletal muscle response to disuse/immobilization. The model incorporates tissue-specific muscle fiber architecture parameters and simulates changes in muscle fiber size as a result of disuse-induced atrophy that are consistent with published experiments. We created simulations of 49 forelimb and hindlimb muscles of the rat by incorporating eight fiber-type and size parameters to explore how these parameters, which vary widely across muscles, influence sensitivity to disuse-induced atrophy. Of the 49 muscles modeled, the soleus exhibited the greatest atrophy after 14 days of simulated immobilization (51% decrease in fiber size), whereas the extensor digitorum communis atrophied the least (32%). Analysis of these simulations revealed that both fiber-type distribution and fiber-size distribution influence the sensitivity to disuse atrophy even though no single tissue architecture parameter correlated with atrophy rate. Additionally, software agents representing fibroblasts were incorporated into the model to investigate cellular interactions during atrophy. Sensitivity analyses revealed that fibroblast agents have the potential to affect disuse-induced atrophy, albeit with a lesser effect than fiber type and size. In particular, muscle atrophy elevated slightly with increased initial fibroblast population and increased production of TNF-α. Overall, the agent-based model provides a novel framework for investigating both tissue adaptations and cellular interactions in skeletal muscle during atrophy. PMID:25722379

  17. Intestinal acariasis in Anhui Province

    Institute of Scientific and Technical Information of China (English)

    Chao-Pin Li; Jian Wang

    2000-01-01

    The mites found in stored food and house comprise a large group of subclass Acari, belonging to the suborder Acardida of the order Acarifornes. They can be found in dust and vacuum samples from floors, furniture, mattresses, Chinese herbal medicine, dry fruit, grain, flour, sugar, and bedding. These mites are nidicolous and feed on organic debris, including sloughed human skin, fungi, spilled food, pollen, etc. These mites are particularly prevalent in Chinese herbal medicine, dry fruit, grain, flour, sugar, beds, though carpeted floors near beds or couches may also have large numbers. The most common species are Acarus siro, Tyrophagus putrescentiae , Dermatophagoides farinae , D . pteronyssinus, Glycyphagus domesticus, G. Ornatus, Carpoglyphus lactis and Tarsonemus granarius, etc. The viability of mites in storage is quite strong and they can invade and parasitize the intestines of humans[1 -15]. They can cause pulmonary acariasis[16-25] , urinary acariasis[26-33] and so on. The dejecta of mites is a quite strong allergen and can cause different allergic diseases[34-44]. Intestinal acariasis can be caused by some mites related to the way of diet intake and invading against intestinal mucosa, intestinal muscle[45-5a]. The first report of intestinal acariasis caused by these mites was made by Hinman et al (1934)[45]. From then on, all kinds of studies on the disease have been reported gradually. In order to make an epidemiological survey of intestinal acariasis the investigation of the disease was taken in some areas of Anhui Province from 1989 to 1996.

  18. Haemorrhage and intestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  19. Adult intestinal failure

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J., E-mail: Jdavidson@doctors.org.u [Salford Royal Hospital, Salford (United Kingdom); Plumb, A.; Burnett, H. [Salford Royal Hospital, Salford (United Kingdom)

    2010-05-15

    Intestinal failure (IF) is the inability of the alimentary tract to digest and absorb sufficient nutrition to maintain normal fluid balance, growth, and health. It commonly arises from disease affecting the mesenteric root. Although severe IF is usually managed in specialized units, it lies at the end of a spectrum with degrees of nutritional compromise being widely encountered, but commonly under-recognized. Furthermore, in the majority of cases, the initial enteric insult occurs in non-specialist IF centres. The aim of this article is to review the common causes of IF, general principles of its management, some commoner complications, and the role of radiology in the approach to a patient with severe IF. The radiologist has a crucial role in helping provide access for feeding solutions (both enteral and parenteral) and controlling sepsis (via drainage of collections) in an initial restorative phase of treatment, whilst simultaneously mapping bowel anatomy and quality, and searching for disease complications to assist the clinicians in planning a later, restorative phase of therapy.

  20. [Malaria and intestinal protozoa].

    Science.gov (United States)

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. Malacoplaquia intestinal Colonic malakoplakia

    Directory of Open Access Journals (Sweden)

    Jacinto José Frem Aun

    1998-04-01

    Full Text Available Malacoplakia is a chronic granulomatous disease of unknown origin. However immunodeficiency states (immunossuppressive medication, old people, renal transplantation, leukaemia, diabetes mellitus, malnutrition and others have been associated with patients with malacoplakia. An infectious cause of malakoplakia is suggested by the finding of coliform bacteria in the phagolysosomes of macrophages. The histologic study is characterized by a infiltrate of large macrophages (Hansenmann cells with pathognomonic inclusions containing siderocalcific structures (Michaelis-Gutmann bodies. Most of the cases reported in literature, involve the genitourinary tract, but other structures can be affected (brain, bone, adrenal glands, lymph nodes, intestine, and others. A 66-year-old man whith a abdominal mass, went to our hospital with a colonic tumour diagnosis. The patient was submitted to a surgery, with resection of the rigth colon. The disease was invading a portion of the retroperitoneal tissue that was removed. The histopatologic study showed the pathognomonic sign of malakoplakia (Hansenmann cells and Michaelis-Gutmann bodies. Norfloxacin have been used to the complementar treatment with total cure of the patient.

  2. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    Directory of Open Access Journals (Sweden)

    Fröbert Ole

    2011-05-01

    Full Text Available Abstract Background The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1 is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA. We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results In prostaglandin F2α (PGF2α, 10 μM-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride(10 μM inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM and the putative NADPH oxidase inhibitor apocynin (10 μM leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene

  3. Stimulation of NTS A1 adenosine receptors evokes counteracting effects on hindlimb vasculature.

    Science.gov (United States)

    McClure, Joseph M; O'Leary, Donal S; Scislo, Tadeusz J

    2005-12-01

    Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of beta-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinejctions into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after beta-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the

  4. Development and Translation of Therapies for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Hannah K. Shorrock

    2016-07-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disorder characterised by widespread loss of lower motor neurons from the spinal cord, leading to progressive weakness and muscle atrophy. SMA is largely caused by homozygous loss of the survival motor neuron (SMN 1 gene, resulting in reduced levels of full-length SMN protein. Although no approved treatment is currently available for SMA, several clinical trials investigating different approaches to increase SMN levels are showing promising early results. Trials investigating the use of therapies targeting muscle strength and neuroprotective pathways are also in progress, generating the possibility of delivering combination therapies utilising both SMN-dependent and SMN-independent targets. Due to an increased understanding of the cellular and molecular consequences of SMN depletion, a second wave of therapies targeted at pathways downstream of SMN are currently undergoing preclinical development. As these therapies move forward towards the clinic, new treatment options are likely to become available, raising the potential to generate an effective ‘cure’ for SMA.

  5. Carbocalcitonin treatment in Sudeck's atrophy

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    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.

    1987-02-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  6. Impaired cognitive performance and hippocampal atrophy in Parkinson disease.

    Science.gov (United States)

    Yildiz, Demet; Erer, Sevda; Zarifoğlu, Mehmet; Hakyemez, Bahattin; Bakar, Mustafa; Karli, Necdet; Varlibaş, Zeynep Nigar; Tufan, Fatih

    2015-01-01

    Dementia is common in Parkinson disease (PD). Since magnetic resonance imaging has been used, hippocampal atrophy has been shown in PD patients with or without dementia. In this study we sought the correlation of cognitive decline with bilateral hippocampal volume in PD patients. Thirty-three patients with diagnosis of idiopathic PD and 16 healthy subjects were included in this study. PD patients were divided into two groups as normal cognitive function and mild cognitive impairment (MCI). The Mini-Mental State Examination and detailed cognitive assessment tests were performed for all patients for cognitive analyses. Depression was excluded by the Geriatric Depression Scale. The mean onset age of disease was 55 years for PD patients without dementia and 59 for PD patients with MCI. According to the Hoehn-Yahr scales, 24% of patients had grade 1, 58% had grade 2, and 18% had grade 3 disease. Right and left hippocampal volumes decreased along with cognitive test scores in PD patients. Increased right hippocampal volume was correlated with forward number test in the MCI-PD group. These findings suggest that memory deficit is associated with hippocampal atrophy in PD patients.

  7. Periorbital muscle atrophy associated with topical bimatoprost therapy

    Directory of Open Access Journals (Sweden)

    Wang PX

    2014-01-01

    Full Text Available Priscilla Xinhui Wang, Victor Teck Chang Koh, Jin Fong ChengDepartment of Ophthalmology, National University Health System, SingaporeAbstract: Topical Bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma. Side effects include ocular hyperaemia, ocular pruritus, and periocular and iris pigmentary changes. Perioribital lipodystrophy is another well-documented outcome associated with chronic use of topical bimatoprost, which results in periorbital hallowing, upper eyelid sulcus deepening, eyelid retraction and enophthalmos. We report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use. Our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye. Clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle, suggesting that effects of topical bimatoprost may not be limited to periorbital fat. She was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully. Ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost, as it may be potentially disfiguring, especially with monocular use. However, its exact mechanism of action needs to be clarified further.Keywords: prostaglandin analog, levator, muscle atrophy, muscle weakness, ptosis, side effects

  8. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

    Science.gov (United States)

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R

    2016-04-23

    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p skills (p skills compared to EOAD patients (p presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

  9. Picture agnosia as a characteristic of posterior cortical atrophy.

    Science.gov (United States)

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Hieda, Sotaro; Kawamura, Mitsuru

    2012-01-01

    Posterior cortical atrophy (PCA) is a degenerative disease characterized by progressive visual agnosia with posterior cerebral atrophy. We examine the role of the picture naming test and make a number of suggestions with regard to diagnosing PCA as atypical dementia. We investigated 3 cases of early-stage PCA with 7 control cases of Alzheimer disease (AD). The patients and controls underwent a naming test with real objects and colored photographs of familiar objects. We then compared rates of correct answers. Patients with early-stage PCA showed significant inability to recognize photographs compared to real objects (F = 196.284, p = 0.0000) as measured by analysis of variants. This difficulty was also significant to AD controls (F = 58.717, p = 0.0000). Picture agnosia is a characteristic symptom of early-stage PCA, and the picture naming test is useful for the diagnosis of PCA as atypical dementia at an early stage. Copyright © 2012 S. Karger AG, Basel.

  10. Connectivity network measures predict volumetric atrophy in mild cognitive impairment.

    Science.gov (United States)

    Nir, Talia M; Jahanshad, Neda; Toga, Arthur W; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2015-01-01

    Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global "small-world" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian "expansion factor maps" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.

  11. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.

    Science.gov (United States)

    Wolf, Nicole I; Koenig, Michel

    2013-01-01

    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  12. Interactive segmentation for geographic atrophy in retinal fundus images.

    Science.gov (United States)

    Lee, Noah; Smith, R Theodore; Laine, Andrew F

    2008-10-01

    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12-21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of pathological images still remains an unsolved problem. In this paper we leverage the watershed transform and generalized non-linear gradient operators for interactive segmentation and present an intuitive and simple approach for geographic atrophy segmentation. We compare our approach with the state of the art random walker [5] algorithm for interactive segmentation using ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean sensitivity/specificity of 98.3/97.7% for our approach and a mean sensitivity/specificity of 88.2/96.6% for the random walker algorithm.

  13. Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Fumiaki Tanaka

    2012-01-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR, a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N and carboxy-terminal (C (N/C interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS, and autophagy could be applicable for all types of polyglutamine diseases.

  14. Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Katsuno, M; Adachi, H; Inukai, A; Sobue, G

    2003-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.

  15. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Katsuno, Masahisa; Tanaka, Fumiaki; Adachi, Hiroaki; Banno, Haruhiko; Suzuki, Keisuke; Watanabe, Hirohisa; Sobue, Gen

    2012-12-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by slowly progressive muscle weakness and atrophy. During the last two decades, basic and clinical research has provided important insights into the disease phenotype and pathophysiology. The cause of SBMA is the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas females homozygous for the AR mutation do not manifest neurological symptoms. The ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is central to the gender-specific pathogenesis of SBMA, although additional steps, e.g., DNA binding, inter-domain interactions, and post-translational modification of AR, modify toxicity. The interactions with co-regulators are another requisite for the toxic properties of the polyglutamine-expanded AR. It is also shown that the polyglutamine-expanded AR induces diverse molecular events, such as transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction, which play causative roles in the neurodegeneration in SBMA. The pathogenic AR-induced myopathy also contributes to the non-cell autonomous degeneration of motor neurons. Pre-clinical studies using animal models show that the pathogenic AR-mediated neurodegeneration is suppressed by androgen inactivation, the efficacy of which has been tested in clinical trials. Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA.

  16. Normalized regional brain atrophy measurements in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Zivadinov, Robert; Locatelli, Laura; Stival, Barbara; Bratina, Alessio; Nasuelli, Davide; Zorzon, Marino [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste, Strada di Fiume, 447-34149, Trieste (Italy); Grop, Attilio [Department of Electrical, Electronics and Computer Science, University of Trieste, Trieste (Italy); Brnabic-Razmilic, Ozana [Statistical Analysis Centre, Heilbronn (Germany)

    2003-11-01

    There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing-remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=-0.37, P=0.011, and r= -0.40, P=0.0005 respectively) and with T1-LL of the pons (r=-0.27, P=0.046, and r=-0.31, P=0.04, respectively), whereas RBPV did not (r=-0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=-0.32, P=0.033) and TRBVF (r=-0.29, P=0.05), but not to RBPV (R=-0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and

  17. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  18. Dissociated small hand muscle atrophy in aging: the 'senile hand' is a split hand.

    NARCIS (Netherlands)

    Voermans, N.C.; Schelhaas, H.J.; Munneke, M.; Zwarts, M.J.

    2006-01-01

    The term 'split hand' refers to a pattern of dissociated atrophy of hand muscles and was first described in ALS. We hypothesize that this phenomenon also occurs in 'normal' aging. We investigated healthy subjects of different ages and found a progressive dissociation in atrophy of the hand muscles,

  19. Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

    NARCIS (Netherlands)

    Korf, E.S.; Straaten, E.C. van; Leeuw, F.E. de; Flier, W.M.; Barkhof, F.; Pantoni, L.; Basile, A.M.; Inzitari, D.; Erkinjuntti, T.; Wahlund, L.O.; Rostrup, E.; Schmidt, R.; Fazekas, F.; Scheltens, P.

    2007-01-01

    HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white

  20. Inhibition of autophagy recovers cardiac dysfunction and atrophy in response to tail-suspension.

    Science.gov (United States)

    Liu, Hong; Xie, Qiong; Xin, Bing-Mu; Liu, Jun-Lian; Liu, Yu; Li, Yong-Zhi; Wang, Jia-Ping

    2015-01-15

    Physical inactivity during space flight or prolonged bed rest may cause cardiac dysfunction and atrophy, but the exact mechanism that governs the regulation of myocardial dysfunction and cardiac atrophy remains poorly understood. Autophagy, a protein degradation pathway, has recently been shown to be involved in the regulation of cardiac dysfunction and atrophy. In this study, we investigated the relationships between dysfunction and inactivity-induced atrophy and autophagy in rat cardiac tissue. Physical inactivity was simulated by a tail suspension model, and cardiac function was examined by echocardiography. Cardiac atrophy was measured by wheat germ agglutinin staining and autophagic activity was detected by Western blot analysis and immunofluorescence staining. We demonstrated that cardiac function, especially contractility, declined and the area of cardiac atrophy increased in the tail-suspended cardiac tissue. Additionally, the cross-sectional area of myocardial cells decreased; however, apoptosis did not increase with tail suspension. Similarly, the expression of autophagy-related proteins and the number of autophagosomes were elevated in the tail-suspended cardiac tissue. Moreover, the administration of chloroquine, an autophagy inhibitor, reversed cardiac dysfunction and atrophy via the suppression of autophagic activity during suspension. Our results indicate that autophagy facilitates the development and progression of cardiac dysfunction and atrophy induced by tail suspension. Our studies hint that the components of the autophagy-related signaling pathway are potential therapeutic targets for the treatment of cardiac diseases induced by physical inactivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  2. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  3. Brain atrophy in patients with arterial disease. The SMART-MR study

    NARCIS (Netherlands)

    Appelman, A.P.A.

    2008-01-01

    Brain atrophy is often observed on magnetic resonance imaging (MRI) in the elderly. This is of clinical importance since the extent and rate of progression of brain atrophy are associated with future cognitive deterioration and conversion to Alzheimer’s dementia. The overall aim of this thesis was t

  4. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  5. Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy.

    NARCIS (Netherlands)

    Schellekens, W.J.M.; Hees, H.W.H. van; Vaneker, M.; Linkels, M.; Dekhuijzen, P.N.R.; Scheffer, G.J.; Hoeven, J.G. van der; Heunks, L.M.A.

    2012-01-01

    BACKGROUND:: Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor

  6. Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models

    Science.gov (United States)

    Abdelnour, Farras; Mueller, Susanne; Raj, Ashish

    2015-01-01

    Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning. PMID:26513579

  7. Correlation of hippocampal atrophy with hyperhomocysteinemia in hemodialysis patients: An exploratory pilot study.

    Science.gov (United States)

    Maesato, Kyoko; Ohtake, Takayasu; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Moriya, Hidekazu; Hidaka, Sumi; Kobayashi, Shuzo

    2017-01-01

    Cognitive impairment is one of the important critical issues in hemodialysis (HD) patients. However, the associating factors of brain atrophy in HD patients have not been fully elucidated. Brain magnetic resonance imaging (MRI) was performed in 34 of total 72 HD outpatients in our dialysis center. These MRI images were analyzed by an application software; Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD). VSRAD quantitatively calculates the extent of brain atrophy (percent of volume reduction) comparing with a MRI imaging database of 80 age-matched healthy controls. The extent of both hippocampal and whole-brain atrophy was evaluated with possible contributing factors. In all patients, the mean extent of hippocampal atrophy was 27.3%, and the mean extent of whole-brain atrophy was 11.2%. The extent of hippocampal atrophy was significantly correlated with low body mass index (BMI), total serum homocysteine (tHcy) levels, and brachial-ankle pulse wave velocity (baPWV). The extent of whole-brain atrophy showed significant correlations with age, hypoalbuminemia, and baPWV. Based on the multiple regression analysis, tHcy was an independent determinant of hippocampal atrophy (β = 0.460, R2 = 0.189, Patrophy (β = 0.594, R2 = 0.333, Patrophy was significantly correlated with hyperhomocysteinemia in HD patients.

  8. Evaluating Alzheimer’s Disease Progression Using Rate of Regional Hippocampal Atrophy

    Science.gov (United States)

    Frankó, Edit; Joly, Olivier

    2013-01-01

    Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects. PMID:23951142

  9. Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy

    DEFF Research Database (Denmark)

    Ulrich, L S G; Naessen, T; Elia, D

    2010-01-01

    The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women.......The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women....

  10. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  11. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    NARCIS (Netherlands)

    De Vis, J B; Zwanenburg, J J|info:eu-repo/dai/nl/290473683; van der Kleij, L A; Spijkerman, J M; Biessels, G J|info:eu-repo/dai/nl/165576367; Hendrikse, J|info:eu-repo/dai/nl/266590268; Petersen, E T

    2016-01-01

    OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were perform

  12. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  13. Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models.

    Science.gov (United States)

    Abdelnour, Farras; Mueller, Susanne; Raj, Ashish

    2015-10-01

    Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.

  14. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly.

    Science.gov (United States)

    Tanenbaum, Marvin E; Macůrek, Libor; Galjart, Niels; Medema, René H

    2008-12-17

    Bipolar spindle assembly critically depends on the microtubule plus-end-directed motor Eg5 that binds antiparallel microtubules and slides them in opposite directions. As such, Eg5 can produce the necessary outward force within the spindle that drives centrosome separation and inhibition of this antiparallel sliding activity results in the formation of monopolar spindles. Here, we show that upon depletion of the minus-end-directed motor dynein, or the dynein-binding protein Lis1, bipolar spindles can form in human cells with substantially less Eg5 activity, suggesting that dynein and Lis1 produce an inward force that counteracts the Eg5-dependent outward force. Interestingly, we also observe restoration of spindle bipolarity upon depletion of the microtubule plus-end-tracking protein CLIP-170. This function of CLIP-170 in spindle bipolarity seems to be mediated through its interaction with dynein, as loss of CLIP-115, a highly homologous protein that lacks the dynein-dynactin interaction domain, does not restore spindle bipolarity. Taken together, these results suggest that complexes of dynein, Lis1 and CLIP-170 crosslink and slide microtubules within the spindle, thereby producing an inward force that pulls centrosomes together.

  15. RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury.

  16. Discussing the undiscussable with the powerful: why and how faculty must learn to counteract organizational silence.

    Science.gov (United States)

    Dankoski, Mary E; Bickel, Janet; Gusic, Maryellen E

    2014-12-01

    Dialogue is essential for transforming institutions into learning organizations, yet many well-known characteristics of academic health centers (AHCs) interfere with open discussion. Rigid hierarchies, intense competition for resources, and the power of peer review in advancement processes all hamper difficult conversations, thereby contributing to organizational silence, and at great cost to the institution. Information necessary for critical decisions is not shared, individuals and the organization do not learn from mistakes, and diverse perspectives from those with less power are not entertained, or worse, are suppressed. When leaders become more skilled at inviting multiple perspectives and faculty more adept at broaching difficult conversations with those in power, differences are more effectively addressed and conflicts resolved. In this article, the authors frame why this skill is an essential competency for faculty and leaders alike and provide the following recommendations to institutions for increasing capacity in this area: (1) develop leaders to counteract organizational silence, (2) develop faculty members' skills in raising difficult issues with those in positions of power, and (3) train mentors to coach others in raising difficult conversations. The vitality of AHCs requires that faculty and institutional leaders develop relational communication skills and partner in learning through challenging conversations.

  17. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  18. Counteracting ammonia inhibition during anaerobic digestion by recovery using submersible microbial desalination cell.

    Science.gov (United States)

    Zhang, Yifeng; Angelidaki, Irini

    2015-07-01

    Ammonia inhibition is one of the most frequent and serious problems in biogas plants. In this study, a novel hybrid system consisting of a submersible microbial desalination cell (SMDC) and a continuous stirred tank reactor (CSTR) was developed for counteracting ammonia inhibition during anaerobic digestion (AD) with simultaneous in situ ammonia recovery and electricity production. The SMDC was powered by acetate in a buffer solution, while synthetic ammonia-rich wastewater was used as the feeding of the CSTR. Under continuous operation, ammonia recovery rate of 86 g-N/m(2) /day and current density of 4.33 A/m(2) were achieved at steady-state condition. As a result, 112% extra biogas was produced due to ammonia recovery by the SMDC. High-throughput sequencing showed that ammonia recovery had an impact on the microbial community structures in the SMDC and CSTR. Considering the additional economic benefits of biogas enhancement and possible wastewater treatment, the SMDC may represent a cost-effective and environmentally friendly method for waste resources recovery and biomethanation of ammonia-rich residues.

  19. Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy.

    Science.gov (United States)

    Gineste, Charlotte; Hernandez, Andres; Ivarsson, Niklas; Cheng, Arthur J; Naess, Karin; Wibom, Rolf; Lesko, Nicole; Bruhn, Helene; Wedell, Anna; Freyer, Christoph; Zhang, Shi-Jin; Carlström, Mattias; Lanner, Johanna T; Andersson, Daniel C; Bruton, Joseph D; Wredenberg, Anna; Westerblad, Håkan

    2015-12-01

    Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function and ultimately muscle weakness in these patients. In a mouse model of lethal mitochondrial myopathy, the muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an excessive mitochondrial Ca(2+) uptake in isolated muscle fibers that could be inhibited by the cyclophilin D (CypD) inhibitor, cyclosporine A (CsA). Here we show that the Tfam KO mice have increased CypD levels, and we demonstrate that this increase is a common feature in patients with mitochondrial myopathy. We tested the effect of CsA treatment on Tfam KO mice during the transition from a mild to terminal myopathy. CsA treatment counteracted the development of muscle weakness and improved muscle fiber Ca(2+) handling. Importantly, CsA treatment prolonged the lifespan of these muscle-specific Tfam KO mice. These results demonstrate that CsA treatment is an efficient therapeutic strategy to slow the development of severe mitochondrial myopathy.

  20. Personal values that support and counteract utilization of a screening test for prostate cancer.

    Science.gov (United States)

    Aavik, Toivo; Aavik, Anu; Punab, Margus

    2014-01-01

    The main aim of the current research was to discover the personal values that may support men's prostate cancer screening decisions in the future. We asked for participants' past behavior and future behavioral intentions, and also considered their real-life behavior. The sample consisted of 371 men, of which 93 were first-time patients at the Andrology Unit. The results show that Security value was related to past participation, while Achievement, Stimulation, and Traditions counteracted this. Present prostate-testing behavior was related only to higher Security values. Predictors of future behavioral intentions were Security, Self-direction, and Benevolence, which described 21% of the total variability. Considering informed decision-making processes, our results suggest that men who hold Security, Self-direction, and Benevolence values are more likely to participate in office-based initial screening. The study indicates the need to offer office-based initial screening to those age-eligible men whose values do not support participation.